研究者総覧

北山 丈二 (キタヤマ ジョウジ)

  • 臨床研究センター TR研究推進部 教授
Last Updated :2021/12/04

研究者情報

学位

  • 医学博士(東京大学)

ホームページURL

J-Global ID

プロフィール

  • Professor of Jichi Medical University

    Department of Surgical Oncology

    Research field is Tumor Biology and main clinical work is the treatment of peritoneal metastasis of gastric cancer (intraperitoneal chemotherapy).

研究キーワード

  • 癌免疫療法   腹膜播種   

研究分野

  • ライフサイエンス / 消化器外科学

研究活動情報

論文

  • Takumi Teratani, Naoya Kasahara, Tetsuo Ijichi, Yasuhiro Fujimoto, Yasunaru Sakuma, Naohiro Sata, Joji Kitayama
    Amino acids 2021年10月 
    Polyamines are important to the survival and activation of organs and tissues via a homeostatic cell-metabolic process, and the polyamine content in cytoplasm decreases with aging. Decreases in cellular polyamine have been known to augment mutagenesis and cell death. Thus, supplementary polyamine in food is important to the prevention of aging. Here we show the anti-aging effects of oral intake of polyamine using luciferase-transgenic rats. Healthy rats, 10-12 weeks old, were given foods containing 0.01% and 0.1% (w/w) of polyamine, as compared a control food without polyamine, for 4 weeks. Using a bioimaging system, the photon intensities seen in the whole bodies and livers of rats consuming 0.1% of polyamine in food were stronger than those in rats consuming 0.01% and 0% of polyamine. However, there were no differences between groups in other characteristics, such as liver damage and body weight. In conclusion, we found that polyamine intake can activate cells throughout the whole body, providing an anti-aging effect.
  • Yoshihiko Kono, Ryo Inoue, Takumi Teratani, Mineyuki Tojo, Yuko Kumagai, So Morishima, Koji Koinuma, Alan Kawarai Lefor, Joji Kitayama, Naohiro Sata, Hisanaga Horie
    Digestion 1 - 9 2021年10月 
    BACKGROUND/AIMS: Recent studies have demonstrated that the populations of several microbes are significantly increased in fecal samples from patients with colorectal cancer (CRC), suggesting their involvement in the development of CRC. The aim of this study was to identify microbes which are increased in distal CRCs and to identify the specific location of microbes increased in mucosal tissue around the tumor. METHODS: Tissue specimens were collected from surgical resections of 28 distal CRCs. Five samples were collected from each specimen (location A: tumor, B: adjacent normal mucosa, C: normal mucosa 1 cm proximal to the tumor, D: normal mucosa 3 cm proximally, and E: normal mucosa 6 cm proximally). The microbiota in the sample were analyzed using 16S rRNA gene amplicon sequencing and the relative abundance (RA) of microbiota compared among the 5 locations. RESULTS: At the genus level, the RA of Fusobacterium and Streptococcus at location A was the highest among the 5 locations, significantly different from that in location E. The dominant species of each genus was Fusobacterium nucleatum and Streptococcus anginosus. The RAs of these species gradually decreased from locations B to E with a statistically significant difference in F. nucleatum. The genus Peptostreptococcus also showed a similar trend, and the RA of Peptostreptococcus stomatis in location A was significantly associated with depth of tumor invasion and tumor size. CONCLUSION: Although the clinical relevance is not clear yet, these results suggest that F. nucleatum, S. anginosus, and P. stomatis can spread to the adjacent normal tissues and may change the surrounding microenvironment to support the progression of CRC.
  • Toru Takagi, Shin Saito, Shinichiro Yokota, Yuki Kaneko, Kazuya Takahashi, Rihito Kanamaru, Kentaro Kurashina, Yoshinori Hosoya, Joji Kitayama, Hirotoshi Kawata, Hiroyuki Osawa, Naohiro Sata
    Surgical case reports 7 1 146 - 146 2021年06月 
    BACKGROUND: Leiomyosarcoma is a rare tumor that could originate from the gastrointestinal tract, uterus, kidney, retroperitoneum, and the soft tissues of the extremities. It accounts for only 1% of all gastrointestinal mesenchymal tumors and primary leiomyosarcoma of the stomach is extremely rare. Most cases reported as leiomyosarcoma of the stomach before the development of KIT immunohistochemistry might be gastrointestinal stromal tumors (GISTs) of the stomach and only 18 cases of leiomyosarcoma of the stomach have been reported since early 2000s. We report here a patient with leiomyosarcoma of the stomach treated by laparoscopic and endoscopic cooperative surgery (LECS). CASE PRESENTATION: A 59-year-old man was referred to our hospital for an early gastric cancer, which was initially treated by endoscopic submucosal dissection. Six months after his initial treatment, a follow-up esophagogastroduodenoscopy revealed a small polypoid lesion at the lesser curvature of the proximal stomach, which appeared to be a hyperplastic polyp. However, one and a half years later, the lesion grew and showed more irregular surface. Biopsy at the time revealed smooth muscle cell proliferation suggestive of leiomyoma. Three years later, the lesion grew even larger and biopsy showed pleomorphic spindle cells. Immunohistochemical study showed positive staining for alpha-smooth muscle actin and desmin, but negative for c-kit and CD34. Ki-67 labeling index was nearly 60%. Based on these findings, the diagnosis of leiomyosarcoma was established. The patient subsequently underwent a partial gastrectomy by LECS. The patient is currently in good condition without recurrence or metastasis at 12 months after surgery. CONCLUSIONS: Leiomyosarcoma of the stomach is extremely rare. This is the first report of leiomyosarcoma of the stomach treated by LECS. We could also follow its appearance change through endoscopic examination for 3 years.
  • Suguru Yamada, Tsutomu Fujii, Tomohisa Yamamoto, Hideki Takami, Isaku Yoshioka, So Yamaki, Fuminori Sonohara, Kazuto Shibuya, Fuyuhiko Motoi, Satoshi Hirano, Yoshiak Murakami, Hitoshi Inoue, Masamichi Hayashi, Daisuke Hashimoto, Kenta Murotani, Joji Kitayama, Hideki Ishikawa, Yasuhiro Kodera, Mitsugu Sekimoto, Sohei Satoi
    Journal of gastrointestinal oncology 12 Suppl 1 S110-S117  2021年04月 
    Background: Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal malignancies globally. We have previously explored the clinical efficacy of intraperitoneal (IP) paclitaxel therapy for patients with PDAC and peritoneal metastasis, which demonstrated favourable response and disease control rates. However, the real implications of conversion surgery after IP therapy remain unclear. Methods: We conducted two multicenter clinical trials of IP therapy with paclitaxel in patients with PDAC and peritoneal metastasis. We focused on patients who underwent conversion surgery and investigated the long-term outcomes, particularly, initial recurrence patterns and long-term survival. Results: Seventy-nine patients with PDAC and peritoneal metastasis were treated, and 33 (41.8%) patients received SP (intravenous IP paclitaxel with S-1) and 46 (58.3%) were administered GAP (intravenous gemcitabine + nab-paclitaxel combined with IP paclitaxel) combination therapy. Of the 79 patients, 16 (20.3%) underwent conversion surgery. The median time to surgery was 9.0 (range, 4.1-13.0) months after the initiation of chemotherapy. Finally, 13 (81.3%) patients underwent R0 resection. Evans grade was IIA in nine patients, IIB in four patients, III in two patients, and IV in one patient. The median overall survival time in patients who underwent conversion surgery was 32.5 (range, 13.5-66.9) months. Twelve (75.0%) patients were found to have experienced recurrence after conversion surgery. Especially, peritoneal recurrence was observed in 50% of patients as the initial recurrence pattern. The median recurrence-free survival time was 9.2 (range, 5.1-32.8) months, and three patients have survived without recurrence to date. Conclusions: Our IP therapy displays promising clinical efficacy with acceptable tolerability in patients with PDAC and peritoneal metastasis. Although we could observe some super-responders in the cohort, further improvements in IP therapy are warranted.
  • Joji Kitayama, Shin Saito, Hironori Yamaguchi, Alan Kawarai Lefor, Hironori Ishigami, Naohiro Sata
    Annals of surgical oncology 28 7 3871 - 3872 2021年01月
  • Akira Saito, Mineyuki Tojo, Yuko Kumagai, Hideyuki Ohzawa, Hironori Yamaguchi, Hideyo Miyato, Ai Sadatomo, Daishi Naoi, Gaku Ota, Koji Koinuma, Hisanaga Horie, Alan Kawarai Lefor, Naohiro Sata, Joji Kitayama
    Heliyon 7 1 e05880  2021年01月 
    Aim: PD-1/PD-L1 blockade therapy is now widely used for the treatment of advanced malignancies. Although PD-L1 is known to be expressed by various host cells as well as tumor cells, the role of PD-L1 on non-malignant cells and its clinical significance is unknown. We evaluated cell type-specific expression of PD-L1 in colorectal cancer (CRC) specimens using multicolor flow cytometry. Methods: Single cell suspensions were made from 21 surgically resected CRC specimens, and immunostained with various mAbs conjugated with different fluorescent dyes. Tumor cells, stromal cells, and immune cells were identified as CD326(+), CD90(+) and CD45(+) phenotype, respectively. CD11b(+) myeloid cells, CD19(+) B cells and CD4(+) or CD8(+) T cells were also stained in different samples, and their frequencies in the total cell population and the ratio of PD-L1(+) cells to each phenotype were determined. Results: PD-L1 was expressed by all the cell types. The ratio of PD-L1(+) cells to CD326(+) tumor cells was 19.1% ± 14.0%, lower than those for CD90(+) stromal cells (39.6% ± 16.0%) and CD11b(+) myeloid cells (31.9% ± 14.3%). The ratio of PD-L1(+) cells in tumor cells correlated strongly with the ratio in stromal cells, while only weakly with that in myeloid cells. Tumor cells were divided into two populations by CD326 expression levels, and the PD-L1 positive ratios were inversely correlated with the rate of CD326 highly expressing cells as well as mean fluorescein intensity of CD326 in tumor cells, while positively correlated with the frequencies of stromal cells or myeloid cells in CRC. Conclusion: PD-L1 is differentially expressed on various cell types in CRC. PD-L1 on tumor cells may be upregulated together with CD326 downregulation in the process of epithelial mesenchymal transition. Quantification of cell type-specific expression of PD-L1 using multicolor flow cytometry may provide useful information for the immunotherapy of solid tumors.
  • Kazuya Takahashi, Kentaro Kurashina, Shin Saito, Rihito Kanamaru, Hideyuki Ohzawa, Hironori Yamaguchi, Hideyo Miyato, Yoshinori Hosoya, Alan Kawarai Lefor, Naohiro Sata, Joji Kitayama
    Cytometry. Part B, Clinical cytometry 2020年12月 [査読有り]
     
    BACKGROUND: The frequency of tumor cell dissemination in the peritoneal cavity is critically related to the progression of peritoneal metastases (PM). Recently, flow cytometry (FCM) has been successfully used to detect tumor cells in malignant effusions. METHODS: A total of 143 single cell suspensions derived from ascites or peritoneal lavages from patients with advanced gastric cancer (GC) were stained with monoclonal antibodies to CD45 and to CD326 as well as 4,6-diamidino-2-phenylindole (DAPI) and FVS780. Using FCM, tumor-leukocyte ratio (TLR) were calculated from CD45(-)CD326(+) tumor cell counts/ CD45(+)CD326(+) leukocyte counts in DAPI (+) FVS780(-) gated area. In 54 patients, the ratios of CD11b(+), CD4(+) and CD8(+) cells in CD45(+) leukocytes were evaluated in parallel. RESULTS: TLR of 69 patients with PM were significantly higher than those of 74 without PM (p < .001) and log(TLR) showed strong correlation with peritoneal cancer index scores in 51 PM (+) patients (r = 0.439). TLR in PM (+) patients also correlated with the ratio of CD11b (+) myeloid cells (r = 0.547), and correlated inversely with those of CD4(+) (r = -0.490) and CD8(+) T cells (r = -0.648). In PM (-) patients who underwent gastrectomy, TLR never exceeded 0.1% in patients with primary GC without serosal involvement (
  • Shin Saito, Hironori Yamaguchi, Hideyuki Ohzawa, Hideyo Miyato, Rihito Kanamaru, Kentaro Kurashina, Yoshinori Hosoya, Alan Kawarai Lefor, Naohiro Sata, Joji Kitayama
    Annals of surgical oncology 28 7 3863 - 3870 2020年12月 [査読有り]
     
    BACKGROUND: Intraperitoneal (IP) administration of paclitaxel (PTX) has a great pharmacokinetic advantage to control peritoneal lesions and can be combined with various systemic chemotherapies. In this study, we evaluate the efficacy and tolerability of a combination of IP-PTX and systemic S-1/oxaliplatin (SOX) for induction chemotherapy for patients with peritoneal metastases (PM) from gastric cancer (GC). PATIENTS AND METHODS: Patients with GC who were diagnosed as macroscopic PM (P1) or positive peritoneal cytology (CY1) by staging laparoscopy between 2016 and 2019 were enrolled. PTX was IP administered at 40 mg/m2 on days 1 and 8. Oxaliplatin was IV administered at 100 mg/m2 on day 1, and S-1 was administered at 80 mg/m2/day for 14 consecutive days, repeated every 21 days. Survival time and toxicities were retrospectively explored. RESULTS: Forty-four patients received SOX + IP-PTX with a median (range) of 16 (1-48) courses, although oxaliplatin was suspended due to the hematotoxicity or intolerable peripheral neuropathy in many patients. The 1-year overall survival (OS) rate was 79.5% (95% CI 64.4-88.8%) with median survival time of 25.8 months. Gastrectomy was performed in 20 (45%) patients who showed macroscopic shrinkage of PM with a 1-year OS rate of 100% (95% CI 69.5-100%). Grade 2 and 3 histological responses was achieved in four (20%) and one (5%) patients. Grade 3/4 toxicities included neutropenia (11%), leukopenia (39%), and anemia (14%). There were no treatment-related deaths. CONCLUSIONS: Combination chemotherapy using SOX + IP-PTX regimen is highly effective and recommended as induction chemotherapy for patients with PM from GC.
  • Hideyuki Ohzawa, Yuki Kimura, Akira Saito, Hironori Yamaguchi, Hideyo Miyato, Yasunaru Sakuma, Hisanaga Horie, Yoshinori Hosoya, Alan Kawarai Lefor, Naohiro Sata, Joji Kitayama
    Annals of surgical oncology 27 13 5057 - 5064 2020年12月 [査読有り]
     
    BACKGROUND: Repeat intraperitoneal (IP) chemotherapy has been successfully used for treatment of peritoneal metastases (PM) from gastric cancer (GC). Exosomes play important roles not only in tumor progression but also in chemoresistance via transfer of microRNAs (miRNAs). However, there is little evidence of an effect of miRNAs in peritoneal exosomes on chemosensitivity of peritoneal lesions. METHODS: In 74 patients with advanced GC who underwent staging laparoscopy, exosomes were isolated from peritoneal fluid and expression levels of miR-21-5p, miR-223-3p, and miR-29b-3p determined using TaqMan Advanced miRNA assays. In 43 patients with PM treated with combination chemotherapy, S-1 plus Oxaliplatin together with IP Paclitaxel, the relationship between their relative expression levels and outcomes was examined. RESULTS: The ratios of miR-21-5p/miR-29b-3p and miR-223-3p/miR-29b-3p were significantly upregulated in patients with PM, especially in patients with high serum CA125 levels. They showed a mild association with Peritoneal Cancer Index (PCI) score and ascites. More impressively, the ratios were significantly higher in 16 patients with progression of PM within 1 year compared with 27 patients with an excellent tumor response (miR-21-5p/miR-29b-3p: median 17.49, range 1.83-50.90 vs. median 4.64, range 0.40-38.96, p = 0.0015, miR-223-3p/miR-29b-3p: median 1.02, range 0.23-25.85 vs. median 0.21, range 0.01-50.07, p = 0.0006). Overall survival of patients with high miR-21/miR-29b or miR-223/miR-29b ratios was significantly worse than in patients with low ratios (p = 0.0117, p = 0.0021). CONCLUSIONS: The ratios of miRNAs in peritoneal exosome correlate with survival of the patients with PM from GC and suggest the possibility that they modify the chemosensitivity against IP chemotherapy.
  • Akira Saito, Joji Kitayama, Hisanaga Horie, Koji Koinuma, Hideyuki Ohzawa, Hironori Yamaguchi, Hiroshi Kawahira, Toshiki Mimura, Alan Kawarai Lefor, Naohiro Sata
    Cancer science 111 11 4012 - 4020 2020年11月 [査読有り]
     
    Accumulating evidence suggests that metformin reduces the incidence and mortality of colorectal cancer (CRC). However, underlying mechanisms have not been fully clarified. The aim of this study was to examine the pathological characteristics of resected CRC from patients treated with metformin for type 2 diabetes mellitus (DM). In total, 267 patients with DM underwent curative colectomy for Stage I-III CRC and 53 (19.9%) patients had been treated medically including metformin. Pathological N-stage was significantly lower in metformin-treated patients (P < .05) with prolonged disease-free survival (DFS) (P < .05). Immunohistochemistry showed that the densities of CD3(+) and CD8(+) tumor-infiltrating lymphocytes (TILs) in the invasive front area were significantly higher in 40 patients treated with metformin compared with propensity score matched cases without metformin (P < .05). The density of tertiary lymphoid structures (TLS) in tumor stroma was markedly increased in metformin-treated patients (P < .001). In those tumors, there were more CD68(+) tumor-associated macrophages (TAM) infiltrated (P < .05), while the ratio of CD163(+) M2-phenotype was markedly reduced (P < .001). Stromal fibrosis tended to be suppressed by metformin intake (P = .051). These findings suggested that metformin drastically changes the characteristics of infiltrating immune cells in CRC and reprograms the tumor microenvironment from immunosuppressive to immunocompetent status, which may lead to suppression of microscopic tumor spread and improve the outcomes of patients with CRC and type 2 DM.
  • Homare Ito, Hiroaki Kimura, Tadayoshi Karasawa, Shu Hisata, Ai Sadatomo, Yoshiyuki Inoue, Naoya Yamada, Emi Aizawa, Erika Hishida, Ryo Kamata, Takanori Komada, Sachiko Watanabe, Tadashi Kasahara, Takuji Suzuki, Hisanaga Horie, Joji Kitayama, Naohiro Sata, Kazuyo Yamaji-Kegan, Masafumi Takahashi
    Journal of immunology (Baltimore, Md. : 1950) 205 5 1393 - 1405 2020年09月 [査読有り][通常論文]
     
    Intestinal ischemia/reperfusion (I/R) injury is a life-threatening complication that leads to inflammation and remote organ damage. The NLRP3 inflammasome regulates the caspase-1-dependent release of IL-1β, an early mediator of inflammation after I/R injury. In this study, we investigated the role of the NLRP3 inflammasome in mice with intestinal I/R injury. Deficiency of NLRP3, ASC, caspase-1/11, or IL-1β prolonged survival after intestinal I/R injury, but neither NLRP3 nor caspase-1/11 deficiency affected intestinal inflammation. Intestinal I/R injury caused acute lung injury (ALI) characterized by inflammation, reactive oxygen species generation, and vascular permeability, which was markedly improved by NLRP3 deficiency. Bone marrow chimeric experiments showed that NLRP3 in non-bone marrow-derived cells was the main contributor to development of intestinal I/R-induced ALI. The NLRP3 inflammasome in lung vascular endothelial cells is thought to be important to lung vascular permeability. Using mass spectrometry, we identified intestinal I/R-derived lipid mediators that enhanced NLRP3 inflammasome activation in lung vascular endothelial cells. Finally, we confirmed that serum levels of these lipid mediators were elevated in patients with intestinal ischemia. To our knowledge, these findings provide new insights into the mechanism underlying intestinal I/R-induced ALI and suggest that endothelial NLRP3 inflammasome-driven IL-1β is a novel potential target for treating and preventing this disorder.
  • Hidenori Tsukui, Hisanaga Horie, Koji Koinuma, Hideyuki Ohzawa, Yasunaru Sakuma, Yoshinori Hosoya, Hironori Yamaguchi, Kotaro Yoshimura, Alan Kawarai Lefor, Naohiro Sata, Joji Kitayama
    BMC cancer 20 1 411 - 411 2020年05月 [査読有り]
     
    BACKGROUND: Anti-tumor effects of radiation therapy (RT) largely depend on host immune function. Adenosine with its strong immunosuppressive properties is an important immune checkpoint molecule. METHOD: We examined how intra-tumoral adenosine levels modify anti-tumor effects of RT in a murine model using an anti-CD73 antibody which blocks the rate-limiting enzyme to produce extracellular adenosine. We also evaluated CD73 expression in irradiated human rectal cancer tissue. RESULTS: LuM-1, a highly metastatic murine colon cancer, expresses CD73 with significantly enhanced expression after RT. Subcutaneous (sc) transfer of LuM-1 in Balb/c mice developed macroscopic sc tumors and microscopic pulmonary metastases within 2 weeks. Adenosine levels in the sc tumor were increased after RT. Selective RT (4Gyx3) suppressed the growth of the irradiated sc tumor, but did not affect the growth of lung metastases which were shielded from RT. Intraperitoneal administration of anti-CD73 antibody (200 μg × 6) alone did not produce antitumor effects. However, when combined with RT in the same protocol, anti-CD73 antibody further delayed the growth of sc tumors and suppressed the development of lung metastases presumably through abscopal effects. Splenocytes derived from RT+ CD73 antibody treated mice showed enhanced IFN-γ production and cytotoxicity against LuM-1 compared to controls. Immunohistochemical studies of irradiated human rectal cancer showed that high expression of CD73 in remnant tumor cells and/or stroma is significantly associated with worse outcome. CONCLUSION: These results suggest that adenosine plays an important role in the anti-tumor effects mediated by RT and that CD73/adenosine axis blockade may enhance the anti-tumor effect of RT, and improve the outcomes of patients with locally advanced rectal cancer.
  • Hideyuki Ohzawa, Akira Saito, Yuko Kumagai, Yuki Kimura, Hironori Yamaguchi, Yoshinori Hosoya, Alan Kawarai Lefor, Naohiro Sata, Joji Kitayama
    Oncology reports 43 4 1081 - 1088 2020年04月 [査読有り]
     
    The peritoneal surface is the most frequent site of metastasis disease in patients with gastric cancer. Even after curative surgery and adjuvant chemotherapy, peritoneal recurrences often develop. Exosomes play pivotal roles in tumor metastasis via the transfer of microRNAs (miRNAs). In the present study, exosomes were isolated from peritoneal lavage fluid or ascites in 85 patients with gastric cancer and the relative expression levels of miR‑29s were examined. The expression of miR‑29a‑3p, miR‑29b‑3p and miR‑29c‑3p in peritoneal exosomes were all downregulated in patients with peritoneal metastases (PM) compared to those without PM. In 30 patients who underwent curative gastrectomy with serosa‑involved (T4) gastric cancer, 6 patients exhibited recurrence in the peritoneum within 12 months. The expression levels of miR‑29s at gastrectomy tended to be lower in these 6 patients than in the other 24 patients with significant differences in miR‑29b‑3p (P=0.003). When the patients were divided into two groups based on median levels of miR‑29s, peritoneal recurrence developed more frequently in patients with low expression of miR‑29b‑3p, and lower expression of miR‑29s were related with worse overall survival. miR‑29s are thought to play a suppressive role in the growth of disseminated peritoneal tumor cells. Reduced expression of miR‑29b in peritoneal exosomes is a strong risk factor of developing postoperative peritoneal recurrence.
  • Yoshiyuki Meguro, Hironori Yamaguchi, Joji Kitayama, Rihito Kanamaru, Shiro Matsumoto, Takashi Ui, Hidenori Haruta, Kentaro Kurashina, Shin Saito, Yoshinori Hosoya, Alan Kawarai Lefor, Naohiro Sata
    Surgical case reports 6 1 63 - 63 2020年03月 [査読有り]
     
    BACKGROUND: Despite recent progress in systemic chemotherapy, the prognosis of patients with peritoneal metastases from gastric cancer is still poor. Efficacious intraperitoneal and systemic combination chemotherapy regimens to treat patients with peritoneal metastases have recently been developed. CASE PRESENTATION: A 74-year-old man with gastric cancer T4b (transverse mesocolon) N3 M1 (peritoneum) received combination chemotherapy with intraperitoneal administration of paclitaxel, intravenous oxaliplatin, and oral S-1. Eight courses of combined chemotherapy had remarkable anti-tumor effects on the primary lesion, lymph node metastases, and peritoneal metastases. Total gastrectomy with regional lymph node dissection was performed. Pathological examination revealed no viable tumor cells in the resected specimens. After gastrectomy, the patient received 25 courses of the same chemotherapy without oxaliplatin and has no evidence of recurrence 24 months later. DISCUSSION: Therapeutic approaches including systemic chemotherapy, extended resection, and heated intraperitoneal chemotherapy have been used to treat patients with peritoneal metastases. Repeat therapy with intraperitoneal paclitaxel has been used recently. Intraperitoneal administration of paclitaxel results in prolonged retention in the peritoneal cavity with effects against peritoneal metastases. Repeated administration of paclitaxel does not cause adhesions in the peritoneal cavity. When combination chemotherapy is effective, salvage gastrectomy is a promising option with minimal morbidity and mortality. CONCLUSION: Combined chemotherapy with intraperitoneal paclitaxel and systemic chemotherapy followed by gastrectomy is a promising strategy for patients with advanced gastric cancer and peritoneal metastases.
  • Yuko Kumagai, Hideyuki Ohzawa, Hideyo Miyato, Hisanaga Horie, Yoshinori Hosoya, Alan Kawarai Lefor, Naohiro Sata, Joji Kitayama
    The Journal of surgical research 246 52 - 61 2020年02月 [査読有り][通常論文]
     
    BACKGROUND: Low-density neutrophils (LDN) have been shown to be increased in peripheral blood in patients with various diseases and closely related to immune-mediated pathology. However, the frequency and function of LDN in circulating blood of the patients following abdominal surgery have not been well understood. METHODS: LDN were determined by CD66b(+) cells, which were copurified with mononuclear cells by density gradient preparations of peripheral blood of surgical patients. The effects of the purified LDN on T cell proliferation and tumor cell lysis were examined in vitro. Neutrophil extracellular traps (NETs) production was examined by extracellular nuclear staining. RESULTS: The number of LDN with an immature phenotype is markedly increased in peripheral blood samples in patients after abdominal surgery. The frequency of LDN correlated positively with operative time and intraoperative blood loss. The purified LDN significantly suppressed the proliferation of autologous T cells stimulated with anti-CD3 mAb coated on plate and partially inhibited the cytotoxicity of lymphocytes activated with recombinant interleukin-2 against a human gastric cancer cell, OCUM-1. The LDN also produced NETs after short-term culture in vitro, which efficiently trap many OCUM-1. These results suggest that surgical stress recruits immunosuppressive LDN in the circulation in the early postoperative period. CONCLUSIONS: The LDN may support the lodging of circulating tumor cells via NETs formation and inhibit T cell-mediated antitumor response in target organs, which may promote postoperative cancer metastases. Functional blockade of LDN might be an effective strategy to reduce tumor recurrence after abdominal surgery.
  • Daisuke Kobayashi, Hironori Ishigami, Mitsuro Kanda, Chie Tanaka, Hironori Yamaguchi, Joji Kitayama, Yasuhiro Kodera
    Oncology 98 1 48 - 52 2020年 [査読有り][通常論文]
     
    INTRODUCTION: Intraperitoneal (IP) chemotherapy is a promising treatment option for gastric cancer (GC) with peritoneal metastasis (PM). Recently, superiority of IP administration of paclitaxel (PTX) combined with S-1 and intravenous PTX over conventional systemic chemotherapy was suggested in a phase III study, although the difference in overall survival did not reach statistical significance in the primary analysis. Thus, attempts to combine IP PTX with other systemic therapies with higher efficacy are warranted. We designed a new regimen combining IP PTX with S-1 plus cisplatin (SP), which is regarded as the standard first-line treatment for metastatic GC in Japan, and subsequently carried out a dose-escalation study. METHODS: The combination was a 5-weekly regimen. IP PTX was to be administered on days 1, 8, and 22 with an initial dose of 15 mg/m2 at level 1 and 20 mg/m2 at level 2. S-1 was to be administered orally at a fixed dose of 80 mg/m2 b.i.d. for 21 days followed by a -14-day rest. Cisplatin was to be administered intravenously at a dose of 60 mg/m2 on day 8. Dose-limiting toxicities (DLTs) were defined as grade 4 leukopenia, grade 3 (G3) febrile neutropenia, G3 thrombocytopenia, and G3 nonhematological toxicity. RESULTS: A total of 9 patients with macroscopic PM were enrolled. No DLTs were observed among the 3 patients at level 1 and 6 patients at level 2. No adverse events or technical problems associated with the IP administration were observed. Consequently, the maximum-tolerated dose was not reached, and the dose for further clinical trials of IP PTX was determined as 20 mg/m2. As for efficacy, peritoneal lavage cytology turned negative after the first course in 4 of 7 patients who had positive cytology before treatment. CONCLUSION: The present study determined the dose for further clinical trials of IP PTX to be 20 mg/m2, when combined with the 5-weekly SP regimen.
  • Hideyuki Ohzawa, Yuko Kumagai, Hironori Yamaguchi, Hideyo Miyato, Yasunaru Sakuma, Hisanaga Horie, Yoshinori Hosoya, Alan Kawarai Lefor, Naohiro Sata, Joji Kitayama
    Annals of gastroenterological surgery 4 1 84 - 93 2020年01月 [査読有り]
     
    Aim: Peritoneal metastases (PM) frequently occur in patients with gastric cancer and result in a poor prognosis. Exosomes play pivotal roles in tumor metastasis through the transfer of microRNAs (miRNAs). We examined the exosomal miRNA profile in peritoneal fluids to identify novel biomarkers to reflect tumor burden in the peritoneum. Methods: Exosomes were isolated from peritoneal fluids of patients of gastric cancer with macroscopic (P1) or microscopic (P0CY1) peritoneal metastasis (PM) and comprehensive miRNA expression analysis was carried out. Expressions of candidate miRNAs were then validated in all 58 samples using TaqMan Advanced miRNA Assays. Results: In initial screening, we carried out comprehensive analysis of exosomal miRNA using peritoneal fluids from 11 and 14 patients with or without PM, respectively, and identified 11 dysregulated miRNAs in PM (+) samples. Validation analysis showed that four miRNAs (miR-21-5p, miR-92a-3p, miR-223-3p, and miR-342-3p) were significantly upregulated in 12 PM (+) samples, and their expression levels showed positive correlation with peritoneal cancer index. In contrast, miR-29 family were all downregulated in patients with PM (+) samples. Moreover, in 24 patients with pT4 tumor, miR-29 at gastrectomy tended to be lower in six patients with peritoneal recurrence with significant differences in miR-29b-3p (P = .012). Conclusion: Expression pattern of miRNAs in peritoneal exosomes well reflects the tumor burden in the peritoneal cavity and could be a useful biomarker in the treatment of PM.
  • Katsushi Suenaga, Shiro Matsumoto, Alan Kawarai Lefor, Yoshimasa Miura, Yoshinori Hosoya, Daigo Kuboki, Hidenori Haruta, Kentaro Kurashina, Atsushi Kihara, Daisuke Matsubara, Yasunari Sakuma, Joji Kitayama, Naohiro Sata
    International journal of surgery case reports 73 319 - 323 2020年 [査読有り][通常論文]
     
    INTRODUCTION: Gastric adenocarcinomas with low grade atypia may be difficult to diagnose as gastric cancer by preoperative biopsy. We report an extremely well-differentiated adenocarcinoma (EWDA) of the stomach which appeared like a submucosal tumor diagnosed by preoperative endoscopic submucosal dissection. PRESENTATION OF CASE: A 70-year-old male was referred with a 3-month history of a submucosal-appearing lesion in the gastric wall found on endoscopy. Biopsies of the lesion were performed and were inconclusive for neoplasia. Endoscopic ultrasonography showed a low echoic tumor growing into the fourth layer of the gastric wall. It was difficult to identify the tumor by repeat biopsy. Endoscopic submucosal dissection of the lesion was performed and revealed adenocarcinoma, and laparoscopic total gastrectomy was performed. Histopathologic evaluation showed that the tumor was stage IIA (T3N0M0). There is no recurrence 12 months after resection. DISCUSSION: Gastric EWDAs are rare lesions, accounting for 0.6% of all gastric cancers. It is difficult to diagnose gastric EWDA especially if it appears like a submucosal tumor. This lesion was finally diagnosed by endoscopic submucosal dissection. CONCLUSION: Endoscopic submucosal dissection may facilitate establishing the preoperative diagnosis of a tumor thought to be a gastric EWDA based on its endoscopic appearance and pathological findings.
  • Yuki Kaneko, Shin Saito, Kazuya Takahashi, Rihito Kanamaru, Yoshinori Hosoya, Hironori Yamaguchi, Joji Kitayama, Toshiro Niki, Alan Kawarai Lefor, Naohiro Sata
    Clinical journal of gastroenterology 12 6 534 - 538 2019年12月 [査読有り][通常論文]
     
    A 68-year-old male was referred with dysphagia. Endoscopic findings showed circular stenosis with a protruding mass in the lower esophagus. Biopsy showed adenocarcinoma and there was no evidence of distant metastases. A subtotal esophagectomy was performed. The resected specimen revealed a mixed neuroendocrine carcinoma with adenocarcinoma. The adenocarcinoma component was on the surface of the tumor and the neuroendocrine component invaded the deeper portion. Immunohistochemically, the neuroendocrine carcinoma component stained positive for cytokeratin 7 and cytokeratin 20, suggesting that the neuroendocrine carcinoma originated from the adenocarcinoma. The adenocarcinoma component stained positive for MUC2, which suggests that the adenocarcinoma component originated from Barrett's epithelium. Taken together, the neuroendocrine carcinoma may have originated from Barrett's epithelium. A metastasis to the liver was found 2 months after the surgical resection. Chemotherapy was administered, but there was no response. Most esophageal neuroendocrine carcinomas are accompanied by adenocarcinoma or squamous cell components, suggesting that these carcinomas originate from pluripotent cells in squamous or Barrett's epithelium. Appropriate chemotherapy for these lesions should be considered based on the cell of origin.
  • Homare Ito, Ai Sadatomo, Yoshiyuki Inoue, Naoya Yamada, Emi Aizawa, Erika Hishida, Ryo Kamata, Tadayoshi Karasawa, Hiroaki Kimura, Sachiko Watanabe, Takanori Komada, Hisanaga Horie, Joji Kitayama, Naohiro Sata, Masafumi Takahashi
    Biochemical and biophysical research communications 519 1 15 - 22 2019年10月 [査読有り][通常論文]
     
    BACKGROUND: Intestinal ischemia/reperfusion (I/R) injury is a life-threatening complication that leads to inflammation and remote organ damage. However, the underlying mechanism is not yet fully understood. Toll-like receptor 5 (TLR5) is highly expressed in mucosa and recognizes flagellin, the main component of the bacterial flagella. Here, we investigated the role of TLR5 in inflammation and tissue damage after intestinal I/R injury using TLR5-deficient mice. METHODS AND RESULTS: Intestinal levels of TLR5 mRNA and flagellin protein were elevated in wild-type mice subjected to intestinal I/R. Although TLR5 deficiency had no effect on intestinal flagellin levels, it significantly attenuated intestinal injury and inflammatory responses after intestinal I/R. TLR5 deficiency also markedly improved survival in mice after intestinal I/R injury. In wild-type mice, intestinal I/R injury induced remote organ damage, particularly in the lung, which was attenuated by TLR5 deficiency. Furthermore, TLR5 deficiency prevented lung inflammatory responses and vascular permeability after intestinal I/R injury. CONCLUSION: These findings demonstrate a novel role of TLR5 and provide new insights into the mechanism underlying inflammation and tissue damage after intestinal I/R injury.
  • Chieko Miyazaki, Mikio Shiozawa, Rintaro Koike, Kasumi Ogihara, Yumiko Sasaki, Satomi Shiba, Saki Nishida, Masako Sakuragi, Hirofumi Mizunuma, Takashi Fujita, Noriyoshi Fukushima, Alan K Lefor, Joji Kitayama, Naohiro Sata
    Journal of medical case reports 13 1 289 - 289 2019年09月 [査読有り][通常論文]
     
    BACKGROUND: Primary sarcoma of the breast is rare. Surgery has been the only curative treatment available. Recently, neoadjuvant chemotherapy including anthracycline/ifosfamide has been reported effective for patients with high-risk sarcomas in a prospective trial. CASE PRESENTATION: A 52-year-old Japanese woman presented with a mass in her left breast. The 10 cm tumor was fixed to her chest wall on examination. A skin biopsy was performed which showed leiomyosarcoma. Neoadjuvant chemotherapy was given and the tumor became mobile. A mastectomy and axillary dissection were performed with surgically negative margins. After neoadjuvant chemotherapy, the amount of necrosis was profoundly influenced by chemotherapy, and the histological effect of neoadjuvant chemotherapy was assessed in reference to pre-neoadjuvant chemotherapy magnetic resonance imaging. CONCLUSION: In contrast to many other cancers, the evaluation of various treatments and of the histological effect of neoadjuvant chemotherapy for sarcoma has been difficult due to the rarity of these tumors. We report the case of a patient with a breast sarcoma, treated with neoadjuvant chemotherapy and discuss the appropriate pathological evaluation and therapeutic management.
  • Akira Saito, Hideyuki Ohzawa, Mineyuki Tojo, Yuko Kumagai, Rihito Kanamaru, Hidenori Tsukui, Satomi Shiba, Homare Ito, Naohiro Sata, Joji Kitayama
    CANCER RESEARCH 79 13 2019年07月
  • Shiro Matsumoto, Yoshinori Hosoya, Alan K Lefor, Yuji Ino, Hidenori Haruta, Kentaro Kurashina, Shin Saito, Joji Kitayama, Naohiro Sata
    Asian journal of endoscopic surgery 12 3 322 - 325 2019年07月 [査読有り][通常論文]
     
    Gastrointestinal stromal tumors (GIST) in patients under 18 years of age are classified as pediatric GIST. Pediatric GIST are extremely rare, and there are no reports of laparoscopic-endoscopic cooperative surgery for these lesions. We report the use of non-exposed endoscopic wall-inversion surgery as a laparoscopic-endoscopic cooperative surgery-related procedure for the treatment of a pediatric GIST. The case involved a 17-year-old male patient who presented with anemia and was found to have a bleeding gastric tumor. The tumor was resected transorally using the non-exposed endoscopic wall-inversion surgery technique. No gene mutation of c-Kit or Platelet-Derived Growth Factor Receptor α (PDGFRα) was found, and the final pathological diagnosis was epithelial-type GIST due to a succinate dehydrogenase abnormality. Follow-up included a CT scan every 4 months. No recurrence has occurred to date.
  • Satomi Shiba, Atsushi Miki, Hideyuki Ohzawa, Takumi Teratani, Yasunaru Sakuma, Alan Kawarai Lefor, Joji Kitayama, Naohiro Sata
    The Journal of surgical research 238 79 - 89 2019年06月 [査読有り][通常論文]
     
    OBJECTIVE: Mucin1 (MUC1), a member of the mucin family, is a glycoprotein which is often expressed in malignant cells. However, the expression and function of MUC1 in human duodenal adenocarcinoma (DAC) has not yet been characterized because of its low frequency. Here, we examined the functional roles of core protein (MUC1-C) in DAC. MATERIALS AND METHODS: Using a human duodenal cancer cell line, HuTu80, proliferation, migration, invasion, ALDH activity was assessed by cell counting kit-8, scratch wound healing, matrigel invasion, and ALDEFUOR assays, respectively. The function of MUC1 protein was evaluated with knockdown using specific siRNA as well as anti-MUC1-C peptide, GO203. MUC1 expression in human DAC was evaluated immunohistochemically in surgically resected tumors. RESULTS: The positive expression of MUC1 in HuTu80 was confirmed by RT-PCR and flow cytometry. In vitro cell growth was inhibited by the addition of 50-100 μM GO203 as well as treatment with siRNA for MUC1-C. Silencing of MUC1-C also significantly reduced migration, invasion, ALDH activity. Local injection of GO-203 (14 mg/kg) significantly suppressed the growth of subcutaneous HuTu80 tumors in nude mice. Immunohistochemically, MUC1 was strongly detected in seven DAC cases, but not in 11 others. The outcome of patients with high MUC1 expression was significantly worse than those without MUC1 expression. CONCLUSIONS: These results suggest that MUC1 is functionally associated with the malignant potential of DAC and could be a novel therapeutic target for this rare tumor.
  • Yuki Kaneko, Shin Saito, Daijiro Takahashi, Takashi Ui, Hidenori Haruta, Kentaro Kurashina, Hironori Yamaguchi, Yoshinori Hosoya, Joji Kitayama, Alan Kawarai Lefor, Naohiro Sata
    International journal of surgery case reports 62 140 - 143 2019年 [査読有り][通常論文]
     
    INTRODUCTION: Immune thrombocytopenic purpura is an acquired thrombocytopenia. Preoperative management of thrombocytopenia is important in patients with gastric cancer. Partial splenic embolization can be effective for patients with thrombocytopenia, but could lead to ischemic necrosis of the remnant stomach when performing subtotal gastrectomy with splenectomy. PRESENTATION OF CASE: The patient is an 84-year old woman evaluated for anemia. Endoscopy revealed an advanced gastric cancer with bleeding. The patient also had immune thrombocytopenic purpura with a platelet count <50,000/μL. Administration of platelets did not increase the platelet count. Partial splenic embolization was performed followed by administration of high-dose immunoglobulin. The platelet count was over 50,000/μL preoperatively. The patient underwent combined subtotal gastrectomy and splenectomy, followed by an uneventful course. DISCUSSION: Patients with immune thrombocytopenic purpura and advanced gastric cancer can have anemia. Partial splenic embolization has been used to treat patients with refractory immune thrombocytopenic purpura as an alternative to splenectomy. Preoperative partial splenic embolization and high-dose immunoglobulin therapy resulted an increased platelet count in this patient. Elderly patients with gastric cancer have a high risk of postoperative complications. Patients with gastric cancer undergoing total gastrectomy have an impaired postoperative quality of life compared to those who undergo subtotal gastrectomy. We performed a subtotal gastrectomy and splenectomy as a function-preserving operation, completed safely by maintaining blood flow to the remnant stomach. CONCLUSION: Partial splenic embolization is effective for patients with immune thrombocytopenic purpura and gastric cancer. Combined subtotal gastrectomy and splenectomy is achieved by preserving blood flow to the remnant stomach.
  • Kazuya Takahashi, Shin Saito, Yuki Kaneko, Shiro Matsumoto, Hironori Yamaguchi, Joji Kitayama, Yoshinori Hosoya, Hirotoshi Kawata, Alan Kawarai Lefor, Naohiro Sata
    International journal of surgery case reports 64 180 - 183 2019年 [査読有り][通常論文]
     
    INTRODUCTION: Gastric hyperplastic polyps are common stomach lesion and these polyps are generally benign. However, they can undergo malignant transformation. Most reported cases of malignant transformation of gastric hyperplastic polyps have been to well or moderately differentiated adenocarcinoma, and those transformed into poorly differentiated adenocarcinoma are extremely rare. No case has been reported that has changed to diffuse type adenocarcinoma with lymphatic invasion. PRESENTATION OF CASE: A 48-year-old woman presented with worsening anemia. A polyp was seen in the gastric cardia seven years prior to presentation. Helicobacter pylori infection was also found at that time. She underwent upper gastrointestinal endoscopy and biopsy of the polyp revealed signet ring cell carcinoma. Total gastrectomy was performed due to concern about possible invasion into the submucosal layer and there was no evidence of distant metastases. Histologic examination revealed both poorly differentiated adenocarcinoma and signet ring cell carcinoma surrounded by hyperplastic epithelium at the head of the polyp. Lymphatic invasion was also found, and malignant cells were limited to the mucosa. DISCUSSION: Gastric hyperplastic polyps are commonly associated with chronic gastritis which is related to Helicobacter pylori infections. Gastric hyperplastic polyps are generally benign and rarely undergo malignant transformation to adenocarcinoma with differentiated histology. The gastric hyperplastic polyp in this patient transformed to poorly differentiated adenocarcinoma with lymphatic invasion. CONCLUSION: Even small polyps may become poorly differentiated adenocarcinoma with invasion, so close follow-up or endoscopic resection are recommended as well as eradication of Helico Pylori infection when appropriate.
  • Rihito Kanamaru, Hideyuki Ohzawa, Hideyo Miyato, Hironori Yamaguchi, Yoshinori Hosoya, Alan Kawarai Lefor, Naohiro Sata, Joji Kitayama
    Journal of visualized experiments : JoVE 138 2018年08月 [査読有り][通常論文]
     
    Activated neutrophils release neutrophil extracellular traps (NETs), which can capture and destroy microbes. Recent studies suggest that NETs are involved in various disease processes, such as autoimmune disease, thrombosis, and tumor metastases. Here, we show a detailed in vitro technique to detect NET activity during the trapping of free tumor cells, which grow after attachment to NETs. First, we collected low density neutrophils (LDN) from postoperative peritoneal lavage fluid from patients who underwent laparotomies. Short-term culturing of LDN resulted in massive NET formation that was visualized with green fluorescent nuclear and chromosome counterstain. After co-incubation of human gastric cancer cell lines MKN45, OCUM-1, and NUGC-4 with the NETs, many tumor cells were trapped by the NETs. Subsequently, the attachment was completely abrogated by the degradation of NETs with DNase I. Time-lapse video revealed that tumor cells trapped by the NETs did not die but instead grew vigorously in a continuous culture. These methods may be applied to the detection of adhesive interactions between NETs and various types of cells and materials.
  • Hironori Ishigami, Yoshiyuki Fujiwara, Ryoji Fukushima, Atsushi Nashimoto, Hiroshi Yabusaki, Motohiro Imano, Haruhiko Imamoto, Yasuhiro Kodera, Yoshikazu Uenosono, Kenji Amagai, Shigenori Kadowaki, Hiroto Miwa, Hironori Yamaguchi, Takuhiro Yamaguchi, Tempei Miyaji, Joji Kitayama
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology 36 19 1922 - 1929 2018年07月 [査読有り][通常論文]
     
    Purpose Intraperitoneal paclitaxel plus systemic chemotherapy demonstrated promising clinical effects in patients with gastric cancer with peritoneal metastasis. We aimed to verify its superiority over standard systemic chemotherapy in overall survival. Patients and Methods This randomized phase III trial enrolled patients with gastric cancer with peritoneal metastasis who had received no or short-term (< 2 months) chemotherapy. Patients were randomly assigned at a two-to-one ratio to receive intraperitoneal and intravenous paclitaxel plus S-1 (IP; intraperitoneal paclitaxel 20 mg/m2 and intravenous paclitaxel 50 mg/m2 on days 1 and 8 plus S-1 80 mg/m2 per day on days 1 to 14 for a 3-week cycle) or S-1 plus cisplatin (SP; S-1 80 mg/m2 per day on days 1 to 21 plus cisplatin 60 mg/m2 on day 8 for a 5-week cycle), stratified by center, previous chemotherapy, and extent of peritoneal metastasis. The primary end point was overall survival. Secondary end points were response rate, 3-year overall survival rate, and safety. Results We enrolled 183 patients and performed efficacy analyses in 164 eligible patients. Baseline characteristics were balanced between the arms, except that patients in the IP arm had significantly more ascites. The median survival times for the IP and SP arms were 17.7 and 15.2 months, respectively (hazard ratio, 0.72; 95% CI, 0.49 to 1.04; stratified log-rank P = .080). In the sensitivity analysis adjusted for baseline ascites, the hazard ratio was 0.59 (95% CI, 0.39 to 0.87; P = .008). The 3-year overall survival rate was 21.9% (95% CI, 14.9% to 29.9%) in the IP arm and 6.0% (95% CI, 1.6% to 14.9%) in the SP arm. Both regimens were well tolerated. Conclusion This trial failed to show statistical superiority of intraperitoneal paclitaxel plus systemic chemotherapy. However, the exploratory analyses suggested possible clinical benefits of intraperitoneal paclitaxel for gastric cancer.
  • Homare Ito, Yoshiyuki Inoue, Ai Sadatomo, Naoya Yamada, Ryo Kamata, Sachiko Watanabe, Tadayoshi Karasawa, Hiroaki Kimura, Yasunaru Sakuma, Hisanaga Horie, Yoshinori Hosoya, Joji Kitayama, Naohiro Sata, Masafumi Takahashi
    GASTROENTEROLOGY 154 6 S497 - S497 2018年05月 
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  • Daishi Naoi, Hisanaga Horie, Koji Koinuma, Yoshiyuki Inoue, Homare Ito, Yosihiko Kono, Katsusuke Mori, Makiko Tahara, Ai Sadatomo, Yasunaru Sakuma, Yoshinori Hosoya, Joji Kitayama, Alan K. Lefor, Naohiro Sata
    GASTROENTEROLOGY 154 6 S1351 - S1351 2018年05月 
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  • Joji Kitayama, Hironori Ishigami, Hironori Yamaguchi, Yasunaru Sakuma, Hisanaga Horie, Yoshinori Hosoya, Alan Kawarai Lefor, Naohiro Sata
    Annals of gastroenterological surgery 2 2 116 - 123 2018年03月 [査読有り][通常論文]
     
    Despite recent advances in chemotherapy, outcomes of patients with peritoneal metastases (PM) from gastric cancer are still very poor and standard treatment has not been established. Although oral S-1 appears to be effective for patients with PM, the effects of systemic chemotherapy are limited. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) yield fewer benefits in patients with PM from gastric cancer than in patients with PM from other malignancies. In comparison, repeated intraperitoneal chemotherapy (RIPEC) with taxanes using an implantable peritoneal access port has a pharmacokinetic advantage for the control of peritoneal lesions and in combination with systemic chemotherapy can result in surprisingly long-term survival in patients with PM from gastric cancer. Herein, we review the results of recent clinical studies specifically targeting PM from gastric cancer and discuss future prospects for an intraperitoneal approach to the ideal treatment of patients with gastric cancer with peritoneal involvement.
  • Rihito Kanamaru, Hideyuki Ohzawa, Hideyo Miyato, Shiro Matsumoto, Hidenori Haruta, Kentaro Kurashina, Shin Saito, Yoshinori Hosoya, Hironori Yamaguchi, Hiroharu Yamashita, Yasuyuki Seto, Alan Kawarai Lefor, Naohiro Sata, Joji Kitayama
    Scientific reports 8 1 632 - 632 2018年01月 [査読有り][通常論文]
     
    Many types of immune cells appear in peritoneal cavity after abdominal surgery. In patients who underwent laparotomy due to gastric cancer, peritoneal lavages were obtained before and after surgical procedure. Cells were recovered from intermediate layer after Ficoll-Hypaque centrifugation and analyzed for phenotypes and functions, especially focused on low density neutrophils (LDN). The number of CD66b (+) LDN with mature phenotype was markedly elevated in postoperative as compared with preoperative lavages. Short term culture of the purified LDN produced many threadlike structures positive for SYTOX, nucleic acid staining, as well as histone and myeloperoxidase, suggesting the NETs formation. Human gastric cancer cells, MKN45, OCUM-1 and NUGC-4, were selectively attached on the NETs, which was totally abolished by the pretreatment of DNAse I. Intraperitoneal (IP) co-transfer of the LDN with MKN45 in nude mice strongly augments the metastasis formation on peritoneum, which was strongly suppressed by the following IP administration of DNAse I. Many NETs-like structures were detected on the surface of human omental tissue resected by gastrectomy. NETs on peritoneal surface can assist the clustering and growth of free tumor cells disseminated in abdomen. Disruption of the NETs by DNAse might be useful to prevent the peritoneal recurrence after abdominal surgery.
  • Shiro Matsumoto, Yoshinori Hosoya, Alan Kawarai Lefor, Hidenori Haruta, Takashi Ui, Kentaro Kurashina, Shin Saito, Kentaro Ashizawa, Takahiro Sasaki, Joji Kitayama, Naohiro Sata
    International journal of surgery case reports 44 118 - 121 2018年 [査読有り][通常論文]
     
    INTRODUCTION: Black adrenal adenoma (BAA) is a rare, benign adrenal lesion with a black or brown appearance. This is the first report of this lesion in a patient with a synchronous esophageal cancer and highlights the importance of considering a false positive finding on a Positron Emission Tomography (PET) scan, which might otherwise preclude resection. PRESENTATION OF CASE: A 73-year-old male was diagnosed with mid-esophagus carcinoma. Computed tomography scan revealed an enlarged left adrenal gland. Plasma adrenocorticotropic hormones levels were normal. To characterize the adrenal lesion, a PET scan was obtained which showed high uptake of 18F-fluoro-2-deoxy-d-glucose (FDG), consistent with a metastasis, suggesting T3N2M1, clinical stage IV esophageal cancer. After two courses of neo-adjuvant therapy, sub-total esophagectomy and left adrenalectomy were performed. The adrenal tumor was soft, and black in color, diagnosed as a BAA on histology. The pathologic stage of the esophageal cancer was T3N0M0, Stage II. Six months after surgery, he is alive without recurrence. DISCUSSION: High FDG uptake by an adrenal lesion on PET scan, as in this patient, usually suggests a metastatic lesion. Although rare, patients with esophageal cancer and adrenal metastases have been reported to have long-term survival, so it is important to characterize an adrenal lesion when found. CONCLUSION: Most adrenal lesions with high FDG uptake are malignant, but BAA is also positive on PET scan. Although rare, BAA should be considered in patients with solitary adrenal lesions with high uptake on PET scan, even in the presence of a malignancy.
  • Shin Saito, Chao Yan, Hisashi Fukuda, Yoshinori Hosoya, Shiro Matsumoto, Daisuke Matsubara, Joji Kitayama, Alan Kawarai Lefor, Naohiro Sata
    International journal of surgery case reports 44 207 - 211 2018年 [査読有り][通常論文]
     
    INTRODUCTION: Gastric leiomyomas are benign mesenchymal tumors, comprising about 2.5% of gastric neoplasms, which can be difficult to differentiate from gastrointestinal stromal tumors which have malignant potential. Granular cell tumors in the abdominal wall are also rare. Since mesenchymal tumors are difficult to diagnose by imaging, further studies are needed to establish the diagnosis. PRESENTATION OF CASE: A 60-year-old asymptomatic woman underwent routine upper endoscopy and was found to have a gastric submucosal lesion. Computed tomography scan also showed an abdominal wall mass. The appearance of both lesions on imaging studies were similar, but it was unclear if the two lesions had the same origin. Endoscopic ultrasound-guided fine needle aspiration biopsy of the gastric lesion was insufficient to establish the diagnosis. Laparoscopic-endoscopic cooperative resection of the gastric lesion and ultrasound-guided core-needle biopsy of the abdominal wall mass enabled pathological diagnosis of both lesions. DISCUSSION: Diagnostic imaging findings of these two lesions were similar. Histologic and immunohistochemical studies are essential to establish a definitive diagnosis. Laparoscopic-endoscopic cooperative surgery may be an effective minimally invasive approach, allowing both pathological diagnosis and complete resection of a gastric submucosal tumor, especially when endoscopic-ultrasound guided fine needle aspiration or biopsy fails to make the diagnosis. CONCLUSION: Laparoscopic-endoscopic cooperative surgery can be an effective minimally invasive approach to resect some lesions. This is first report of the patient with a synchronous gastric leiomyoma and an intramuscular granular cell tumor in the abdominal wall.
  • Kazuhito Sato, Toshiaki Tanaka, Jiro Sato, Eisuke Shibata, Yuzo Nagai, Koji Murono, Koji Yasuda, Kensuke Otani, Takeshi Nishikawa, Junichiro Tanaka, Tomomichi Kiyomatsu, Keisuke Hata, Kazushige Kawai, Hiroaki Nozawa, Shinsuke Kazama, Hironori Yamaguchi, Soichiro Ishihara, Eiji Sunami, Joji Kitayama, Kuni Ohtomo, Toshiaki Watanabe
    Asian journal of surgery 40 6 438 - 443 2017年11月 [査読有り][通常論文]
     
    BACKGROUND: Computed tomographic colonography (CTC) is reported to be feasible for screening of colorectal polyps; however, its efficacy in preoperative workup remains unknown. This study was done to define our CTC methodology and assess CTC's potential for preoperative examination in patients with colon cancer. METHODS: A total of 86 colon cancer patients underwent CTC prior to laparoscopic colectomy in our department from February 2014 to November 2015. The location of primary colon cancer determined by CTC was compared with that confirmed during the surgery. CTC was performed just after preoperative colonoscopy; for a small colon cancer, we performed clipping during colonoscopy to enhance CTC detectability. We classified wall deformities and compared them with the pathological T stage. RESULTS: CTC accurately located all 87 primary colon cancers prior to surgery. No patient experienced complications associated with CTC. The deformity classification correlated significantly with the pathological T stage (p < 0.001, Kruskal-Wallis nonparametric tests). CTC provided reconstructed images depicting the feeding artery of the primary colon cancer; feeding artery information obtained by CTC facilitated precise lymph node dissection. CONCLUSION: CTC appears to be a feasible and useful preoperative examination modality for colon cancer treatment.
  • Hironori Yamaguchi, Yumiko Satoh, Hironori Ishigami, Makiko Kurihara, Yutaka Yatomi, Joji Kitayama
    Annals of surgical oncology 24 11 3345 - 3352 2017年10月 [査読有り][通常論文]
     
    BACKGROUND: The outcome of gastric cancer patients with peritoneal metastasis remains poor. We treated these patients with intraperitoneal and intravenous paclitaxel plus oral S-1 (tegafur/gimeracil/oteracil), followed by gastrectomy in responders. We evaluated the clinical significance of peritoneal lavage carcinoembryonic antigen (CEA) messenger RNA (mRNA) levels as a biomarker for indication of conversion gastrectomy. METHODS: The peritoneal lavage of 68 patients who received the above regimen as induction chemotherapy was repeatedly collected via intraperitoneal access ports. Gastrectomy was considered when improvement of peritoneal metastasis was confirmed by a second laparoscopic examination with negative peritoneal cytology. CEA and porphobilinogen deaminase mRNAs were chronologically quantified using the transcription reverse-transcription concerted reaction method. The CEA mRNA index (CmRI) was calculated as CEA mRNA/porphobilinogen deaminase mRNA × 10,000. RESULTS: Thirty-nine patients underwent gastrectomy and 29 patients did not (median survival time, 27.8 vs. 10.7 months, respectively; P < 0.001). In gastrectomy-positive patients, the outcome largely differed according to CmRI values immediately prior to surgery. Patients with a preoperative CmRI value <100 (n = 20) were associated with a significantly longer survival than those with a preoperative CmRI value >100 (n = 19) (41.8 vs. 20.1 months, respectively; P < 0.001). A preoperative CmRI value <100 was confirmed as an independent predictor of survival for gastrectomy-positive patients in the multivariate analysis. CONCLUSIONS: The CmRI reflects the response of peritoneal metastases to induction intraperitoneal chemotherapy. It may be a useful biomarker for indicating gastrectomy in gastric cancer patients with peritoneal metastasis.
  • Shin Saito, Misuzu Nakamura, Yoshinori Hosoya, Joji Kitayama, Alan Kawarai Lefor, Naohiro Sata
    Annals of medicine and surgery (2012) 22 34 - 38 2017年10月 [査読有り][通常論文]
     
    BACKGROUND: Patients with esophageal cancer and a history of gastrectomy or concurrent gastric cancer undergo not only esophagectomy but also total gastrectomy. The goal of this study is to evaluate the postoperative quality of life (QOL) and dysfunction of these patients using two postoperative questionnaires. MATERIALS AND METHODS: From 1999 to 2015, 41 patients underwent concurrent esophagectomy and total gastrectomy. A jejunal pedicle with the subcutaneous supercharge technique was used for reconstruction. Patients were divided into two groups, including those undergoing concurrent esophagostomy and gastrectomy (Group 1), and those undergoing esophagectomy alone (Group 2, history of previous gastrectomy). Patients were analyzed by time interval, including patients within three years of surgery (Group A) and those more than three years after surgery (Group B). RESULTS: Eighteen patients completed the questionnaires. The mean DAUGS20 score was 26.4 ± 13.2. The DAUGS20 scores of groups 1 (N = 7) and 2 (N = 11) were 25.4 ± 12.5 and 27 ± 15.4 (p = 0.58), respectively. Global health status scored by the EORTC QLQC-30 were 71.4 ± 18.5 in group 1 and 67.4 ± 22.8 in group 2 (p = 0.85). DAUGS20 scores of group A (N = 10) and B (N = 8) were 28.1 ± 12.4 and 23.3 ± 14.4 (p = 0.35). No significant differences were found between groups A and B regarding the QLQ-C30 scores. CONCLUSION: DAUGS20 and QLQ-C30 scores showed no significant differences between groups 1 and 2 or groups A and B. These results suggest that postoperative QOL and dysfunction may be influenced more by current status than by surgical history and postoperative interval. Previous reports describe a DAUGS 20 score after gastrectomy of 27.8 and after esophagectomy of 36.1. The DAUGS20 score of these 18 patients is lower than DAUGS20 scores for patients undergoing either operation alone. Reconstruction using a subcutaneously placed jejunal segment seems to be reasonable.
  • Seiichi Ohta, Shota Hiramoto, Yuki Amano, Shigenobu Emoto, Hironori Yamaguchi, Hironori Ishigami, Joji Kitayama, Taichi Ito
    Molecular pharmaceutics 14 9 3105 - 3113 2017年09月 [査読有り][通常論文]
     
    Intraperitoneal administration of chemotherapeutics is expected for the treatment of peritoneally disseminated gastric cancer because of poor migration of the drugs from the systemic circulation to the peritoneal cavity. In this study, for intraperitoneal delivery of cisplatin (CDDP), we developed a hyaluronan (HA)-based hybrid system in which CDDP-loaded HA nanogels were either physically encapsulated in or chemically conjugated to injectable HA hydrogels. Physical encapsulation enabled sustained release of HA nanogels from the HA hydrogel matrix for over a week. This was a longer release period than that of encapsulated free CDDP, which released 80% of the drug in 2 days. The longer release was attributed to delayed diffusion of HA nanogels from the hydrogel matrix network. The release profile could be tuned by modifying the chemical conjugation of HA nanogels to the HA hydrogel matrix, as well as the type of chelating ligands used to load CDDP to the nanogel. Furthermore, intraperitoneally administered hybrid had significant antitumor activity in a mouse model of peritoneally disseminated gastric cancer, especially for nodules smaller than 1.0 mm.
  • H. Ishigami, H. Yamaguchi, H. Yamashita, M. Asakage, J. Kitayama
    ANNALS OF ONCOLOGY 28 2017年09月 [査読無し][通常論文]
  • H. Yamaguchi, Y. Sato, H. Ishigami, H. Oozawa, M. Kurihara, Y. Yatomi, J. Kitayama
    ANNALS OF ONCOLOGY 28 2017年09月 [査読無し][通常論文]
  • Hidenori Tsukui, Rihito Kanamaru, Ai Sadatomo, Daishi Naoi, Tetsuichiro Shimizu, Makiko Tahara, Katsusuke Mori, Homare Ito, Mitsuaki Morimoto, Yoshihiko Kono, Yoshiyuki Inoue, Hiroyuki Maruyama, Koji Koinuma, Hisanaga Horie, Yasunaru Sakuma, Yoshinori Hosoya, Naohiro Sata, Joji Kitayama
    CANCER RESEARCH 77 2017年07月
  • Joji Kitayama, Hironori Ishigami, Hironori Yamaguchi, Jun Yamada, Daisuke Soma, Hideyo Miyato, Takao Kamei, Alan Kawarai Lefor, Naohiro Sata
    Pleura and peritoneum 2 2 95 - 102 2017年06月 [査読有り][通常論文]
     
    Background: Repeated intraperitoneal (IP) administration of paclitaxel (PTX) with concurrent systemic chemotherapy is clinically effective for the treatment of peritoneal metastases (PM) from gastric cancer. However, it is unclear how biochemical modifications may affect the pharmacokinetics and bioavailability of IP administered PTX. Methods: In a xenograft PM model using human gastric cancer cells, MKN45, fluorescein-conjugated PTX (OG-PTX) was given IP and the intra-tumor distribution of PTX examined with fluorescein microscopy. Results: After IP injection, PTX was seen to directly infiltrate up to several hundred micrometers from the surface of the PM. Co-injection with 5 % non-animal stabilized hyaluronic acid increased PTX infiltration and suppressed the development of PM more efficiently than PTX alone. PTX solubilized with amphiphilic polymer composed of 2-methacryloyloxyethyl phosphorylcholine (MPC) and n-butyl methacrylate (BMA) efficiently formed a micellar formation 50-100 nm in diameter. IP injection of the nanomicellar PTX (PTX-30W) also showed significantly enhanced tumor infiltration and further inhibition of the growth of PM compared with PTX solubilized with Cremophor-ethanol (PTX-Cre). Finally, IP administration of NK105, another nanomicellar PTX, inhibited the growth of subcutaneous tumors as well as PM, compared with conventional PTX-Cre in the same murine model. Conclusions: PTX administered IP directly infiltrates PM and are thus a useful strategy for the treatment of PM. Drug modification with nanotechnology may further enhance penetration of PM resulting in improved clinical efficacy.
  • Ryoji Fukushima, Hironori Ishigami, Hiroto Miwa, Motohiro Imano, Daisuke Kobayashi, Yasushi Tsuji, Akio Hidemura, Tetsuya Kusumoto, Takeshi Omori, Hiroshi Yabusaki, Norifumi Ohashi, Mitsuhiko Ota, Hironori Yamaguchi, Joji Kitayama
    JOURNAL OF CLINICAL ONCOLOGY 35 2017年05月 [査読無し][通常論文]
  • Shigenobu Emoto, Makoto Kurano, Kuniyuki Kano, Keisuke Matsusaki, Hiroharu Yamashita, Masako Nishikawa, Koji Igarashi, Hitoshi Ikeda, Junken Aoki, Joji Kitayama, Yutaka Yatomi
    Journal of lipid research 58 4 763 - 771 2017年04月 [査読有り][通常論文]
     
    Lysophosphatidic acid (LysoPA) has been proposed to be involved in the pathogenesis of various cancers. Moreover, glycero-lysophospholipids (glycero-LysoPLs) other than LysoPA are now emerging as novel lipid mediators. Therefore, we aimed to elucidate the possible involvement of glycero-LysoPLs in the pathogenesis of gastric cancer by measuring glycero-LysoPLs, autotaxin (ATX), and phosphatidylserine-specific phospholipase A1 (PS-PLA1) in ascites obtained from patients with gastric cancer and those with cirrhosis (as a control). We observed that after adjustments according to the albumin levels, the lysophosphatidylserine (LysoPS) and lysophosphatidylglycerol (LysoPG) levels were significantly higher, while the LysoPA and ATX levels were lower, in the ascites from patients with gastric cancer. We also found that multiple regression analyses revealed that ATX was selected as a significant explanatory factor for all the detectable LysoPA species only in the cirrhosis group and that a significant positive correlation was observed between LysoPS and PS-PLA1 only in the gastric cancer group. In conclusion, the LysoPA levels might be determined largely by LysoPC and LysoPI (possible precursors) and the PS-PLA1-mediated pathway might be involved in the production of LysoPS in gastric cancer. Glycero-LysoPLs other than LysoPA might also be involved in the pathogenesis of cancer directly or through being converted into LysoPA.
  • Shin Saito, Yoshinori Hosoya, Hirofumi Fujii, Hideyuki Ohzawa, Akira Tanaka, Joji Kitayama, Alan Kawarai Lefor, Naohiro Sata
    International Surgery 102 3-4 137 - 140 2017年03月 
    Gastric cancer is a common malignancy and remains potentially lethal. The prognosis of patients with stage IV gastric cancer is thought to be poor, but new molecular targeted therapy may benefit patients with advanced gastric cancer. Currently, conversion surgery after chemotherapy with a trastuzumab-containing regimen is reported to be effective in these patients. We present 3 patients with human epidermal growth factor receptor 2 (HER2)–positive advanced gastric cancer who underwent conversion surgery after receiving a trastuzumab-containing chemotherapy regimen. Interestingly, the primary lesion acquired resistance to the trastuzumab-containing regimen, although the metastatic lesions maintained a complete response. The reason why the primary lesions became resistant to trastuzumab remains unclear. More studies are needed to clarify the mechanism of resistance. Conversion surgery, made possible by the use of molecular-targeted therapy, may improve the prognosis of patients with stage IV gastric cancer, particularly if metastatic lesions show a complete response to therapy.
  • Shin Saito, Yoshinori Hosoya, Misuzu Nakamura, Takashi Ui, Kentaro Kurashina, Shiro Matsumoto, Rihito Kanamru, Joji Kitayama, Alan Lefor, Naohiro Sata
    ANNALS OF BEHAVIORAL MEDICINE 51 S1877 - S1878 2017年03月 [査読無し][通常論文]
  • Shigenobu Emoto, Hironori Ishigami, Hironori Yamaguchi, Soichiro Ishihara, Eiji Sunami, Joji Kitayama, Toshiaki Watanabe
    Surgery today 47 3 280 - 283 2017年03月 [査読有り][通常論文]
     
    Although the incidence of port-site metastasis after laparoscopic surgery for colorectal cancer has markedly decreased since laparoscopic colectomy was first reported in 1991, it still has not reached zero. In colorectal cancer, the safety of laparoscopic surgery, including the low incidence of port-site metastasis, has been proven in large, randomized trials. In gastric cancer, reports of port-site metastasis are extremely rare, but we should await the results of ongoing trials. This brief review summarizes the current knowledge regarding port-site metastasis after laparoscopic surgery for colorectal and gastric cancer.
  • Hironori Ishigami, Hironori Yamaguchi, Hiroharu Yamashita, Masahiro Asakage, Joji Kitayama
    Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 20 Suppl 1 128 - 134 2017年03月 [査読有り][通常論文]
     
    BACKGROUND: Despite recent progress in systemic chemotherapy, the prognosis of gastric cancer patients with peritoneal metastasis (P1) or positive peritoneal cytology findings (CY1) is still poor. We developed a regimen combining intraperitoneal (IP) paclitaxel (PTX) with S-1 and PTX, which can produce notable efficacy with regard to peritoneal lesions. Surgery after response to combination chemotherapy is a promising option for P1 or CY1 gastric cancer. A retrospective study was performed to evaluate the safety and efficacy. METHODS: This study enrolled 100 primary P1 or CY1 gastric cancer patients treated with IP PTX plus S-1 and PTX at the University of Tokyo Hospital between 2005 and 2011. Radical gastrectomy was performed when peritoneal cytology findings became negative, and the disappearance or obvious shrinkage of peritoneal metastasis was confirmed by laparoscopy. The same chemotherapy regimen was restarted after surgery and repeated with appropriate dose reduction. RESULTS: Gastrectomy was performed in 64 (P1 56, P0CY1 8) of 100 (P1 90, P0CY1 10) patients. R0 resection was achieved in 44 patients (69%). The median survival time was 30.5 months [95% confidence interval (CI) 23.6-37.7 months] from the initiation of intraperitoneal chemotherapy and 34.6 months (95% CI 26.8-39.4 months) from the diagnosis of gastric cancer. Postoperative complications included anastomotic leakage and pancreatic fistula, each in two patients, which were cured conservatively. There were no treatment-related deaths. The median survival time of the 36 patients who did not undergo surgery was 14.3 months (95% CI 10.0-17.8 months). CONCLUSIONS: Surgery after response to intraperitoneal and systemic chemotherapy is safe and may prolong the survival of P1 and CY1 gastric cancer patients.
  • Tsuyoshi Ozawa, Soichiro Ishihara, Kazushige Kawai, Hiroaki Nozawa, Hironori Yamaguchi, Joji Kitayama, Toshiaki Watanabe
    Clinical colorectal cancer 15 4 e157-e163 - E163 2016年12月 [査読有り][通常論文]
     
    INTRODUCTION: Carbohydrate antigen (CA) 19-9 is a widely used tumor marker in colorectal cancer (CRC). However, its prognostic impact in patients with stage IV CRC who have undergone curative resection is not clear. We evaluated the prognostic power of preoperative serum CA 19-9 in these patients. PATIENTS AND METHODS: We performed a retrospective review of 173 patients with stage IV CRC who had undergone curative resection at our institution. Patients were categorized into normal and high CA 19-9 groups, and relapse-free survival and overall survival were compared using Kaplan-Meier curves. Multivariate analyses were performed using a Cox proportional hazard model. RESULTS: The preoperative serum CA 19-9 level was elevated in 80 patients (46%). The 3-year relapse-free survival of the high CA 19-9 group was significantly worse than that of the normal CA 19-9 group (18% vs. 28%, respectively; P = .026). The 3-year overall survival of the high CA 19-9 group was significantly lower than that of the normal CA 19-9 group (75% vs. 82%; P = .047). Multivariate analyses indicated that elevated preoperative serum CA 19-9 level was an independent prognostic factor for poor relapse-free survival and overall survival, with a hazard ratio of 1.46 (95% confidence interval, 1.03-2.06; P = .035) and 1.90 (95% confidence interval, 1.10-3.29; P = .023), respectively. CONCLUSION: The preoperative serum CA 19-9 level is a good predictive marker of tumor recurrence and prognosis in patients with stage IV CRC who have undergone curative resection.
  • Hironori Yamaguchi, Hironori Ishigami, Joji Kitayama
    Gan to kagaku ryoho. Cancer & chemotherapy 43 13 2481 - 2485 2016年12月 [査読有り][通常論文]
     
    Peritoneal metastasis of gastric cancer remains a refractory disease, and the standard treatment strategy is still unclear. Intraperitoneally administered paclitaxel(PTX)remains in the intraperitoneal(IP)cavity for a long time and directly infiltrates peritoneal metastatic nodules, thereby producing antitumor effects. We designed an IP chemotherapy regimen of S-1 combined with weekly intravenous(IV)and IP PTXadministration. In our phase I study, the recommended dose of IP PTXwas determined to be 20mg/m2. In our phase II study for patients with P1(macroscopic peritoneal metastasis-positive)or CY1 (cytology-positive)gastric cancer, the 1-year overall survival(OS)rate was 78%and the median survival time(MST)was 23.6 months. In another phase II study of patients with P1 gastric cancer, the 1-year OS rate was 77%and the MST was 17.1 months. A phase III PHOENIX-GC trial comparing IP chemotherapy to S-1 plus cisplatin has recently been completed. Phase II studies of the IP administration of docetaxel have also shown favorable results. Recently, the results of several clinical studies investigating the effects of S-1 combined with weekly IV and IP PTXadministration for peritoneal metastasis of pancreatic cancer have been published.
  • Y. Fujiwara, H. Ishigami, R. Fukushima, A. Nashimoto, H. Yabusaki, H. Imamoto, M. Imano, Y. Kodera, Y. Uenosono, K. Amagai, S. Kadowaki, H. Miwa, H. Yamaguchi, T. Yamaguchi, J. Kitayama
    ANNALS OF ONCOLOGY 27 2016年10月 [査読無し][通常論文]
  • Keisuke Hata, Yoko Yamamoto, Tomomichi Kiyomatsu, Toshiaki Tanaka, Shinsuke Kazama, Hiroaki Nozawa, Kazushige Kawai, Junichiro Tanaka, Takeshi Nishikawa, Kensuke Otani, Koji Yasuda, Junko Kishikawa, Yuzo Nagai, Hiroyuki Anzai, Takahide Shinagawa, Keiichi Arakawa, Hironori Yamaguchi, Soichiro Ishihara, Eiji Sunami, Joji Kitayama, Toshiaki Watanabe
    SURGERY TODAY 46 10 1115 - 1122 2016年10月 [査読有り][通常論文]
     
    Gastrointestinal (GI) cancer, including gastric and colorectal cancer, is a major cause of death worldwide. A substantial proportion of patients with GI cancer have a familial history, and several causative genes have been identified. Gene carriers with these hereditary GI syndromes often harbor several kinds of cancer at an early age, and genetic testing and specific surveillance may save their lives through early detection. Gastroenterologists and GI surgeons should be familiar with these syndromes, even though they are not always associated with a high penetrance of GI cancer. In this review, we provide an overview and discuss the diagnosis, genetic testing, and management of four major hereditary GI cancers: familial adenomatous polyposis, Lynch syndrome, hereditary diffuse gastric cancer, and Li-Fraumeni syndrome.
  • Naminatsu Takahara, Hiroyuki Isayama, Yousuke Nakai, Hironori Ishigami, Sohei Satoi, Suguru Mizuno, Hirofumi Kogure, Saburo Matsubara, Natsuyo Yamamoto, Hironori Yamaguchi, Minoru Tada, Joji Kitayama, Toshiaki Watanabe, Kazuhiko Koike
    Investigational new drugs 34 5 636 - 42 2016年10月 [査読有り][通常論文]
     
    UNLABELLED: Objectives The aim of this study was to evaluate the safety and efficacy of intravenous and intraperitoneal paclitaxel (PTX) combined with S-1 for treatment of gemcitabine-refractory pancreatic cancer with malignant ascites. Methods After the feasibility of this regimen was first confirmed in an interim analysis in 10 patients, a total of 35 patients were enrolled between April 2011 and December 2014. PTX was administered intravenously (50 mg/m(2)) and intraperitoneally (20 mg/m(2)) on days 1 and 8, and 80 mg/m(2) S-1 was administered on days 1-14 every 3 weeks. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), the objective tumor response, efficacy against malignant ascites, and safety. Result In all 35 patients, the median OS and PFS were 4.8 (95 % confidence interval [CI], 2.1-5.3) months and 2.8 (95 % CI, 0.9-4.1) months, respectively. The 26 patients who were evaluable for efficacy achieved a response rate of 8 % and a disease control rate of 69 %. Malignant ascites had disappeared or decreased in 18 (69 %) patients, including complete resolution in 4 (15 %), and a negative change in cytological status was achieved in 8 (31 %) patients. The major grade 3/4 adverse events included neutropenia (34 %), anemia (31 %), nausea (9 %), and catheter-related infections (6 %). Conclusion Combination chemotherapy consisting of intravenous and intraperitoneal PTX with S-1 showed acceptable toxicity and favorable efficacy in pancreatic cancer patients with malignant ascites. ( CLINICAL TRIAL REGISTRATION NUMBER: UMIN000005306).
  • Yoshihiro Kawasaki, Mimon Komiya, Kosuke Matsumura, Lumi Negishi, Sakiko Suda, Masumi Okuno, Naoko Yokota, Tomoya Osada, Takeshi Nagashima, Masaya Hiyoshi, Mariko Okada-Hatakeyama, Joji Kitayama, Katsuhiko Shirahige, Tetsu Akiyama
    Cell reports 16 10 2554 - 2564 2016年09月 [査読有り][通常論文]
     
    Aberrant activation of Wnt/β-catenin signaling is a major driving force in colon cancer. Wnt/β-catenin signaling induces the expression of the transcription factor c-Myc, leading to cell proliferation and tumorigenesis. c-Myc regulates multiple biological processes through its ability to directly modulate gene expression. Here, we identify a direct target of c-Myc, termed MYU, and show that MYU is upregulated in most colon cancers and required for the tumorigenicity of colon cancer cells. Furthermore, we demonstrate that MYU associates with the RNA binding protein hnRNP-K to stabilize CDK6 expression and thereby promotes the G1-S transition of the cell cycle. These results suggest that the MYU/hnRNP-K/CDK6 pathway functions downstream of Wnt/c-Myc signaling and plays a critical role in the proliferation and tumorigenicity of colon cancer cells.
  • Keiichi Arakawa, Soichiro Ishihara, Kazushige Kawai, Junichi Shibata, Kensuke Otani, Koji Yasuda, Takeshi Nishikawa, Toshiaki Tanaka, Tomomichi Kiyomatsu, Keisuke Hata, Hiroaki Nozawa, Hironori Yamaguchi, Eiji Sunami, Joji Kitayama, Toshiaki Watanabe
    World journal of surgical oncology 14 1 180 - 180 2016年07月 [査読有り][通常論文]
     
    BACKGROUND: We present a case of asynchronously occurring adenocarcinomas 29 and 36 years after ureterosigmoidostomy for bladder cancer, respectively, at both anastomosis sites. CASE PRESENTATION: A colonoscopy that was performed on a 69-year-old man because of bloody stool and an elevated carcinoembryonic antigen (CEA) level revealed a polypoid lesion at the right ureterosigmoid anastomosis site 29 years after the patient's ureterosigmoidostomy. Endoscopic resection was performed, and the lesion was diagnosed as adenocarcinoma. Seven years later (36 years after ureterosigmoidostomy), an elevated lesion was detected at the left ureterosigmoid anastomosis site by colonoscopy performed after detection of high CEA levels. Biopsy revealed an adenocarcinoma that was immunohistologically positive for CDX2; sigmoidectomy and ureterectomy were subsequently performed. The pathological diagnosis of the second tumor was adenocarcinoma arising in the ureterosigmoid anastomosis site and invading the left ureter. CONCLUSIONS: Diligent long-term follow-up of patients who underwent ureterosigmoidostomy is essential.
  • Hideyuki Ohzawa, Kentaro Kurashina, Atsushi Miki, Yasunari Okuda, Misuzu Mori, Masuzu Ueda, Yoshinori Hosoya, Joji Kitayama, Naohiro Sata, Hirofumi Fujii
    ANNALS OF ONCOLOGY 27 2016年07月 [査読無し][通常論文]
  • Junko Kishikawa, Shinsuke Kazama, Koji Oba, Kiyoshi Hasegawa, Hiroyuki Anzai, Yuzo Harada, Hiroyuki Abe, Keisuke Matsusaka, Kumiko Hongo, Masaru Oba, Koji Yasuda, Kensuke Otani, Takeshi Nishikawa, Toshiaki Tanaka, Junichiro Tanaka, Tomomichi Kiyomatsu, Keisuke Hata, Kazushige Kawai, Hiroaki Nozawa, Hironori Yamaguchi, Soichiro Ishihara, Eiji Sunami, Tetsuo Ushiku, Joji Kitayama, Masashi Fukayama, Norihiro Kokudo, Toshiaki Watanabe
    Annals of surgical oncology 23 6 1916 - 23 2016年06月 [査読有り][通常論文]
     
    BACKGROUND: CD133 is a transmembrane protein that is proposed to be a stem cell marker of colorectal cancer (CRC); however, the correlation between CD133 expression and survival of CRC patients with liver metastasis has not been fully examined. METHODS: CD133 expression was evaluated immunohistochemically, both in primary tumors and synchronous liver metastases of 88 consecutive CRC patients, as well as recurrent lesions in the remnant liver of 27 of these 88 patients. The relationship between CD133 expression and clinicopathological characteristics, recurrence-free survival, and overall survival (OS) was analyzed. RESULTS: CD133 expression in liver metastases (mCD133) was detected in 50 of 88 patients (56.8 %), and had significant correlation with CD133 expression in primary lesions (pCD133) (p < 0.001). CD133 expression in liver recurrent lesions (recCD133) also had a significant correlation with mCD133 (p < 0.001). mCD133+ patients had significantly longer disease-free survival (p = 0.043) and OS (p = 0.014) than mCD133- patients. In addition, mCD133+ patients had a significantly lower rate of extrahepatic recurrence (p < 0.001). CONCLUSIONS: Patients without CD133 expression in liver metastasis had significantly shorter survival, perhaps because mCD133- patients had a significantly higher rate of extrahepatic recurrence.
  • Soichiro Ishihara, Kensuke Otani, Koji Yasuda, Takeshi Nishikawa, Toshiaki Tanaka, Junichiro Tanaka, Tomomichi Kiyomatsu, Kazushige Kawai, Keisuke Hata, Hioaki Nozawa, Shinsuke Kazama, Hironori Yamaguchi, Eiji Sunami, Joji Kitayama, Kenichi Sugihara, Toshiaki Watanabe
    INTERNATIONAL JOURNAL OF COLORECTAL DISEASE 31 6 1149 - 1155 2016年06月 [査読有り][通常論文]
     
    Colon cancers in male and female patients are suggested to be oncologically different. The aim of this study is to elucidate the prognostic impact of lymph node dissection (LND) in male and female colon cancer patients. A total of 5941 stage I-III colon cancer patients who were curatively operated on during the period from 1997 to 2007 were retrospectively studied. Cancer-specific survival (CSS) was individually compared between for male and female patients treated with D3, D2, and D1 LND. Background differences of the patients were matched using propensity scores. D3, D2, and D1 LND were performed in 3756 (63 %), 1707 (29 %), and 478 (8 %), respectively, and more extensive LND was indicated for younger patients and more advanced disease. D2 LND was significantly associated with decreased cancer-specific mortality compared to D1 LND in male patients (HR 0.54, 95 % CI 0.32-0.89, p = 0.04), but not in female patients. D3 LND did not correlate to an improved prognosis compared to D2 LND both in male and female patients. D2 LND was associated with an improved CSS in male, but not female colon cancer patients, compared to D1 LND. This suggested that colon cancer in male and female patients might be oncologically different, and that the prognostic impact of the extent of surgical intervention for colon cancer might therefore be different between sexes.
  • Yoshiko Ota, Soichiro Ishihara, Koji Yasuda, Kazushige Kawai, Keisuke Hata, Hiroaki Nozawa, Hironori Yamaguchi, Eiji Sunami, Joji Kitayama, Toshiaki Watanabe
    Biology and Medicine 8 4 2016年05月 [査読有り][通常論文]
     
    Background: Diabetes mellitus (DM) is suggested to be associated with colorectal cancer (CRC) however, the direct relationship between DM and CRC has not been proven. Objective: The aim of this study is to clarify oncological behavior of CRC with DM. Methods: This study is a retrospective cohort study. We investigated 1216 patients with curatively resected CRC. Clinicopathological factors and prognosis were compared between the patients with and without DM. Results: DM was observed in 34% of the patients. The patients with DM were significantly older, were predominantly males, had larger tumors, and died more frequently of causes other than CRC than those without DM. While overall survival (OS) was significantly inferior in the patients with DM than in those without (83% vs. 88%, p=0.01), there was no difference in cancer-specific survival (CSS) between the two groups (91% vs. 91%, p=0.6). The examination of survival at each cancer stage showed that CSS of the patients with DM tended to be superior in stage II cancer (97% vs. 93%, p=0.07) and was worse in stage IV cancer (54% vs. 70%, p=0.05). Conclusions: OS was worse in the CRC patients with DM who more often died of causes other than CRC, and thus, DM did not affect CSS as a whole. However, with the progression of CRC, DM appeared to worsen CSS. It is unclear whether this is attributed to differences in malignancy or in treatment this should be further examined.
  • Yoshiyuki Fujiwara, Hironori Ishigami, Hiroto Miwa, Tsutomu Tanaka, Yasuhiro Kodera, Haruhiko Imamoto, Motohiro Imano, Ryoji Fukushima, Akio Hidemura, Shugo Ueda, Atsushi Nashimoto, Hiroshi Yabusaki, Tetsuya Kusumoto, Yoshikazu Uenosono, Hiroharu Yamashita, Hironori Yamaguchi, Toshiaki Watanabe, Joji Kitayama
    JOURNAL OF CLINICAL ONCOLOGY 34 15 2016年05月 [査読無し][通常論文]
  • Hironori Ishigami, Yoshiyuki Fujiwara, Ryoji Fukushima, Atsushi Nashimoto, Hiroshi Yabusaki, Haruhiko Imamoto, Motohiro Imano, Yasuhiro Kodera, Yoshikazu Uenosono, Kenji Amagai, Shigenori Kadowaki, Hiroto Miwa, Takuhiro Yamaguchi, Hironori Yamaguchi, Toshiaki Watanabe, Joji Kitayama
    JOURNAL OF CLINICAL ONCOLOGY 34 15 2016年05月 [査読無し][通常論文]
  • Masanobu Taguchi, Katsuya Dezaki, Masaru Koizumi, Kentaro Kurashina, Yoshinori Hosoya, Yasunaru Sakuma, Hisanaga Horie, Joji Kitayama, Clarence Foster, Alan K. Lefor, Naohiro Sata, Toshihiko Yada
    GASTROENTEROLOGY 150 4 S1197 - S1197 2016年04月 [査読無し][通常論文]
  • Keisuke Hata, Junko Kishikawa, Hiroyuki Anzai, Takahide Shinagawa, Shinsuke Kazama, Hiroaki Ishii, Hiroaki Nozawa, Kazushige Kawai, Tomomichi Kiyomatsu, Junichiro Tanaka, Toshiaki Tanaka, Takeshi Nishikawa, Kensuke Otani, Koji Yasuda, Hironori Yamaguchi, Soichiro Ishihara, Eiji Sunami, Joji Kitayama, Toshiaki Watanabe
    DIGESTIVE ENDOSCOPY 28 3 260 - 265 2016年04月 [査読有り][通常論文]
     
    Long-standing ulcerative colitis patients are known to be at high risk for the development of colorectal cancer. Therefore, surveillance colonoscopy has been recommended for these patients. Because colitis-associated colorectal cancer may be difficult to identify even by colonoscopy, a random biopsy method has been recommended. However, the procedure of carrying out a random biopsy is tedious and its effectiveness has also not yet been demonstrated. Instead, targeted biopsy with chromoendoscopy has gained popularity in European and Asian countries. Chromoendoscopy is generally considered to be an effective tool for ulcerative colitis surveillance and is recommended in the guidelines of the British Society of Gastroenterology and the European Crohn's and Colitis Organisation. Although image-enhanced endoscopy, such as narrow-band imaging and autofluorescence imaging, has been investigated as a potential ulcerative colitis surveillance tool, it is not routinely applied for ulcerative colitis surveillance in its present form. The appropriate intervals of surveillance colonoscopy have yet to be determined. Although the Japanese and American guidelines recommend annual or biannual colonoscopy, the British Society of Gastroenterology and the European Crohn's and Colitis Organisation stratified their guidelines according to the risks of colorectal cancer. A randomized controlled trial comparing random and targeted biopsy methods has been conducted in Japan and although the final analysis is still ongoing, the results of this study should address this issue. In the present review, we focus on the current detection methods and characterization of dysplasia/cancer and discuss the appropriate intervals of colonoscopy according to the stratified risks.
  • Ota Y, Ishihara S, Otani K, Yasuda K, Nishikawa T, Tanaka T, Tanaka J, Kiyomatsu T, Kawai K, Hata K, Nozawa H, Kazama S, Yamaguchi H, Sunami E, Kitayama J, Watanabe T
    Molecular and clinical oncology 4 4 607 - 610 2016年04月 [査読有り][通常論文]
  • Takayuki Okuno, Hironori Yamaguchi, Joji Kitayama, Hironori Ishigami, Takeshi Nishikawa, Junichiro Tanaka, Toshiaki Tanaka, Tomomichi Kiyomatsu, Keisuke Hata, Hiroaki Nozawa, Kazushige Kawai, Shinsuke Kazama, Soichiro Ishihara, Eiji Sunami, Toshiaki Watanabe
    WORLD JOURNAL OF SURGICAL ONCOLOGY 14 107  2016年04月 [査読有り][通常論文]
     
    Background: Clinical studies of intraperitoneal chemotherapy with paclitaxel in patients of gastric cancer with peritoneal carcinomatosis is well tolerated and effective, and rare cases of metastasis and recurrence have experienced during the treatment. Disseminated carcinomatosis of the bone marrow is highly rare in gastric cancer and associated with a poor prognosis. Case presentation: A 59-year-old woman of gastric cancer with peritoneal carcinomatosis received five courses of chemotherapy with intraperitoneal administration of paclitaxel, and laparoscopy showed disappearance of the peritoneal carcinomatosis. She subsequently underwent total gastrectomy, and the histopathological findings showed a complete response to the chemotherapy. Postoperatively, chemotherapy with intraperitoneal administration of paclitaxel was continued for 30 months, without apparent recurrence. However, the gastric cancer recurred as disseminated carcinomatosis of the bone marrow with disseminated intravascular coagulation, and we hence changed the chemotherapy regimen to weekly irinotecan. Remission was achieved, and she did not experience any major symptoms; however, she died 6 months after the diagnosis of disseminated carcinomatosis of the bone marrow. Conclusions: Since intraperitoneal paclitaxel administration can strongly suppress peritoneal carcinomatosis of gastric cancer, careful attention should be paid not only to peritoneal recurrence but also for rare site metastases, such as bone marrow metastases.
  • H. Anzai, K. Hata, J. Kishikawa, H. Ishii, T. Nishikawa, T. Tanaka, J. Tanaka, T. Kiyomatsu, K. Kawai, H. Nozawa, S. Kazama, H. Yamaguchi, S. Ishihara, E. Sunami, J. Kitayama, T. Watanabe
    COLORECTAL DISEASE 18 3 O97 - O102 2016年03月 [査読有り][通常論文]
     
    AimThe rate of extension of proctitis in Western countries has been reported, but no data regarding long-term follow-up have been described for the Japanese population. Additionally, patients with long-standing or extensive ulcerative colitis have an increased risk for developing colorectal cancer. This study evaluated both the rate of extension of the disease and the development of neoplasia among patients with an initial diagnosis of ulcerative proctitis. MethodWe retrospectively investigated the medical charts of patients with proctitis from 1979 to 2014. The primary focus of this research was the extension of the inflammatory area. The secondary focus included risk factors for disease extension and the development of neoplasia. ResultsSixty-six patients satisfied the inclusion criteria. Proximal extension of the disease occurred in 34 patients: 19 patients had left-sided colitis and 15 had pancolitis. According to a multivariate analysis, disease extension was significantly higher in patients with disease onset before 25years of age (P-value=0.043). The cumulative rates of disease extension at 10 and 20years were 33.8% and 52.2%, respectively. Three patients were diagnosed with dysplasia during follow-up, all of whom experienced disease extension before the development of dysplasia. ConclusionThe rate of extension of ulcerative colitis in the Japanese population was comparable to that in Western countries. A younger age of disease onset was associated with disease extension. Extension of proctitis may be associated with an increased risk of colorectal cancer.
  • Hiroaki Nozawa, Soichiro Ishihara, Mitsuhiro Fujishiro, Shinya Kodashima, Kensuke Ohtani, Koji Yasuda, Takeshi Nishikawa, Toshiaki Tanaka, Junichiro Tanaka, Tomomichi Kiyomatsu, Kazushige Kawai, Keisuke Hata, Shinsuke Kazama, Eiji Sunami, Joji Kitayama, Toshiaki Watanabe
    SURGERY 159 3 713 - 720 2016年03月 [査読有り][通常論文]
     
    Background. Recent advances in endoscopic therapy, including conventional endoscopic resection and endoscopic submucosal dissection (ESD), have led to a large number of patients with early colorectal cancer (CRC) being cured; however, when resected specimens obtained by these procedures manifest risk factors for lymph node metastasis, additional treatments need to be considered. The aim of our study was to evaluate the outcomes of salvage surgery in CRC patients treated initially by advanced therapeutic endoscopy. Methods. We investigated 145 patients who underwent salvage surgery in our department after endoscopic therapy for CRC between April 2006 and March 2015. Demographic and pathological data, endoscopic procedures, reasons for surgery, and operative outcomes, including perioperative details and recurrence-free and disease-specific survival after surgery, were analyzed. These data were further compared with those of 59 patients with submucosal invasive CRC treated by conventional endoscopic resection/ESD alone and 133 patients treated by surgery alone. Results. Overall lymph node metastases were observed in 14 % of patients who underwent salvage surgery after therapeutic endoscopy and 16% of those who received abdominal surgery alone. In analyses of surgical cases, patients with lymph node metastases more frequently included cases with lymphatic infiltration (63 %) and ESD-treated cases (45 %) than those without metastases (21 %, P < .0001 and 22%, P = .02; respectively). A logistic regression analysis identified lymphatic infiltration as an independent predictive factor for lymph node metastases (odds ratio: 8.77, 95 % confidence interval: 2.90-33.31, P < .0001). Long-term outcomes were favorable in both lymphatic infiltration negative and positive cases. Moreover, survivals were comparable among the different treatment groups. Conclusion. Because of the high rate of nodal involvement, adequate lymphadenectomy need to be performed in salvage surgery after upfront endoscopic therapy.
  • Seiichi Ohta, Syota Hiramoto, Yuki Amano, Mayu Sato, Yukimitsu Suzuki, Marie Shinohara, Shigenobu Emoto, Hironori Yamaguchi, Hironori Ishigami, Yasuyuki Sakai, Joji Kitayama, Taichi Ito
    BIOCONJUGATE CHEMISTRY 27 3 504 - 508 2016年03月 [査読有り][通常論文]
     
    Hyaluronan (HA) is a promising drug carrier for cancer therapy because of its CD44 targeting ability, good biocompatibility, and biodegradability. In this study, cisplatin (CDDP)-incorporating HA nanogels were fabricated through a chelating ligand metal coordination cross-linking reaction. We conjugated chelating ligands, iminodiacetic acid or nalonic acid, to HA and used them as a precursor polymer. By mixing the ligand-conjugated HA with CDDP, cross-linking occurred via coordination of the ligands with the platinum in CDDP, resulting in the spontaneous formation of CDDP-loaded HA nanogels. The nanogels showed pH-responsive release of CDDP, because the stability of the ligand platinum complex decreases in an acidic environment. Cell viability assays for MKN45P human gastric cancer cells and Met-5A human mesothelial cells revealed that the HA nanogels selectively inhibited the growth of gastric cancer cells. In vivo experiments using a mouse model of peritoneal dissemination of gastric cancer demonstrated that HA nanogels specifically localized in peritoneal nodules after the intraperitoneal administration. Moreover, penetration assays using multicellular tumor spheroids indicated that HA nanogels had a significantly higher ability to penetrate tumors than conventional, linear HA. These results suggest that chelating-ligand conjugated HA nanogels will be useful for targeted cancer therapy.
  • Hiroshi Nagata, Yuji Kondo, Kazushige Kawai, Soichiro Ishihara, Shinsuke Kazama, Takako Nirei, Daisuke Soma, Jun Yamada, Eiji Sunami, Joji Kitayama, Yoshiro Kubota, Toshiaki Watanabe
    WORLD JOURNAL OF SURGICAL ONCOLOGY 14 64  2016年03月 [査読有り][通常論文]
     
    Background: Mucinous cystadenocarcinoma is the second most common etiology of appendiceal mucocele. We report a relatively rare case of a giant appendiceal mucocele caused by mucinous cystadenocarcinoma, which occupied the entire abdomen of an adult woman. Case presentation: A 63-year-old woman presented with a chief complaint of abdominal distention. Imaging studies showed a giant cystic mass occupying her entire abdomen. Laparotomy confirmed a giant appendiceal mucocele, and the patient underwent ileocecal resection. A mucinous deposit was not found in her abdominal cavity, and the ovaries were grossly normal bilaterally. The pathological diagnosis was mucinous adenocarcinoma with a low-grade mucinous neoplasm that invaded the subserosa. Regional lymph node metastasis was not found. She has had recurrence-free survival for 5 years. Conclusions: The present case is the largest appendiceal cystadenocarcinoma ever reported. The optimal treatment of an appendiceal neoplasm requires further research based on consensus terminology of an appendiceal mucocele.
  • Hiroaki Ishii, Keisuke Hata, Junko Kishikawa, Hiroyuki Anzai, Kensuke Otani, Koji Yasuda, Takeshi Nishikawa, Toshiaki Tanaka, Junichiro Tanaka, Tomomichi Kiyomatsu, Kazushige Kawai, Hiroaki Nozawa, Shinsuke Kazama, Hironori Yamaguchi, Soichiro Ishihara, Eiji Sunami, Joji Kitayama, Toshiaki Watanabe
    WORLD JOURNAL OF SURGICAL ONCOLOGY 14 75  2016年03月 [査読有り][通常論文]
     
    Background: The incidence of neoplasia after surgery has not been sufficiently evaluated in patients with ulcerative colitis (UC), particularly in the Japanese population, and it is not clear whether surveillance endoscopy is effective in detecting dysplasia/cancer in the remnant rectum or pouch. The aims of this study were to assess and compare postoperative development of dysplasia/cancer in patients with UC who underwent ileorectal anastomosis (IRA) or ileal pouch-anal anastomosis (IPAA) and to evaluate the effectiveness of postoperative surveillance endoscopy. Methods: One hundred twenty patients who received postoperative surveillance endoscopy were retrospectively reviewed for development of dysplasia/cancer in the remnant rectal mucosa or pouch. Results: Three hundred seventy-nine endoscopy sessions were conducted for 30 patients after IRA, while 548 pouch endoscopy sessions were conducted for 90 patients after IPAA. In the IRA group, 5 patients developed dysplasia/cancer during postoperative surveillance and in all cases, neoplasia was detected at an early stage. In the IRA group, no patient developed neoplasia within 10 years of diagnosis; the cumulative incidence of neoplasia after disease onset was 7.2, 12.0, and 23.9 % at 15, 20, and 25 years, respectively. In one case after stapled IPAA, dysplasia was found at the ileal pouch; a subsequent 9 endoscopy sessions in 8 years did not detect any dysplasia. Neoplasia was found more frequently during postoperative surveillance in the IRA group than in the IPAA group (p =.0028). The cumulative incidence of neoplasia after IRA was 3.8, 8.7, and 21.7 % at 10, 15, and 20 years, respectively, and that after IPAA was 1.6 % at 20 years. Conclusions: The cumulative incidence of neoplasia after IPAA was minimal. Those who underwent IRA had a greater risk of developing neoplasia than those who underwent IPAA, although postoperative surveillance endoscopy was able to detect dysplasia/cancer at an early stage. IRA can be the surgical procedure of choice only in selected cases in which it would be of benefit to the patient, with more careful surveillance.
  • Yuichiro Yoshioka, Hiroaki Nozawa, Junichiro Tanaka, Takeshi Nishikawa, Toshiaki Tanaka, Tomomichi Kiyomatsu, Kazushige Kawai, Keisuke Hata, Shinsuke Kazama, Hironori Yamaguchi, Soichiro Ishihara, Eiji Sunami, Joji Kitayama, Toshiaki Watanabe
    ONCOLOGY LETTERS 11 3 2137 - 2139 2016年03月 [査読有り][通常論文]
     
    Patients with hereditary hemorrhagic telangiectasia (HHT) are reportedly at a lower overall risk of malignancies, and small bowel adenocarcinoma (SBA) arising in a HHT patient is extremely rare. In this study, the case of a 37-year-old female with HHT who developed a poorly differentiated jejunal adenocarcinoma five years after ileocecal resection for multiple colonic adenomas is presented. The patient underwent curative resection of the cancer invading the ileum and the mesentery of the transverse colon, but had to overcome critical complications perioperatively, stemming from HHT-associated peripheral capillary dilatation and arteriovenous malformation, including nosebleeds and possible infusion-induced air embolism through pulmonary shunts. The patient subsequently received adjuvant chemotherapy including capecitabine and oxaliplatin for 6 months, and currently remains alive without any evidence of recurrence 12 months after the second surgery. This patient with SBA was an instructive case demonstrating the necessity of careful attention during major surgery in HHT.
  • Daisuke Kobayashi, Hironori Ishigami, Mitsuro Kanda, Chie Tanaka, Hironori Yamaguchi, Joji Kitayama, Yasuhiro Kodera
    JOURNAL OF CLINICAL ONCOLOGY 34 4 2016年02月 [査読無し][通常論文]
  • Kenzui Taniue, Akiko Kurimoto, Hironobu Sugimasa, Emiko Nasu, Yasuko Takeda, Kei Iwasaki, Takeshi Nagashima, Mariko Okada-Hatakeyama, Masaaki Oyama, Hiroko Kozuka-Hata, Masaya Hiyoshi, Joji Kitayama, Lumi Negishi, Yoshihiro Kawasaki, Tetsu Akiyama
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 113 5 1273 - 1278 2016年02月 [査読有り][通常論文]
     
    Many long noncoding RNAs (lncRNAs) are reported to be dysregulated in human cancers and play critical roles in tumor development and progression. Furthermore, it has been reported that many lncRNAs regulate gene expression by recruiting chromatin remodeling complexes to specific genomic loci or by controlling transcriptional or posttranscriptional processes. Here we show that an lncRNA termed UPAT [ubiquitin-like plant homeodomain (PHD) and really interesting new gene (RING) finger domain-containing protein 1 (UHRF1) Protein Associated Transcript] is required for the survival and tumorigenicity of colorectal cancer cells. UPAT interacts with and stabilizes the epigenetic factor UHRF1 by interfering with its alpha-transducin repeat-containing protein (TrCP)-mediated ubiquitination. Furthermore, we demonstrate that UHRF1 up-regulates Stearoyl-CoA desaturase 1 and Sprouty 4, which are required for the survival of colon tumor cells. Our study provides evidence for an lncRNA that regulates protein ubiquitination and degradation and thereby plays a critical role in the survival and tumorigenicity of tumor cells. Our results suggest that UPAT and UHRF1 may be promising molecular targets for the therapy of colon cancer.
  • Hironori Yamaguchi, Joji Kitayama, Hironori Ishigami, Shigenobu Emoto, Takeshi Nishikawa, Junichiro Tanaka, Toshiaki Tanaka, Tomomichi Kiyomatsu, Kazushige Kawai, Keisuke Hata, Hiroaki Nozawa, Shinsuke Kazama, Soichiro Ishihara, Eiji Sunami, Toshiaki Watanabe
    Journal of Medical Case Reports 10 1 14  2016年01月 [査読有り][通常論文]
     
    Background: Peritoneal dissemination of gastric cancer is still a dismal disease and has extremely poor prognosis even with systemic intensive chemotherapy. However, intraperitoneal chemotherapy using paclitaxel has recently shown good results. In order to perform optimal intraperitoneal chemotherapy, laparoscopic examination is necessary to assess the condition of peritoneal disseminated lesions. This is the first report of a case of a patient with gastric cancer with massive peritoneal metastasis treated with intraperitoneal administration of paclitaxel and repeated laparoscopic examinations who survived more than 5 years. Case presentation: Here we report a case of a 60-year-old Japanese woman with peritoneal carcinomatosis of gastric cancer who underwent intraperitoneal chemotherapy receiving repeated laparoscopic examinations. The patient was referred to our institution for the treatment of peritoneal carcinomatosis of gastric cancer. The staging laparoscopy showed peritoneal metastasis in the whole peritoneal space with a peritoneal cancer index score of 23. An intraperitoneal access port was subcutaneously implanted. Paclitaxel was intraperitoneally and intravenously administered with oral administration of S-1. The second-look laparoscopy, which was performed after nine courses of intraperitoneal chemotherapy, revealed the disappearance of peritoneal carcinomatosis. A total gastrectomy with D2 lymphadenectomy was performed and intraperitoneal chemotherapy was continued after the surgery. The third laparoscopic examination, which was performed after 67 courses of intraperitoneal chemotherapy showed bilateral ovarian metastasis without recurrence of peritoneal carcinomatosis. Since multiple bone metastases developed after the third-look laparoscopy, bilateral adnexectomy was not performed and the chemotherapy was changed to the regimen including CPT-11. Our patient survived more than 5 years since the intraperitoneal chemotherapy started. Conclusions: Sequential intraperitoneal chemotherapy could strongly suppress the development of peritoneal metastasis for several years. Repeated laparoscopic examinations are considered to be essential to evaluate the efficacy of intraperitoneal chemotherapy on peritoneal carcinomatosis of gastric cancer.
  • Shin Saito, Yoshinori Hosoya, Kentaro Kurashina, Shiro Matsumoto, Rihito Kanamaru, Takashi Ui, Hidenori Haruta, Joji Kitayama, Alan K. Lefor, Naohiro Sata
    International Journal of Surgery Case Reports 19 51 - 54 2016年 [査読有り][通常論文]
     
    Introduction Spontaneous esophageal perforation, or Boerhaave's syndrome, is a life-threating condition which usually requires emergent surgery. An upside down stomach is defined as a gastric volvulus in a huge supradiaphragmatic sac. In general, this condition can result in ischemia and perforation of the stomach. This is the first report of a patient with Boerhaave's syndrome and an upside down stomach. Case presentation A 79-year-old woman presented with sudden epigastric pain following hematemesis. Evaluation of the patient showed both an esophageal perforation and an upside down stomach. Surgical drainage and irrigation of the mediastinum and pleural cavities were undertaken emergently. Due to the concurrent gastric volvulus, a gastrostomy was placed to fix and decompress the stomach. The patient had an uneventful hospital course and was discharged. Discussion and conclusion Boerhaave's syndrome is a rare but severe complication caused by excessive vomiting, due to a sudden elevation in intraluminal esophageal pressure resulting in esophageal perforation. Acute gastric volvulus can result in ischemia and perforation of the stomach, but has not previously been reported with esophageal perforation. The most likely mechanism associating an upside down stomach with Boerhaave's syndrome is acute gastric outlet obstruction resulting in vomiting, and subsequent esophageal perforation. Perforation of the esophagus as well as perforation of the stomach must be considered in patients with an upside down stomach although both upside down stomach and Boerhaave's syndrome are rare clinical entities.
  • Yuichi Tachikawa, Hiroaki Nozawa, Junichiro Tanaka, Takeshi Nishikawa, Toshiaki Tanaka, Tomomichi Kiyomatsu, Keisuke Hata, Kazushige Kawai, Shinsuke Kazama, Hironori Yamaguchi, Soichiro Ishihara, Eiji Sunami, Joji Kitayama, Madoka Fujisawa, Katutoshi Takahashi, Yoshiki Sakaguchi, Tetsuo Ushiku, Masashi Fukayama, Toshiaki Watanabe
    International Journal of Surgery Case Reports 23 70 - 73 2016年 [査読有り][通常論文]
     
    Introduction Cytomegalovirus (CMV) infection of the gastrointestinal tract is an uncommon illness, but can be observed in immunocompromised patients. Systemic lupus erythematosus (SLE) patients are generally at high risk of CMV infection. Here we report a subacute progressive case of colitis in SLE accompanied by cytomegalovirus infection. Presentation of case The patient, a 79-year-old woman, was hospitalized complaining of fever, polyarthritis, and skin ulcer that had lasted seven days. She additionally manifested vomiting, high fever, and right abdominal pain within two weeks thereafter, and was diagnosed with perforation of the intestine. Emergency operation was carried out for panperitonitis due to perforation of one of the multiple colon ulcers. Multidisciplinary postoperative treatment could not save her life. Pathological examination suggested that cytomegalovirus infection as well as cholesterin embolization contributed to the rapid progression of colitis. Discussion There have been only a limited number of case reports of CMV enteritis in SLE. Moreover, only two SLE patients on multiple medications have been reported to experience gastrointestinal perforation. Viral infections, including CMV, can induce clinical manifestations resembling SLE and for this reason we suspect that there are potentially many more patients misdiagnosed and/or unreported. Conclusion Our case underscores the importance of exploring the possibility of CMV infection as a differential diagnosis in SLE patients with obvious gastrointestinal symptoms who were treated by immunosuppressive drugs.
  • Kazuma Rifu, Koji Koinuma, Hisanaga Horie, Mitsuaki Morimoto, Yoshihiko Kono, Makiko Tahara, Yasunaru Sakuma, Yoshinori Hosoya, Joji Kitayama, Alan Kawarai Lefor, Naohiro Sata, Tsukasa Suzuki, Noriyoshi Fukushima
    International journal of surgery case reports 23 151 - 6 2016年 [査読有り][通常論文]
     
    INTRODUCTION: Neuroendocrine tumors of the colon and rectum are relatively rare compared to sporadic colorectal carcinoma. There are few reports of neuroendocrine tumors of the colon and rectum in patients with ulcerative colitis. PRESENTATION OF CASE: A patient with sigmoid colon carcinoma with focal neuroendocrine features is presented. A 32-year-old man, who had been followed for ulcerative colitis for 14 years, was found to have carcinoma of the sigmoid colon on routine annual colonoscopy, and he underwent laparoscopic total colectomy. Pathologic examination showed sigmoid colon adenocarcinoma with focal neuroendocrine features. DISCUSSION: Most colorectal carcinomas associated with inflammatory bowel disease are histologically similar to the sporadic type, and tumors with neuroendocrine features are very unusual. CONCLUSION: Very rare case of sigmoid colon carcinoma with neuroendocrine features arising in a patient with UC was described.
  • Joji Kitayama, Hironori Yamaguchi, Hironori Ishigami, Keisuke Matsuzaki, Naohiro Sata
    PloS one 11 5 e0154542  2016年 [査読有り][通常論文]
     
    The human peritoneal cavity contains a small number of free cells of mesenchymal cell lineage. Intraperitoneal mesenchymal cells (PMC) play supportive roles in metastasis formation on the peritoneum. In this study, we found that PMC, when co-cultuerd with human gastric cancer cells, MKN45, enhanced the proliferation of MKN45 when cultured at low, but not high, cellular density. Also, PMC suppressed apoptotic cell death of MKN45 only under low density culture conditions. Time-lapse videoanalysis clearly demonstrated that PMC randomly migrated more vigorously than did MKN45, and strongly enhanced the migration behavior of co-cultured MKN45. In fact, the majority of MKN45 migrated together in direct physical contact with PMC, and the sum of migration lengths from original position of co-cultured MKN45 for 48 hours was approximately 10 times longer than that of MKN45 cultured alone. Our data suggest that enhanced migration can increase the chance of direct contact or positional proximity among sparcely distributed MKN45, which may bring survival advantages to tumor cells. This may be one of the important mechanisms of peritoneal metastasis, since only a small number of tumor cells are considered to be disseminated in the early step of metastasis formation on the peritoneum.
  • Tsuyoshi Ozawa, Soichiro Ishihara, Kazushige Kawai, Shinsuke Kazama, Hironori Yamaguchi, Eiji Sunami, Joji Kitayama, Toshiaki Watanabe
    JOURNAL OF SURGICAL RESEARCH 199 2 386 - 392 2015年12月 [査読有り][通常論文]
     
    Background: Recent studies have proposed that the use of the lymphocyte-to-monocyte ratio (LMR) is a good prognostic indicator for patients with nonmetastatic colorectal cancer (CRC). In the present study, we aimed to evaluate the prognostic impact of the LMR in stage IV CRC patients who have undergone curative resection. Methods: We performed a retrospective review of 117 stage IV CRC patients who underwent curative resection at our institute between 1997 and 2012. Patients were divided into a lowLMR group and a high-LMR group according to their LMR. The cutoff value of the LMR was determined based on receiver operating characteristics curve analysis. The relationships between the LMR and disease-free survival (DFS) and cancer-specific survival (CSS) rates were assessed. Results: The cutoff value for LMR was 3.00. DFS was not significantly different between the high-and low-LMR groups (P = 0.277). By contrast, CSS was significantly better in the high-LMR group than in the low-LMR group (P = 0.001). Multivariate analysis indicated that the LMR was an independent prognostic factor for CSS in patients with stage IV CRC who had undergone curative resection (hazard ratio: 2.75; 95% confidence interval: 1.40-5.44; P = 0.004), but not for DFS. Conclusions: The preoperative LMR is a simple and useful prognostic indicator in patients with stage IV CRC who have undergone curative resection. (C) 2015 Elsevier Inc. All rights reserved.
  • Junichi Shibata, Kazushige Kawai, Takeshi Nishikawa, Toshiaki Tanaka, Junichiro Tanaka, Tomomichi Kiyomatsu, Keisuke Hata, Hiroaki Nozawa, Shinsuke Kazama, Hironori Yamaguchi, Soichiro Ishihara, Eiji Sunami, Joji Kitayama, Kenichi Sugihara, Toshiaki Watanabe
    ANNALS OF SURGICAL ONCOLOGY 22 S621 - S629 2015年12月 [査読有り][通常論文]
     
    Background. This study aimed to clarify differences in prognostic factors, metastatic features, and recurrence rates between histologic types in patients with stage 4 colorectal cancer (CRC) who had undergone curative resection. Methods. The data from 1131 patients with stage 4 colorectal cancer from the databases of referral institutions were analyzed. The patients were divided into two groups according to histologic types as follows: patients with poorly differentiated adenocarcinoma, mucinous adenocarcinoma, or signet-ring cell carcinoma (Por/Muc/Sig) and patients with well-differentiated or moderately differentiated adenocarcinoma (Wel/Mod). Differences in clinicopathologic features, relapse-free survival (RFS) rates, and cancer-specific survival (CSS) rates between the groups were evaluated. Results. Although RFS did not differ between the Por/Muc/Sig and Wel/Mod groups, CSS was significantly shorter in the Por/Muc/Sig group's than in the Wel/Mod group, and survival after recurrence was significantly worse in the Por/Muc/Sig group than in theWel/Mod group. The incidence of peritoneal or local recurrence was significantly higher for the Por/Muc/Sig patients, whereas the resection recurrence rate was 16.4 %. Multivariate analysis suggested that histologic type was an independent prognostic factor for survival after recurrence. Conclusions. The patients with Por/Muc/Sig CRC synchronous metastasis had significantly shorter survival times than the patients with other CRC histologies, even if the metastases were curatively resected.
  • Kazushige Kawai, Eiji Sunami, Hironori Yamaguchi, Soichiro Ishihara, Shinsuke Kazama, Hiroaki Nozawa, Keisuke Hata, Tomomichi Kiyomatsu, Junichiro Tanaka, Toshiaki Tanaka, Takeshi Nishikawa, Joji Kitayama, Toshiaki Watanabe
    WORLD JOURNAL OF GASTROENTEROLOGY 21 41 11877 - 11886 2015年11月 [査読有り][通常論文]
     
    AIM: To assist in the selection of suitable nomograms for obtaining desired predictions in daily clinical practice. METHODS: We conducted electronic searches for journal articles on colorectal cancer (CRC)-associated nomograms using the search terms colon/rectal/colorectal/nomogram. Of 174 articles initially found, we retrieved 28 studies in which a nomogram for CRC was developed. RESULTS: We discuss the currently available CRC-associated nomograms, including those that predict the oncological prognosis, the short-term outcome of treatments, such as surgery or neoadjuvant chemoradiotherapy, and the future development of CRC. Developing nomograms always presents a dilemma. On the one hand, the desire to cover as wide a patient range as possible tends to produce nomograms that are too complex and yet have C-indexes that are not sufficiently high. Conversely, confining the target patients might impair the clinical applicability of constructed nomograms. CONCLUSION: The information provided in this review should be of use in selecting a nomogram suitable for obtaining desired predictions in daily clinical practice.
  • Hironori Yamaguchi, Joji Kitayama, Hironori Ishigami, Shinsuke Kazama, Hiroaki Nozawa, Kazushige Kawai, Keisuke Hata, Tomomichi Kiyomatsu, Toshiaki Tanaka, Junichiro Tanaka, Takeshi Nishikawa, Kensuke Otani, Koji Yasuda, Soichiro Ishihara, Eiji Sunami, Toshiaki Watanabe
    WORLD JOURNAL OF GASTROINTESTINAL ONCOLOGY 7 11 285 - 291 2015年11月 [査読有り][通常論文]
     
    The effect of chemotherapy on peritoneal carcinomatosis (PC) of gastric cancer remains unclear. Recently, the intraperitoneal (IP) administration of taxanes [e.g., paclitaxel (PTX) and docetaxel (DOC)] during the perioperative period has shown promising results. Herein, we summarized the rationale and methodology for using IP chemotherapy with taxanes and reviewed the clinical results. IP administered taxanes remain in the IP space at an extremely high concentration for 48-72 h. The drug directly infiltrates peritoneal metastatic nodules from the surface and then produces antitumor effects, making it ideal for IP chemotherapy. There are two types of perioperative IP chemotherapy with taxanes: neoadjuvant intraperitoneal and systemic chemotherapy and sequential perioperative intraperitoneal chemotherapy (SPIC). In SPIC, patients receive neoadjuvant IP chemotherapy and the same regimen of IP chemotherapy after cytoreductive surgery (CRS) until disease progression. Usually, a taxane dissolved in 500-1000 mL of saline at ordinary temperature is administered through an IP access port on an outpatient basis. According to phase. studies, the recommended doses (RD) are as follows: IP DOC, 45-60 mg/m(2); IP PTX [without intravenous (IV) PTX], 80 mg/m(2); and IP PTX (with IV PTX), 20 mg/m(2). Phase. studies have reported a median survival time of 14.4-24.6 mo with a 1-year overall survival of 67%-78%. A phase. study comparing S-1 in combination with IP and IV PTX to S-1 with IV cisplatin started in 2011. The prognosis of patients who underwent CRS was better than that of those who did not; however, this was partly due to selection bias. Although several phase. studies have shown promising results, a randomized controlled study is needed to validate the effectiveness of IP chemotherapy with taxanes for PC of gastric cancer.
  • J. Kitayama, H. Ishigami, H. Yamaguchi
    EUROPEAN JOURNAL OF CANCER 51 S409 - S409 2015年09月 [査読無し][通常論文]
  • Tsuyoshi Ozawa, Soichiro Ishihara, Takeshi Nishikawa, Toshiaki Tanaka, Junichiro Tanaka, Tomomichi Kiyomatsu, Keisuke Hata, Kazushige Kawai, Hiroaki Nozawa, Shinsuke Kazama, Hironori Yamaguchi, Eiji Sunami, Joji Kitayama, Toshiaki Watanabe
    INTERNATIONAL JOURNAL OF COLORECTAL DISEASE 30 9 1165 - 1171 2015年09月 [査読有り][通常論文]
     
    The platelet to lymphocyte ratio (PLR) is a potential prognostic marker in a number of different cancers. The aim of this study was to evaluate the prognostic impact of the PLR in patients with stage II colorectal cancer (CRC) who have undergone curative resection but not adjuvant chemotherapy. A retrospective review was performed on 234 patients with stage II CRC who underwent curative resection, but not adjuvant chemotherapy, in our institute. The patients were divided into low and high PLR groups, and patient survival as well as several clinicopathological factors were compared between the groups. Disease-free survival (DFS) and cancer-specific survival (CSS) were analyzed by using the Kaplan-Meier method, and multivariate analysis was performed by using the Cox proportional hazard model. The cutoff value of the PLR determined by using a receiver-operating characteristic curve analysis was 25.4. DFS and CSS were significantly better in patients with a low PLR compared to patients with a high PLR (P = 0.002 and P = 0.011, respectively). On multivariate analysis, we identified the PLR as an independent prognostic factor for DFS and CSS, with a hazard ratio of 2.65 (95 % confidence interval [CI], 1.26-5.45; P = 0.011) and 3.61 (95 % CI, 1.08-12.64; P = 0.038, respectively). The PLR is a good prognostic indicator in patients with stage II CRC who have undergone curative surgery but not adjuvant chemotherapy.
  • Hiroaki Nozawa, Takeshi Nishikawa, Toshiaki Tanaka, Junichiro Tanaka, Tomomichi Kiyomatsu, Kazushige Kawai, Keisuke Hata, Shinsuke Kazama, Hironori Yamaguchi, Soichiro Ishihara, Eiji Sunami, Joji Kitayama, Toshiaki Watanabe
    ANTICANCER RESEARCH 35 9 5073 - 5078 2015年09月 [査読有り][通常論文]
     
    Aim: The postoperative administration of oxaliplatin reduces the frequency of relapse in selected patients with colorectal cancer following surgical resection. However, factors associated with recurrence despite adjuvant therapy are largely unknown. Patients and Methods: We investigated 68 patients who were pathologically diagnosed with stage II or III colorectal cancer and received oxaliplatin-including chemotherapy, FOLFOX (5-fluorouracil, folinic acid and oxaliplatin) or CapeOX (capecitabine and oxaliplatin), after curative surgery. Results: Nineteen patients developed recurrence during the median follow-up period of 17.8 months. Multivariate analyses using the Cox proportional-hazards model revealed that primary tumor size >= 45 mm was a significant predictor of recurrence (hazard ratio = 3.16, 95% confidence interval = 1.06-11.54, p = 0.039). A primary tumor of 45 mm or more in size was associated with poor recurrence-free survival. Conclusion: Our results suggest that large colorectal carcinoma needs to be recognized as a high-risk factor for recurrence even after surgery and subsequent treatment with oxaliplatin.
  • Yoshihiro Kawasaki, Kosuke Matsumura, Masaya Miyamoto, Shinnosuke Tsuji, Masumi Okuno, Sakiko Suda, Masaya Hiyoshi, Joji Kitayama, Tetsu Akiyama
    SCIENTIFIC REPORTS 5 14291  2015年09月 [査読有り][通常論文]
     
    The transcription factor GATA6 is a critical regulator of cell proliferation and development in the gastrointestinal tract. We have recently reported that GATA6 induces the expression of the intestinal stem cell marker LGR(5) and enhances the clonogenicity and tumorigenicity of colon cancer cells, but not the growth of these cells cultured under adherent conditions. Here we show that REG(4), a member of the regenerating islet-derived (REG) family, is also a target of GATA6. We further demonstrate that REG(4) is downregulated by overexpression of miR-(3)6(3), which suppresses GATA6 expression. Moreover, we show that GATA6-mediated activation of REG(4) enhances the growth of colon cancer cells under adherent conditions and is required for their tumorigenicity. Taken together, our findings demonstrate that GATA6 simultaneously induces the expression of genes essential for the growth of colon cancer cells under adherent conditions (REG(4)) and genes required for their clonogenicity (LGR(5)), and that the miR-(3)6(3)-GATA6-REG(4)/LGR(5) signaling cascade promotes the tumorigenicity of colon cancer cells.
  • Nozawa H, Tanaka J, Nishikawa T, Tanaka T, Kiyomatsu T, Kawai K, Hata K, Kazama S, Yamaguchi H, Ishihara S, Sunami E, Kitayama J, Nakajima J, Kokudo N, Watanabe T
    Molecular and clinical oncology 3 5 1041 - 1047 2015年09月 [査読有り][通常論文]
  • Keisuke Hata, Shinsuke Kazama, Hiroaki Nozawa, Kazushige Kawai, Tomomichi Kiyomatsu, Junichiro Tanaka, Toshiaki Tanaka, Takeshi Nishikawa, Hironori Yamaguchi, Soichiro Ishihara, Eiji Sunami, Joji Kitayama, Toshiaki Watanabe
    SURGERY TODAY 45 8 933 - 938 2015年08月 [査読有り][通常論文]
     
    Despite the development of new therapies, including anti-TNF alpha antibodies and immunosuppressants, a substantial proportion of patients with ulcerative colitis (UC) still require surgery. Restorative proctocolectomy with ileal-pouch anal anastomosis is the standard surgical treatment of choice for UC. With the advent of laparoscopic techniques for colorectal surgery, ileal-pouch anal anastomosis has also been performed laparoscopically. This paper reviews the history and current trends in laparoscopic surgery for UC. The accumulation of experience and improvement of laparoscopic devices have shifted the paradigm of UC surgery towards laparoscopic surgery over the past decade. Although laparoscopic surgery requires a longer operation, it provides significantly better short and long-term outcomes. The short-term benefits of laparoscopic surgery over open surgery include shorter hospital stays and fasting times, as well as better cosmesis. The long-term benefits of laparoscopy include better fecundity in young females. Some surgeons favor laparoscopic surgery even for severe acute colitis. More efforts are being made to develop newer laparoscopic methods, such as reduced port surgery, including single incision laparoscopic surgery and robotic surgery.
  • Soichiro Ishihara, Kensuke Otani, Koji Yasuda, Takeshi Nishikawa, Junichiro Tanaka, Toshiaki Tanaka, Tomomichi Kiyomatsu, Keisuke Hata, Kazushige Kawai, Hiroaki Nozawa, Shinsuke Kazama, Hironori Yamaguchi, Eiji Sunami, Joji Kitayama, Toshiaki Watanabe
    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY 20 4 633 - 640 2015年08月 [査読有り][通常論文]
     
    Robotic technology, which has recently been introduced to the field of surgery, is expected to be useful, particularly in treating rectal cancer where precise manipulation is necessary in the confined pelvic cavity. Robotic surgery overcomes the technical drawbacks inherent to laparoscopic surgery for rectal cancer through the use of multi-articulated flexible tools, three-dimensional stable camera platforms, tremor filtering and motion scaling functions, and greater ergonomic and intuitive device manipulation. Assessments of the feasibility and safety of robotic surgery for rectal cancer have reported similar operation times, blood loss during surgery, rates of postoperative morbidity, and circumferential resection margin involvement when compared with laparoscopic surgery. Furthermore, rates of conversion to open surgery are reportedly lower with increased urinary and male sexual functions in the early postoperative period compared with laparoscopic surgery, demonstrating the technical advantages of robotic surgery for rectal cancer. However, long-term outcomes and the cost-effectiveness of robotic surgery for rectal cancer have not been fully evaluated yet; therefore, large-scale clinical studies are required to evaluate the efficacy of this new technology.
  • Kazuki N. Sugahara, Pablo Scodeller, Gary B. Braun, Tatiana Hurtado de Mendoza, Chisato M. Yamazaki, Michael D. Kluger, Joji Kitayama, Edwin Alvarez, Stephen B. Howell, Tambet Teesalu, Erkki Ruoslahti, AndrewM. Lowy
    JOURNAL OF CONTROLLED RELEASE 212 59 - 69 2015年08月 [査読有り][通常論文]
     
    Peritoneal carcinomatosis is a major source of morbidity and mortality in patients with advanced abdominal neoplasms. Intraperitoneal chemotherapy (IPC) is an area of intense interest given its efficacy in ovarian cancer. However, IPC suffers from poor drug penetration into peritoneal tumors. As such, extensive cytoreductive surgery is required prior to IPC. Here, we explore the utility of iRGD, a tumor-penetrating peptide, for improved tumor-specific penetration of intraperitoneal compounds and enhanced IPC in mice. Intraperitoneally administered iRGD significantly enhanced penetration of an attached fluorescein into disseminated peritoneal tumor nodules. The penetration was tumor-specific, circulation-independent, and mediated by the neuropilin-binding RXXK tissue-penetration peptide motif of iRGD. Q-iRGD, which fluoresces upon cleavage, including the one that leads to RXXK activation, specifically labeled peritoneal metastases displaying different growth patterns in mice. Importantly, iRGD enhanced intratumoral entry of intraperitoneally co-injected dextran to approximately 300% and doxorubicin to 250%. Intraperitoneal iRGD/doxorubicin combination therapy inhibited the growth of bulky peritoneal tumors and reduced systemic drug toxicity. iRGD delivered attached fluorescein and co-applied nanoparticles deep into fresh human peritoneal metastasis explants. These results indicate that intraperitoneal iRGD co-administration serves as a simple and effective strategy to facilitate tumor detection and improve the therapeutic index of IPC for peritoneal carcinomatosis. (C) 2015 Elsevier B.V. All rights reserved.
  • Hiroaki Nozawa, Soichiro Ishihara, Teppei Morikawa, Junichiro Tanaka, Koji Yasuda, Kensuke Ohtani, Takeshi Nishikawa, Toshiaki Tanaka, Tomomichi Kiyomatsu, Kazushige Kawai, Keisuke Hata, Shinsuke Kazama, Hironori Yamaguchi, Eiji Sunami, Joji Kitayama, Masashi Fukayama, Toshiaki Watanabe
    DIAGNOSTIC PATHOLOGY 10 139  2015年08月 [査読有り][通常論文]
     
    Anal canal adenoma is an extremely rare disease that has the potential to transform into a malignant tumor. We herein presented a rare case of metachronous multiple adenomas of the anal canal. A 48-year-old woman underwent total colonoscopy following a positive fecal blood test. A 9-mm villous polyp arising from the posterior wall of the anal canal was removed by snare polypectomy. Histologically, the tumor was tubulovillous adenoma with high-grade dysplasia and the cut end was negative for tumor cells. Six years later, an elevated lesion, macroscopically five millimeters in size, was detected in the left wall of the anal canal in a follow-up colonoscopy. Local excision of the tumor was performed, and the lesion was pathologically confirmed to be tubular adenoma with high-grade dysplasia limited to the mucosa. The patient is currently alive without any evidence of recurrence for six months after surgery. Although she had a past history of cervical cancer, the multiple tumors arising in the anal canal were unlikely to be related to human papilloma virus infection. Our case report underscores the importance of careful observations throughout colonoscopy to detect precancerous lesions, particularly in anatomically narrow segments.
  • H. Yamaguchi, J. Kitayama, S. Emoto, H. Ishigami, T. Ito, N. Hanafusa, T. Watanabe
    EJSO 41 7 875 - 880 2015年07月 [査読有り][通常論文]
     
    Background: Massive malignant ascites originating from peritoneal metastasis of gastric cancer is difficult to control and resistant to chemotherapy. Cell-free and Concentrated Ascites Reinfusion Therapy (CART) is one of the types of apheresis therapy, by which filtered and concentrated ascites containing albumin and globulin is reinfused intravenously to patients. We retrospectively studied the feasibility of intraperitoneal (IP) chemotherapy combined with CART in gastric cancer patients with massive malignant ascites. Methods: Paclitaxel (PTX) was administered via an FP access port implanted in the subcutaneous space. If patient had massive ascites at the start of treatment, paracentesis was performed through a percutaneous IP catheter and then CART was performed. PTX was administered through the catheter until the ascites diminished. Results: A total of 127 CART procedures in 30 patients were analyzed. The average volume of processed ascites was 3.1 L, which was concentrated to 0.33 L containing 85.5 g protein on average. Significant increases in urine volume, serum total protein and albumin level were found after the CART. Increase in body temperature (0.3 degrees C), decrease in platelet count (3.8 x 10(4)/mu l), and changes in blood pressure (2 mm Hg) were found after the CART procedure, but no clinically significant adverse event was experienced. The median survival time and 1-year survival of 30 patients who received IP chemotherapy combined with the CART procedure was 10.2 months and 43.3% respectively. Conclusions: IP chemotherapy combined with CART might be a promising strategy for patients with massive malignant ascites originating from peritoneal metastasis of gastric cancer. (C) 2015 Elsevier Ltd. All rights reserved.
  • Joji Kitayama, Shigenobu Emoto, Hironori Yamaguchi, Hironori Ishigami, Haruna Onoyama, Hiroharu Yamashita, Yasuyuki Seto, Keisuke Matsuzaki, Toshiaki Watanabe
    ANNALS OF SURGICAL ONCOLOGY 22 7 2336 - 2342 2015年07月 [査読有り][通常論文]
     
    The frequency of intraperitoneal free tumor cells (IPTC) is considered to reflect the severity of peritoneal metastasis (PM). We quantified the relative number of IPTC against leukocytes in peritoneal fluid and evaluated its clinical relevance in gastric cancer (GC) patients, particularly those with PM. Cells recovered from ascites or peritoneal lavage fluid were immunostained with monoclonal antibodies (mAb) to CD45 and CD326 (EpCAM). Using flow cytometry (FACS), CD326(+) and CD45(+) cells were classified as either tumor cells (T) or leukocytes (L) and the T/L ratio (TLR) was calculated in a total of 506 samples obtained from 300 patients with GC and 33 patients with liver cirrhosis (LC). Median (M) of the TLR of the initial samples obtained from 199 patients with PM(+) GC was 1.32 % (0-1,868.44 %), which was significantly higher than that in patients with PM(-) GC (M = 0 %, 0-0.35 %; n = 101) or LC (M = 0 %, 0-0.031 %; n = 33). In 104 PM(+) patients who received combination chemotherapy including intraperitoneal paclitaxel, the TLR was repeatedly measured in peritoneal fluid obtained from the port. In these patients, the TLR showed a strong correlation with clinical features as well as cytological findings and carcinoembryonic antigen messenger RNA status. Finally, the median survival time of the 11 patients with initial TLR > 10 % was significantly shorter than that of the 52 patients with TLR < 10 % (271 vs. 627 days; p = 0.0002). The TLR excellently reflected tumor burden in the peritoneal cavity, and could be a reliable biomarker to determine the outcome, as well as the effectiveness, of chemotherapy in patients with PM(+) GC.
  • Hiroaki Ishii, Kazushige Kawai, Keisuke Hata, Yasutaka Shuno, Takeshi Nishikawa, Toshiaki Tanaka, Junichiro Tanaka, Tomomichi Kiyomatsu, Hiroaki Nozawa, Shinsuke Kazama, Hironori Yamaguchi, Soichiro Ishihara, Eiji Sunami, Joji Kitayama, Toshiaki Watanabe
    INTERNATIONAL SURGERY 100 7-8 1169 - 1176 2015年07月 [査読有り][通常論文]
     
    Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the standard surgical treatment for patients with ulcerative colitis (UC). The purpose of this study was to investigate the long-term functional outcomes and quality of life (QOL) associated with hand-sewn and stapled IPAA. Ninety-one patients with UC had undergone IPAA using hand-sewn anastomosis with mucosectomy (32 patients) or stapled anastomosis (59 patients) from January 1988 to May 2010. Patients were evaluated according to patient characteristics, postoperative complications, functional outcomes and QOL. The QOL of patients were evaluated using the Medical Outcomes Study Short Form 36 (SF-36) and the Inflammatory Bowel Disease Questionnaire (IBDQ). Numbers of patients with colorectal cancer or dysplasia were significantly greater in the hand-sewn IPAA group (P < 0.01). These patients had longer disease durations and were older (both P < 0.01). There was no difference in the incidence of complications between the groups, except for a greater incidence of postoperative anal fistula in the stapled group (P = 0.03). In the early postsurgery period, both the frequency of bowel movements and the rate of soiling were significantly higher in the hand-sewn group, but in a later period, there was no difference in these events >3 years after surgery. The SF-36 and IBDQ results were similar in the two groups, indicating that hand-sewn and stapled IPAA result in similar QOL in the late postoperative period. Postoperative complications, functional outcomes, and long-term QOL were similar in patients who had received hand-sewn or stapled IPAA.
  • Soichiro Ishihara, Takeshi Nishikawa, Toshiaki Tanaka, Junichiro Tanaka, Tomomichi Kiyomatsu, Kazushige Kawai, Keisuke Hata, Hioaki Nozawa, Shinsuke Kazama, Hironori Yamaguchi, Eiji Sunami, Joji Kitayama, Kenichi Sugihara, Toshiaki Watanabe
    INTERNATIONAL JOURNAL OF COLORECTAL DISEASE 30 6 807 - 812 2015年06月 [査読有り][通常論文]
     
    Retrospective studies have shown that primary tumor resection improves the prognosis of patients with colorectal cancer (CRC) with unresectable metastasis (mCRC). The aim of this study was to investigate the prognostic impact of primary tumor resection in various subgroups of mCRC patients. A total of 1982 patients with mCRC from January 1997 to December 2007 were retrospectively evaluated. The impact of primary tumor resection on cancer-specific survival (CSS) was analyzed using propensity score analysis to mitigate selection bias. Covariates in the models for propensity scores included treatment period, age, gender, tumor location, depth, lymph node metastasis, number of metastatic organs, and carcinoembryonic antigen (CEA) levels. Among the whole patient population, primary tumor resection significantly improved CSS [hazard ratio (HR) 0.46, 95 % confidence interval (CI) 0.32-0.66, p < 0.01]. However, primary tumor resection did not significantly improve CSS in the following subgroups: patients treated in the first 5 years of the study (HR 0.56, 95 % CI 0.28-1.13, p = 0.08), patients aged > 65 years (HR 0.72, 95 % CI 0.36-1.42, p = 0.31), female patients (HR 0.60, 95 % CI 0.31-1.17, p = 0.13), patients with right-sided colon cancer (HR 0.68, 95 % CI 0.39-1.20, p = 0.17), and patients without nodal involvement (HR 0.54, 95 % CI 0.25-1.17, p = 0.09). Our study suggests that primary tumor resection improves the survival of patients with mCRC. However, the prognostic benefit is different among patient subpopulations.
  • Junichiro Tanaka, Takeshi Nishikawa, Toshiaki Tanaka, Tomomichi Kiyomatsu, Keisuke Hata, Kazushige Kawai, Shinsuke Kazama, Hiroaki Nozawa, Hironori Yamaguchi, Soichiro Ishihara, Eiji Sunami, Joji Kitayama, Toshiaki Watanabe
    Annals of Medicine and Surgery 4 2 183 - 186 2015年06月 [査読有り][通常論文]
     
    Background: The incidence of anastomotic leakage in rectal surgery is around 10 percent. Poor blood supply to the anastomosis, high anastomotic pressure and tension, increased operative blood loss, long operative time, and male sex are risk factors of anastomotic leakage. In the present study, we examined anastomotic leakage cases in rectal surgery at our institute and tried to ascertain the risk factors. Methods: Three hundred fifty-seven consecutive patients who underwent rectal resection with anastomosis between January 2008 and October 2013 were included in the study. Patients were divided into two groups according to the existence of anastomotic leakage. Clinicopathological features, operative procedures, and intraoperative outcomes were compared between the two groups. Regarding intraoperative procedure, we focused on the ligation level of the inferior mesenteric artery, installing a transanal drainage tube in the rectum, and constructing a diverting stoma. Results: Anastomotic leakage occurred in eight patients. All of them were male (p=0.0284). There were no statistical differences in other characteristics of the patients or tumors, in operative procedures, or in intraoperative outcomes. Conclusions: In the present study, no statistically significant risk factors for anastomotic leakage in rectal surgery were detected, except for male sex. However, the rate of anastomotic leakage at our institute was revealed to be rather low. Our exertion to preserve good blood flow and to prevent high tension and pressure on the anastomosis in operation may have led to this result.
  • Ozawa T, Ishihara S, Tanaka T, Tanaka J, Kiyomatsu T, Kawai K, Kanazawa T, Nozawa H, Kazama S, Yamaguchi H, Sunami E, Kitayama J, Watanabe T
    Hepato-gastroenterology 62 140 853 - 858 2015年06月 [査読有り][通常論文]
  • J. Shibata, S. Ishihara, N. Tada, K. Kawai, N. H. Tsuno, H. Yamaguchi, E. Sunami, J. Kitayama, T. Watanabe
    TECHNIQUES IN COLOPROCTOLOGY 19 5 275 - 280 2015年05月 [査読有り][通常論文]
     
    The perioperative immune status of colorectal robotic surgery (RS), laparoscopic surgery (LS), and open surgery (OS) patients has not been compared. Our aim was to evaluate perioperative stress and immune response after RS, LS and OS. This prospective study included 46 colorectal surgery patients from the Department of Surgical Oncology of the University of Tokyo Hospital. Peripheral venous blood samples were obtained preoperatively and on postoperative days 1, 3, and 6. We evaluated expression of HLA-DR (marker of immune competence), C-reactive protein (CRP) levels, and lymphocyte subset counts (natural killers, cytotoxic T cells and helper T cells). Fifteen, 23, and 8 patients underwent RS, LS and OS, respectively. HLA-DR expression was the lowest on day 1 and gradually increased on days 3 and 6 in all the groups. There was no significant difference in postoperative HLA-DR expression between the RS and LS group. However, on day 3, HLA-DR expression in the RS group was significantly higher than in the OS group (p = 0.04). On day 1, CRP levels in the LS group were significantly lower than in the RS group (p = 0.038). There were no significant perioperative changes in the lymphocyte subset cell count between the three groups. Perioperative surgical stress, as evaluated by immunological parameters, was comparable between robotic and laparoscopic surgery and higher with open surgery. Robotic surgery may be an alternative to laparoscopic surgery, as a minimally invasive surgery option for colorectal cancer.
  • Kazushige Kawai, Soichiro Ishihara, Hironori Yamaguchi, Eiji Sunami, Joji Kitayama, Hiroaki Miyata, Toshiaki Watanabe
    ANNALS OF SURGERY 261 5 926 - 932 2015年05月 [査読有り][通常論文]
     
    Objective: To construct a predictive model of postoperative colorectal neoplasm development using a nomogram. Background: Although patients with colorectal cancer (CRC) are known to be at high risk of developing metachronous adenoma or CRC, no statistical model for predicting the incidence of postoperative colorectal lesions has been reported. Methods: A total of 309 CRC patients who underwent surgical resection received regular endoscopic follow-up to detect the development of metachronous adenoma or adenocarcinoma. The patients were divided into the derivation set (n = 209) and the validation set (n = 100). The nomogram to predict the 3- and 5-year adenoma-free survival rates was constructed using the derivation set, and a calibration plot and concordance index (c-index) were calculated. The predictive utility of the nomogram was validated in the validation set. Results: Sex, age, and number of synchronous lesions at the time of surgery for primary CRC were adopted as variables for the nomogram. The nomogram showed moderate calibration, with a c-index of 0.709 in the derivation set and 0.712 in the validation set. Conclusions: A nomogram based on sex, age, and number of synchronous lesions at the time of surgery has the ability to predict postoperative adenoma-free survival.
  • Tsuyoshi Ozawa, Soichiro Ishihara, Takeshi Nishikawa, Toshiaki Tanaka, Junichiro Tanaka, Tomomichi Kiyomatsu, Keisuke Hata, Kazushige Kawai, Hiroaki Nozawa, Takamitsu Kanazawa, Shinsuke Kazama, Hironori Yamaguchi, Eiji Sunami, Joji Kitayama, Toshiaki Watanabe
    ANNALS OF SURGICAL ONCOLOGY 22 5 1513 - 1519 2015年05月 [査読有り][通常論文]
     
    The lymph node ratio (LNR) was proposed as a prognostic indicator in Stage III colorectal cancer (CRC) patients in recent studies. The purpose of this study was to evaluate the prognostic impact of the LNR in Stage IV CRC patients who have undergone curative resection. A retrospective review of 119 Stage IV CRC patients who underwent curative resection in our institute from 1997 to 2009 was performed. Patients were divided into two groups (low LNR and high LNR) by means of their median LNR. A disease-free survival (DFS) and an overall survival (OS) were analyzed using the Kaplan-Meier curve; multivariate analysis was performed using the Cox proportional hazard model. The cutoff value for the LNR was 0.111. For the entire study group, the 5-year DFS was 22 % and the 5-year OS was 65 %. DFS was not significantly different between patients in the low LNR group and the high LNR group (25 and 19 %, respectively; P = 0.317), but OS was significantly higher in the low LNR group patients compared with the high LNR group patients (77 and 54 %, respectively; P < 0.001). Using multivariate analysis, we identified the LNR as an independent prognostic factor for OS, with a hazard ratio of 3.08 (95 % CI 1.38-8.19; P = 0.005). LNR is a potent prognostic indicator for stratification in Stage IV CRC patients who have undergone curative resection.
  • Shinsuke Kazama, Joji Kitayama, Masaya Hiyoshi, Yoshitaka Taketomi, Makoto Murakami, Takeshi Nishikawa, Toshiaki Tanaka, Junichiro Tanaka, Tomomichi Kiyomatsu, Kazushige Kawai, Keisuke Hata, Hironori Yamaguchi, Hiroaki Nozawa, Soichiro Ishihara, Eiji Sunami, Toshiaki Watanabe
    ANTICANCER RESEARCH 35 5 2983 - 2990 2015年05月 [査読有り][通常論文]
     
    Background: Although secretory phospholipase A2 (sPLA2) has been shown to be involved in various biological processes, its specific roles in sub-types of cancer development remain to be elucidated. Materials and Methods: We examined the expression of sPLA2 group III (GIII) in 142 patients with colorectal cancer using immunohistochemistry, and its correlation with clinicopathological features and outcomes. In addition, we examined the co-expression of sPLA2GIII and sPLA2GX using serial tissue sections to clarify the roles of both proteins in colorectal carcinogenesis. Results: In 66 cases, diffuse staining of sPLA2GIII was seen; this was defined as the group with high expression. High expression was associated with a significantly higher rate of lymph node metastasis (p=0.02) and poorer survival (p=0.03) compared with low expression. Patients with low sPLA2GIII and high sPLA2GX expression had a significantly higher survival rate than those with high sPLA2GIII and low sPLA2GX expression (p=0.038). Conclusion: sPLA2GIII expression may be used as a risk factor for lymph node metastasis and a prognostic marker in colorectal cancer. In addition, sPLA2GIII and sPLA2GX may play opposing roles in colorectal carcinogenesis.
  • K. Kawai, S. Ishihara, H. Yamaguchi, E. Sunami, J. Kitayama, H. Miyata, K. Sugihara, T. Watanabe
    EJSO 41 4 457 - 465 2015年04月 [査読有り][通常論文]
     
    Purpose: Although stage IV colorectal cancer (CRC) encompasses a wide variety of clinical conditions with diverse prognoses, no statistical model for predicting the postoperative prognosis of stage IV CRC has been established. Thus, we here aimed to construct a predictive model for disease-free survival (DFS) and overall survival (OS) after curative surgery for stage IV CRC using nomograms. Methods: The study included 1133 stage IV CRC patients who underwent curative surgical resection in 19 institutions. Patients were divided into derivation (n = 586) and validation (n = 547) groups. Nomograms to predict the 1- and 3-year DFS rates and the 3- and 5-year OS rates were constructed using the derivation set. Calibration plots were constructed, and concordance indices (c-indices) were calculated. The predictive utility of the nomogram was validated in the validation set. Results: The postoperative carcinoembryonic antigen (CEA) level, depth of tumor invasion (T factor), lymph node metastasis (N factor), and number of metastatic organs were adopted as variables for the DFS-predicting nomogram, whereas the postoperative CEA level, T factor, N factor, and peritoneal dissemination were adopted for the nomogram to predict OS. The nomograms showed moderate calibration, with c-indices of 0.629 and 0.640 in the derivation set and 0.604 and 0.637 in the validation set for DFS and OS, respectively. Conclusions: The nomograms developed were capable of estimating the probability of DFS and OS on the basis of only 4 variables, and may represent useful tools for postoperative surveillance of stage IV CRC patients in routine practice. (C) 2015 Elsevier Ltd. All rights reserved.
  • Soichiro Ishihara, Keiji Matsuda, Toshiaki Tanaka, Junichiro Tanaka, Tomomichi Kiyomatsu, Kazushige Kawai, Hiroaki Nozawa, Shinsuke Kazama, Takamitsu Kanazawa, Hironori Yamaguchi, Eiji Sunami, Joji Kitayama, Yojiro Hashiguchi, Toshiaki Watanabe
    SURGICAL LAPAROSCOPY ENDOSCOPY & PERCUTANEOUS TECHNIQUES 25 2 168 - 172 2015年04月 [査読有り][通常論文]
     
    The aim of this study was to clarify patient factors contributing to complications after laparoscopic surgery for colorectal cancers. A total of 333 colorectal cancer patients who underwent laparoscopic colorectal resection between January 2007 and December 2012 were enrolled. The association between patient factors and the incidence of complications were analyzed. Postoperative complications were divided into 2 categories: infectious complications and noninfectious complications. The overall complication rate was 13% and mortality rate 0%. Multivariate analysis showed that body mass index > 25 kg/m(2) [odds ratio (OR) = 3.02, P = 0.0254] and tumor location (right colon cancer/rectal cancer: OR = 0.11, P = 0.0083) were risk factors for infectious complications; in addition, male sex (OR = 3.91, P = 0.0102) and cancer stage (stage 2/stage 4: OR = 0.17, P = 0.0247) were risk factors for noninfectious complications. This study shows that different patient factors are associated with the risk of different types of complications.
  • Yuichiro Yokoyama, Keisuke Hata, Takamitsu Kanazawa, Hironori Yamaguchi, Soichiro Ishihara, Eiji Sunami, Joji Kitayama, Toshiaki Watanabe
    WORLD JOURNAL OF SURGICAL ONCOLOGY 13 164  2015年04月 [査読有り][通常論文]
     
    Solitary fibrous tumors (SFTs) rarely develop in the pelvis. When they do arise, they are usually treated using surgery, although SFTs are often very large by the time of diagnosis, which makes surgical excision difficult. We report a case of a 63-year-old man who was referred to our hospital for the treatment of a giant tumor of the pelvis. Computed tomography (CT) revealed a 30 x 25 x 19 cm sized hypervascular tumor that almost completely filled the pelvic cavity. The diagnosis of SFT was made by CT-assisted needle biopsy. The feeding arteries of the tumor were embolized twice. The first embolization aimed to reduce the tumor volume, while the second one was planned a day prior to the surgery to obtain hematostasis during the operation. Tumor resection was then performed. The blood loss during the operation was 440 ml, and there was no uncontrollable bleeding. The postoperative course was uneventful. No recurrence of SFT was observed during a 2-year follow-up.
  • Shigenobu Emoto, Joji Kitayama, Hironori Ishigami, Hironori Yamaguchi, Toshiaki Watanabe
    ANNALS OF SURGICAL ONCOLOGY 22 3 780 - 786 2015年03月 [査読有り][通常論文]
     
    Background. A positive cytology of peritoneal lavage fluid (CY1) is a poor prognostic factor in patients with gastric cancer (GC). We have recently reported that CY1 often changes to negative (CY0) following combination chemotherapy including intraperitoneal (IP) paclitaxel (PTX), which results in marked prolongation of survival in GC patients with peritoneal dissemination (P1). Methods. A total of 95 P1 GC patients who received combination chemotherapy with S-1 and intravenous and IP PTX were enrolled. Peritoneal lavage fluid was periodically examined cytologically at the start of every cycle of chemotherapy, and the impact of CY status on patient outcome was retrospectively evaluated. Results. Seventy-three (76.8 %) of 95 patients were diagnosed as CY1 before initial treatment. Median survival time (MST) of the CY1 group was significantly shorter than that of the CY0 group (19.1 vs. 32.5 months, P = 0.033). Cytological status changed from CY1 to CY0 in 68 (93.2 %) of 73 CY1 patients during the whole treatment period and MST of patients who showed a negative change was significantly longer than that of the unchanged group (20.0 vs. 13.0 months, P = 0.0017). In 64 patients who achieved CY0 by IP PTX regimen, the median time to achieve CY0 was 1.4 months, and patients who achieved a negative change within 1 month showed a particularly good outcome (MST = 26.1 months). Conclusions. Periodic cytological examination of peritoneal lavage fluid is clinically useful to evaluate the efficacy of treatment as well as to predict the outcome of patients with P1 GC.
  • Tsuyoshi Ozawa, Soichiro Ishihara, Eiji Sunami, Joji Kitayama, Toshiaki Watanabe
    JOURNAL OF SURGICAL ONCOLOGY 111 4 465 - 471 2015年03月 [査読有り][通常論文]
     
    BackgroundRecent studies have proposed the use of log odds of positive lymph nodes (LODDS) as a prognostic indicator in colorectal cancer (CRC) patients without distant synchronous metastasis. In the present study, we aimed to evaluate the prognostic impact of the LODDS in Stage IV CRC patients who have undergone curative resection. MethodsWe performed a retrospective review of 117 Stage IV CRC patients who underwent curative resection at our institute from 1998 to 2011. Patients were categorized into 3 groups (LODDS1-3) according to the ratio of their LODDS. The relationship between the LODDS and disease-free survival (DFS) and overall survival (OS) rates were assessed. ResultsDFS was not significantly different between patients in each LODDS group. The association between the LODDS classification and OS was statistically significant (P=0.021). Multivariate analysis indicated that LODDS classification was an independent prognostic factor for OS, with a hazard ratio of 2.95 for LODDS2 (95% confidence interval [CI]: 1.18-8.35; P=0.021), and 2.98 for LODDS3 (95% CI: 1.20-8.37; P=0.017). ConclusionsThe LODDS is a good prognostic indicator in Stage IV CRC patients who have undergone curative resection. J. Surg. Oncol. 2015 111:465-471. (c) 2015 Wiley Periodicals, Inc.
  • Yuuki Iida, Eiji Sunami, Hiroharu Yamashita, Masaya Hiyoshi, Soichiro Ishihara, Hironori Yamaguchi, Asuka Inoue, Kumiko Makide, Nelson H. Tsuno, Junken Aoki, Joji Kitayama, Toshiaki Watanabe
    ANTICANCER RESEARCH 35 3 1459 - 1464 2015年03月 [査読有り][通常論文]
     
    Background: The function of phosphatidylserine-specific phospholipase A1 (PS-PLA(1)), a phospholipase that acts specifically on phosphatidylserine and produces lysophosphatidylserine, a lysophospholipid mediator, has not been fully elucidated. We evaluated the role of PS-PLA(1) in oncogenesis and metastasis of colorectal cancer (CRC). Materials and Methods: Specimens from 85 patients with CRC were immunostained with a monoclonal antibody against PS-PLA(1). The correlation between PS-PLA(1) expression and the clinicopathological variables was analyzed. Results: Tumor depth and hematogenous metastasis independently positively correlated with PS-PLA(1) expression. High PS-PLA(1) expression was associated with shorter disease-free survival, although it was not an independent predictive factor. Conclusion: PS-PLA(1) expression in CRC is associated with tumor invasion and metastasis.
  • Noriko Tada, Kazushige Kawai, Nelson H Tsuno, Soichiro Ishihara, Hironori Yamaguchi, Eiji Sunami, Joji Kitayama, Koji Oba, Toshiaki Watanabe
    World journal of surgical oncology 13 30 - 30 2015年02月 [査読有り][通常論文]
     
    BACKGROUND: Although neoadjuvant chemoradiotherapy (CRT) has become a standard procedure to downstage locally advanced rectal cancer prior to surgery, markers to predict the response to CRT have not been fully identified. The aim of this study was to identify predictive factors of response to CRT, especially focusing on peripheral blood leukocyte subsets. METHODS: A total of 45 consecutive patients diagnosed with primary rectal cancer were prospectively enrolled and received CRT followed by curative resection. The numbers of each lymphocyte subset in peripheral blood pre- and post-CRT were analyzed using flow cytometry. According to the pathological response to CRT, patients were classified into high (Hi-R) and low (Lo-R) response groups. RESULTS: Hi-R cases had significantly higher numbers of pre-CRT lymphocytes (p = 0.018), T lymphocytes (p = 0.009) and helper T lymphocytes (Th lymphocytes, p = 0.015) compared to the Lo-R cases. With the receiver-operating characteristic curve for numbers of pre-CRT T lymphocytes, the area under the curve (AUC) was 0.733, and the optimal cutoff value was 1196/μl, with 76.5% sensitivity, 67.8% specificity, 59.1% positive and 82.6% negative predictive values. The numbers of pre-CRT Th lymphocytes and cytotoxic lymphocytes were both independent predictors of the high CRT response in the multivariate analysis. CONCLUSIONS: In addition to the direct cytotoxicity of CRT, recent studies have demonstrated the induction of an immunological host response, which also contributed to the tumor regression induced by CRT. Our result suggested the potential role of circulating T lymphocytes in predicting the response to CRT in colorectal cancer patients.
  • H. Ishii, K. Hata, T. Nishikawa, T. Tanaka, T. Kiyomatsu, K. Kawai, H. Nozawa, S. Kazama, H. Yamaguchi, S. Ishihara, E. Sunami, J. Kitayama, T. Watanabe
    JOURNAL OF CROHNS & COLITIS 9 S54 - S55 2015年02月 [査読無し][通常論文]
  • Koji Murono, Shinsuke Kazama, Hironori Yamaguchi, Kazushige Kawai, Soichiro Ishihara, Eiji Sunami, Joji Kitayama, Yumiko Satoh, Makiko Kurihara, Yutaka Yatomi, Toshiaki Watanabe
    SURGERY 157 2 322 - 330 2015年02月 [査読有り][通常論文]
     
    Background. Peritoneal dissemination and positive peritoneal lavage cytology are associated with poor prognosis in colorectal cancer. Carcinoembryonic antigen (CEA) messenger RNA (mRNA) is often used as a marker to detect micrometastases. We aimed to evaluate the prognostic significance of CEA mRNA in the peritoneal lavage of colon cancer patients. Methods. Colon cancer patients (n = 201) who underwent curative operative resection between August 2009 and February 2013 were enrolled. CEA mRNA in peritoneal lavage was measured using the transcription-reverse transcription concerted method, a quantitative RNA amplification method. The correlation between CEA mRNA and overall and peritoneal recurrence-free survival was evaluated. Results. Positive CEA mRNA in peritoneal lavage was an independent risk factor for overall recurrence-free survival in colon cancer (1, < .0001). Positive CEA mRNA was a risk factor for poorer overall recurrence in stage II and III patients (P = .04 and P = .02, respectively). Moreover, among stage III patients with positive CEA mRNA, the postoperative chemotherapy group had significantly lower overall and peritoneal recurrence rates than the no postoperative chemotherapy group (P = .001). Conclusion. Positive cm mRNA in peritoneal lavage was associated with high overall recurrence rates in stage II and III colon cancer Further study is necessary to determinate the efficacy of aggressive postoperative chemotherapy for stage II and III colon cancerpatients with positive CEA mRNA.
  • Koji Murono, Kazushige Kawai, Shinsuke Kazama, Soichiro Ishihara, Hironori Yamaguchi, Eiji Sunami, Joji Kitayama, Toshiaki Watanabe
    DISEASES OF THE COLON & RECTUM 58 2 214 - 219 2015年02月 [査読有り][通常論文]
     
    BACKGROUND: The branching of the inferior mesenteric artery and vein varies among individuals. Three-dimensional CT angiography is a less invasive modality than traditional angiographic examination to assess the artery and vein. OBJECTIVE: We aimed to demonstrate the clinical applicability of CT angiography by evaluating bifurcations of the inferior mesenteric artery and the positional relationship between the inferior mesenteric artery and vein. DESIGN: This was a prospective observational study of patients undergoing preoperative CT angiography. SETTINGS: This study was conducted at a single tertiary care institution in Japan. PATIENTS: A total of 471 consecutive patients who underwent preoperative CT angiography from April 2012 to December 2013 were prospectively enrolled. MAIN OUTCOME MEASURES: The branching pattern of the inferior mesenteric artery, the positional relationship between the inferior mesenteric artery and vein, and the associations between inferior mesenteric artery length and clinical features were evaluated. RESULTS: The length of the inferior mesenteric artery varied widely, from 10.1 to 82.2 mm. In 41.2% patients, the left colic artery arose independently from the sigmoid artery, and in 44.7% of the patients, the left colic artery and sigmoid artery had a common trunk, whereas the left colic artery did not exist in 5.1%. The left colic artery was located lateral to the inferior mesenteric vein at the level of the origin of the inferior mesenteric artery in 73.0% of the patients. The incidence of a short inferior mesenteric artery was significantly increased in men with high BMIs (75.0%). LIMITATIONS: Three-dimensional reconstruction was performed by the use of a single software, and angiographic examination was not performed. Therefore, accuracy and reliability of the 3-dimensional reconstruction could not be established for each modality. CONCLUSIONS: Using 3-dimensional CT angiography, preoperative understanding of the anatomic vascular variations can be easily obtained, which would help surgeons to safely perform laparoscopic surgery in the left-side colon and rectum.
  • Nirei T, Kazama S, Hiyoshi M, Tsuno NH, Nishikawa T, Tanaka T, Tanaka J, Kiyomatsu T, Hata K, Kawai K, Nozawa H, Kanazawa T, Yamaguchi H, Ishihara S, Sunami E, Kitayama J, Watanabe T
    Journal of clinical medicine research 7 1 59 - 61 2015年01月 [査読有り][通常論文]
  • Tsuyoshi Ozawa, Hironori Yamaguchi, Tomomichi Kiyomatsu, Shinsuke Saito, Soichiro Ishihara, Eiji Sunami, Joji Kitayama, Toshiaki Watanabe
    INTERNATIONAL SURGERY 100 1 58 - 62 2015年01月 [査読有り][通常論文]
     
    A 57-year-old woman without any past medical history underwent abdominoperineal resection for rectal cancer in our department. On postoperative day 15, the patient complained of sudden abdominal pain, and high fever was noted in addition to the appearance of erythema around the stoma. The diagnosis of phlegmon was made, and antibiotic infusion was started. However, a few days later, the patient developed hypovolemic shock with hypoalbuminemia and hemoconcentration. Fasciotomy was performed to exclude the necrotizing fasciitis, though all cultures were negative. Upon exclusion of the differential diagnoses, idiopathic systemic capillary leak syndrome (ISCLS) was diagnosed. She was successfully treated with massive fluid infusion under ventilation and continuous hemodiafiltration. Here, we report the first case of ISCLS that occurred during the postoperative period of colorectal surgery.
  • Kumiko Hongo, Shinsuke Kazama, Nelson H. Tsuno, Soichiro Ishihara, Eiji Sunami, Joji Kitayama, Toshiaki Watanabe
    WORLD JOURNAL OF SURGICAL ONCOLOGY 13 7  2015年01月 [査読有り][通常論文]
     
    Background: High-mobility group box 1 (HMGB1) is a nucleoprotein that is related to inflammation. It has been implicated in a variety of biologically important processes, including transcription, DNA repair, differentiation, development, and extracellular signaling. Recently, its important role in the process of tumor invasion, metastasis, and resistance to anti-cancer therapies has been demonstrated. In this study, we aimed to investigate the correlation of HMGB1 expression and resistance of rectal cancer patients to chemoradiotherapy (CRT) prior to curative operation. Methods: We retrospectively reviewed the data of 75 lower rectal cancer patients without complete pathological response who had received preoperative CRT and had undergone curative resection at the University of Tokyo Hospital between May 2003 and June 2010. HMGB1 expression in surgically resected specimens was evaluated using immunohistochemical detection and specimens were classified into high or low HMGB1 expression groups. Clinicopathologic features, degree of tumor reduction, regression of tumor grade, and patient survival were compared between the groups using non-paired Student's t-tests and Kaplan-Meier analysis. Results: A total of 52 (69.3%) patients had high HMGB1 expression, and 23 (30.7%) had low expression. HMGB1 expression was significantly correlated with histologic type (P = 0.02), lymphatic invasion (P = 0.02), and venous invasion (P = 0.05). Compared to patients with low HMGB1 expression, those with high expression had a poorer response to CRT, in terms of tumor reduction ratio (42.2 versus 28.9%, respectively; P < 0.01) and post-CRT histological tumor regression grade (56.5 versus 30.8% grade 2; respectively; P = 0.03). However, no significant correlation was found between HMGB1 expression and recurrence-free and overall survival rates. Conclusions: HMGB1 expression may be one of the key factors regulating the response of rectal cancer to preoperative CRT in terms of tumor invasiveness and resistance to therapy.
  • Masaya Hiyoshi, Kazushige Kawai, Mihoko Shibuya, Tsuyoshi Ozawa, Junko Kishikawa, Takako Nirei, Toshiaki Tanaka, Junichiro Tanaka, Tomomichi Kiyomatsu, Tomohiro Tada, Takamitsu Kanazawa, Shinsuke Kazama, Hirofumi Shoda, Shuji Sumitomo, Kanae Kubo, Hironori Yamaguchi, Soichiro Ishihara, Eiji Sunami, Joji Kitayama, Kazuhiko Yamamoto, Toshiaki Watanabe
    INTERNAL MEDICINE 54 7 749 - 753 2015年 [査読有り][通常論文]
     
    We herein report the case of a 42-year-old man with a one-year history of ulcerative colitis who presented with exacerbated bloody diarrhea, a productive cough and increasing breathing difficulties. Colonoscopy revealed typical deep ulcers in the rectosigmoid colon and atypical multiple sucker-like ulcers in the transverse colon, and computed tomography of the chest demonstrated wall thickening of the trachea and bronchi. In addition, bronchoscopy showed ulcers in the trachea, and histopathology disclosed findings of necrosis and inflammation of the subepithelial tissue of the trachea. Based on these findings, the patient's respiratory symptoms were strongly suspected to be due to ulcerative colitis-related tracheobronchitis. Treatment with systemic corticosteroids subsequently resulted in a rapid clinical improvement.
  • Shigenobu Emoto, Eiji Sunami, Hironori Yamaguchi, Soichiro Ishihara, Joji Kitayama, Toshiaki Watanabe
    SURGERY TODAY 44 12 2209 - 2220 2014年12月 [査読有り][通常論文]
     
    Intraperitoneal (IP) chemotherapy for peritoneal carcinomatosis (PC) from gastrointestinal cancer has been investigated and applied clinically for several decades. Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy have been considered to be the optimal treatment options for selected patients with colorectal and gastric cancers with PC. Accumulating evidence suggests that the administration of IP paclitaxel for patients with PC from gastric cancer may improve the patient survival. The pharmacokinetics of such treatment should be considered to optimize IP chemotherapy. In addition, newly emerging molecular-targeted therapies and research into new drug delivery systems, such as nanomedicine or controlled absorption/release methods, are essential to improve the effects of IP chemotherapy. This review summarizes the current status and future prospects of IP chemotherapy for the treatment of gastrointestinal cancer.
  • Yuuki Iida, Kazushige Kawai, Nelson H. Tsuno, Soichiro Ishihara, Hironori Yamaguchi, Eiji Sunami, Joji Kitayama, Toshiaki Watanabe
    CLINICAL COLORECTAL CANCER 13 4 213 - 218 2014年12月 [査読有り][通常論文]
     
    This study reviewed 1059 patients with colorectal cancers (CRCs) to evaluate the age-related changes in the clinicopathologic features, according to the gender. The presence of concomitant adenoma was the only independent age-related factor in men (P = .0044), whereas the presence of right-sided CRC was the only one in women (P < .0001). The results suggest the oncologic background difference between men and women among the elderly. Introduction: Although several reports have documented the increased incidence of right-sided colorectal cancer (CRC) in the elderly, especially in women, the gender-specific, age-related changes in the characteristics of CRCs, especially related to the cancer localization, have not been fully investigated. This study evaluated the age-related changes in the clinicopathologic features of CRCs, according to the gender. Materials and Methods: A total of 1059 consecutive patients with CRCs who were admitted to the authors' surgical department between February 2005 and June 2012 were retrospectively reviewed. The patients were divided into male (n = 632) and female (n = 427) groups and then according to the age group, and the correlation between the age group and the other clinicopathologic features was analyzed by univariate and multivariate analysis. Results: The number of concomitant adenomas found was significantly increased along with increasing age in men, and the presence of concomitant adenoma was the only independent age-related factor of male CRC in the multivariate analysis (P = .0044). In contrast, in women, the location of the CRC progressively shifted to the right side (proximal colon) with increasing age, and the presence of right-sided CRC was the only independent factor of female CRC in the multivariate analysis (P < .0001). Conclusion: There was a significant gender-specific difference in the age-related changes in the characteristics of CRC. Increasing the number of concomitant adenomas and the shift of CRC localization to the proximal colon were the gender-specific characteristics of male and female CRC, respectively.
  • Yasuhiro Okumura, Hiroharu Yamashita, Susumu Aikou, Koichi Yagi, Yukinori Yamagata, Masato Nishida, Kazuhiko Mori, Sachiyo Nomura, Joji Kitayama, Toshiaki Watanabe, Yasuyuki Seto
    WORLD JOURNAL OF SURGICAL ONCOLOGY 12 364  2014年11月 [査読有り][通常論文]
     
    Background: Either palliative distal gastrectomy or gastrojejunostomy are the initial treatment options for locally advanced gastric cancer with outlet obstruction when curative-intent resection is not feasible. Since chemotherapy is the mainstay for unresectable gastric cancer, the clinical value of palliative distal gastrectomy is controversial. Methods: We retrospectively reviewed the clinical data of patients with gastric cancer with outlet obstruction treated at our institution between January 2002 and December 2012. We compared the clinical outcomes of palliative distal gastrectomy with those of gastrojejunostomy patients and the factors affecting overall survival were evaluated. Results: Elective palliative distal gastrectomy and gastrojejunostomy were performed in 18 and 25 patients, respectively. The median overall survival times in the gastrojejunostomy and palliative distal gastrectomy groups were statistically equivalent at 8.8 and 8.3 months, respectively (P = 0.73), despite the more locally advanced tumors in the gastrojejunostomy as compared with the palliative distal gastrectomy group. A multivariate Cox regression analysis showed absence of postoperative chemotherapy and higher postoperative complication grade to be associated with worse clinical outcomes. Conclusions: Palliative distal gastrectomy offers neither survival nor palliative benefit as compared to gastrojejunostomy. Minimizing the morbidity of intervention for outlet obstruction, followed by chemotherapy, appears to be the optimal initial strategy for incurable gastric cancer with outlet obstruction.
  • Kazushige Kawai, Eiji Sunami, Takeshi Nishikawa, Junichiro Tanaka, Toshiaki Tanaka, Tomomichi Kiyomatsu, Keisuke Hata, Hiroaki Nozawa, Shinsuke Kazama, Soichiro Ishihara, Hironori Yamaguchi, Joji Kitayama, Toshiaki Watanabe
    SPRINGERPLUS 3 681  2014年11月 [査読有り][通常論文]
     
    Introduction: We report a rare case of delayed abdominal wall abscess after abdominoperineal resection (APR) for rectal cancer. Case description: A 63-year-old woman was diagnosed with rectal cancer and received chemo-radiotherapy, followed by APR. One year after surgery, the patient complained of pain and skin redness in the lower abdomen. A low-density mass lesion with 5.9-cm diameter was found in the lower abdominal wall by computed tomography, which showed high uptake on positron-emission tomography. These findings suggested the possibilities of either delayed abscess formation or abdominal wall recurrence of rectal cancer with central necrosis. Percutaneous drainage was performed. The content was a purulent exudate, without neoplastic cells in the cytology. The lesion quickly disappeared after the drainage, and no recurrence of the tumor was observed for more than 2 years. Discussion and evaluation: In this case, the un-absorbable yarn, such as silk, has not been used during the operation, no foreign body was retained in the abdominal wall, and there was no associated inflammatory bowel disease. Use of neoadjuvant chemoradiotherapy was the only possible cause of delayed abscess formation in this case. Conclusion: In case local recurrence is suspected by imaging modalities in the postoperative of colorectal cancer, especially those with precedent chemoradiotherapy or radiotherapy, although rare, the possibility of a delayed abscess formation should also be considered.
  • Yuuki Iida, Eiji Sunami, Soichiro Ishihara, Hironori Yamaguchi, Nelson H. Tsuno, Joji Kitayama, Toshiaki Watanabe
    CANCER RESEARCH 74 19 2014年10月 [査読無し][通常論文]
  • Joji Kitayama, Shiegenobu Emoto, Hironori Yamaguchi, Hironori Ishigami, Toshiaki Watanabe
    CANCER RESEARCH 74 19 2014年10月 [査読無し][通常論文]
  • Yuuki Iida, Nelson H. Tsuno, Junko Kishikawa, Kensuke Kaneko, Koji Murono, Kazushige Kawai, Toshiyuki Ikeda, Soichiro Ishihara, Hironori Yamaguchi, Eiji Sunami, Joji Kitayama, Yutaka Yatomi, Toshiaki Watanabe
    ANTICANCER RESEARCH 34 10 5465 - 5472 2014年10月 [査読有り][通常論文]
     
    Background: Lysophosphatidylserine (lysoPS) is a type of lysophospholipid mediator, which is involved in allergic conditions and tumor progression. We investigated the physiological function of lysoPS on colorectal cancer (CRC) cell lines, as well as the involved receptor and signaling pathways. Materials and Methods: Expression of lysoPS receptors on six cell lines was examined by reverse transcription-polymerase chain reaction (RT-PCR). The physiological functions of lysoPS were investigated, and experiments using small interfering RNA (siRNA) or inhibitors of the signaling pathways were conducted. Results: Among the three lysoPS receptors, GPR34 was highly expressed on all cell lines. LysoPS stimulated the chemotactic migratory ability. Wortmannin inhibited the migratory ability, as well as the GPR34 knock-down, strongly suggestive of the involvement of this receptor in the PI3K/Akt pathway. Conclusion: The involved receptor and pathways in the migratory ability in response to lysoPS was demonstrated, which opens premises for targeting as a new strategy for prevention and treatment of colorectal cancer.
  • Takahara N, Isayama H, Nakai Y, Sasaki T, Ishigami H, Yamashita H, Yamaguchi H, Hamada T, Uchino R, Mizuno S, Miyabayashi K, Mohri D, Kawakubo K, Kogure H, Yamamoto N, Sasahira N, Hirano K, Ijichi H, Tateishi K, Tada M, Kitayama J, Watanabe T, Koike K
    Journal of gastrointestinal cancer 45 3 307 - 311 2014年09月 [査読有り][通常論文]
  • Soichiro Ishihara, Tamuro Hayama, Hideki Yamada, Keijiro Nozawa, Keiji Matsuda, Hiroaki Miyata, Satomi Yoneyama, Toshiaki Tanaka, Junichiro Tanaka, Tomomichi Kiyomatsu, Kazushige Kawai, Hioaki Nozawa, Takamitsu Kanazawa, Shinsuke Kazama, Hironori Yamaguchi, Eiji Sunami, Joji Kitayama, Yojiro Hashiguchi, Kenichi Sugihara, Toshiaki Watanabe
    ANNALS OF SURGICAL ONCOLOGY 21 9 2949 - 2955 2014年09月 [査読有り][通常論文]
     
    Background. Retrospective studies have shown that primary tumor resection improves the prognosis of patients with colorectal cancer with unresectable metastasis (mCRC). Prognostic significance of lymph node dissection (LND) in mCRC has not been examined previously. The aim of this study was to investigate the prognostic impact of primary tumor resection and LND in mCRC. Methods. A total of 1,982 patients with mCRC from January 1997 to December 2007 were retrospectively studied. The impact of primary tumor resection and LND on overall survival (OS) was analyzed using Cox proportional hazards model and propensity score analysis to mitigate the selection bias. Covariates in the models for propensity scores included treatment period, institution, age, sex, carcinoembryonic antigen, tumor location, histology, depth, lymph node metastasis, lymphovascular invasion, and number of metastatic organs. Results. In a multivariate analysis, primary tumor resection and treatment in the latter period were associated with an improved OS, and age over 70 years, female sex, lymph node metastasis, and multiple organ metastasis were associated with a decreased OS. In the propensity-matched cohort, patients treated with primary tumor resection showed a significantly better OS than those without tumor resection (median OS 13.8 vs. 6.3 months; p = 0.0001). Furthermore, among patients treated with primary tumor resection, patients treated with D3 LND showed a significantly better OS than those with less extensive LND (median OS 17.2 vs. 13.7 months; p < 0.0001). Conclusions. It was suggested that primary tumor resection with D3 LND improves the survival of patients with mCRC.
  • Tsuyoshi Ozawa, Shinsuke Kazama, Takashi Akiyoshi, Koji Murono, Satomi Yoneyama, Toshiaki Tanaka, Junichiro Tanaka, Tomomichi Kiyomatsu, Kazushige Kawai, Hiroaki Nozawa, Takamitsu Kanazawa, Hironori Yamaguchi, Soichiro Ishihara, Eiji Sunami, Joji Kitayama, Teppei Morikawa, Masashi Fukayama, Toshiaki Watanabe
    ANNALS OF SURGICAL ONCOLOGY 21 8 2650 - 2658 2014年08月 [査読有り][通常論文]
     
    The importance of Notch signaling in colorectal cancer (CRC) tumorigenesis has been recently recognized. However, the significance of Notch3 expression and its association with Notch1 expression in CRC is unclear. In the present study, we investigated Notch1 and Notch3 expression in Stage II and III CRC to assess their association with clinicopathological characteristics. The protein expression of Notch1 and Notch3 was examined using immunohistochemistry in 305 CRC specimens. Nuclear expression of Notch1 and Notch3 and their associations with clinicopathological characteristics and distant relapse-free survival (dRFS) were evaluated. Nuclear Notch1 was overexpressed in 37 % of specimen, and nuclear Notch3 in 38 %. Nuclear Notch3 expression correlated with tumor differentiation status (P = 0.0099). Nuclear expression of Notch1 and Notch3 was associated with tumor recurrence (P = 0.0311 and P = 0.0053, respectively). In multivariate analysis, nuclear Notch3 expression [hazard ratio (HR) = 1.71; 95 % confidence interval (CI), 1.06-2.78; P = 0.0271), lymph node metastasis, and venous involvement were independently correlated with dRFS. In subgroup analysis, nuclear Notch3 expression was strongly associated with dRFS in Stage II CRC (HR = 3.47; 95 % CI 1.44-9.22; P = 0.0055). Both nuclear Notch1 and Notch3 were positive in 67 specimens (22 %) and both were negative in 144 specimens (47 %). Coexpression of nuclear Notch1 and Notch3 had an additive effect toward poorer dRFS compared with a negative subtype (HR = 2.48; 95 % CI, 1.41-4.40; P = 0.0019). Nuclear Notch3 expression might be a novel predictive marker for recurrence in Stage II and III CRC.
  • Hiroaki Nozawa, Takamitsu Kanazawa, Toshiaki Tanaka, Masao Takahashi, Soichiro Ishihara, Eiji Sunami, Joji Kitayama, Masako Ikemura, Issei Komuro, Toshiaki Watanabe
    WORLD JOURNAL OF SURGICAL ONCOLOGY 12 211  2014年07月 [査読有り][通常論文]
     
    Surgery is the mainstay of treatment for gastrointestinal stromal tumors (GISTs). However, complete resection of rectal GISTs is sometimes difficult because of bulkiness and/or anatomical reasons. Neoadjuvant imatinib therapy has gained attention as an alternative treatment to increase the chance of en bloc resection of rectal GISTs, although it usually takes several months. In this case report, we first demonstrated that neoadjuvant imatinib therapy can be performed safely not only to downsize tumors, but also to allow adequate time for the effective treatment of major comorbid illnesses. A 74-year-old man was diagnosed with a 45 mm GIST of the lower rectum. He also had severe stenosis in the proximal segment of the left anterior descending coronary artery. Following the implantation of a drug-eluting stent, the patient received imatinib together with dual anti-platelet therapy for 12 months without obvious side effects. Follow-up image studies revealed tumor shrinkage as well as stent patency. En bloc resection of the GIST was performed laparoscopically, which preserved the anus. The patient is currently alive without any evidence of relapse for 12 months after surgery.
  • Joji Kitayama
    SURGICAL ONCOLOGY-OXFORD 23 2 99 - 106 2014年06月 [査読有り][通常論文]
     
    Peritoneal carcinomatosis (PC), caused by advanced abdominal malignancies, such as those of the ovarian and gastrointestinal tracts, has an extremely poor prognosis. Intraperitoneal (IP) chemotherapy has been clinically applied for several decades, but its clinical efficacy has not been fully determined. An accumulating body of evidence suggests that cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) is the optimal treatment for selected patients with ovarian and colorectal cancers with PC. Recent studies suggest that IP administration of taxane with systemic chemotherapy in a neoadjuvant setting improves patient survival in gastric cancer with PC. The pharmacokinetics of IP-administered drugs should be primarily considered in order to optimize IP chemotherapy. Therefore, the development of specific IP drugs using newly emerging molecular targeted reagents or new drug delivery systems, such as nanomedicine or controlled absorption/release methods, is essential to improve the efficacy of IP chemotherapy. (c) 2014 Elsevier Ltd. All rights reserved.
  • Koji Murono, Kazushige Kawai, Nelson H. Tsuno, Soichiro Ishihara, Hironori Yamaguchi, Eiji Sunami, Joji Kitayama, Toshiaki Watanabe
    DISEASES OF THE COLON & RECTUM 57 6 715 - 724 2014年06月 [査読有り][通常論文]
     
    BACKGROUND: Preoperative chemoradiotherapy has been widely used for the prevention of local recurrence of locally advanced rectal cancer, and the effect of chemoradiotherapy is known to be associated with overall survival. OBJECTIVE: We aimed to evaluate the association of the pathologic response grade with tumor recurrence rate after chemoradiotherapy, using radiographic analysis and the Response Evaluation Criteria in Solid Tumors as the parameters. DESIGN: This study was conducted at a single tertiary care institution in Japan. SETTING: This was a retrospective cohort study of patients undergoing preoperative chemoradiotherapy. PATIENTS: A total of 101 low rectal cancer patients receiving preoperative chemoradiotherapy from July 2004 to August 2012 were enrolled. MAIN OUTCOME MEASURES: The tumor reduction rate was measured with the use of traditional Response Evaluation Criteria in Solid Tumors, barium enema, and CT volumetry, and the correlation between the reduction rate and the pathologic response grade was examined. RESULTS: The tumor reduction rate assessed according to Response Evaluation Criteria in Solid Tumors showed no association with the pathologic response grade (p =0.61). In contrast, the radiographic response rate by both barium enema and CT volumetry strongly correlated with the pathologic response grade (p < 0.0001 and p = 0.001). In terms of local tumor recurrence, those diagnosed as high responders by the pathologic response grade, Response Evaluation Criteria in Solid Tumors, barium enema, and CT volumetry had a lower recurrence rate (p =0.03, p =0.03, p =0.0002, and p =0.001). The difference between high responders and low responders was especially prominent by barium enema and CT volumetry. LIMITATIONS: The study is limited by its retrospective nature. CONCLUSIONS: Double-contrast barium enema and CT volumetry were superior to Response Evaluation Criteria in Solid Tumors in evaluating the effect of chemoradiotherapy and predicting the likelihood of tumor recurrence.
  • Joji Kitayama, Hironori Ishigami, Hironori Yamaguchi, Shigenobu Emoto, Hiroharu Yamashita, Yasuyuki Seto, Keisuke Matsusaki, Toshiaki Watanabe
    JOURNAL OF CLINICAL ONCOLOGY 32 15 2014年05月 [査読無し][通常論文]
  • Shinnosuke Tsuji, Yoshihiro Kawasaki, Shiori Furukawa, Kenzui Taniue, Tomoatsu Hayashi, Masumi Okuno, Masaya Hiyoshi, Joji Kitayama, Tetsu Akiyama
    NATURE COMMUNICATIONS 5 2014年05月 [査読無し][通常論文]
  • Shigenobu Emoto, Hironori Yamaguchi, Takao Kamei, Hironori Ishigami, Takashi Suhara, Yukimitsu Suzuki, Taichi Ito, Joji Kitayama, Toshiaki Watanabe
    SURGERY TODAY 44 5 919 - 926 2014年05月 [査読有り][通常論文]
     
    To develop a drug-delivery system for the prolonged retention of intraperitoneally (i.p.) administered cisplatin (CDDP) to deliver intraperitoneal chemotherapy against peritoneal carcinomatosis effectively. CDDP was encapsulated inside an in situ cross-linkable hyaluronic acid (HA)-based hydrogel. The gelation and degradation kinetics of the hydrogel and the release kinetics of CDDP were investigated in vitro, and the antitumor effect was investigated in a mouse model of peritoneal dissemination of human gastric cancer. The gelation time varied according to the concentration of two polymers: HA-adipic dihydrazide and HA-aldehyde. CDDP was released from the hydrogel for more than 4 days. A cell proliferation assay showed that the polymers themselves were not cytotoxic toward MKN45P, a human gastric cancer cell line. By mixing the two polymers in the peritoneum, in situ gelation was achieved. The weight of peritoneal nodules decreased in the hydrogel-conjugated CDDP group, whereas no significant antitumor effect was observed in the free CDDP group. In situ cross-linkable HA hydrogels represent a promising biomaterial to prolong the retention and sustain the release of intraperitoneally administered CDDP in the peritoneal cavity and to enhance its antitumor effects against peritoneal dissemination.
  • Manabu Kaneko, Hiroaki Nozawa, Masaya Hiyoshi, Noriko Tada, Koji Murono, Takako Nirei, Shigenobu Emoto, Junko Kishikawa, Yuuki Iida, Eiji Sunami, Nelson H. Tsuno, Joji Kitayama, Koki Takahashi, Toshiaki Watanabe
    JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY 140 5 769 - 781 2014年05月 [査読有り][通常論文]
     
    Temsirolimus (TEM) is a novel, water-soluble mammalian target of rapamycin (mTOR) inhibitor that has shown activity against a wide range of cancers in preclinical models, but its efficacy against colorectal cancer (CRC) has not been fully explored. We evaluated the antitumor effect of TEM in CRC cell lines (CaR-1, HT-29, Colon26) in vitro and in vivo. In vitro, cell growth inhibition was assessed using a MTS assay. Apoptosis induction and cell cycle effects were measured using flow cytometry. Modulation of mTOR signaling was measured using immunoblotting. Antitumor activity as a single agent was evaluated in a mouse subcutaneous tumor model of CRC. The effects of adding chloroquine, an autophagy inhibitor, to TEM were evaluated in vitro and in vivo. In vitro, TEM was effective in inhibiting the growth of two CRC cell lines with highly activated AKT, possibly through the induction of G1 cell cycle arrest via a reduction in cyclin D1 expression, whereas TEM reduced HIF-1 alpha and VEGF in all three cell lines. In a mouse subcutaneous tumor model, TEM inhibited the growth of tumors in all cell lines, not only through direct growth inhibition but also via an anti-angiogenic effect. We also explored the effects of adding chloroquine, an autophagy inhibitor, to TEM. Chloroquine significantly potentiated the antitumor activity of TEM in vitro and in vivo. Moreover, the combination therapy triggered enhanced apoptosis, which corresponded to an increased Bax/Bcl-2 ratio. Based on these data, we propose TEM with or without chloroquine as a new treatment option for CRC.
  • Shinsuke Kazama, Joji Kitayama, Eiji Sunami, Aya Niimi, Akira Nomiya, Yukio Homma, Toshiaki Watanabe
    BMC SURGERY 14 31  2014年05月 [査読有り][通常論文]
     
    Background: Urethral metastatic adenocarcinoma is extremely rare. Moreover, only 9 previous cases with metastases from colorectal cancer have been reported to date, and not much information on urethral metastases from colorectum is available so far. Case presentation: We report our experience in the diagnosis and the management of the case with urethral metastasis from a sigmoid colon cancer. A 68-year-old man, who underwent laparoscopic sigmoidectomy for sigmoid colon carcinoma four years ago, presented gross hematuria with pain. Urethroscopy identified a papillo-nodular tumor 7 mm in diameter in the bulbar urethra. CT-scan imaging revealed the small mass of bulbous portion of urethra and solitary lung metastasis. Histological examination of the tumor obtained by transurethral resection showed moderately differentiated adenocarcinoma, which was diagnosed as a metastasis of a sigmoid colon carcinoma pathologically by morphological examination. Immunohistochemical analysis of the urethral tumor revealed the positive for cytokertin 20 and CDX2, whereas negative for cytokertin 7. These features were consistent with metastatic adenocarcinoma of the sigmoid colon cancer. As the management of this case with urethral and lung metastasis, 6-cycle of chemotherapy with fluorouracil with leucovorin plus oxaliplatin was administered to the patient, and these metastases were disappeared with no recurrence of disease for 34 months. Conclusion: Urethral metastasis from colorectal cancer is a very rare occurrence. However, in the presence of urinary symptoms, the possibility of the urethral metastasis should be considered.
  • Yuichiro Yokoyama, Kazushige Kawai, Shinsuke Kazama, Satomi Yoneyama, Junichiro Tanaka, Toshiaki Tanaka, Tomomichi Kiyomatsu, Hiroaki Nozawa, Takamitsu Kanazawa, Hironori Yamaguchi, Soichiro Ishihara, Eiji Sunami, Joji Kitayama, Toshiaki Watanabe
    WORLD JOURNAL OF SURGICAL ONCOLOGY 12 141  2014年05月 [査読有り][通常論文]
     
    Published reports concerning internal hernias after extraperitoneal stoma construction are scarce. In our present report, we describe the case of a 56-year-old man who was referred to our hospital for the treatment of rectal cancer. He underwent abdominoperineal resection of the rectum with sigmoidostomy using an extraperitoneal route. On the ninth postoperative day, the patient experienced sudden and intense abdominal pain and was diagnosed with strangulation of the small intestine due to a stoma-associated internal hernia. Therefore, an emergency laparotomy was performed. The surgical findings showed that the small intestine protruded through the space between the sigmoid colon loop and the abdominal wall in a cranial-to-caudal direction. The strangulated portion of the small intestine was recovered, and the orifice of herniation was closed. No recurrence of internal herniation was observed during the follow-up period.
  • Joji Kitayama, Shigenobu Emoto, Hironori Yamaguchi, Hironori Ishigami, Toshiaki Watanabe
    CANCER CHEMOTHERAPY AND PHARMACOLOGY 73 3 605 - 612 2014年03月 [査読有り][通常論文]
     
    Intraperitoneal (IP) administration of paclitaxel (PTX) can enable direct infiltrate of high amount of PTX into peritoneal nodules and elicit remarkable clinical responses against peritoneal metastases. In this study, we examined the mechanisms leading to tumor shrinkage after IP PTX. We compared the microscopic features of peritoneal metastases before and after IP PTX in surgically removed human samples, as well as in a murine xenograft model using immunohistochemistry. We found that many microvessels exist in the peripheral areas of metastatic nodules in human samples before treatment. However, peripheral vessels were greatly reduced in number, and luminal obstructions were observed in lesions showing complete response after chemotherapy including IP PTX. Similar changes were observed in peripheral vessels of peritoneal tumors in MKN45-inoculated nude mice treated with IP-PTX. Moreover, pimonidazole staining revealed that highly hypoxic regions were produced by IP PTX at the tumor periphery. These findings strongly suggest that the remarkable efficacy of IP PTX in the treatment of peritoneal metastases is, at least in part, dependent on the destruction of peripheral microvessels by exposure to infiltrated PTX.
  • Joji Kitayama, Shigenobu Emoto, Hironori Yamaguchi, Hironori Ishigami, Hiroharu Yamashita, Yasuyuki Seto, Keisuke Matsuzaki, Toshiaki Watanabe
    CELLULAR IMMUNOLOGY 288 1-2 8 - 14 2014年03月 [査読有り][通常論文]
     
    In this study, we analyzed intraperitoneal cells recovered from human samples and found that CD90(+)CD45(-) cells exist as a minor population but vigorously grow in culture, showing the morphological features of mesothelial cells (MC). Interestingly, the MC highly expressed arginase I and markedly suppressed T cell proliferation with the reduction of CD3 chain expression in T cells stimulated by coated anti-CD3 mAb. The addition of nor-NOHA (500 mu M), or L-arginine (1 mM) mostly restored the inhibitory effect of MC on T cell proliferation as well as the reduced expression of CD3 zeta chain. The expression level of CD3 zeta chain in T cells in the peritoneal cavity was significantly down-regulated from circulating T cells. These results suggest that intraperitoneal free MC have immunomodulatory functions through the control of L-arginine level, and thus may play significant roles in the pathogenesis of various diseases in the peritoneal cavity. (c) 2014 Elsevier Inc. All rights reserved.
  • Joji Kitayama, Hironori Ishigami, Hironori Yamaguchi, Hiroharu Yamashita, Shigenobu Emoto, Shoich Kaisaki, Toshiaki Watanabe
    ANNALS OF SURGICAL ONCOLOGY 21 2 539 - 546 2014年02月 [査読有り][通常論文]
     
    Background. Peritoneal metastasis of gastric cancer has extremely poor clinical outcomes. Recently, we developed a combination chemotherapy that used intraperitoneal (IP) paclitaxel (PTX) and produced excellent antitumor effects against peritoneal lesions. However, no information is available about the benefit of gastrectomy in cases with malignant ascites. Methods. A total of 64 patients with severe peritoneal metastasis and ascites received IP PTX at 20 mg/m(2) via implanted subcutaneous peritoneal access ports as well as intravenous (IV) PTX at 50 mg/m(2) on days 1 and 8. S-1 was administered at 80 mg/m(2) day for 14 consecutive days, followed by 7 days of rest. In all patients, investigative laparoscopy was performed around the combination chemotherapy, and gastrectomy was performed on patients who showed apparent shrinkage of their peritoneal nodules as well as negative peritoneal cytology at the second laparoscopy. Results. Gastrectomy was performed in 34 patients. The median course of chemotherapy before surgery was 5 courses (range 2-16). R0 operation was achieved in 22 patients (65 %), and grade 2 and 3 histological responses were obtained in 7 (21 %) and 1 (3 %) patient(s), respectively. The median survival time and 1-year overall survival of the gastrectomized patients were 26.4 months and 82 %, and those of the 30 patients who did not receive gastrectomy were 12.1 months and 26 %, respectively. Morbidity was minimal, and there was no mortality. Conclusions. Salvage gastrectomy after chemotherapy of S-1 with IV and IP PTX is promising, even for patients with highly advanced gastric cancer and severe peritoneal metastasis and malignant ascites.
  • Joji Kitayama, Shigenobu Emoto, Hironori Yamaguchi, Hironori Ishigami, Takao Kamei, Hiroharu Yamashita, Yasuyuki Seto, Keisuke Matsuzaki, Toshiaki Watanabe
    CYTOMETRY PART B-CLINICAL CYTOMETRY 86 1 56 - 62 2014年01月 [査読有り][通常論文]
     
    BackgroundPeritoneal metastasis (PM) is the most life-threatening type of metastasis in abdominal malignancy. To improve the diagnostic accuracy of cytologic detection (CY) of free tumor cells (FTC) in the peritoneal cavity, we tried to quantify the FTC to leukocyte ratio using flow cytometry in patients with peritoneal metastasis. MethodsCells were recovered from ascites or peritoneal lavages from 106 patients who underwent abdominal surgery and additional 89 samples which were obtained from peritoneal catheter or access port in patients with PM (+) gastric cancer. The cells were immunostained with monoclonal antibodies to CD45 and to CD326 (EpCAM). Using flow cytometry, CD326 (+) and CD45 (+) cells were classified as either tumor cells (T) or leukocytes (L) and the T/L ratio (TLR) was calculated. ResultsIn 106 samples obtained by laparotomy, Median (M) of the TLR of PM (+) patients was 1.39% (0-807.87%) which was significantly higher than PM (-) patients (M=0%, 0-2.14%, P<0.001). In PM (+) patients, 86 CY (+) samples showed higher TLR than 61 CY (-) samples (M=2.81%, 0.02-1868.44% vs. M=0%, 0-3.45%, p<0.0001). In all of the 24 patients who were monitored for TLR before and after intraperitoneal (IP) chemotherapy, the TLR was reduced which was more dramatic than the results of the change in cytology. ConclusionsTLR measured with FACS is an excellent reflection of the tumor spread in the peritoneal cavity and could be a reliable diagnostic biomarker to determine the severity of PM as well as effectiveness of IP chemotherapy. (c) 2013 International Clinical Cytometry Society
  • Noriko Tada, Nelson H. Tsuno, Kazushige Kawai, Koji Murono, Takako Nirei, Soichiro Ishihara, Eiji Sunami, Joji Kitayama, Toshiaki Watanabe
    ONCOLOGY REPORTS 31 1 463 - 471 2014年01月 [査読有り][通常論文]
     
    In the present study, we aimed to characterize the predictive value of cytokines/chemokines in rectal cancer (RC) patients receiving chemoradiation therapy (CRT). Blood samples were obtained pre- and post-CRT from 35 patients with advanced RC, who received neoadjuvant CRT followed by surgery, and the correlation between plasma levels of cytokines/chemokines and the response to CRT was analyzed. The pre-CRT levels of soluble CD40-ligand (sCD40L) and the post-CRT levels of chemokine ligand-5 (CCL-5) were significantly associated with the depth of tumor invasion and with venous invasion. In addition, a significant decrease in sCD40L and CCL-5, as well as in platelet counts, was associated with a favorable response to CRT. A significant correlation between pre-CRT platelet counts and sCD40L was observed in patients with a favorable response. By contrast, higher post-CRT interleukin (IL)-6 was associated with a poor response. Platelets, immune system and cancer cells, cross-linked through various cytokines/chemokines, appear to play an important role in the response to CRT, and by understanding their roles, new approaches for the improvement of the therapy might be proposed.
  • Shinnosuke Tsuji, Yoshihiro Kawasaki, Shiori Furukawa, Kenzui Taniue, Tomoatsu Hayashi, Masumi Okuno, Masaya Hiyoshi, Joji Kitayama, Tetsu Akiyama
    NATURE COMMUNICATIONS 5 3150  2014年01月 [査読有り][通常論文]
     
    Aberrant activation of Wnt signalling results in colorectal tumours. Lgr5 is specifically expressed in stem cells of the intestine and has an essential role in maintaining tissue homeostasis. Lgr5-positive stem cells are responsible for the intestinal adenoma initiated by mutations in adenomatous polyposis coli. Furthermore, Lgr5 interacts with R-spondins and thereby activates Wnt signalling. However, the function of Lgr5 in colorectal tumourigenesis is unclear. Here we show that LGR5 is required for the tumourigenicity of colorectal cancer cells. We show that the transcription factor GATA6 directly enhances the expression of LGR5. We further demonstrate that GATA6 is upregulated in colorectal cancer cells due to the downregulation of miR-363, which directly targets GATA6. Moreover, we show that overexpression of miR-363 suppresses the tumourigenicity of colorectal cancer cells. These results suggest that the miR-363-GATA6-LGR5 pathway is critical for colorectal tumourigenesis and would be a promising target for the treatment of colorectal cancer.
  • Joji Kitayama, Shigenobu Emoto, Hironori Yamaguchi, Hironori Ishigami, Toshiaki Watanabe
    PLOS ONE 9 1 e86516  2014年01月 [査読有り][通常論文]
     
    The peritoneal cavity is a common target of metastatic gastrointestinal and ovarian cancer cells, but the mechanisms leading to peritoneal metastasis have not been fully elucidated. In this study, we examined the roles of cells in peritoneal fluids on the development of peritoneal metastasis. We found that a minor subset of human intraperitoneal cells with CD90(+)/CD45(2) phenotype vigorously grew in culture with mesothelial-like appearance. The mesothelial-like cells (MLC) displayed the characteristics of mesenchymal stem cell, such as differentiating into adipocytes, osteocytes, and chondrocytes, and suppressing T cell proliferation. These cells highly expressed type I collagen, vimentin, alpha-smooth muscle actin and fibroblast activated protein-a by the stimulation with TGF-beta, which is characteristic of activated myofibroblasts. Intraperitoneal co-injection of MLCs with the human gastric cancer cell line, MKN45, significantly enhanced the rate of metastatic formation in the peritoneum of nude mice. Histological examination revealed that many MLCs were engrafted in metastatic nodules and were mainly located at the fibrous area. Dasatinib, a potent tyrosine kinase inhibitor, strongly inhibited the proliferation of MLCs but not MKN45 in vitro. Nevertheless, oral administration of Dasatinib significantly inhibited the development of peritoneal metastasis of MKN45, and resulted in reduced fibrillar formation of metastatic nodules. These results suggest floating MLCs in the peritoneal fluids support the development of peritoneal metastasis possibly through the production of the permissive microenvironment, and thus the functional blockade of MLCs is a reasonable strategy to treat recurrent abdominal malignancies.
  • Joji Kitayama, Hironori Ishigami, Hironori Yamaguchi, Shigenobu Emoto, Toshiaki Watanabe
    Case Reports in Oncology 7 1 58 - 64 2014年 [査読有り][通常論文]
     
    Background: Intraperitoneal administration of paclitaxel (PTX) can elicit a marked clinical response in peritoneal metastases of gastric cancer. Methods: In this study, we retrospectively analyzed the clinical outcome of 17 patients who underwent R0 resection with D2 dissection for advanced gastric cancer with macroscopic serosal exposure and received intraperitoneal PTX as adjuvant therapy. Results: A pathological study revealed that the depth of invasion of the primary tumor was pT4a or pT4b in 10 cases, and that the pN stage was more than pN2 in 8 cases. Genetic analysis of peritoneal lavage fluid was performed in 14 cases, all of which were positive for carcinoembryonic antigen mRNA. In these patients, PTX was intraperitoneally administered at 20-60 mg/m2 with oral S-1 for 3-36 months after surgery. In a median follow-up period of 66 months, recurrence occurred in the liver and peritoneum in 2 (11.7%) and 1 (5.9%) patients, respectively, and no nodal recurrence was observed. Five-year overall survival and disease-free survival were 88.2 and 82.3%, respectively. Conclusion: Since these patients are considered to be a high-risk group for peritoneal recurrence, this result strongly suggests that adjuvant chemotherapy including intraperitoneal PTX is a promising protocol to improve the outcome of patients with advanced gastric cancer with serosal exposure. © 2014 S. Karger AG, Basel.
  • Soichiro Ishihara, Takeshi Nishikawa, Toshiaki Tanaka, Junichiro Tanaka, Tomomichi Kiyomatsu, Kazushige Kawai, Keisuke Hata, Hioaki Nozawa, Takamitsu Kanazawa, Shinsuke Kazama, Hironori Yamaguchi, Eiji Sunami, Joji Kitayama, Yojiro Hashiguchi, Kenichi Sugihara, Toshiaki Watanabe
    INTERNATIONAL JOURNAL OF SURGERY 12 9 925 - 930 2014年 [査読有り][通常論文]
     
    Background: Right-sided colon cancer is considered to be biologically different from left-sided colon cancer; however, conflicting results have been reported regarding differences in prognosis. We aimed to clarify the prognostic impact of tumor location in stage IV colon cancer. Methods: Stage IV colon cancer treated from January 1997 to December 2007 (n = 2208) were retrospectively studied. Clinical and pathological features were compared between right-sided colon cancer (cecum, ascending, and transverse colon) and left-sided colon cancer (descending, sigmoid, and rectosigmoid colon). The impact of tumor location on cancer-specific survival (CSS) was analyzed in a multivariate analysis and propensity score analysis to mitigate the differences in background features. Results: Right-sided colon cancer was associated with older age, female sex, larger tumor size, poorly differentiated adenocarcinoma, mucinous adenocarcinoma, and signet-ring cell carcinoma, a more advanced state within stage IV disease, and a worse CSS. In the cohort matched by propensity scores for background clinicopathological features, tumor location in the right-sided colon was associated with a significantly worse CSS (hazard ratio 1.2, 95% confidence interval 1.1-1.4, p = 0.008) in patients treated with palliative primary tumor resection, but not in those treated with R0 resection or no resection. Conclusion: Right-sided colon cancer were diagnosed at a more advanced state within stage IV disease and showed a significantly worse prognosis than left-sided colon cancer, suggesting that stage IV right-sided colon cancer is oncologically more aggressive than left-sided colon cancer. (C) 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.
  • Hiroaki Nozawa, Takeshi Nishikawa, Toshiaki Tanaka, Junichiro Tanaka, Tomomichi Kiyomatsu, Kazushige Kawai, Keisuke Hata, Shinsuke Kazama, Hironori Yamaguchi, Soichiro Ishihara, Eiji Sunami, Joji Kitayama, Toshiaki Watanabe
    CHEMOTHERAPY 60 5-6 360 - 367 2014年 [査読有り][通常論文]
     
    Background: The identification of responders is an important issue in chemotherapy for metastatic colorectal cancer (mCRC). 'Deepness of response' (DpR), defined as the maximum rate of reduction from the initial tumor burden, was recently proposed as a novel hypothetical parameter associated with overall survival (OS) in first-line chemotherapy plus cetuximab for mCRC. We determined whether this concept was universally applicable to diverse standard chemotherapeutic regimens for mCRC. Methods: We reviewed mCRC patients who received the first-line systemic chemotherapy regimens FOLFOX, CapeOX or FOLFIRI (with biologics) at our department between June 2005 and March 2015. Data such as clinicopathological parameters, metastasized organs, chemotherapeutic regimens, the best response by RECIST v1.1, progression-free survival (PFS) and OS were retrospectively retrieved for patients who exhibited tumor shrinkage. DpR was calculated as the uni-dimensional maximum reduction rate of measurable tumors. We addressed the association between DpR and survival. Results: Of the 156 patients receiving first-line chemotherapy regimens, tumor shrinkage was observed in 63 (41 of whom were men; median age 62 years). Complete remission was achieved in 6 patients, partial remission in 42 and stable disease in 15. The median DpR was 44.2% and was employed as the cutoff, in line with previous reports. DpR >= 45% (31 patients) was correlated with longer PFS (median 16.4 vs. 8.1 months for DpR <45%, p = 0.006) and OS (median 58.6 vs. 30.9 months for DpR <45%, p = 0.041). There was basically no difference in the subsequent chemotherapy between the DpR >= 45% and DpR <45% groups. Conclusion: DpR correlated with OS in various first-line systemic upfront chemotherapy regimens for mCRC. (C) 2015 S. Karger AG, Basel
  • Shiori Furukawa, Yoshihiro Kawasaki, Masaya Miyamoto, Masaya Hiyoshi, Joji Kitayama, Tetsu Akiyama
    PLOS ONE 8 11 e80609  2013年11月 [査読有り][通常論文]
     
    The tumor suppressor adenomatous polyposis coli (APC) is mutated in sporadic and familial colorectal tumors. APC stimulates the activity of the Cdc42- and Rac1-specific guanine nucleotide exchange factor Asef and promotes the migration and invasion of colorectal tumor cells. Furthermore, Asef is overexpressed in colorectal tumors and is required for colorectal tumorigenesis. It is also known that NOTCH signaling plays critical roles in colorectal tumorigenesis and fate determination of intestinal progenitor cells. Here we show that NOTCH3 up-regulates Asef expression by activating the Asef promoter in colorectal tumor cells. Moreover, we demonstrate that microRNA-1 (miR-1) is down-regulated in colorectal tumors and that miR-1 has the potential to suppress NOTCH3 expression through direct binding to its 3'-UTR region. These results suggest that the miR-1-NOTCH3-Asef pathway is important for colorectal tumor cell migration and may be a promising molecular target for the treatment of colorectal tumors.
  • Sasaki K, Fujiwara Y, Kishi K, Motoori M, Sugimura K, Miyoshi N, Akita H, Gotoh K, Takahashi H, Marubashi S, Noura S, Ohue M, Yano M, Sakon M, Ishigami H, Kitayama J
    Gan to kagaku ryoho. Cancer & chemotherapy 40 12 2319 - 2321 2013年11月 [査読有り][通常論文]
     
    A phase III clinical trial to evaluate the efficacy of combination chemotherapy with intraperitoneal administration of paclitaxel for gastric cancer with peritoneal metastasis has been ongoing in Japan. A male patient in his 50s who was diagnosed as having advanced gastric cancer with peritoneal metastasis was enrolled in this trial. The patient was assigned to receive a regimen of intravenous and intraperitoneal paclitaxel combined with S-1. Although an intraperitoneal access port had been implanted to provide access to the peritoneal cavity, tube obstruction occurred twice. Laparoscopic examination revealed that the tube in the abdominal cavity had been totally covered with the great omentum. Therefore, the intraperitoneal regimen was discontinued. Although intraperitoneal chemotherapy for the treatment of peritoneal dissemination in gastric cancer is promising, precaution should be taken to avoid tube obstruction, which is a complication of the intraperitoneal tube placement.
  • Hironori Ishigami, Joji Kitayama, Hironori Yamaguchi, Shigenobu Emoto, Toshiaki Watanabe
    Japanese Journal of Cancer and Chemotherapy 40 10 1269 - 1273 2013年10月 [査読有り][通常論文]
     
    As no treatment method has a sufficient level of evidence of success in the treatment of gastric cancer with peritoneal metastasis, there is an urgent need to develop a new treatment that takes into account the pathophysiology of the disease. A novel multidisciplinary treatment approach combining intraperitoneal (IP) paditaxel (PTX), systemic chemotherapy, and gastrectomy is one of the promising treatment options. We designed a combination chemotherapy regimen of S-1, weekly intravenous and IP PTX and determined the recommended dose in a phase I study. In the phase II study, the median survival time (MST) was 23.6 months. Out of 100 patients treated with this regimen, we performed gastrectomy on 62 patients after disappearance or obvious shrinkage of the peritoneal metastasis, and the MST was 34.5 months. Currently, we are carrying out a phase III trial (PHOENIX-GC trial) comparing our IP regimen to S-1 plus CDDP.
  • Hironori Yamaguchi, Joji Kitayama, Hironori Ishigami, Shigenobu Emoto, Hiroharu Yamashita, Toshiaki Watanabe
    CANCER 119 18 3354 - 3358 2013年09月 [査読有り][通常論文]
     
    BACKGROUND The prognosis of patients with gastric cancer with peritoneal metastasis is extremely poor. This phase 2 study evaluated the benefits and tolerability of weekly intravenous and intraperitoneal paclitaxel (PTX) treatment combined with oral S-1 in patients with gastric cancer who had macroscopic peritoneal metastasis. METHODS Patients with gastric cancer who had primary tumors with macroscopic peritoneal metastasis were enrolled. PTX was administered intravenously at 50 mg/m(2) and intraperitoneally at 20 mg/m(2) on days 1 and 8, respectively. S-1 was administered at 80 mg/m(2) per day for 14 consecutive days, followed by 7 days of rest. The primary endpoint was the 1-year overall survival (OS) rate. The secondary endpoints were the response rate, efficacy against malignant ascites, and safety. RESULTS Thirty-five patients were enrolled. The median number of treatment courses was 11 (range, 2-35). The 1-year OS rate was 77.1% (95% confidence interval, 60.5-88.1). The overall response rate was 71% in 7 patients with target lesions. Malignant ascites disappeared or decreased in 15 of 22 (68%) patients. The frequent grade 3/4 toxic effects were neutropenia (34%), leukopenia (23%), and anemia (9%). CONCLUSIONS Combination chemotherapy consisting of intravenous and intraperitoneal PTX with S-1 is well-tolerated and effective in patients with gastric cancer who have macroscopic peritoneal metastasis. Cancer 2013;119:3354-8. (c) 2013 American Cancer Society.
  • Koji Murono, Joji Kitayama, Nelson H. Tsuno, Hiroaki Nozawa, Kazushige Kawai, Eiji Sunami, Masaaki Akahane, Toshiaki Watanabe
    INTERNATIONAL JOURNAL OF COLORECTAL DISEASE 28 8 1065 - 1072 2013年08月 [査読有り][通常論文]
     
    Both hepatic steatosis (HS) and colorectal cancer (CRC) are conditions associated with metabolic syndrome. The liver is the most frequent site of distant metastasis of CRC; however, the impact of HS on the incidence of liver metastasis of CRC is not clearly defined. Then, the correlation with the presence or absence of HS was analyzed. A total of 604 CRC patients receiving curative surgical resection who had a preoperative non-enhanced computed tomography (CT) were enrolled. The mean attenuation values (in Hounsfield units) of the liver and spleen were obtained on a plain CT slice, and the patients with liver-spleen attenuation ratio lower than 1.1 were objectively defined as HS. The clinicopathological features of these patients were analyzed, and the association between HS and the clinical features of CRC was examined. Sixty-three (10.4 %) among the 604 patients were diagnosed as HS. Recurrence-free survival (RFS) and hepatic RFS, but not extrahepatic RFS, were significantly higher in the group with HS (p = 0.04 and p = 0.006). However, this effect was not evident in the group of patients with obesity, defined as body mass index > 25.0. Among the stage I similar to III cases, HS was significantly associated with lower hepatic, but not extrahepatic, RFS. Moreover, absence of HS was an independent risk factor for hepatic RFS (p = 0.003). Metastases of CRC are less frequent in fatty liver. Steatosis may be an unfavorable microenvironment for metastatic formation in the liver.
  • Kitayama J, Emoto S, Yamaguchi H, Ishigami H, Kamei T, Yamashita H, Seto Y, Matsuzaki K, Watanabe T
    Cytometry. Part B, Clinical cytometry 2013年08月 [査読有り][通常論文]
     
    Background: Peritoneal metastasis (PM) is the most life-threatening type of metastasis in abdominal malignancy. To improve the diagnostic accuracy of cytologic detection (CY) of free tumor cells (FTC) in the peritoneal cavity, we tried to quantify the FTC to leukocyte ratio using flow cytometry in patients with peritoneal metastasis. Methods: Cells were recovered from ascites or peritoneal lavages from 106 patients who underwent abdominal surgery and additional 89 samples which were obtained from peritoneal catheter or access port in patients with PM (+) gastric cancer. The cells were immunostained with monoclonal antibodies to CD45 and to CD326 (EpCAM). Using flow cytometry, CD326 (+) and CD45 (+) cells were classified as either tumor cells (T) or leukocytes (L) and the T/L ratio (TLR) was calculated. Results: In 106 samples obtained by laparotomy, Median (M) of the TLR of PM (+) patients was 1.39% (0-807.87%) which was significantly higher than PM (-) patients (M=0%, 0-2.14%, p<0.001). In PM (+) patients, 86 CY (+) samples showed higher TLR than 61 CY (-) samples (M=2.81%, 0.02-1868.44% vs. M=0%, 0-3.45%, p<0.0001). In all of the 24 patients who were monitored for TLR before and after intraperitoneal chemotherapy, the TLR was reduced which was more dramatic than the results of the change in cytology. Conclusion: TLR measured with FACS is an excellent reflection of the tumor spread in the peritoneal cavity and could be a reliable diagnostic biomarker to determine the severity of PM as well as effectiveness of IP chemotherapy. © 2013 Clinical Cytometry Society.
  • Kumiko Hongo, Nelson H. Tsuno, Kazushige Kawai, Kazuhito Sasaki, Manabu Kaneko, Masaya Hiyoshi, Koji Murono, Noriko Tada, Takako Nirei, Eiji Sunami, Koki Takahashi, Hirokazu Nagawa, Joji Kitayama, Toshiaki Watanabe
    JOURNAL OF SURGICAL RESEARCH 182 1 75 - 84 2013年06月 [査読有り][通常論文]
     
    Background: A hypoxic environment exists in most solid tumors because in rapidly growing tumors, the development of angiogenic vasculature is heterogenous, usually not enough to overcome the necessary oxygen supply. In an ischemic condition, cancer cells develop escape mechanisms to survive and leave the unfavorable environment. That result in the acquisition of increased potential for local invasion and evasion to distant organs. However, the escapemechanisms of cancer cells from hypoxic stress have not been fully characterized. Materials and methods: The human colon cancer cell line LoVo was cultured in hypoxia, and the adhesive and migratory properties were analyzed. The expression of cell surface and cytoplasmic molecules was also investigated. Results: Under hypoxic conditions, cells developed epithelial-mesenchymal transition. The expression levels of alpha 2, alpha 5, and beta 1 integrins were significantly upregulated and, as a consequence, the ability to adhere to and migrate on collagen and fibronectin was increased. On the other hand, the expression of 67-kDa laminin receptor and the abilities to adhere to and migrate on laminin were decreased. Additionally, the expression of CXCR4 was significantly increased on cells cultured in hypoxia, and the chemotactic activity to stromal cell-derived factor 1 alpha was remarkably increased. Conclusions: Hypoxic stress induced active epithelial-mesenchymal transition in colon cancer cells, with the typical morphologic and functional changes. These morphologic and functional changes of b1 integrins, the 67-kDa laminin receptor, and CXCR4 may be essential for the acquisition of the invasive and metastatic features in colorectal cancer. (C) 2013 Elsevier Inc. All rights reserved.
  • Kumiko Hongo, Shinsuke Kazama, Eiji Sunami, Joji Kitayama, Toshiaki Watanabe
    HEPATO-GASTROENTEROLOGY 60 124 720 - 726 2013年06月 [査読有り][通常論文]
     
    Background/Aims: Perianal adenocarcinoma associated with anal fistula is a rare disease with a poor prognosis. The relatively small number of patients with this disease has led to a lack of any consensus regarding diagnosis and appropriate treatment. The purpose of this study was to present our experience of 11 cases of this disease, and to highlight its clinical features, treatments and outcomes. Methodology: The patients were divided into three groups according to the modality of treatment. Four patients received surgical resection without preoperative therapy (operation group), 3 patients were treated with radiotherapy prior to surgery (RT group), and 4 were treated with combined chemoradiation therapy prior to surgery (CRT group). Results: The resection stump was pathologically negative for cancer in 6 (85.7%) patients in RT or CRT group, and 3 of 6 are alive with no evidence of disease recurrence. However, the resection stump was negative in only 1 (25%) patient in the operation group. Moreover, among the patients who underwent neoadjuvant RT/CRT and abdominoperineal resection with a cancer-free resection stump, 2 patients with postoperative adjuvant therapy had no recurrence of disease. Conclusions: Multimodality therapy including neoadjuvant RT or CRT and adjuvant chemotherapy is considered to be effective for treatment of this disease.
  • Joji Kitayama, Takao Kamei, Shigenobu Emoto, Hironori Yamaguchi, Hironori Ishigami
    JOURNAL OF CLINICAL ONCOLOGY 31 15 2013年05月 [査読無し][通常論文]
  • Kazushige Kawai, Joji Kitayama, Nelson H. Tsuno, Eiji Sunami, Toshiaki Watanabe
    INTERNATIONAL JOURNAL OF COLORECTAL DISEASE 28 4 527 - 535 2013年04月 [査読有り][通常論文]
     
    Although thrombocytosis has been reported in patients with various cancers including the colorectal one, the impact of elevated platelet counts on the response to chemoradiotherapy (CRT) for rectal cancer has not been fully investigated. We investigated the clinical significance of pre- and post-CRT platelet counts in patients with rectal cancer. The medical records of 101 patients with rectal cancer, who had received CRT followed by surgical resection, were retrospectively reviewed. The correlations between the clinicopathological variables and the pre- or post-CRT platelet counts were analyzed. The correlations between tumor regression rate induced by CRT, as evaluated by barium enema and pathological examination, and the pre- or post-CRT platelet counts were also evaluated. Finally, the impact of pre-CRT thrombocytosis on the prognosis of these patients was assessed. The pre-CRT platelet count correlated with venous invasion and tumor size, and it strongly correlated with the response rate evaluated by barium enema and the grade of pathological tumor regression. Furthermore, patients with pre-CRT thrombocytosis had significantly shorter local recurrence-free survival. Platelet count before CRT should be a promising biomarker for predicting the efficacy of CRT and the risk of local recurrence in rectal cancer patients after CRT.
  • J. Kitayama, H. Ishigami, H. Yamaguchi, S. Emoto
    ANNALS OF SURGICAL ONCOLOGY 20 S34 - S35 2013年02月 [査読無し][通常論文]
  • Joji Kitayama, Hironori Ishigami, Hironori Yamaguchi, Shigenobu Emoto, Toshiaki Watanabe
    JOURNAL OF CLINICAL ONCOLOGY 31 4 2013年02月 [査読無し][通常論文]
  • Takahara Naminatsu, Isayama Hiroyuki, Nakai Yousuke, Sasaki Takashi, Ishigami Hironori, Yamaguchi Hironori, Kogure Hirofumi, Yamamoto Natsuyo, Hirano Naoki, Sasahira Kenji, Tada Minoru, Kitayama Joji, Watanabe Toshiaki, Koike Kazuhiko
    JOURNAL OF CLINICAL ONCOLOGY 31 4 2013年02月 [査読有り][通常論文]
  • Masaya Hiyoshi, Joji Kitayama, Shinsuke Kazama, Yoshitaka Taketomi, Makoto Murakami, Nelson H. Tsuno, Kumiko Hongo, Manabu Kaneko, Eiji Sunami, Toshiaki Watanabe
    ONCOLOGY LETTERS 5 2 533 - 538 2013年02月 [査読有り][通常論文]
     
    Among the secretory phospholipase A2s (sPLA2), sPLA2 group X (PLA2GX) has the most potent hydrolyzing activity toward phosphatidylcholine, and has recently been shown to be implicated in chronic inflammatory diseases. The aim of the present study was-to investigate PLA2GX expression in colorectal cancer (CRC) and its correlation with patient clinicopathological features. The present study comprises a series of 158 patients who underwent surgical resection for primary CRC. PLA2GX expression in CRC tissues was examined by immunohistochemistry and compared with patient clinicopathological findings and survival. A total of 64% of the tumors expressed PLA2GX at high levels. Statistical analysis revealed that PLA2GX expression was inversely correlated with hematogenous metastasis (P=0.005). In the subgroup analysis, left-sided tumors with high PLA2GX expression showed an inverse correlation with lymph node metastasis (P=0.018) and hematogenous metastasis (P=0.017). Patients with high PLA2GX expression tended to have a longer disease-specific survival compared with those with low PLA2GX expression in left-sided, but not right-sided, CRC (P=0.08). In light of the present results, we suggest that PLA2GX has an inhibitory effect on the progression of CRC.
  • Koji Murono, Kazushige Kawai, Shinsuke Kazama, Nelson H. Tsuno, Eiji Sunami, Joji Kitayama, Toshiaki Watanabe
    International Surgery 98 1 49 - 54 2013年 [査読有り][通常論文]
     
    A 63-year-old man underwent a colectomy for sigmoid colon cancer in 1997. The upper lobe of his left lung and his left adrenal gland were resected because of metachronous metastases, 7 and 10 years after the initial surgery, respectively. Recurrence of metastases to the middle lobe of the right lung and left adrenal gland were sequentially detected in 2007, and a multimodal therapy, consisting of the combination of radiotherapy and chemotherapy, was conducted since 2007. The chemotherapy included drugs such as FOLFOX, FOLFIRI, bevacizumab, capecitabine, and cetuximab. In 2011, the complete response of all metastatic lesions could be achieved, and no recurrence was detected for more than 1 year. In spite of repeated recurrences, by the combination of surgical resection, chemotherapy, and radiotherapy, the complete response could be achieved 14 years after the initial surgical resection, which can be attributed to the development of new treatment modalities and new agents for colorectal cancer.
  • Kumiko Hongo, Shinsuke Kazama, Eiji Sunami, Nelson H. Tsuno, Koki Takahashi, Hirokazu Nagawa, Joji Kitayama
    MEDICAL ONCOLOGY 29 4 2849 - 2857 2012年12月 [査読有り][通常論文]
     
    CD133 has been identified as a putative cancer stem cell (CSC) marker in various cancers including colorectal cancer. The relation between CD133 expression and biological characteristics of colorectal cancer remains to be clarified. Protein expression of CD133 was immunohistochemically evaluated in surgical specimens of 225 patients with colorectal cancer who were treated by surgery, as well as those of 78 patients with rectal cancer who received preoperative chemoradiotherapy (CRT) followed by curative resection. The correlation between CD133 expression and clinicopathological features, tumor recurrence and overall survival was analyzed in both populations. Among 225 colorectal cancers without CRT, 93 (41.3%) were positive for CD133 expression, which was enhanced in cases with advanced T stage and venous invasion. Moreover, CD133 was positive in 47 (60.3%) of 78 cases with CRT, which was significantly higher than the CD133-positive rate in non-CRT specimens (P = 0.05). Expression of CD133 was independently correlated with the histological tumor regression grade (P < 0.01). These results suggest that CD133 is not a distinctive colorectal CSC marker; expression of CD133 is suggested to be one of the key factors associated with resistance to CRT in colorectal cancer.
  • Yousuke Nakai, Hironori Ishigami, Hiroyuki Isayama, Takashi Sasaki, Kazumichi Kawakubo, Hirofumi Kogure, Shigenobu Emoto, Hironori Yamaguchi, Joji Kitayama, Natsuyo Yamamoto, Naoki Sasahira, Kenji Hirano, Minoru Tada, Kazuhiko Koike
    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 27 12 1796 - 1800 2012年12月 [査読有り][通常論文]
     
    Background and Aim: Gastrointestinal (GI) luminal obstruction or malignant biliary obstruction (MBO) is not a rare condition in gastric cancer patients with peritoneal metastasis. The role of endoscopic or percutaneous interventions is not fully elucidated in this setting. Methods: A total of 123 patients with unresectable or recurrent gastric adenocarcinoma with peritoneal metastasis receiving intravenous and intraperitoneal paclitaxel combined with S-1 were retrospectively studied. Safety and efficacy of interventions for GI luminal obstruction and MBO were evaluated. Results: A total of 27 patients (22%) underwent GI luminal and/or biliary interventions; GI luminal alone in 10, biliary alone in 10 and both in seven, with a technical success rate of 100%. Clinical success rate was 65% in self-expandable metallic stents (SEMS) placement for GI luminal obstruction. Eastern Cooperative Oncology Group (ECOG) performance status (PS) was prognostic of clinical success in GI luminal stenting (100% in PS of 1 vs 14% in PS of 23, P?<?0.001). Biliary drainage (endoscopic SEMS placement in four and percutaneous transhepatic biliary drainage in 12) relieved obstructive jaundice in 94%. Six complications were observed: four after GI luminal stenting (two occlusion and one aspiration pneumonia) and two after biliary stenting (one cholangitis and one cholecystitis). Median survival after the initial intervention was 5.7?months. PS at interventions was prognostic of survival after interventions (12.3?months in PS of 1 vs 2.2?months in PS of 2 or 3, P?<?0.001). Conclusion: Endoscopic or percutaneous interventions for GI luminal obstruction or MBO were feasible and effective in gastric cancer patients with peritoneal dissemination receiving combination chemotherapy.
  • Shigenobu Emoto, Hironori Ishigami, Akio Hidemura, Hironori Yamaguchi, Hiroharu Yamashita, Joji Kitayama, Toshiaki Watanabe
    JAPANESE JOURNAL OF CLINICAL ONCOLOGY 42 11 1013 - 1019 2012年11月 [査読有り][通常論文]
     
    The efficacy of intraperitoneal chemotherapy for gastric cancer with peritoneal metastasis has been verified by clinical trials. To perform intraperitoneal chemotherapy safely and effectively, the appropriate management of intraperitoneal access ports is essential. The aim of this study was to investigate the occurrence of port complications during cyclically repeated intraperitoneal chemotherapy. The medical records of 131 gastric cancer patients with peritoneal metastases who received intraperitoneal paclitaxel between 2005 and 2011 were retrospectively analyzed. The median period of intraperitoneal chemotherapy using a port system was 12.9 months (range: 0.861.5 months), and a total of 27 (20.6) patients experienced port complications. Inflow obstruction (7.6) and infection (6.9) were the main complications, followed by reflux (3.1), subcutaneous masses (1.5) and fistulae (1.5). The median interval between port implantation and port complication was 5.4 months (range: 0.340.9 months). Complications were controllable and chemotherapy was not terminated by complications. Survival was not affected by the presence or absence of port complications (median survival time: 22.5 vs. 17.2 months, respectively; P 0.65). Intraperitoneal chemotherapy for gastric cancer using a port is safe and feasible under appropriate management.
  • Hideyo Miyato, Nelson Hirokazu Tsuno, Joji Kitayama
    CANCER SCIENCE 103 11 1961 - 1966 2012年11月 [査読有り][通常論文]
     
    Malignant tumors are often associated with denervation, suggesting the functional implication of axonal guidance molecules in tumor growth. Here, we assessed the role of semaphorin 3C (sema3C) in the progression of gastric cancer. Immunohistochemistry of human samples revealed that sema3C was strongly expressed in neoplastic cells, especially at the invasion front. Stable transfection of target sequences of sema3C miRNA did not affect the in vitro proliferative activity of human gastric cancer AZ-521 cells. However, when the tumor growth was examined in vivo using an orthotopic model in nude mice, primary stomach tumors as well as metastatic liver tumors were significantly suppressed by sema3C silencing with the reduction of microvessel density. Immunostaining of primary tumor indicated the rate of Ki-67 positive carcinoma cells was decreased, whereas that of apoptotic cells was significantly increased in sema3C-silenced tumor. In addition, capillary-like tubular formation was reduced by the addition of culture media of sema3C miRNA cells compared with the media of control miRNA cells. Semaphorin 3C is positively expressed in gastric cancer cells and may be involved in tumor progression, presumably through the stimulation of angiogenesis. (Cancer Sci 2012; 103: 1961-1966)
  • H. Ishigami, H. Yamaguchi, H. Yamashita, S. Emoto, J. Kitayama
    ANNALS OF ONCOLOGY 23 82 - 82 2012年10月 [査読無し][通常論文]
  • N. Takahara, H. Isayama, Y. Nakai, T. Sasaki, H. Ishigami, H. Yamashita, H. Yamaguchi, S. Mizuno, H. Kogure, N. Yamamoto, K. Hirano, M. Tada, J. Kitayama, T. Watanabe, K. Koike
    PANCREAS 41 7 1159 - 1159 2012年10月 [査読無し][通常論文]
  • H. Ishigami, J. Kitayama, H. Yamaguchi, S. Emoto, T. Watanabe
    ANNALS OF ONCOLOGY 23 233 - 233 2012年09月 [査読無し][通常論文]
  • Hiroaki Nozawa, Joji Kitayama, Eiji Sunami, Toshiaki Watanabe
    DISEASES OF THE COLON & RECTUM 55 9 948 - 956 2012年09月 [査読有り][通常論文]
     
    BACKGROUND: Chronic kidney disease, a disease entity increasing in number, may be an obstacle in various aspects of treatment for malignant neoplasm, such as perisurgical management and implementation of chemotherapy. OBJECTIVE: The aim of this study was to evaluate both short- and long-term outcomes of patients with colorectal cancer who have chronic kidney disease. DESIGN: This study is a retrospective cohort study of patients. SETTINGS: This study as conducted at an academic tertiary hospital in Japan. PATIENTS AND INTERVENTIONS: We investigated 1127 consecutive patients with stages 0 to III primary colorectal cancer who underwent curative resection in our department from January 2001 to December 2010. Based on estimated glomerular filtration rate, patients were classified into stages 0 to 2 (including normal renal function, 882 patients, 78.2%), stages 3 to 4 (226 patients, 20.1%), or stage 5 chronic kidney disease (19 patients, 1.7%). MAIN OUTCOME MEASURES: Clinicopathological data, perioperative course, frequencies of postoperative complications, adjuvant chemotherapy, and recurrence-free and overall survivals after surgery for colorectal cancer were compared among the 3 different chronic kidney disease stage groups. RESULTS: Patients with chronic kidney disease stage 5 frequently experienced diabetes mellitus and cardiovascular comorbidities. They were also hypoalbuminemic and anemic and more likely to receive blood transfusions, although estimated blood loss was smaller during surgery than in the other patients. Perioperative cardiovascular complications were more frequent in the chronic kidney disease stages 3 to 4 and 5 groups (5.3%) than those in the stages 0 to 2 group (0.8%, p < 0.0001). However, the frequencies of other complications were similar. There were no differences in the frequency of adjuvant chemotherapy and recurrence-free survival among different chronic kidney disease stages; in contrast, the chronic kidney disease stage 5 group showed a poorer overall survival. LIMITATIONS: The study is limited by its retrospective nature. CONCLUSIONS: From these data, we conclude that surgical resection for colorectal cancer in patients with chronic kidney disease can be performed with acceptable outcomes.
  • Kaisaki S, Kato M, Sanuki J, Kitayama J
    Nihon rinsho. Japanese journal of clinical medicine 70 Suppl 7 524 - 527 2012年09月 [査読有り][通常論文]
  • Kazushige Kawai, Eiji Sunami, Nelson H. Tsuno, Joji Kitayama, Toshiaki Watanabe
    INTERNATIONAL JOURNAL OF COLORECTAL DISEASE 27 8 1087 - 1093 2012年08月 [査読有り][通常論文]
     
    Although it is known that those patients who have developed colorectal cancer (CRC) are at a higher risk to develop metachronous adenoma or CRC, no study has been performed to analyze the relationship between the risk factors and the time course for the formation of postoperative adenoma using survival analysis. One hundred seventy-six patients with CRC, who had received surgical resection, were endoscopically followed-up to detect the development of metachronous adenoma or adenocarcinoama. The association between the risk factors such as age, synchronous adenomas with index CRC or other clinicopathological variables and the formation of postoperative adenoma was assessed using the logrank test and the Cox proportional hazard model. Age over 60, synchronous lesions at the time of surgery for primary CRCs and presence of diabetes mellitus (DM) as the associated disease were positively related to the formation of postoperative adenoma. Among those patients with the three risk factors, only 27.8% remained adenoma-free during 5 years after operation, whereas in the group without any risk factor, it was 90.4%. From our data, age over 60, synchronous adenomas or CRCs and DM were the potential risk factors for the postoperative formation of adenoma or CRC, and they should be taken into consideration when defining the appropriate interval of postoperative colonoscopy.
  • Kazuhito Sasaki, Nelson H. Tsuno, Eiji Sunami, Kazushige Kawai, Kumiko Hongo, Masaya Hiyoshi, Manabu Kaneko, Koji Murono, Noriko Tada, Takako Nirei, Koki Takahashi, Joji Kitayama
    ANTI-CANCER DRUGS 23 7 675 - 682 2012年08月 [査読有り][通常論文]
     
    Autophagy is a complex of adaptive cellular response that enhances cancer cell survival in the face of cellular stresses such as chemotherapy. Recently, chloroquine diphosphate (CQ), a widely used antimalarial drug, has been studied as a potential inhibitor of autophagy. Here, we aimed to investigate the role of CQ in potentiating the effect of 5-fluorouracil (5-FU), the chemotherapeutic agent of first choice for the treatment of colorectal cancer, in an animal model of colon cancer. The mouse colon cancer cell line colon26 was used. For the in-vivo study, colon26 cells were injected subcutaneously into BALB/c mice, which were treated with saline as a control, CQ (50 mg/kg/day), 5-FU (30 mg/kg/day), or the combination therapy (CQ plus 5-FU). The tumor volume ratio and body weight were monitored. After the sacrifice, tumor tissue protein extracts and tumor sections were prepared and subjected to immunoblotting for the analysis of autophagy-related and apoptosis-related proteins, and the terminal transferase uridyl end labeling assay. The combination of CQ resulted in the inhibition of 5-FU-induced autophagy and a significant enhancement in the 5-FU-induced inhibition of tumor growth. Furthermore, the combination treatment of CQ and 5-FU resulted in a significant increase in the ratio of apoptotic cells compared with other treatments. The expression levels of the proapoptotic proteins, namely Bad and Bax, were increased by the CQ treatment in the protein extracts from tumors. Our findings suggest that the combination therapy of CQ and 5-FU should be considered as an effective strategy for the treatment of colorectal cancer. Anti-Cancer Drugs 23:675-682 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
  • Shigenobu Emoto, Hironori Yamaguchi, Junko Kishikawa, Hiroharu Yamashita, Hironori Ishigami, Joji Kitayama
    CANCER SCIENCE 103 7 1304 - 1310 2012年07月 [査読有り][通常論文]
     
    The intraperitoneal administration of paclitaxel has been shown to be a promising treatment strategy for peritoneal malignancy. The present study evaluated the effects of intraperitoneal administration of NK105, a paclitaxel-incorporating micellar nanoparticle, which has been shown to have a remarkable effect in a mouse model of gastric cancer. Intraperitoneal NK105 significantly reduced peritoneal tumors in vivo compared with the conventional paclitaxel formulation of paclitaxel solubilized in Cremophor EL and ethanol (PTX-Cre). Moreover, intraperitoneal NK105 significantly reduced the size of subcutaneously inoculated tumors, whereas no such effect was seen with PTX-Cre. Similar systemic toxic effects were observed following the intraperitoneal administration of both NK105 and PTX-Cre. Although NK105 disappeared rapidly almost within a day from the peritoneal cavity, the paclitaxel concentration in peritoneal nodules 4h after intraperitoneal administration was significantly higher in the NK105 group than in the PTX-Cre group (P<0.05), whereas there were no significant differences in liver paclitaxel concentrations between the two groups. We also evaluated the pharmacokinetics following intraperitoneal administration of NK105 and PTX-Cre. Serum paclitaxel concentrations 6, 12, 24, and 48h after the intraperitoneal administration of the drugs were significantly higher in the NK105 than the PTX-Cre group. Furthermore, the peak serum concentration was higher in the NK105 than PTX-Cre group (24100 +/- 3560 vs 108 +/- 25 similar to ng/mL, respectively; P<0.001), as was the area under the concentrationtime curve from 0 to 48h (191000 +/- 32100 vs 1500 +/- 108ng center dot h/mL, respectively; P<0.001). Therefore, intraperitoneal chemotherapy with nanoparticulate paclitaxel NK105 may offer a novel treatment strategy for improving drug delivery in gastric cancer with peritoneal dissemination because of enhanced drug penetration into peritoneal nodules and its prolonged presence in the systemic circulation. (Cancer Sci 2012; 103: 13041310)
  • Shinsuke Kazama, Kumiko Hongo, Eiji Sunami, Yasuhiko Sugawara, Norihiro Kokudo, Joji Kitayama
    JAPANESE JOURNAL OF CLINICAL ONCOLOGY 42 7 586 - 590 2012年07月 [査読有り][通常論文]
     
    Liver-transplant patients have an increased risk of developing primary malignancies, possibly due to prolonged immunosuppression. However, no information on the incidence and biological characteristics of colorectal cancer after living-donor liver transplantation is available. The medical records of 392 consecutive adult patients who had undergone living-donor liver transplantation were retrospectively analyzed. Colorectal cancer developed in 6 (1.5) patients; 3 of 204 (1.5) presented with hepatic cirrhosis, 2 of 77 (2.5) with primary biliary cirrhosis and 1 (2.6) of 39 with subacute fulminant hepatitis, but none of 13 patients with primary sclerosing cholangitis. Four patients were successfully treated with curative surgery and one with endoscopic resection, while another patient died 3 months after palliative surgery because of the progression of peritoneal metastasis. A pathological study revealed vessel invasion in all the five cases of surgically removed colorectal cancer and nodal metastasis in four (80) cases. Colorectal cancer develops at a relatively high frequency after living-donor liver transplantation, even in non-primary sclerosing cholangitis cases, and might have high malignant potential. The screening program for colorectal cancer should be more intensified after living-donor liver transplantation compared with that in the general population.
  • Kitayama J, Hiyoshi M
    Nihon rinsho. Japanese journal of clinical medicine 70 Suppl 5 556 - 560 2012年07月 [査読有り][通常論文]
  • Koji Yasuda, Eiji Sunami, Kazushige Kawai, Hirokazu Nagawa, Joji Kitayama
    Journal of Gastrointestinal Cancer 43 2 236 - 243 2012年06月 [査読有り][通常論文]
     
    Introduction: Although neoadjuvant chemoradiotherapy (CRT) is the standard treatment for advanced rectal cancer (RC), markers predicting response have not been adequately defined. Patients and Methods: In 73 cases with advanced RC, we evaluated the tumor response with the reduction rate of the longitudinal size of RC using barium enema image taken before and after CRT. Then, we retrospectively examined the association with various blood values taken before CRT. The tumor size reduction rate was significantly greater in ten CR cases than in 63 non-CR cases (p< 0.001). Results: Interestingly, the size reduction ratio was positively associated with hemoglobin, albumin level and lymphocyte percentage in leukocytes, while being negatively associated with platelet counts, C-reactive protein and fibrinogen levels as well as neutropliles percentage. Moreover, high lymphocyte counts (> 1,800/mm3) had an independent association with disease-free survival. Conclusions: Blood data have a major impact on the tumor response to CRT. Control of host condition may improve the effectiveness of CRT in advanced RC. © Springer Science+Business Media, LLC 2011.
  • Hongo K, Tanaka J, Tsuno NH, Kawai K, Nishikawa T, Shuno Y, Sasaki K, Kaneko M, Hiyoshi M, Sunami E, Kitayama J, Takahashi K, Nagawa H
    The Journal of surgical research 175 2 278 - 288 2012年06月 [査読有り][通常論文]
     
    Background and Aim. Recently, the cancer stem cells (CSCs) theory has been proposed, and CD133 has been suggested as a potential marker of CSCs in various cancer types. In the present study, we aimed evaluate CD133 as a potential marker of colorectal CSCs and, for this purpose, isolated CD133(+) and CD133(-) cells from a single colorectal cancer cell line, and compared their features, especially related to the tumor-forming and differentiation abilities, and the sensitivity to chemotherapy. Methods and Results. CD133(+) cells had higher in vivo tumor-forming ability than CD133(-) cells, and in culture, they progressively differentiated into CD133(-) cells, but not vice-versa. On the other hand, CD133(-) cells were more resistant to 5-fluorouracil (FU) treatment than CD133(+) cells, and it was found to be dependent on the higher expression of beta 1-integrins, and consequently, higher ability to bind collagen. Disruption of the beta 1-integrin function abrogated the chemoresistance. Conclusion. From the present results, we concluded that colorectal cancer CD133(+) cells, although showing some features of CSCs, are not more resistant to 5-FU than CD133(-) cells. Therefore, definite conclusions can not be drawn yet, but it is strongly suggestive that CD133 should not be used as a single CSC marker of colorectal cancer. (C) 2012 Elsevier Inc. All rights reserved.
  • Hideyo Miyato, Joji Kitayama, Hirokazu Nagawa
    HEPATO-GASTROENTEROLOGY 59 116 1299 - 1301 2012年06月 [査読有り][通常論文]
     
    Background/Aims: Although preservation of the vaguas nerve is recommended in surgery for early-stage gastric cancer, the physiological effect of vagotomy on the postoperative course has not been well documented. We assessed the effect of vagotomy on the change in fat volume after gastrectomy. Methodology: Subcutaneous fat area (SFA) and visceral fat area (VFA) were separately measured in computed tomographic images taken before and more than 6 months after surgery, using Fat Scan software. The ratios of postoperative/preoperative values of these two fat areas as well as body weight were calculated in 45 patients who underwent DG with (n=24) or without (n=21) vagotomy. Results: Vagotomy did not affect the change in body weight (91.3 +/- 1.7% vs. 92.1 +/- 1.7%). In patients with vagotomy, VFA was reduced to 59.0 +/- 5.1%, which was significantly greater than the reduction in SFA (74.3 +/- 8.7%, p=0.042). In contrast, the reduction ratios of VFA and SFA were equal in vagus nerve-preserved patients (78.4 +/- 6.7% vs. 78.2 +/- 6.9%, p=0.97). Conclusions: The vagus nerve may have a function to locally regulate the intra-abdominal fat volume and preservation of the vagus nerve results in the maintenance of visceral fat after DG.
  • Joji Kitayama, Hiroaki Nozawa, Toshiaki Watanabe, Eiji Sunami
    JOURNAL OF CLINICAL ONCOLOGY 30 15 2012年05月 [査読無し][通常論文]
  • Hironori Yamaguchi, Hironori Ishigami, Shigenobu Emoto, Hiroharu Yamashita, Joji Kitayama
    JOURNAL OF CLINICAL ONCOLOGY 30 15 2012年05月 [査読無し][通常論文]
  • Kitayama J, Ishigami H, Yamaguchi H, Yamashita H, Emoto S, Kaisaki S
    Gastrointestinal cancer research : GCR 5 3 Suppl 1 S10 - 3 2012年05月 [査読有り][通常論文]
     
    Peritoneal metastasis is the most frequent and life-threatening type of metastasis in patients with advanced gastric cancer. Despite recent advances in chemotherapeutic agents, any treatment, if administered only via the intravenous (IV) route, cannot satisfactorily control peritoneal metastasis in gastric cancer. Although intraperitoneal (IP) chemotherapy has been proposed as a treatment option, the clinical efficacy of IP chemotherapy for peritoneal lesions has not been examined in gastrointestinal cancer. One hundred patients with gastric cancer received combination chemotherapy of S-1 plus IV (50 mg/m(2)) and IP (20 mg/m(2)) paclitaxel (PTX) via a subcutaneously implanted peritoneal access port. S-1 was administered at 80 mg/m(2) per day for 14 consecutive days, followed by 7 days' rest. Radical gastrectomy was performed in a salvage setting when macroscopic curative resection was made feasible by the downstaging achieved by the combined chemotherapy. The median survival time (MST) of the patient sample was 23.6 months, with a 1-year survival of 80%. Combination chemotherapy of S-1 plus IV and IP PTX is well tolerated and very effective in patients with gastric cancer and peritoneal metastasis. Systemic chemotherapy combined with repeated IP administration of paclitaxel is a promising strategy for peritoneal carcinomatosis in gastrointestinal cancer.
  • Manabu Kaneko, Hiroaki Nozawa, Nelson H. Tsuno, Kazushige Kawai, Kazuhito Sasaki, Kumiko Hongo, Masaya Hiyoshi, Eiji Sunami, Koki Takahashi, Joji Kitayama
    CANCER RESEARCH 72 2012年04月 [査読無し][通常論文]
  • Masaya Hiyoshi, Nelson H. Tsuno, Kensuke Otani, Kazushige Kawai, Takeshi Nishikawa, Yasutaka Shuno, Kazuhito Sasaki, Kumiko Hongo, Manabu Kaneko, Koji Murono, Noriko Tada, Takako Nirei, Eiji Sunami, Koki Takahashi, Joji Kitayama
    CANCER RESEARCH 72 2012年04月 [査読無し][通常論文]
  • Noriko Tada, Nelson Hirokazu Tsuno, Kazushige Kawai, Koji Murono, Takako Nirei, Manabu Kaneko, Masaya Hiyoshi, Kazuhito Sasaki, Kumiko Hongo, Eiji Shunami, Joji Kitayama, Koki Takahashi
    CANCER RESEARCH 72 2012年04月 [査読無し][通常論文]
  • Koji Murono, Nelson H. Tsuno, Kazushige Kawai, Kazuhito Sasaki, Kumiko Hongo, Manabu Kaneko, Masaya Hiyoshi, Noriko Tada, Takako Nirei, Eiji Sunami, Koki Takahashi, Joji Kitayama
    CANCER RESEARCH 72 2012年04月 [査読無し][通常論文]
  • Shigenobu Emoto, Hironori Ishigami, Hiroharu Yamashita, Hironori Yamaguchi, Shoichi Kaisaki, Joji Kitayama
    GASTRIC CANCER 15 2 154 - 161 2012年04月 [査読有り][通常論文]
     
    Serum tumor markers have been shown to correlate with the clinical status of patients with advanced gastric cancer. However, the clinical significance of each tumor marker in patients with peritoneal dissemination has not been fully verified. Four serum markers, carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, CA125, and CA72-4, were periodically measured in 102 patients with peritoneal dissemination who received combination intravenous and intraperitoneal chemotherapy. The initial values at diagnosis and after treatment were analyzed in association with clinicopathological factors, response to chemotherapy, and overall survival. The sensitivities of CEA, CA19-9, CA125, and CA72-4 for peritoneal metastasis at the initial diagnosis were 19, 36, 46, and 45%, respectively. The CA125 level was significantly correlated with the degree of peritoneal dissemination and the existence of malignant ascites. Patients with ovarian metastasis showed significantly higher levels of CA72-4. The median survival time of patients with an elevated CA125 level was significantly shorter than that of patients with a normal CA125 level (36.7 vs. 16.6 months, p < 0.001). Multivariate analysis showed that the degree of peritoneal metastasis and an elevated CA125 level were independent prognostic factors. Normalization of the CA125 level after 3 courses of chemotherapy was correlated with reduced ascites and improved survival. Serum CA125 and CA72-4 are clinically useful markers in diagnosis, evaluating the efficacy of chemotherapy, and predicting the prognosis of patients with peritoneal dissemination. From an academic point of view, periodic measurements of these markers are warranted in gastric cancer patients with possible peritoneal dissemination.
  • Masaya Hiyoshi, Nelson H. Tsuno, Kensuke Otani, Kazushige Kawai, Takeshi Nishikawa, Yasutaka Shuno, Kazuhito Sasaki, Kumiko Hongo, Manabu Kaneko, Eiji Sunami, Koki Takahashi, Hirokazu Nagawa, Joji Kitayama
    ONCOLOGY LETTERS 3 4 756 - 760 2012年04月 [査読有り][通常論文]
     
    Adiponectin is a hormone secreted by adipose tissue and has a variety of functions including the inhibition of tumor growth. The expression and function of the two major adiponectin receptors, AdipoR1 and AdipoR2, in malignant tissue have not been well characterized. In the present study, we evaluated the mRNA levels of AdipoR1 and AdipoR2 expression in 48 surgically resected colorectal cancer specimens, as well as normal colonic mucosa, by quantitative RT-PCR. The values obtained were standardized by beta-actin m RNA, and the correlation between their relative expression levels and the clinicopathological characteristics of the patients was examined. The relative expression levels of AdipoR1 and AdipoR2 were significantly reduced in cancer tissue compared with normal tissue (AdipoR1: 0.97 +/- 0.39 vs. 1.37 +/- 0.41, P<0.0001; AdipoR2: 0.92+/-0.31 vs. 1.60+/-0.46, P<0.0001). AdipoR1 and AdipoR2 levels were further reduced in tumors with nodal metastases and the difference was statistically significant in the case of AdipoR2 (0.79+/-0.27 vs. 1.02+/-0.30, P=0.012). The results of this study demonstrated that the expression levels of adiponectin receptors are reduced in cancer specimens compared to normal tissue, indicating a downregulation in the course of the development and progression of colorectal cancer. Since adiponectin is abundantly present in the whole body and has inhibitory effects on cancer cells, this downregulation of the receptors may be an escape mechanism of malignant cells from the suppressive effects of adiponectin.
  • Hideyo Miyato, Joji Kitayama, Akio Hidemura, Hironori Ishigami, Shoichi Kaisaki, Hirokazu Nagawa
    JOURNAL OF SURGICAL RESEARCH 173 1 60 - 67 2012年03月 [査読有り][通常論文]
     
    Background. Body weight loss is a well-known complication after gastrectomy, and is mainly due to reduced fat volume. The effect of vagotomy on the postoperative fat volume was investigated in patients with early stage gastric cancer who underwent gastrectomy. Methods. Subcutaneous fat area (SFA) and visceral fat area (VFA) were separately measured in a computed tomographic (CT) image at the level of the umbilicus using Fat Scan software. The changes in these two fat areas were determined by comparing CT images taken before and more than 6 mo after gastrectomy, and the ratio of postoperative to preoperative fat area was calculated in 77 patients. Results. VFA was reduced significantly greater after total gastrectomy (TG) than distal gastrectomy (DG) (P = 0.0003). In 63 patients who underwent DG, the reduction in VFA, but not in SFA, was significantly less in vagus nerve-preserved than in vagus nerve-nonpreserved cases (59.0% +/- 24.2% versus 74.9% +/- 28.2%, P = 0.027). If compared in each case, VFA showed a significantly greater decrease than did SFA in vagus-nonpreserving, but not in vagus-preserving, gastrectomy (68.2% +/- 37.0% versus 52.7% +/- 25.2%, P < 0.0001; 76.3% +/- 30.0% versus 74.9% +/- 28.2%, P = 0.79). Conclusions. The vagus nerve has a function to locally regulate the amount of intra-abdominal fat tissue, and selective vagotomy in gastrectomy results in a preferential reduction of visceral fat in gastrectomy. Surgical denervation of vagus may be reconsidered as a reasonable treatment for excessive obesity. (C) 2012 Published by Elsevier Inc.
  • Koji Murono, Nelson H. Tsuno, Kazushige Kawai, Kazuhito Sasaki, Kumiko Hongo, Manabu Kaneko, Masaya Hiyoshi, Noriko Tada, Takako Nirei, Eiji Sunami, Koki Takahashi, Joji Kitayama
    ANTICANCER RESEARCH 32 3 865 - 872 2012年03月 [査読有り][通常論文]
     
    Background: Cancer cells can acquire resistance to therapy under hypoxic condition. We aimed to investigate the mechanisms regulating chemoresistance induced by hypoxia. Materials and Methods: Human colorectal cancer cells, HT-29 and SW480, were cultured under hypoxic conditions and the sensitivity to 5-fluorouracil (FU), oxaliplatin, and SN-38 (active metabolite of irinotecan) was tested. The cell cycle was evaluated by flow cytometry after staining of cells with propidium iodide (PI). hypoxia-inducible factor 1 alpha (HIP-1 alpha) expression was evaluated by western blot analysis. Results: Hypoxia induced strong G(0)/G(1) cell cycle arrest of cancer cells and abrogated the cytotoxic effects of 5-FU and oxaliplatin, but not that of SN-38. This effect was dependent on the significant inhibition of the accumulation of HIF-1 alpha in cancer cells cultured under hypoxia by SN-38. Neither 5-FU nor oxaliplatin affected HIP-I a expression. Conclusion: SN-38, through inhibition of HIF-1 alpha can overcome chemoresistance under hypoxic conditions of colon cancer cells.
  • Hiroaki Nozawa, Eiji Sunami, Jun Nakajima, Hirokazu Nagawa, Joji Kitayama
    EXPERIMENTAL AND THERAPEUTIC MEDICINE 3 3 449 - 456 2012年03月 [査読有り][通常論文]
     
    There is little information regarding the recent trend of synchronous and metachronous pulmonary metastases in patients with primary colorectal cancer. We investigated patients with sporadic colorectal cancer who underwent surgery in our department between 1990 and 2009. Clinicopathological parameters of primary cancer and lung metastases and survival time were retrospectively reviewed. Of the 2,286 patients included in this study, 64 (2.8%) had synchronous lung metastases at the time of colorectal surgery. A total of 18 patients (28%) received pulmonary metastasectomy for these lesions with curative intent. Out of 2,082 curatively operated cases, 212 (10.2%) developed metachronous lung metastases. The frequency of synchronous and/or metachronous lung metastases detected in curative cases increased from 8.9% in the 1990s to 11.9% in the 2000s (p=0.03). Among predictive factors for metachronous lung metastases, the presence of distant organ metastases, i.e. initial stage IV, significantly increased over time. Notably, patients with unresectable metachronous lung metastases in the 2000s. characterized by smaller size, exhibited more favorable prognosis than in the 1990s (p=0.003). Recent improvement of imaging modalities is considered to have facilitated the prompt diagnosis of lung metastases. Moreover, marked progress in multidisciplinary treatment has presumably achieved more favorable prognosis in an increasing number of patients with advanced colorectal cancer.
  • Hironori Ishigami, Shoichi Kaisaki, Hironori Yamaguchi, Hiroharu Yamashita, Shigenobu Emoto, Joji Kitayama
    JOURNAL OF CLINICAL ONCOLOGY 30 4 2012年02月 [査読無し][通常論文]
  • Yumiko Satoh, Kazuhiko Mori, Kentaro Kitano, Joji Kitayama, Hiromitsu Yokota, Hiroki Sasaki, Hiroshi Uozaki, Masashi Fukayama, Yasuhiro Seto, Hirokazu Nagawa, Yutaka Yatomi, Daiya Takai
    JAPANESE JOURNAL OF CLINICAL ONCOLOGY 42 2 148 - 152 2012年02月 [査読有り][通常論文]
     
    Prediction of peritoneal recurrence in gastric cancer patients is important for application of adjuvant chemotherapy. After surgery, occasional patients have peritoneal recurrence despite negative cytology of the peritoneal washings. Thus, molecular detection of a subliminal number of cancer cells in peritoneal washings may overcome the sensitivity limitation of conventional cytology. In this study, expressions of five specific marker genes, namely, TFF1, TFF2, CK20, FABP1 and MUC2, were evaluated for their usefulness as markers of micro-dissemination. It was found that reverse transcriptase-polymerase chain reaction for these five genes yielded results highly specific for the depth of invasion and disease stage. Furthermore, the expression of CK20, FABP1 and MUC2 was a reliable prognostic indicator of peritoneal metastasis. Our results suggest that evaluation of the expression of CK20, FABP1 and MUC2 in peritoneal washings is a useful tool for identifying patients at high risk of peritoneal recurrence who may need adjuvant chemotherapy.
  • Kazuhito Sasaki, Kazushige Kawai, Nelson H. Tsuno, Eiji Sunami, Joji Kitayama
    WORLD JOURNAL OF SURGERY 36 1 192 - 200 2012年01月 [査読有り][通常論文]
     
    Although thrombocytosis has been reported in patients with various types of cancer, the association between thrombocytosis and the clinicopathological features of patients with colorectal cancer (CRC) has not been fully investigated. We evaluated the clinical features associated with thrombocytosis in CRC. The medical records of 636 consecutive CRC patients undergoing surgery in our department between January 2002 and July 2008 were retrospectively reviewed. The correlation between the clinicopathological variables and the preoperative platelet count was analyzed by univariate and multivariate analyses. The impact of thrombocytosis on the prognosis of these patients was assessed, in comparison with the other clinicopathological variables. Platelet count showed significant correlation with gender, age, venous involvement, tumor size, depth of invasion, regional lymph node metastasis, distant metastasis in univariate analysis, and tumor size and depth of invasion were independent factors in multivariate analysis. The cancer-specific survival (CSS) of CRC patients with thrombocytosis was significantly shorter than that for those without thrombocytosis (P < 0.001), specifically in patients with stage III CRC (P < 0.001). Multivariate analysis indicated that thrombocytosis was an independent prognostic factor of CSS (hazard ratio = 2.96, 95% confidence interval [CI] = 1.72-5.00). Moreover, within stage II CRC, the univariate analysis revealed that disease-free survival (DFS) was associated with preoperative thrombocytosis, but not the other clinicopathological variables. Preoperative thrombocytosis is not only an independent indicator of poor CSS in CRC patients but also an independent predictor of poor DFS in patients with stage II CRC.
  • Kazuhito Sasaki, Shinsuke Kazama, Eiji Sunami, Nelson H. Tsuno, Hiroaki Nozawa, Hirokazu Nagawa, Joji Kitayama
    DISEASES OF THE COLON & RECTUM 55 1 72 - 78 2012年01月 [査読有り][通常論文]
     
    BACKGROUND: Intraoperative colonic irrigation and intraoperative on-table colonoscopy may be useful for a more accurate diagnosis of colorectal cancer before colectomy in patients with obstructive left-sided colorectal cancer, but the clinical benefit of this technique has not been investigated in large-scale studies. OBJECTIVE: The aim of this study was to evaluate the usefulness of intraoperative colonic irrigation with a Y-shaped irrigation device and intraoperative colonoscopy in the management of obstructive colorectal cancer in patients undergoing elective surgery. DESIGN AND SETTING: This was a retrospective cohort study of patients undergoing surgical treatment at a single tertiary care institution in Japan. PATIENTS AND INTERVENTION: Among 715 consecutive patients with left-sided colorectal cancer, 101 patients (14.1%) with obstructing tumor received intraoperative colonic irrigation and intraoperative colonoscopy before colectomy and primary anastomosis, and 614 patients with nonobstructive colorectal cancer underwent preoperative colonoscopy with mechanical bowel preparation. MAIN OUTCOME MEASURES: Detection rates of proximal synchronous lesions, occurrence of postoperative complications, and changes in the surgical procedure prompted by the results of the intraoperative colonoscopy were evaluated. RESULTS: Intraoperative colonoscopy detected synchronous adenomatous polyps in 27 patients (26.8%), carcinoma in 4 patients (4%), and obstructive colitis in 2 patients (2%). Findings of the intraoperative colonoscopy prompted changes in surgical procedure in 9 patients (8.9%). The overall morbidity in the intraoperative group was 17%, with anastomotic leakages in 3 patients, wound infection in 5, and postoperative ileus in 3 patients. The risk of these complications was not increased in patients with intraoperative colonoscopy with intraoperative colonic irrigation compared with those receiving preoperative colonoscopy with mechanical bowel preparation. The operation time was 28 minutes longer in the intraoperative than in the preoperative group, but neither the time to start of oral intake nor the length of postoperative hospital stay was significantly different between the 2 groups. LIMITATIONS: The study is limited by its retrospective nature. CONCLUSIONS: In patients with obstructive colorectal cancer, intraoperative colonic irrigation with intraoperative colonoscopy is a useful strategy for detecting synchronous lesions located proximally to the obstructing tumor, without increasing patient morbidity.
  • Ishigami H, Kaisaki S, Kitayama J
    Nihon Geka Gakkai zasshi 113 1 18 - 21 2012年01月 [査読有り][通常論文]
  • Manabu Kaneko, Hiroaki Nozawa, Kazuhito Sasaki, Kumiko Hongo, Masaya Hiyoshi, Noriko Tada, Koji Murono, Takako Nirei, Kazushige Kawai, Eiji Sunami, Nelson H. Tsuno, Joji Kitayama
    ONCOLOGY 82 5 261 - 268 2012年 [査読有り][通常論文]
     
    Background: The aim of this study was to assess whether the neutrophil to lymphocyte ratio (NLR) and other laboratory markers may predict the prognosis of advanced colorectal cancer (CRC) patients receiving palliative chemotherapy. Methods: The study population included 50 patients with far advanced or recurrent unresectable CRC who received oxaliplatin-based combination chemotherapy as first-line treatment in our hospital between June 2005 and November 2010. Seven clinical variables and 7 laboratory indices before chemotherapy were evaluated retrospectively as the possible prognostic factors of overall and progression-free survival. Results: During the study period, 27 patients (54%) died of CRC. Elevated NLR (>= 4.0) was observed in 15 patients (30%). By univariate analysis, elevated NLR, performance status and hypoalbuminemia were significantly associated with both poor overall and progression-free survivals. Multivariate analysis showed that elevated NLR (hazard ratio 4.39, 95% confidence interval 1.82-10.7; p = 0.0013) and thrombo-cytosis (hazard ratio 5.02, 95% confidence interval 1.69-13.4; p = 0.0066) were independently associated with overall survival. Conclusion: Elevated NLR is a powerful predictor of poor response to oxaliplatin-based chemotherapy in patients with unresectable CRC. The ratio is a simply accessible and inexpensive but useful biomarker in CRC patients receiving chemotherapy. Copyright (C) 2012 S. Karger AG, Basel
  • Hironori Ishigami, Joji Kitayama, Hironori Yamaguchi, Shigenobu Emoto, Toshiaki Watanabe
    Japanese Journal of Cancer and Chemotherapy 39 13 2460 - 2463 2012年 [査読有り][通常論文]
     
    The standard of care for gastric cancer with peritoneal metastasis is systemic chemotherapy. However, there is no chemotherapy regimen with a sufficient level of evidence supporting its effectiveness, and thus S-1 plus cisplatin (CDDP), which is regarded as the standard regimen for advanced metastatic gastric cancer, is widely applied. Meanwhile, the efficacy of intraperitoneal (IP) administration of taxanes has been verified, and the novel multidisciplinary treatment combining chemotherapy and surgery is now being tested. We developed a combination chemotherapy regimen of S-1, weekly intravenous and IP paclitaxel (PTX), and determined the recommended dose of IP PTX to be 20 mg/m2 in our phase I study. In our phase II study, the median survival time (MST) of 40 patients enrolled was 23.6 months, and peritoneal cytology turned negative for 86% of 28 patients. Moreover, we performed gastrectomy on 60 patients after the disappearance or obvious shrinkage of peritoneal metastasis, and the MST was 34.5 months. Multidisciplinary treatment combining IP-containing chemotherapy and surgery is safe and effective for gastric cancer patients with peritoneal metastasis. We have started a phase III trial (PHOENIX-GC trial) comparing our IP regimen to S-1 plus CDDP.
  • Shinsuke Kazama, Joji Kitayama, Junken Aoki, Ken Mori, Hirokazu Nagawa
    Journal of Gastrointestinal Cancer 42 4 204 - 211 2011年12月 [査読有り][通常論文]
     
    Purpose: Autotaxin (ATX) is molecularly identical to lysophospholipase D (lysoPLD) and is a main enzyme producing lysophosphatidic acid (LPA), which mediates a broad range of cellular responses including stimulation of cell motility. Patients and Methods: Using immunohistochemical staining, we examined the expression of ATX/lysoPLD in 98 cases of early colorectal cancer with submucosal invasion. ATX/lysoPLD was highly expressed in infiltrating cells in tumor tissue in the submucosal layer, which were characterized as mast cells. Results: The number of ATX/lysoPLD-positive cells was significantly greater in tumors with a macroscopically depressed lesion than in tumors without depression. The density of ATX/lysoPLD-positive cells tended to have a positive correlation with microvessel vascular density (MVD), while it was not correlated with vessel invasion and nodal metastases as well as lymphovascular vessel density (LVD). Conclusion: Our results suggest that local production of LPA through ATX/lysoPLD may weakly correlate with formation of a depressive lesion and tumor angiogenesis in the early stage of colorectal cancer. © 2010 Springer Science+Business Media, LLC.
  • J. Kitayama, H. Ishigami, H. Yamaguchi, H. Yamashita, S. Emoto, S. Kaisaki
    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 26 264 - 264 2011年10月 [査読無し][通常論文]
  • Shigenobu Emoto, Hironori Ishigami, Hironori Yamaguchi, Hiroharu Yamashita, Shoichi Kaisaki, Joji Kitayama
    GASTRIC CANCER 14 4 390 - 395 2011年10月 [査読有り][通常論文]
     
    We detected 7 cases of leptomeningeal carcinomatosis in 126 patients with peritoneal dissemination of gastric cancer who received combined systemic and intraperitoneal chemotherapy. Leptomeningeal carcinomatosis was diagnosed 79-1540 days after the diagnosis of the primary gastric cancer. Patients presenting with various neurological symptoms were diagnosed by cerebrospinal fluid (CSF) cytology and radiological imaging. Irradiation to the whole brain and spine was performed in 4 patients, and provided palliation and increased survival for 1 patient. Intrathecal chemotherapy and drainage of CSF was performed in 1 patient each, but produced no significant clinical benefit in either of them. Survival after the diagnosis of leptomeningeal carcinomatosis was between 3 and 155 days. As patients with peritoneal dissemination of gastric cancer are living longer because of improved chemotherapy, clinicians must recognize the possibility of leptomeningeal carcinomatosis when patients complain of neurological symptoms.
  • Hiroaki Nozawa, Joji Kitayama, Eiji Sunami, Shinsuke Saito, Takamitsu Kanazawa, Shinsuke Kazama, Kentaro Yazawa, Kazushige Kawai, Ken Mori, Hirokazu Nagawa
    Japanese Journal of Cancer and Chemotherapy 38 10 1627 - 1632 2011年10月 [査読有り][通常論文]
     
    We investigated the effectiveness of prophylactic FOLFOX after curative resection of synchronous metastases in patients with colorectal cancer (CRC). Clinicopathological information including postoperative chemotherapy, such as a therapeutic regimen, relapse-free survival (RFS), site of recurrence, etc., was retrospectively analyzed in 116 CRC patients with synchronous distant metastases, and 63 patients with metachronous metastases who had received surgery in our hospital between 2000 and 2009. Fifty-three patients (84%) out of 63 without adjuvant chemotherapy, and 38 (83%) out of 46 patients that received oral or intravenous 5-fluorouracil (5-FU) (alone or with leucovorin (LV) orisovorin) developed recurrent tumor (s) afterwards. The median RFSs were 119 and 281 days, respectively. By contrast, a single patient among 6 who underwent FOLFOX (up to 12 therapeutic courses) showed recurrence 476 days after surgery. The RFS of the FOLFOX was significantly higher than that of the 5-FU (+LV) or surgery alone (p=0. 03, p=0. 007, respectively). In conclusion, the FOLFOX regimen is more beneficial for CRC patients with synchronous metastasis as adjuvant chemotherapy than 5-FU (+LV) or other follow-up strategies.
  • H. Ishigami, S. Kaisaki, H. Yamaguchi, H. Yamashita, S. Emoto, J. Kitayama
    EUROPEAN JOURNAL OF CANCER 47 S449 - S449 2011年09月 [査読無し][通常論文]
  • K. Hongo, S. Kazama, E. I. J. I. Sunami, T. Nelson, H. Nagawa, J. Kitayama
    EUROPEAN JOURNAL OF CANCER 47 S398 - S398 2011年09月 [査読無し][通常論文]
  • Hideyo Miyato, Joji Kitayama, Hironori Ishigami, Shoichi Kaisaki, Hirokazu Nagawa
    ANNALS OF SURGICAL ONCOLOGY 18 8 2281 - 2288 2011年08月 [査読有り][通常論文]
     
    The role and clinical significance of the alteration of sympathetic nerve fibers (SNF) was assessed in gastric cancer. Loss of nerve fibers in malignant tumors has previously been described; however, how dysfunction of the nervous system is involved in cancer progression has not been clarified in clinical studies. The distribution of SNF was examined in 82 surgically resected gastric cancer specimens with immunohistochemical staining of tyrosine hydroxylase (TH), and the association with clinicopathological findings as well as the clinical outcome of the patients was retrospectively evaluated. Arterioles in the normal gastric wall were totally covered with SNF, while the immunoreactivity to TH was markedly reduced around arterioles in cancer tissue. The degree of loss of SNF was significantly correlated with the depth of invasion (P < .0001) and lymph node metastasis (P < .0001) as well as microvessel density (MVD) (P = .0043). Moreover, patients who had tumors with marked loss of SNF showed a markedly worse clinical outcome, with an independent association by multivariate analysis. Loss of periarteriolar SNF is associated with aggressive phenotype of gastric cancer possibly through enhanced angiogenesis and thus could be a useful marker to predict the clinical outcome.
  • Koji Yasuda, Takako Nirei, Nelson Hirokazu Tsuno, Hirokazu Nagawa, Joji Kitayama
    CANCER SCIENCE 102 7 1257 - 1263 2011年07月 [査読有り][通常論文]
     
    Recent studies have suggested that tumor shrinkage in response to radiotherapy (RT) is greatly dependent on the host immune response. A Balb/c mouse model of simultaneous subcutaneous tumor and liver metastasis of Colon26 was prepared and, after irradiation of the subcutaneous tumor (2 Gy x 5 day x 2 cycles), interleukin-2 (IL-2) (2 x 10(4) U) was injected intra-tumorally, and the fate of both the subcutaneous tumor and liver metastatic lesions was evaluated. Intratumoral injection of IL-2 greatly enhanced the anti-tumor effects of RT and completely eradicated the established subcutaneous tumor. Interestingly, although RT was given locally to the subcutaneous tumor, liver metastasis formation was also inhibited in mice receiving only local RT. More impressively, the combination of RT + IL-2 completely inhibited liver metastasis formation. Splenocytes in mice receiving RT + IL-2 contained a higher percentage of CD4(+) T cells, but lower percentages of CD4(+)CD25(+) regulatory T cells and CD11b(+) Gr-1(+) myeloid-derived suppressor cells. Immunohistochemical investigation of human rectal cancer revealed that the density of CD8(+) cells infiltrating into irradiated rectal tumor was positively associated with a lower frequency of distant metastasis as well as histological response grade. Local administration of IL-2 not only enhances shrinkage of the irradiated tumor itself, but can also suppress the development of distant metastasis located outside the RT field, possibly though the induction of a systemic T cell response. Augmentation of T-cell-mediated antitumor immunity during RT might be critical for improvement of the clinical efficacy of neoadjuvant RT for the treatment of advanced rectal cancer. (Cancer Sci 2011; 102: 1257-1263)
  • Hironori Yamaguchi, Masahiro Kato, Noriko Tada, Koji Murono, Hironori Ishigami, Shoichi Kaisaki, Joji Kitayama, Hirokazu Nagawa
    ESOPHAGUS 8 2 137 - 141 2011年06月 [査読有り][通常論文]
     
    Gastropericardial fistulae are rare and may cause fatal complications such as acute purulent carditis and cardiac tamponade. The present report describes a case of a gastropericardial fistula caused by a peptic ulcer perforating a retrosternal reconstructed gastric tube 2 years after subtotal esophagectomy for esophageal cancer. Surgical intervention involved left thoracotomy, pericardium fenestration, and drainage of the pericardium and left thoracic cavity. The patient suffered postoperative complications including septic shock, acute respiratory distress syndrome, and cardiac insufficiency; however, he recovered after successful surgical intervention. In this case, the withdrawal of proton pump inhibitors and the patient's sustained drinking habit after esophageal replacement surgery may have caused peptic ulcers in the gastric tube. Early diagnosis and surgical treatment of gastropericardial fistulae are essential to avoid fatal complications.
  • Shigenobu Emoto, Hironori Ishigami, Hironori Yamaguchi, Hiroharu Yamashita, Shoichi Kaisaki, Joji Kitayama
    ANNALS OF ONCOLOGY 22 v41 - v41 2011年06月 [査読無し][通常論文]
  • Kazushige Kawai, Nelson H. Tsuno, Joji Kitayama, Eiji Sunami, Koki Takahashi, Hirokazu Nagawa
    IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY 33 2 391 - 397 2011年06月 [査読有り][通常論文]
     
    Context: Previously, we demonstrated that CD11b is expressed on peripheral blood memory B cells, and it plays an important role in the migration of B cells. And epigallocatechin gallate (EGCG), a bioactive component of green tea, by binding to CD11b, expressed on CD8(+) cytotoxic T cells, inhibited their migratory ability, one possible mechanism of the antiallergic activity of EGCG. Objective: Here, we investigated whether EGCG also affected CD11b expressed on B cells, similar to cytotoxic T cells. Materials and methods: Isolated peripheral blood CD19(+) B cells were treated with EGCG and the change in the expression of CD11b was analyzed using flow cytometry. The effects of EGCG on the ability of B cells to adhere to and to transmigrate through the endothelial cell layer were evaluated using the transwell assay. Results: EGCG significantly suppressed the apparent expression of CD11b on B cells, in the flow-cytometric analysis, and this apparent suppression was speculated to be dependent on the competitive binding of EGCG to CD11b. EGCG also significantly suppressed CD11b-mediated migration and adhesion of B cells to endothelial cells. Discussion and conclusion: EGCG has a strong suppressive activity on the adhesive and migratory abilities of peripheral blood B cells. This suppressive activity was mediated by the binding of EGCG to CD11b on B cells, and the consequent suppression of B-cell extravasation to the extravascular space. Because B cell plays an important role in the humoral immunity, EGCG could be a promising drug for the prevention and/or treatment of allergic and/or autoimmune diseases.
  • H. Ishigami, S. Kaisaki, H. Yamaguchi, H. Yamashita, S. Emoto, H. Nagawa, J. Kitayama
    JOURNAL OF CLINICAL ONCOLOGY 29 15 2011年05月 [査読無し][通常論文]
  • Baker S. Habeeb, Joji Kitayama, Hirokazu Nagawa
    CANCER SCIENCE 102 5 999 - 1006 2011年05月 [査読有り][通常論文]
     
    Adiponectin is known to have suppressive effects on tumor growth and is thought to be a key molecule in the positive correlation between obesity and cancer. However, the detailed mechanisms regulating tumor cell activity have not been elucidated. In this study, we found that both full-length (f-Ad) and globular adiponectin (g-Ad) inhibited cell growth in colon cancer cell lines in glucose-containing medium, whereas it supported cell survival in glucose-deprived medium, with an increase in AdipoR1 and AdipoR2 expression. The latter effect of adiponectin in glucose deprivation was significantly inhibited by adding autophagy inhibitors, chloroquine, 3-methyl adenine or a combination of pepstatin A and E-64d, suggesting that the effect of supporting cell growth was dependent, at least in part, on the induction of autophagy. The enhancement of autophagy was confirmed morphologically using green fluorescent protein (GFP)-microtubule-associated protein 1 light chain 3 (LC3) fusion proteins under a fluorescence microscope using stably transfected DLD-1 cells expressing GFP-LC3. Western blot analysis revealed that adiponectin increased the expression of LC3-1, LC3-2, phosphorylated AMPK alpha and PPAR alpha but decreased that of phosphorylated mTOR, insulin like growth factor (IGF)-1, phosphorylated serine/threonine kinase (Akt) and phosphorylated phosphatidylinositol 3-kinase (PI3K) in glucose-deprived medium. We conclude that adiponectin supports cell survival in glucose deprivation through enhancement of the autophagic machinery by AMPK alpha and PPAR alpha activation and IGF-1/PI3k/Akt/mTOR pathway inhibition. The bimodal effects of adiponectin are thought to be clinically important in the pathophysiology of tumor development and progression. (Cancer Sci 2011; 102: 999-1006).
  • Kazuhito Sasaki, Nelson H. Tsuno, Eiji Sunami, Kazushige Kawai, Yasutaka Shuno, Kumiko Hongo, Masaya Hiyoshi, Manabu Kaneko, Koji Murono, Noriko Tada, Takako Nirei, Joji Kitayama, Koki Takahashi, Hirokazu Nagawa
    ONCOLOGY LETTERS 2 3 471 - 476 2011年05月 [査読有り][通常論文]
     
    Ultraviolet light B (UVB) phototherapy is widely used to treat dermatological diseases and therefore may be a potential optional strategy in the treatment of a skin lesion infiltrated by a malignant tumor. Currently, little is known regarding the effect of UVB phototherapy on human breast cancer cells. The present study aimed to investigate the effect of UVB phototherapy, as well as the potential effect of 5-fluorouracil (5-FU), the first-line anticancer drug for breast cancer, on radiosensitizing MCF-7 human breast cancer cells, in an attempt to develop new therapeutic strategies for the treatment of locoregional recurrence of breast cancer. MCF-7 cells were incubated in the presence of 5-FU for 48 h, and UVB irradiation at 750 mJ/cm(2) was administered in the midterm of 5-FU treatment. The viability of MCF-7 cells was analyzed by the trypan blue staining method. Apoptosis was quantified by flow cytometry and Hoechst 33258 staining. The cell cycle was evaluated by flow cytometry after the staining of cells with propidium iodide. The combination treatment of 5-FU and UVB resulted in a strong potentiation of the inhibitory effect of MCF-7 cell growth, dependent on the intra-S phase cell cycle arrest and induction of apoptosis, when compared to treatment with 5-FU or UVB alone. In conclusion, 5-FU sensitized human breast cancer cells to UVB phototherapy, and this combination therapy is an effective and promising strategy for the treatment of breast cancer, particularly for locoregional recurrence.
  • Koji Yasuda, Takako Nirei, Eiji Sunami, Hirokazu Nagawa, Joji Kitayama
    RADIATION ONCOLOGY 6 49  2011年05月 [査読有り][通常論文]
     
    Background: Although preoperative radiotherapy (RT) is widely used as the initial treatment for locally advanced rectal cancer (RC) in the neoadjuvant setting, factors determining clinical response have not been adequately defined. Radiosensitivity has recently been shown to be greatly affected by immune function of the host. Methods: In 48 cases of advanced RC, we retrospectively examined the density of tumor infiltrating CD4(+) and CD8(+) T cells using immunohistochemical staining of biopsy samples before CRT, and examined the correlation with tumor response. Results: The numbers of both CD4(+) and CD8(+) tumor-infiltrating lymphocytes (TIL) in pre-CRT biopsy samples were strongly correlated with tumor reduction ratio evaluated by barium enema. Moreover, the densities of CD4(+) and CD8(+) TIL were significantly associated with histological grade after CRT. The density of CD8(+) TIL was an independent prognostic factor for achieving complete response after CRT. Conclusions: In RC patients, T lymphocyte-mediated immune reactions play an important role in tumor response to CRT, and the quantitative measurement of TIL in biopsy samples before CRT can be used as a predictor of the clinical effectiveness of CRT for advanced RC.
  • S. Emoto, J. Kitayama, H. Ishigami, H. Yamaguchi, H. Yamashita, S. Kaisaki, H. Nagawa
    JOURNAL OF CLINICAL ONCOLOGY 29 4 2011年02月 [査読無し][通常論文]
  • H. Ishigami, J. Kitayama, S. Kaisaki, H. Yamaguchi, H. Yamashita, S. Emoto, H. Nagawa
    JOURNAL OF CLINICAL ONCOLOGY 29 4 2011年02月 [査読無し][通常論文]
  • Joji Kitayama, Koji Yasuda, Kazushige Kawai, Eiji Sunami, Hirokazu Nagawa
    BMC CANCER 11 64  2011年02月 [査読有り][通常論文]
     
    Background: Although preoperative radiotherapy (RT) is widely used as the initial treatment for locally advanced rectal cancer (RC) in the neoadjuvant setting, factors determining clinical response have not been adequately defined. In order to find other factors possibly related with radiosensitivity, we evaluated the relationships between circulating blood cell counts and RT effects. Methods: In 179 cases with advanced RC, we retrospectively examined hemoglobin (Hb) levels and counts of white blood cells (WBC), platelets and WBC subsets before and after RT and investigated their associations with the complete response (CR) rate together with other clinicopathological factors. Results: The ratio of lymphocytes in WBC taken before RT was significantly greater in 15 CR cases as compared with those in non-CR cases. Patients with high lymphocyte percentages (25.7%) showed better outcome than the counterparts. Conversely, the ratio of neutrophiles was reduced in CR cases. The lymphocyte ratio showed an independent association with CR with multivariate analysis, and tended to be maintained at relatively high levels in CR cases. Conclusions: In RC patients, peripheral blood lymphocytes have a significant impact on the CR rate in response to RT. Lymphocyte-mediated immune reactions are supposed to have positive roles on clinical response in radiotherapy for RC.
  • A case of hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease) with multiple polyps arising in the cecum and appendix
    Kaneko M, Nozawa H, Kitayama J, Sunami E, Akahane M, Yamauchi N, Furukawa Y, Nagawa H
    Acta Gastroenterol Belg 74 2 352 - 354 2011年 [査読無し][通常論文]
  • Kazushige Kawai, Joji Kitayama, Nelson H. Tsuno, Eiji Sunami, Hirokazu Nagawa
    INTERNATIONAL JOURNAL OF COLORECTAL DISEASE 26 1 45 - 51 2011年01月 [査読有り][通常論文]
     
    Although hyperfibrinogenemia has been reported in patients with colorectal cancer, neither its clinical implications nor the effect of chemoradiotherapy (CRT) on the fibrinogen levels have been fully investigated. We investigated the clinical significance of pre- and post-CRT fibrinogen levels in patients with rectal cancer. The medical records of 82 patients with rectal cancer, who had received CRT followed by surgical resection, were retrospectively reviewed. The correlation between the clinicopathological variables and the pre- and post-CRT plasma fibrinogen levels, and that between the changes of fibrinogen, C-reactive protein (CRP), or carcinoembryonic antigen (CEA) levels after CRT and the pathological tumor regression grading was analyzed. Furthermore, the impact of post-CRT fibrinogen levels on the prognosis of these patients was assessed. Plasma fibrinogen markedly decreased after CRT. The post-CRT fibrinogen level significantly correlated with lymphatic invasion, venous invasion, tumor size, depth of invasion, and the pathological tumor regression grading. The CRT-induced pathological tumor regression grading well correlated with the decrease of fibrinogen level, but not with that of CRP or CEA. Furthermore, patients with high post-CRT fibrinogen had significantly shorter disease-free survival. Reduction of plasma fibrinogen induced by CRT should be a promising biomarker for evaluating the efficacy of CRT in rectal cancer patients.
  • Takao Kamei, Joji Kitayama, Hironori Yamaguchi, Daisuke Soma, Shigenobu Emoto, Tomohiro Konno, Kazuhiko Ishihara, Hironori Ishigami, Shoichi Kaisaki, Hirokazu Nagawa
    CANCER SCIENCE 102 1 200 - 205 2011年01月 [査読有り][通常論文]
     
    Intraperitoneal (i.p.) administration of paclitaxel nanoparticles (PTX-30W) prepared by solubulization with the amphiphilic copolymer of 2-methacryloxyethyl phosphorylcholine and n-butyl methacrylate can efficiently suppress the growth of peritoneal metastasis. In this study, we characterized the drug distribution of i.p. injected PTX-30W in peritoneal tumor and liver in a mouse model using MKN45, human gastric cancer cells. Oregon green-conjugated PTX-30W showed perivascular accumulation in MKN45 tumor in the peritoneum at 24 h after intravenous (i.v.) injection; however, the amount of PTX in tumor was markedly less than that in liver. In contrast, a larger amount of PTX accumulated in the peripheral area of disseminated nodules at 1 h after i.p. injection and the area gradually enlarged. The depth of PTX infiltration reached 1 mm from the tumor surface at 48 h after i.p. injection, and the fluorescence intensity was markedly greater than that in liver. Interestingly, i.p. injected PTX preferentially accumulated in relatively hypovascular areas, and many tumor cells in the vicinity of PTX accumulation showed apoptosis. This unique accumulation pattern and lesser washout in hypovascular areas are thought to be attributable to the superior penetrating activity of PTX-30W, and thus, PTX-30W is considered to be highly suitable for i.p. chemotherapy for peritoneal dissemination. (Cancer Sci 2011; 102: 200-205).
  • Hiroaki Nozawa, Joji Kitayama, Eiji Sunami, Shinsuke Saito, Takamitsu Kanazawa, Shinsuke Kazama, Kentaro Yazawa, Kazushige Kawai, Ken Mori, Hirokazu Nagawa
    ONCOLOGY 80 1-2 84 - 91 2011年 [査読有り][通常論文]
     
    Objectives: The prophylactic effect of FOLFOX regimen, a standard regimen for unresectable colorectal cancer (CRC), was investigated in the adjuvant setting of CRC cases with distant metastases. Methods: The study population included 116 CRC patients with synchronous metastases and 91 patients with metachronous metastases who had undergone curative operation in our hospital between 2000 and 2009. Clinicopathological parameters of CRC, postoperative chemotherapeutic regimen, recurrence rate, and relapse-free survival (RFS) were analyzed retrospectively. Results: After resection of CRC and synchronous metastases, 53 (84%) out of 63 patients without chemotherapy, and 38 (83%) out of 46 that received 5-fluorouracil (5-FU) alone or with leucovorin (LV) developed recurrent tumors. By contrast, only 1 (17%) among 6 patients who underwent FOLFOX treatment showed recurrence. The FOLFOX group exhibited significantly improved RFS as compared to the 5-FU (+ LV) or surgery-alone group (p = 0.03, p = 0.007, respectively). On the other hand, in patients with metachronous metastases, tumor-relapse rate and RFS were not significantly influenced by post-metastasectomy therapies. Conclusions: In this retrospective analysis, the adjuvant administration of FOLFOX appeared to reduce the risk of relapse in a small group of CRC patients with synchronous metastases. Prospective randomized trials will be required to confirm the benefits of this management strategy. Copyright (C) 2011 S. Karger AG, Basel
  • Shuno Y, Hata K, Sunami E, Shinozaki M, Kawai K, Kojima T, Tsurita G, Hiyoshi M, Tsuno NH, Kitayama J, Nagawa H
    ISRN gastroenterology 2011 509251  2011年 [査読有り][通常論文]
  • Kensuke Otani, Joji Kitayama, Takao Kamei, Daisuke Soma, Hideyo Miyato, Toshimasa Yamauchi, Takashi Kadowaki, Hirokazu Nagawa
    JOURNAL OF GASTROENTEROLOGY 45 9 918 - 927 2010年09月 [査読有り][通常論文]
     
    Background Adiponectin has been shown to have suppressive effects on tumor development, but the expression of adiponectin receptors in tumor tissue has not been fully elucidated. The purpose of this study was to quantitatively evaluate the expression of two adiponectin receptors, AdipoR1 and AdipoR2, in gastric cancer tissue. Methods The mRNA levels of AdipoR1 and AdipoR2 were evaluated by quantitative reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemical staining in 67 gastric cancer tissues and their normal counterparts. In addition, the effects of cytokines on AdipoR1 and AdipoR2 expression in cultured gastric cancer cells were examined. Results As compared to findings in the normal counterparts, AdipoR1 mRNA expression, standardized by beta-actin mRNA, tended to be lower (cancer 0.488 +/- 0.039, normal 0.955 +/- 0.281, p = 0.0726) and AdipoR2 expression was significantly lower (0.818 +/- 0.081, 1.500 +/- 0.222, p = 0.0035) in gastric cancer tissue. Immunohistochemical examination showed the same tendency for AdipoR1 and AdipoR2 expression in epithelial cells. Moreover, AdipoR2 was strongly expressed in interstitial cells. However, the expression levels of these receptors did not show a strong correlation with various pathological factors. An in vitro experiment using two gastric cancer cell lines, MKN-74 and NUGC-3, showed that the expression levels of AdipoR1 and AdipoR2 were significantly decreased by transforming growth factor (TGF)-beta in a dose-dependent manner. Conclusions Two major adiponectin receptors were decreased in gastric cancer as compared to findings in normal gastric epithelium. TGF-beta may be involved in this receptor downregulation. This downregulation may be an ideal strategy for cancer cells to escape the antiproliferative effects of adiponectin in the initial phase of tumor development.
  • Takeshi Nishikawa, Nelson H. Tsuno, Yurai Okaji, Eiji Sunami, Yasutaka Shuno, Kazuhito Sasaki, Kumiko Hongo, Manabu Kaneko, Masaya Hiyoshi, Kazushige Kawai, Joji Kitayama, Koki Takahashi, Hirokazu Nagawa
    ANGIOGENESIS 13 3 227 - 238 2010年09月 [査読有り][通常論文]
     
    Sulforaphane (SUL), a kind of isothiocyanate, has recently been focused due to its strong pro-apoptotic effect on cancer cells as well as tumor vascular endothelial cells (ECs). And recently, we demonstrated the induction of autophagy by colon cancer cells as a protective mechanism against SUL. In the present study, we aimed to investigate the possible role of autophagy induction by ECs as a defense mechanism against SUL. Human umbilical vein endothelial cells (HUVECs) were used as the in vitro model of angiogenic ECs. The induction of autophagy was evaluated by the detection of acidic vesicular organelles (AVOs) by flow-cytometry, after the staining with acridine orange, as well as the detection of light chain 3(LC3) by Western blot. Finally, the functional implication of autophagy inhibition and SUL treatment in ECs was investigated by their ability to form vascular-like structures on Matrigel. Treatment of HUVECs with relatively low concentrations of SUL for 16 h resulted in the evident formation of AVOs and the recruitment of LC3 to autophagosomes, the pathognomonic features of autophagy. Co-treatment of cells with the specific autophagy inhibitor (3-methyladenine) potentiated the proapoptotic effect of SUL. And inhibition of autophagy potentiated the inhibitory effect of SUL on the ability of ECs to form capillary-like structures. Similar to cancer cells, ECs induced autophagy in response to the pro-apoptotic agent, SUL, and the inhibition of autophagy potentiated the pro-apoptotic effect. These findings open premises for the use of autophagy inhibitors in combination with anti-angiogenic agents.
  • Shigenobu Emoto, Joji Kitayama, Hironori Yamaguchi, Hironori Ishigami, Shoichi Kaisaki, Hirokazu Nagawa
    Case Reports in Oncology 3 3 344 - 348 2010年09月 [査読有り][通常論文]
     
    Objective: Oxygen is one of the most important environmental factors for tumor development. In this study, we examined pO2 in malignant ascites in patients with peritoneal carcinomatosis. Methods: In 21 patients with peritoneal dissemination of gastric cancer, ascitic fluid was collected and its pH, pCO2 and pO2 were determined using a blood gas analyzer. Results: In 21 patients, pH of malignant ascites was significantly lower than that of arterial blood (7.39 ± 0.07, 7.44 ± 0.02, p < 0.05). Accordingly, pCO2 tended to be higher in ascites than in arterial blood. Unexpectedly, pO2 in malignant ascites showed relatively high values (90.4 ± 27.72 mm Hg), which were mostly the same as those of arterial blood (97.09 ± 10.33 mm Hg, p = 0.858). Even in 19 patients whose samples were collected at bedside in room air, pO2 of malignant ascites was 85.94 ± 23.94 mm Hg, which was patently higher than that in venous blood or in solid tumor tissues. Conclusion: Since the oxygen level critically affects the sensitivity of tumor cells to chemotherapeutic agents through metabolic transformation, the oxygenic condition in the peritoneal cavity may be beneficial for the progression of peritoneal metastasis, and also clinically important in considering the efficacy of chemotherapy. © 2010 S. Karger AG, Basel.
  • Kazuhito Sasaki, Nelson H. Tsuno, Eiji Sunami, Giichiro Tsurita, Kazushige Kawai, Yurai Okaji, Takeshi Nishikawa, Yasutaka Shuno, Kumiko Hongo, Masaya Hiyoshi, Manabu Kaneko, Joji Kitayama, Koki Takahashi, Hirokazu Nagawa
    BMC CANCER 10 370  2010年07月 [査読有り][通常論文]
     
    Background: Chloroquine (CQ), the worldwide used anti-malarial drug, has recently being focused as a potential anti-cancer agent as well as a chemosensitizer when used in combination with anti-cancer drugs. It has been shown to inhibit cell growth and/or to induce cell death in various types of cancer. 5-Fluorouracil (5-FU) is the chemotherapeutic agent of first choice in colorectal cancer, but in most cases, resistance to 5-FU develops through various mechanisms. Here, we focused on the combination of CQ as a mechanism to potentiate the inhibitory effect of 5-FU on human colon cancer cells. Methods: HT-29 cells were treated with CQ and/or 5-FU, and their proliferative ability, apoptosis and autophagy induction effects, and the affection of the cell cycle were evaluated. The proliferative ability of HT-29 was analyzed by the MTS assay. Apoptosis was quantified by flow-cytometry after double-staining of the cells with AnnexinV/PI. The cell cycle was evaluated by flow-cytometry after staining of cells with PI. Autophagy was quantified by flow-cytometry and Western blot analysis. Finally, to evaluate the fate of the cells treated with CQ and/or 5-FU, the colony formation assay was performed. Results: 5-FU inhibited the proliferative activity of HT-29 cells, which was mostly dependent on the arrest of the cells to the G0/G1-phase but also partially on apoptosis induction, and the effect was potentiated by CQ pretreatment. The potentiation of the inhibitory effect of 5-FU by CQ was dependent on the increase of p21(Cip1) and p27(Kip1) and the decrease of CDK2. Since CQ is reported to inhibit autophagy, the catabolic process necessary for cell survival under conditions of cell starvation or stress, which is induced by cancer cells as a protective mechanism against chemotherapeutic agents, we also analyzed the induction of autophagy in HT-29. HT-29 induced autophagy in response to 5-FU, and CQ inhibited this induction, a possible mechanism of the potentiation of the anti-cancer effect of 5-FU. Conclusion: Our findings suggest that the combination therapy with CQ should be a novel therapeutic modality to improve efficacy of 5-FU-based chemotherapy, possibly by inhibiting autophagy-dependent resistance to chemotherapy.
  • Yasutaka Shuno, Nelson H. Tsuno, Yurai Okaji, Takeshi Tsuchiya, Daisuke Sakurai, Takeshi Nishikawa, Naoyuki Yoshikawa, Kazuhito Sasaki, Kumiko Hongo, Giichiro Tsurita, Eiji Sunami, Joji Kitayama, Katsushi Tokunaga, Koki Takahashi, Hirokazu Nagawa
    JOURNAL OF SURGICAL RESEARCH 161 1 76 - 82 2010年06月 [査読有り][通常論文]
     
    Background. The Id (inhibitor of DNA binding/differentiation) proteins belong to the helix-loop-helix transcriptional regulatory factors, and play important roles in tumor development. Previously, we and others have shown that targeting Id in tumor cells could have important clinical implications. In the present study, we aimed to evaluate the effects of Id inhibition in human pancreatic cancer cells. Materials and Methods. Id1 and Id3 were stably double-knockdown in human pancreatic cancer cell line MIA-Paca2 by means of RNA interference. Expression of Id and integrins were analyzed by flow-cytometry. Cell proliferation was evaluated by MTS assay. Migration was measured by wound closure assay. Adhesion assay was performed to evaluate binding capacity for different extracellular matrix proteins. Finally, in vivo properties of tumor cells were observed in a mouse model of peritoneal metastasis. Results. Id1/Id3 double-knockdown resulted in decreased ability of pancreatic cancer cells to proliferate and migrate. In addition, Id1/Id3 double-knockdown caused decreased expression of integrins alpha 3, alpha 6, and in, and consequently reduced adhesion of tumor cells to laminin. Finally, peritoneal metastases of Id1/Id3 double-knockdown tumor cells were significantly reduced. Conclusions. We concluded that the Id proteins play a pivotal role in the development of peritoneal metastasis of pancreatic cancer, and consequently, their targeting would be a novel strategy for the prevention and treatment of pancreatic cancer. (C) 2010 Elsevier Inc. All rights reserved.
  • Joji Kitayama, Koji Yasuda, Kazushige Kawai, Eiji Sunami, Hirokazu Nagawa
    RADIATION ONCOLOGY 5 47  2010年06月 [査読有り][通常論文]
     
    Although neoadjuvant chemoradiotherapy (CRT) is the standard treatment for advanced rectal cancer (RC), markers to predict the treatment response have not been fully established. In 73 patients with advanced RC who underwent CRT in a neoadjuvant setting, we retrospectively examined the associations between the clinical effects of CRT and blood cell counts before and after CRT. Clinical or pathological complete response (CR) was observed in 10 (14%) cases. The CR rate correlated significantly with the size and the circumferential extent of the tumor. Hemoglobin level, white blood cell (WBC) count and platelet count before CRT did not show a significant difference between CR and non-CR cases. Interestingly, however, lymphocyte ratio in WBC was significantly higher (p = 0.020), while neutrophil ratio tended to be lower (p = 0.099), in CR cases, which was shown to be an independent association by multivariate analysis. When all the blood data obtained in the entire treatment period were evaluated, circulating lymphocyte count was most markedly decreased in the CRT period and gradually recovered by the time of surgery, while the numbers of neutrophils and monocytes were comparatively stable. Moreover, the lymphocyte percentage in samples obtained from CR patients was maintained at a relatively higher level than that from non-CR patients. Since tumor shrinkage is known to be dependent not only on the characteristics of tumor cells but also on various host conditions, our data raise the possibility that a lymphocyte-mediated immune reaction may have a positive role in achieving complete eradication of tumor cells. Maintenance of circulating lymphocyte number may improve the response to CRT in rectal cancer.
  • H. Ishigami, J. Kitayama, S. Kaisaki, M. Kato, H. Yamaguchi, K. Otani, T. Kamei, H. Nagawa
    JOURNAL OF CLINICAL ONCOLOGY 28 15 2010年05月 [査読無し][通常論文]
  • J. Kitayama, K. Kawai, K. Yasuda, E. Sunami, H. Nagawa
    JOURNAL OF CLINICAL ONCOLOGY 28 15 2010年05月 [査読無し][通常論文]
  • Shinji Ogino, Noritaka Nishida, Ryo Umemoto, Miho Suzuki, Mitsuhiro Takeda, Hiroaki Terasawa, Joji Kitayama, Masanori Matsumoto, Haruko Hayasaka, Masayuki Miyasaka, Ichio Shimada
    STRUCTURE 18 5 649 - 656 2010年05月 [査読有り][通常論文]
     
    The hyaluronan (HA) receptor CD44 mediates cell adhesion in leukocyte trafficking and tumor metastasis. Our previous nuclear magnetic resonance (NMR) studies revealed that the CD44 hyaluronan-binding domain (HABD) alters its conformation upon HA binding, from the ordered (O) to the partially disordered (PD) conformation. Here, we demonstrate that the HABD undergoes an equilibrium between the O and PD conformations, in either the presence or absence of HA, which explains the seemingly contradictory X-ray and NMR structures of the HA-bound HABD. An HABD mutant that exclusively adopts the PD conformation displayed a higher HA affinity than the wild-type. Rolling of the cells expressing the mutant CD44 was less efficient than those expressing the wild-type, due to the decreased tether frequency and the slow cellular off rate. Considering that the mutant CD44, devoid of the low-affinity state, exhibited impaired rolling, we conclude that the coexistence of the high- and low-affinity states of the HABD is essential for the CD44-mediated rolling.
  • Yasutaka Shuno, Nelson H. Tsuno, Yurai Okaji, Takeshi Nishikawa, Kumiko Hongo, Kazuhito Sasaki, Manabu Kaneko, Masaya Hiyoshi, Kazushige Kawai, Eiji Sunanni, Joji Kitayama, Koki Takahashi, Hirokazu Nagawa
    CANCER RESEARCH 70 2010年04月 [査読無し][通常論文]
  • Takeshi Nishikawa, Masaya Hiyoshi, Nelson H. Tsuno, Yurai Okaji, Eiji Sunami, Yasutaka Shuno, Kazuhito Sasaki, Kumiko Hongo, Manabu Kaneko, Kazushige Kawai, Joji Kitayama, Koki Takahashi, Hirokazu Nagawa
    CANCER RESEARCH 70 2010年04月 [査読無し][通常論文]
  • Masaya Hiyoshi, Joji Kitayama, Nelson H. Tsuno, Eiji Sunami, Kazusige Kawai, Kensuke Otani, Takeshi Nishikawa, Yasutaka Shuno, Koji Yasuda, Kumiko Hongo, Yoshiko Kikkawa, Kazuhito Sasaki, Manabu Kaneko, Koki Takahashi, Hirokazu Nagawa
    CANCER RESEARCH 70 2010年04月 [査読無し][通常論文]
  • Masaya Hiyoshi, Joji Kitayama, Nelson H. Tsuno, Eiji Sunami, Kazusige Kawai, Kensuke Otani, Takeshi Nishikawa, Yasutaka Shuno, Koji Yasuda, Kumiko Hongo, Yoshiko Kikkawa, Kazuhito Sasaki, Manabu Kaneko, Koki Takahashi, Hirokazu Nagawa
    CANCER RESEARCH 70 2010年04月 [査読無し][通常論文]
  • Kazuhito Sasaki, Nelson H. Tsuno, Eiji Sunami, Giichiro Tsurita, Yurai Okaji, Kazushige Kawai, Takeshi Nishikawa, Yasutaka Shuno, Kumiko Hongo, Manabu Kaneko, Masaya Hiyoshi, Joji Kitayama, Koki Takahashi, Hirokazu Nagawa
    CANCER RESEARCH 70 2010年04月 [査読無し][通常論文]
  • Takeshi Nishikawa, Nelson H. Tsuno, Yasutaka Shuno, Kazuhito Sasaki, Kumiko Hongo, Yurai Okaji, Eiji Sunami, Joji Kitayama, Koki Takahashi, Hirokazu Nagawa
    JOURNAL OF SURGICAL RESEARCH 159 2 696 - 704 2010年04月 [査読有り][通常論文]
     
    Background. Serotonin (5-hydroxytryptamine, 5-HT) is reported to regulate cell growth in a wide variety of cell types in different carcinomas. 5-HT exerts complex actions on blood vessels, dependent on its interactions with a multiplicity of 5-HT receptors. In the present study, we aimed to investigate the potential antiangiogenic effect of mosapride citrate, a selective 5-HT4 receptor agonist, known to have prokinetic properties on the gastrointestinal tract. For this purpose, cultured human umbilical vein endothelial cells (HUVECs) were used as an in vitro model. Material and Methods. The effect of mosapride citrate on the proliferative activity of HUVECs was assessed by the MTS assay. Then, the apoptosis and the cell cycle detection assays were performed. The effect of mosapride citrate on the ability of HUVECs to adhere and migrate on extracellular matrix proteins (ECMs), as well as their ability to form vascular-like structures on Matrigel was investigated. Results. Mosapride citrate inhibited the proliferative activity of HUVECs, dependent on cell cycle arrest, and not on apoptosis. A dose-dependent increase in the percentage of cells in the G0/G1 phase of the cell cycle in mosapride-treated HUVECs was observed. Mosapride citrate also significantly inhibited the ability of HUVECs to migrate, but not to adhere on ECMs. Additionally, mosapride citrate dose-dependently inhibited the tube-like formation ability of HUVECs on matrigel, an important event in the process of angiogenesis. Conclusion. The present results demonstrate the antiangiogenic activity of mosapride citrate in vitro and the possibility of its application as a new anticancer agent is suggested. (C) 2010 Elsevier Inc. All rights reserved.
  • Kensuke Otani, Joji Kitayama, Koji Yasuda, Yasunori Nio, Masato Iwabu, Shinichi Okudaira, Junken Aoki, Toshimasa Yamauchi, Takashi Kadowaki, Hirokazu Nagawa
    CANCER LETTERS 288 2 177 - 182 2010年02月 [査読有り][通常論文]
     
    Recent reports have shown that adiponectin has a suppressive effect on various types of malignancy. In order to clarify the role of adiponectin in colorectal carcinogenesis, we examined the effect of exogenous administration of adiponectin on intestinal polyp formation in C57BL/6J-Apc(Min/+) mice, which possess a point mutation in the Apc gene. And we found that adiponectin treatment significantly decreased the number of adenomatous polyps, especially polyps larger than 2 mm in diameter, in the small intestine. Two major receptors for adiponectin, AdipoR1 and AdipoR2, were expressed in adenomatous polyps, and their expression levels were not altered by adiponectin injection. in conclusion, adiponectin suppresses the growth of intestinal adenomas in the Apc(Min/+) mice. Increasing the adiponectin level may be a new strategy for the prevention of colorectal cancer at an early step of carcinogenesis. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
  • Takeshi Nishikawa, Nelson H. Tsuno, Yurai Okaji, Yasutaka Shuno, Kazuhito Sasaki, Kumiko Hongo, Eiji Sunami, Joji Kitayama, Koki Takahashi, Hirokazu Nagawa
    ANNALS OF SURGICAL ONCOLOGY 17 2 592 - 602 2010年02月 [査読有り][通常論文]
     
    Background. Sulforaphane (SUL), an isothiocyanate naturally present in widely consumed vegetables, particularly broccoli, has recently attracted attention due to its inhibitory effects on tumor cell growth by inducing apoptosis. We investigated the ability of SUL to induce autophagy in human colon cancer cells and whether inhibition of autophagy could potentiate the proapoptotic effect of SUL. Methods. The proliferation of cells treated with SUL was assessed by MTS assay and colony-forming assay. Apoptosis and caspases activity were investigated by flow cytometry. The formation of acidic vesicular organelles (AVOs) was detected in acridine-orange-stained cells by flow cytometry. Western blotting was used for the detection of light chain 3 (LC3). Localizations of LC3 and cytochrome c were analyzed by immunocytochemistry. Results. The proapoptotic effect was observed by treatment of cells with relatively high concentrations of SUL for long periods of time. After 16 h of treatment, evident formation of AVOs and recruitment of LC3 to autophagosomes, features of autophagy, were observed. Treatment of cells with a specific autophagy inhibitor (3-methyladenine) potentiated the proapoptotic effect of SUL, which was dependent on the activation of caspases and the release of cytochrome c to the cytosol. Conclusion. The present results demonstrate induction of autophagy in colon cancer cells as a protective reaction against the proapoptotic effect of SUL, and consequently, the potentiation of the proapoptotic effect by autophagy inhibition. These findings provide a premise for use of autophagy inhibitors in combination with chemotherapeutic agents for treatment of colorectal cancer.
  • H. Ishigami, J. Kitayama, S. Kaisaki, A. Hidemura, M. Kato, K. Otani, T. Kamei, D. Soma, H. Miyato, H. Yamashita, H. Nagawa
    ANNALS OF ONCOLOGY 21 1 67 - 70 2010年01月 [査読有り][通常論文]
     
    Patients and methods: Gastric cancer patients with peritoneal dissemination and/or cancer cells on peritoneal cytology were enrolled. PTX was administered i.v. at 50 mg/m(2) and i.p. at 20 mg/m(2) on days 1 and 8. S-1 was administered at 80 mg/m(2)/day for 14 consecutive days, followed by 7 days rest. The primary end point was the 1-year overall survival (OS) rate. Secondary end points were the response rate, efficacy against malignant ascites and safety. Results: Forty patients were enrolled, including 21 with primary tumors with peritoneal dissemination, 13 with peritoneal recurrence and six with positive peritoneal cytology only. The median number of courses was 7 (range 1-23). The 1-year OS rate was 78% (95% confidence interval 65% to 90%). The overall response rate was 56% in 18 patients with target lesions. Malignant ascites disappeared or decreased in 13 of 21 (62%) patients. The frequent grade 3/4 toxic effects included neutropenia (38%), leukopenia (18%) and anemia (10%). Conclusion: Combination chemotherapy of i.v. and i.p. PTX with S-1 is well tolerated and active in gastric cancer patients with peritoneal metastasis.
  • Hiroshi Kawasaki, Joji Kitayama, Hironori Ishigami, Akio Hidemura, Shoichi Kaisaki, Hirokazu Nagawa
    SURGERY TODAY 40 1 60 - 63 2010年01月 [査読有り][通常論文]
     
    Solitary metastasis of a malignancy to the spleen is rare. We herein describe a case of splenic metastasis from early gastric cancer. A 76-year-old man underwent an endoscopic mucosal resection (EMR) for early gastric carcinoma in the cardia. Pathologically, the tumor showed invasion into the submucosal layer, and the stump of the surgical specimen appeared to be positive for malignant cells. He thus underwent a proximal gastrectomy with nodal dissection. One year later, serum carcinoembryonic antigen was elevated, and a splenic mass was detected by computed tomography and ultrasonography. Because the tumor increased in size very gradually and no metastatic lesions were detected at the other sites, we performed a splenectomy. The lesion was pathologically diagnosed as metastasis from the previous gastric carcinoma, and the patient remains healthy to date without recurrence, more than 2 years after the splenectomy. When solitary metastasis to the spleen is suspected during the postoperative follow-up of a patient with gastric cancer, a splenectomy is a potentially effective treatment.
  • Joji Kitayama, Hironori Ishigami, Shoichi Kaisaki, Akio Hidemura, Masahiro Kato, Kensuke Otani, Takao Kamei, Daisuke Soma, Hideyo Miyato, Hiroharu Yamashita, Hirokazu Nagawa
    ONCOLOGY 78 1 40 - 46 2010年 [査読有り][通常論文]
     
    Malignant ascites caused by gastric cancer are chemotherapy resistant and carry a poor prognosis. The efficacy of a regimen including intraperitoneal paclitaxel (PTX) was evaluated in 33 gastric cancer patients with ascetic fluid in the peritoneal cavity diagnosed with computed tomography (CT) scanning. Synchronous administration of intravenous (50 mg/m(2)) and intraperitoneal (20 mg/m(2)) PTX was performed via a subcutaneously placed intraperitoneal catheter on days 1 and 8, and S-1 was administered twice daily at 80 mg/m(2) /day for 14 consecutive days from day 1 to day 14, followed by 7 days of rest. The ascitic fluid volume was calculated with NIH Image J software using continuous CT images. After 2-4 treatment cycles, 23 (70%) patients showed reductions in their ascitic volumes of > 50%. Ascites disappeared completely in 8 patients and were markedly reduced (to <3% of the original volume) in 4 of the 9 patients (44%) who initially had massive (>2,500 ml) ascites. Median overall survival was significantly better in patients with ascitic reduction. Weekly intravenous and intraperitoneal PTX combined with S-1 was highly effective in gastric cancer with malignant ascites. The change in ascitic fluid volumes determined by CT image measurements is a useful predictor of outcome in these patients. Copyright (C) 2010 S. Karger AG, Basel
  • Masahiro Kato, Joji Kitayama, Hironori Yamaguchi, Junichi Sanuki, Shoichi Kaisaki, Hirokazu Nagawa
    Japanese Journal of Cancer and Chemotherapy 37 5 903 - 906 2010年 [査読有り][通常論文]
     
    We experienced 3 cases of recurrent breast cancer treated with S-1 therapy, delaying tumor progression and improving their quality of life (QOL). All the patients had been previously treated with both anthracyclines and/or taxanes prior to S-1 chemotherapy. All patients almost completed the full dose through the whole course of treatment, and the drug showed good tolerability. Long-term (more than 12 weeks) therapeutic efficacy and the patients' QOL have been maintained for all patients. No major side effects were seen. It is thought that less toxicity enabled patient 3 to undergo long-term therapy. It is especially important that one patient had therapeutic efficacy and QOL improvement from treatment with S-1 and aromatase inhibitor for over 3 years, after being treated with anthracyclines, taxanes and vinorelbine. We conclude that S-1 is effective and well tolerated in patients with metastatic breast cancer, and will accommodate a long-time progression with respect to efficacy and maintaining the patients' QOL. Further evaluation of S-1 is necessary to elucidate its clinical role in breast cancer treatment.
  • Hironori Ishigami, Joji Kitayama, Shoichi Kaisaki, Hironori Yamaguchi, Hiroharu Yamashita, Shigenobu Emoto, Hirokazu Nagawa
    ONCOLOGY 79 3-4 269 - 272 2010年 [査読有り][通常論文]
     
    Objectives: A phase I study of biweekly intravenous (IV) paclitaxel (PTX) plus intraperitoneal (IP) cisplatin (CDDP) and PTX was performed to determine the maximum tolerated dose (MTD) and recommended dose (RD) in gastric cancer patients. Methods: Nine gastric cancer patients with peritoneal metastasis were enrolled. PTX was administered intravenously at a dose of 100 mg/m(2) and intraperitoneally with an initial dose of 20 mg/m(2) (level 1), stepped up to 30 or 40 mg/m(2) depending on observed toxicity. CDDP was administered intraperitoneally at a dose of 30 mg/m(2) over 24 h. PTX and CDDP were administered on days 1 and 15 in 4-week cycles. Results: The MTD was determined to be dose level 1, as 2 of 3 patients experienced dose-limiting toxicities (DLTs), grade 4 leukopenia and grade 3 vomiting. Therefore, the doses of IV PTX, IP CDDP and IP PTX were reduced to 80, 25 and 20 mg/m2, respectively (level 0). Consequently, the RD was determined to be dose level 0, as only 1 of 6 patients experienced DLT, grade 3 nausea. Conclusions: Combination chemotherapy of IV PTX plus IP CDDP and PTX was shown to be a safe regimen that should be further explored in clinical trials. Copyright (C) 2011 S. Karger AG, Basel
  • Toshiaki Tanaka, Toshiaki Watanabe, Joji Kitayama, Takamitsu Kanazawa, Yoshihiro Kazama, Junichiro Tanaka, Shinsuke Kazama, Hirokazu Nagawa
    DIAGNOSTIC MOLECULAR PATHOLOGY 18 4 219 - 225 2009年12月 [査読有り][通常論文]
     
    Currently, surgical treatment for colorectal hepatic metastasis is performed with low mortality and morbidity rates. However, there is no definitive marker that predicts patient outcome. The aim of this study is to identify the molecular predictor of survival along with its clinical properties. Fifty-six patients were surgically treated for colorectal cancer and synchronous hepatic metastasis from January 1994 to December 2004. Clinicopathologic and molecular factors were reviewed in association with overall survival (OS) and disease-free survival (DFS). Chromosome 18q deletion in the primary tumor was a molecular predictor that affected OS (P = 0.021). Decreased expression of the Smad4 protein tended to affect the outcome; however, no statistical significance was observed (P = 0.29:OS, P = 0.45:DFS). Preoperative carcinoembryonic antigen (P = 0.013) and carbohydrate antigen 19-9 (CA19-9) (P<0.0001) levels were poor clinical predictors of OS. The number of primary lymph nodes was the only pathologic factor that affected DFS (P = 0.0052). The number and diameter of hepatic metastasis had no influence on survival. In conclusion, we demonstrated that chromosome 18q deletion, in conjunction with high carcinoembryonic antigen and CA19-9 levels, is an unfavorable prognostic factor. This novel Molecular predictor is helpful in identifying patients who would benefit from surgical resection.
  • Takeshi Nishikawa, Toshiaki Watanabe, Eiji Sunami, Nelson H. Tsuno, Joji Kitayama, Hirokazu Nagawa
    DISEASES OF THE COLON & RECTUM 52 12 2016 - 2021 2009年12月 [査読有り][通常論文]
     
    PURPOSE: The value of positive peritoneal cytology in colorectal cancer has been controversial. In this study, we aimed to clarify the prognostic significance of peritoneal cytology and the impact of the combination of peritoneal dissemination and peritoneal cytology on the prognostic evaluation of colorectal cancer. METHODS: From January 1997 to December 2005, intraoperative peritoneal cytology was performed on 410 patients who had at least serosal invasion. RESULTS: Thirty-one patients (7.6%) had positive peritoneal cytology. Patients with negative cytology showed a significantly better survival rate at five years than those with positive cytology (negative cytology, 68.0%; positive cytology, 20.6%; P < 0.0001). Multivariate analysis revealed that peritoneal cytology is one of the significant prognostic factors. Sixty percent of patients with positive cytology and 30.4% of patients with negative cytology recurred (P = 0.08). Regarding the recurrence site, patients with positive cytology showed a significantly higher recurrence rate of peritoneal dissemination than those with negative cytology (P = 0.0038). Some patients with positive cytology but without evident peritoneal dissemination achieved long-term survival. Additionally, some patients with macroscopic peritoneal dissemination and negative peritoneal cytology also achieved long-term survival. But for those patients with both positive cytology and evident macroscopic peritoneal dissemination, the five-year survival rate was zero. CONCLUSIONS: Patients with negative peritoneal cytology had a significantly better five-year survival rate than those with positive peritoneal cytology. In some cases in which either peritoneal cytology or peritoneal dissemination was negative, long-term survival could be achieved.
  • Daisuke Soma, Joji Kitayama, Tomohiro Konno, Kazuhiko Ishihara, Jun Yamada, Takao Kamei, Hironori Ishigami, Shoichi Kaisaki, Hirokazu Nagawa
    CANCER SCIENCE 100 10 1979 - 1985 2009年10月 [査読有り][通常論文]
     
    Intraperitoneal (i.p.) administration of paclitaxel (PTX) is a hopeful therapeutic strategy for peritoneal malignancy. Intravenously (i.v.) injected nanoparticle anticancer drugs are known to be retained in the blood stream for a long time and favorably extravasated from vessels into the interstitium of tumor tissue. In this study, we evaluated the effect of i.p. injection of PTX (PTX-30W), which was prepared by solubulization with water-soluble amphiphilic polymer composed of PMB-30W, a co-polymer of 2-methacryloxyethyl phosphorylcholineand n-butyl methacrylate, for peritoneal dissemination of gastric cancer. In a peritoneal metastasis model with transfer of MKN45P in nude mice, the effct of i.p. administration of PTX-30W was compared with conventional PTX dissolved in Cremophor EL (PTX-Cre). The drug accumulation in peritoneal nodules was evaluated with intratumor PTX concentration and fluorescence microscopic observation. PTX-30W reduced the number of metastatic nodules and tumor volume significantly more than did conventional PTX dissolved in Cremophor EL (PTX-Cre), and prolonged the survival time (P < 0.05). PTX concentration in disseminated tumors measured by HPLC was higher in the PTX-30W than in the PTX-Cre group up to 24 h after i.p. injection. Oregon green-conjugated PTX-30W, i.p. administered, preferentially accumulated in relatively hypovascular areas in the peripheral part of disseminated nodules, which was significantly greater than the accumulation of PTX-Cre. I.p. administration of PTX-30W may be a promising strategy for peritoneal dissemination, due to its superior characteristics to accumulate in peritoneal lesions. (Cancer Sci 2009; 100: 1979-1985).
  • H. Ishigami, J. Kitayama, S. Kaisaki, A. Hidemura, M. Kato, K. Otani, T. Kamei, D. Soma, H. Miyato, H. Nagawa
    EJC SUPPLEMENTS 7 2 368 - 368 2009年09月 [査読無し][通常論文]
  • J. Kitayama, S. Kaisaki, H. Ishigami, A. Hidemura, H. Nagawa
    DISEASES OF THE ESOPHAGUS 22 5 418 - 421 2009年08月 [査読有り][通常論文]
     
    P>Anastomotic leakage after radical esophagectomy is mostly caused by the hypoxia and high tension at the esophagogastric anastomotic site. Here, we introduce a new surgical technique, 'Angleplasty,' to enable the tensionless anastomosis at a highly oxygenic site of gastric conduit. In short, the seromuscular layer is cut for a perpendicular direction against a lesser curvature at a gastric angle and the gastric wall is carefully divided between the muscular and submucosal layers for longitudinal direction for 4-5 cm in length. Then, the wound is closed with seromuscular sutures for longitudinal direction. With this maneuver, the lesser curvature of the gastric roll is significantly elongated and the anastomosis site of the gastric conduit can be moved more distal on the greater curvature of the stomach where it is expected to receive more oxygen supply. This technique takes only several minutes, but provides highly favorable conditions for esophagogastric anastomosis and thus is clinically useful to reduce the risk of anastomotic leakage after esophagectomy.
  • Daisuke Soma, Joji Kitayama, Hironori Ishigami, Shoichi Kaisaki, Hirokazu Nagawa
    JOURNAL OF SURGICAL RESEARCH 155 1 142 - 146 2009年07月 [査読有り][通常論文]
     
    Purpose. Paclitaxel is considered to be suitable for disseminated cancer in the peritoneal cavity because of its high molecular weight and lipophilic characteristics. However, the difference in pharmacokinetics of paclitaxel after intraperitoneal (i.p.) and intravenous (i.v.) administration is not fully defined. Here, we investigated the tissue concentration of paclitaxel in various organs at various time points after i.p. or i.v. administration. Methods. Paclitaxel (5 mg/kg) was administrated in an ear vein or in the abdominal cavity of rabbits. At 0.5, 6, 24, and 48 h after administration, the rabbits were sacrificed, and organs as well as peripheral blood were harvested. The serum and tissue concentrations of paclitaxel were measured by HPLC procedure. Result. The concentration of paclitaxel was high in the i.v. group at 0.5 h, whereas it was significantly higher in the i.p. group at 6 and 24 h. The AUC (area under the curve) was markedly higher in the omentum, mesenteric lymph nodes as well as ovary and stomach in the i.p. group. Conclusion. Compared with i.v. administration, paclitaxel concentration was maintained at a high level in the whole body by i.p. administration. Repeated i.p. paclitaxel can produce more marked clinical effects than i.v. administration for metastatic lymph nodes and primary lesions as well as peritoneal dissemination. (C) 2009 Elsevier Inc. All rights reserved.
  • Hideyo Miyato, Joji Kitayama, Hiroharu Yamashita, Daisuke Souma, Masahiro Asakage, Jun Yamada, Hirokazu Nagawa
    JOURNAL OF SURGICAL RESEARCH 155 1 40 - 47 2009年07月 [査読有り][通常論文]
     
    Orally applicable Delta 9-tetrahydrocannabinol and its synthetic derivatives have been used as antiemetic drugs during chemotherapy in cancer patients. However, it is not well known how cannabinoids influence the effects of chemotherapeutic agents on malignant tumors. In this study, we investigated how the endogenous cannabinoid anandamide (AEA) changes the effect of paclitaxel on gastric cancer cell lines. In the human gastric cancer cell line, HGC-27, which express cannabinoid receptor 1 (CB1), AEA stimulated proliferation at concentrations under 1 mu M, while it strongly suppressed proliferation through the induction of apoptosis at 10 mu M. This bimodal effect was reproduced by a selective CB1 agonist, arachidonyl-2-chloroethylamide, although the effects were less marked. When AEA was used with paclitaxel, AEA at 10 mu M synergistically enhanced the cytotoxic effect of paclitaxel, whereas it showed no significant effect at lower concentrations. Flow cytometric analysis revealed that addition of 10 mu M AEA synergistically enhanced paclitaxel-induced apoptosis, possibly through the activation of caspase-3, -8, and -9. Our results suggest that cannabinoids could be a good palliative agent for cancer patients receiving paclitaxel. Crown Copyright (C) 2009 Published by Elsevier Inc. All rights reserved.
  • Takao Kamei, Joji Kitayama, Hiroharu Yamashita, Hirokazu Nagawa
    WORLD JOURNAL OF SURGERY 33 6 1240 - 1246 2009年06月 [査読有り][通常論文]
     
    Perioperative blood transfusion has been shown to be associated with poor outcome in various types of malignancy. However, the relationship between the amount of blood loss and specific types of cancer recurrence has not been documented. We retrospectively examined the amount of intraoperative blood loss and the recurrence pattern in 146 patients who underwent curative gastrectomy for advanced gastric cancer and assessed the possible correlation between intraoperative blood loss and peritoneal, locoregional, and hematogenous recurrences. The amount of intraoperative blood loss in patients who developed peritoneal recurrence was significantly greater than that in patients without peritoneal recurrence, irrespective of blood transfusion. In contrast, the blood loss was not associated with nodal or hematogenous recurrence. Multivariate analysis demonstrated that large blood loss as well as operative curability B and adjuvant chemotherapy were independent risk factors for peritoneal recurrence and a worse outcome in advanced gastric cancer. Intraoperative blood loss in curative gastrectomy for advanced gastric cancer may have a specific association with the development of peritoneal recurrence. Surgeons must remember that clean and dry surgery may lessen not only 30-day mortality and morbidity but long-term peritoneal recurrence in gastric cancer.
  • Hiroharu Yamashita, Joji Kitayama, Masataka Taguri, Hirokazu Nagawa
    WORLD JOURNAL OF SURGERY 33 6 1298 - 1305 2009年06月 [査読有り][通常論文]
     
    Disorders in the blood coagulation system are often associated with malignancy. Patients with colorectal cancer (CRC) have been shown to have abnormal data for various coagulation tests. We retrospectively analyzed the relation between the preoperative plasma fibrinogen level and tumor recurrence in 569 patients with CRC who underwent curative surgical resection and were followed up without adjuvant chemotherapy. The plasma fibrinogen level showed a positive association with tumor recurrence, age, sex, T stage, and TNM classification. When divided with the median value, hyperfibrinogenemia is positively correlated with tumor recurrence, although it lost independence in the multivariate analysis. In the C-reactive protein (CRP)-negative population, hyperfibrinogenemia is independently correlated with tumor recurrence and recurrence-free survival. In contrast, hyperfibrinogenemia has no effect on recurrence in CRP-positive patients. Hyperfibrinogenemia is clinically relevant in tumor recurrence before a systemic inflammatory response and thus can be a useful predictor of recurrence in the preinflammatory stage of CRC.
  • Hiroharu Yamashita, Joji Kitayama, Hirokazu Nagawa
    GASTROINTESTINAL ENDOSCOPY 69 7 1407 - 1408 2009年06月 [査読有り][通常論文]
  • Takeshi Nishikawa, Nelson Tsuno, Yasutaka Shuno, Kazuhito Sasaki, Kumiko Hongo, Yurai Okaji, Eiji Sunami, Joji Kitayama, Koki Takahashi, Hirokazu Nagawa
    CANCER RESEARCH 69 2009年05月 [査読無し][通常論文]
  • Kazuhito Sasaki, Nelson Tsuno, Eiji Sunami, Giichiro Tsurita, Yurai Okaji, Takeshi Nishikawa, Yasutaka Syuno, Kumiko Hongo, Joji Kitayama, Koki Takahashi, Hirokazu Nagawa
    CANCER RESEARCH 69 2009年05月 [査読無し][通常論文]
  • Kumiko Hongo, Junichiro Tanaka, Nelson Tsuno, Takeshi Nishikawa, Yasutaka Shuno, Kazuhito Sasaki, Eiji Sunami, Joji Kitayama, Koki Takahashi, Hirokazu Nagawa
    CANCER RESEARCH 69 2009年05月 [査読無し][通常論文]
  • J. Kitayama, H. Ishigami, S. Kaisaki, A. Hidemura, M. Kato, H. Nagawa
    JOURNAL OF CLINICAL ONCOLOGY 27 15 2009年05月 [査読無し][通常論文]
  • Yasutaka Shuno, Nelson Tsuno, Yurai Okaji, Takeshi Nishikawa, Kazuhito Sasaki, Kumiko Hongo, Eiji Sunami, Joji Kitayama, Koki Takahashi, Hirokazu Nagawa
    CANCER RESEARCH 69 2009年05月 [査読無し][通常論文]
  • Yasutaka Shuno, Nelson Tsuno, Yurai Okaji, Takeshi Nishikawa, Kazuhito Sasaki, Kumiko Hongo, Eiji Sunami, Joji Kitayama, Koki Takahashi, Hirokazu Nagawa
    CANCER RESEARCH 69 2009年05月 [査読無し][通常論文]
  • S. Koketsu, T. Watanabe, M. Minami, J. Kitayama, Y. Kawamura, H. Nagawa
    HEPATO-GASTROENTEROLOGY 56 91-92 696 - 698 2009年05月 [査読有り][通常論文]
     
    We report a case of sigmoido-vesical fistula due to sigmoid diverticulitis. Magnetic resonance imaging enabled us to visualize the fistula itself in the bladder wall. Magnetic resonance imaging was highly effective in making a precise diagnosis and also provided important additional information for the preoperative work-up of the patient.
  • H. Ishigami, J. Kitayama, S. Kaisaki, A. Hidemura, M. Kato, K. Otani, T. Kamei, D. Soma, H. Miyato, H. Yamashita, H. Nagawa
    JOURNAL OF CLINICAL ONCOLOGY 27 15 2009年05月 [査読無し][通常論文]
  • Jun Suzuki, Shinsuke Kazama, Joji Kitayama, Hiroshi Uozaki, Tetsuro Miyata, Hirokazu Nagawa
    SURGERY TODAY 39 3 235 - 240 2009年03月 [査読有り][通常論文]
     
    Appendiceal cancer is rare and associated with a poor prognosis because it is usually found at an advanced stage. We report a case of appendiceal adenocarcinoma manifesting as a colonic obstruction with a lower abdominal mass. Laparotomy revealed bilateral ovarian tumors and a small appendiceal tumor with peritoneal metastases. We performed ileocecal resection, colectomy, and oophorectomy, following which a histological diagnosis of signet ring cell carcinoma was made. Immunohistochemical analysis revealed positive expression of cytokeratin 7 and 20, and mucin core protein 2 (MUC2), compatible with appendiceal cancer and Kruckenberg metastases. When a patient is found to have disseminated pelvic signet ring cell carcinoma of unknown origin, the appendix should be considered as a possible primary site.
  • Takeshi Nishikawa, Nelson H. Tsuno, Takeshi Tsuchiya, Satomi Yoneyama, Jun Yamada, Yasutaka Shuno, Yurai Okaji, Junichiro Tanaka, Joji Kitayama, Koki Takahashi, Hirokazu Nagawa
    ANNALS OF SURGICAL ONCOLOGY 16 2 534 - 543 2009年02月 [査読有り][通常論文]
     
    Sulforaphane (SUL) is an isothiocyanate naturally present in widely consumed vegetables, particularly in broccoli. SUL has recently been focused as a result of its inhibitory effects on tumor cell growth in vitro and in vivo. We used endothelial progenitor cells (EPCs) as an in vitro model to investigate the effect of SUL on the various steps of vasculogenesis and angiogenesis. Peripheral blood mononuclear cells from blood of normal human volunteers were plated on fibronectin-coated 100 mm dishes and incubated for 7 days. The viability of EPCs, treated with SUL at different doses, was assessed by MTS assay. Cell apoptosis was analyzed by flow cytometry. To determine the relative contributions of caspase-8 and caspase-9 pathways to SUL-induced apoptosis, the effect of caspase inhibitors was determined. The expression of apoptosis-related proteins (Bax, Bcl-2) was investigated by Western blot test. Finally, the effect of SUL on the ability of EPCs to form vascular-like structures on Matrigel was investigated. We clearly demonstrated that SUL induced the dose-dependent inhibition of EPCs' viability by induction of apoptosis. All caspases (caspase-3, -8, and -9) were activated during apoptosis induction by SUL, but the effect of caspase-9 was more prominent than that of caspase-8. Also, the expression of Bax was upregulated by SUL treatment. In addition to apoptosis induction, SUL dose-dependently inhibited the tube-like formation by EPCs on Matrigel. The present results demonstrate the antivasculogenic/antiangiogenic activity of SUL in vitro and open premise for the use of SUL as a multipotent anticancer agent that targets both cancer cells and the angiogenic endothelium.
  • H. Ishigami, J. Kitayama, S. Kaisaki, A. Hidemura, M. Kato, K. Otani, T. Kamei, D. Soma, H. Miyato, H. Yamashita, H. Nagawa
    ANNALS OF ONCOLOGY 20 82 - 83 2009年 [査読無し][通常論文]
  • Jun Yamada, Nelson H. Tsuno, Joji Kitayama, Takeshi Tsuchiya, Satomi Yoneyama, Masahiro Asakage, Yurai Okaji, Yasutaka Shuno, Takeshi Nishikawa, Junichiro Tanaka, Koki Takahashi, Hirokazu Nagawa
    JOURNAL OF SURGICAL RESEARCH 151 1 115 - 120 2009年01月 [査読有り][通常論文]
     
    Background. Zoledronic acid (ZOL) is clinically available for the treatment of skeletal complications. In preclinical studies, strong anti-cancer activities against breast cancer, prostate cancer, and leukemia were reported. It also inhibited the proliferation of cultured human endothelial cells, suggestive of an anti-angiogenic activity. Since ZOL has the tendency to accumulate in bone, we investigated the effect of ZOL on endothelial progenitor cells (EPCs), which originate from the bone marrow, and play important roles in angiogenesis. Materials and methods. Human peripheral blood mononuclear cells were cultured for 7 d to differentiate into EPCs. Cells were treated without/with ZOL or with geranylgeraniol (GGOH). Their endothelial phenotype was confirmed by the expression of CD144 and vascular endothelial growth factor receptor 2 and the tube-like formation ability on Matrigel (Becton Dickinson, Bedford, MA). Annexin V/propidium iodide staining was used to analyze apoptosis. Results. ZOL treatment, even at low doses, from d 2 to 7 of culture resulted in impaired EPC differentiation and could be restored by co-treatment with GGOH. On the other hand, treatment of putative EPCs with ZOL at concentrations higher than 10 gm resulted in induction of apoptosis. Conclusion. ZOL dose-dependently inhibited the differentiation of EPCs, the effect being observed even at low drug levels. At high concentrations, ZOL also induced the apoptotic death of putative EPCs. Since GGOH restored the inhibitory effect of ZOL on EPCs differentiation, the effect of ZOL appears to be dependent on the inhibition of prenylation of small-G-proteins. From these findings, we conclude that ZOL could be a potential anticancer agent by inhibiting angiogenesis. (C) 2009 Elsevier Inc. All rights reserved.
  • Joji Kitayama, Masafumi Tabuchi, Giichiro Tsurita, Makoto Ishikawa, Kensuke Otani, Hirokazu Nagawa
    DIGESTION 79 26 - 32 2009年 [査読有り][通常論文]
     
    Recent epidemiologic studies have shown a positive association between obesity and certain cancers. Our retrospective studies show that hypertriglyceridemia is an independent risk factor for the development of colonic adenoma and nodal metastasis in early gastric and esophageal cancer in men. High-fat condition may be favorable for the growth of malignant cells. Serum level of adiponectin is reduced in patients with advanced gastric cancer, which may be associated with the positive link between adiposity and cancer. In early gastric cancer, patients with undifferentiated type have lower fat volume than those with differentiated type. Adiposity appears to be closely related with various aspects in pathophysiology of gastrointestinal malignancy. Copyright (c) 2009 S. Karger AG, Basel
  • Hironori Ishigami, Joji Kitayama, Kensuke Otani, Takao Kamei, Daisuke Soma, Hideyo Miyato, Hiroharu Yamashita, Akio Hidemura, Shoichi Kaisaki, Hirokazu Nagawa
    ONCOLOGY 76 5 311 - 314 2009年 [査読有り][通常論文]
     
    Objectives: A dose-escalation study of weekly intraperitoneal paclitaxel (PTX) combined with S-1 and intravenous PTX was performed to determine the maximum-tolerated dose (MTD) and recommended dose (RD) in gastric cancer patients. Patients and Methods: Nine gastric cancer patients with peritoneal dissemination and/or cancer cells on peritoneal cytology were enrolled. PTX was administered intravenously on days 1 and 8 at a fixed dose of 50 mg/m(2), and intraperitoneally with an initial dose of 20 mg/m(2), stepped up to 30 or 40 mg/m(2). S-1 was administered at a fixed dose of 80 mg/m(2)/day for 14 consecutive days, followed by 7 days of rest. A pharmacokinetic study of PTX was also performed. Results: The MTD was determined to be 30 mg/m(2), as 2 of 3 patients developed dose-limiting toxicities, grade 3 febrile neutropenia and diarrhea. Therefore, the RD was determined to be 20 mg/m(2). The intraperitoneal and serum PTX concentration remained effective for over 72 and 48 h, respectively. Conclusions: Combined chemotherapy of S-1 plus weekly intravenous and intraperitoneal PTX was shown to be a safe regimen that should be further explored in clinical trials. Copyright (C) 2009 S. Karger AG, Basel
  • Jun Yamada, Joji Kitayama, Nelson H. Tsuno, Hiroharu Yamashita, Hideyo Miyato, Daisuke Soma, Kensuke Otani, Takao Kamei, Hironori Ishigami, Akio Hidemura, Shoichi Kaisaki, Koki Takahashi, Hirokazu Nagawa
    CANCER LETTERS 272 2 307 - 315 2008年12月 [査読有り][通常論文]
     
    Background and aim: Intra-peritoneal administration (i.p.) of Taxanes has recently been reported to be effective for the treatment of peritoneal dissemination, presumably because extremely high concentration of the drug is achievable onto the disseminated nodules as compared to intra-venous administration. Here, we aimed to investigate the ability of non-animal stabilized hyaluronic acid (NASHA) to retain the anti-cancer drugs in the peritoneal cavity, and, consequently, improve the efficacy of i.p. administration of paclitaxel. Methods: Mice were inoculated i.p. with MKN45P gastric cancer cells. The mice received i.p. administrations of paclitaxel, without or with NASHA, once a week for 3 consecutive weeks, and the intra-peritoneal nodules were counted after 4 weeks. The ability of NASHA to retain the i.p. administered liquid and paclitaxel in abdominal cavity was also investigated. Finally, the concentration of paclitaxel in metastatic nodule was measured with HPLC. Results: In the group receiving paclitaxel with NASHA, the number of disseminated nodules were significantly smaller than in those receiving paclitaxel without NASHA. The fluid volumes and concentration of paclitaxel recovered from the abdominal cavity as well as the concentrations of paclitaxel in metastatic nodule were significantly increased by the addition of NASHA. Conclusion: Our results indicate that NASHA improves the exposure time of i.p. administrated paclitaxel to disseminated nodules by retaining the drug in the abdominal cavity. Since the material is used in cosmetic surgery with few adverse effects, NASHA can be clinically used as the vehicle for the i.p. administration of anti-cancer agents for advanced gastric cancer with peritoneal dissemination. (c) 2008 Elsevier Ireland Ltd. All rights reserved.
  • Daisuke Soma, Joji Kitayama, Hiroharu Yamashita, Hideyo Miyato, Makoto Ishikawa, Hirokazu Nagawa
    JOURNAL OF SURGICAL RESEARCH 149 1 9 - 14 2008年09月 [査読有り][通常論文]
     
    Excessive fat mass is a risk factor for postmenopausal breast cancer. Leptin, a fat cell-derived peptide hormone, elicits a growth-stimulating effect in breast cancer cells with leptin receptor expression, although the leptin-induced signal in malignant cells is not fully understood. Here, we found that exogenous leptin induced tyrosine phosphorylation of HER2 in SKBR3 cells, which showed marked overexpression of HER2. Phosphorylation of HER2 was detected at 2 min and continued up to 120 min after the start of stimulation. Leptin-induced HER2 phosphorylation was partially reduced by an epidermal growth factor receptor inhibitor, AG1478, or a Janus-activated kinase inhibitor, AG490. Leptin also induced phosphorylation of extracellular signal-regulated kinase 1/2, which was mostly abrogated by a HER2 tyrosine kinase inhibitor, AG825. In a proliferation assay, addition of 500 ng/mL leptin increased the proliferation of SKBR3, which was totally inhibited by AG825. Collectively, our data suggest that leptin can transactivate HER2 through both epidermal growth factor receptor and Janus-activated kinase 2 activation, which can cause the growth of breast cancer cells with HER2 overexpression. (c) 2008 Elsevier Inc. All rights reserved.
  • Suzuki H, Tsurita G, Ishihara S, Akahane M, Kitayama J, Nagawa H
    Case reports in gastroenterology 2 3 509 - 516 2008年09月 [査読有り][通常論文]
  • Tatsuya Ohnishi, Toshiaki Watanabe, Hiroaki Nozawa, Joji Kitayama, Hirokazu Nagawa
    HEPATO-GASTROENTEROLOGY 55 86-87 1513 - 1518 2008年09月 [査読有り][通常論文]
     
    Background/Aims: Recurrence, which Occurs in about 20-30% of colorectal cancer patients after curative surgical treatment, is an important factor in determining prognosis. Therefore, early detection and prediction of recurrence is an Important issue in the treatment of the disease. Telomerase is a reverse transcriptase that synthesizes telomere DNA, thereby compensating for telomere loss that occurs with each replication cycle, and limits proliferation cells. Telomerase is expressed in the majority of primary human tumors and hTERT is considered one of the most important proteins affecting telomerase activity. We evaluated telomerase activity in mesenteric and peripheral blood samples in addition to hTERT expression in cancerous tissues by means of immunohistochemistry in 120 patients who underwent curative surgical treatment at our department. Methodology: We investigated the factors correlated with recurrence. Results: In univariate analysis, we found recurrence was significantly correlated with positive telomerase activity In the mesenteric vein (p=0.0021), positive telomerase activity in the peripheral vein (p=0.0032), histological type except well differentiated adenocarcinoma (p=0.0013), lymphatic infiltration (p=0.044), lymph node metastasis at surgery (p<0.0001), positive CEA (p=0.0004) and negative TERT immunoreactivity (p=0.012). In multivariate analysis, we found lymph node involvement at surgery (p=0.0045, hazard ratio: 6.21) and positive telomerase activity in peripheral vein (p=0.037, hazard ratio: 3.13) were significantly associated with the existence of recurrence. Conclusions: Our results show that measuring telomerase activity in peripheral blood samples is effective in predicting future recurrence to a degree greater than macroscopically examined tumor depth or other clinicopathological parameters.
  • Masafumi Tabuchi, Joji Kitayama, Hirokazu Nagawa
    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 23 6 985 - 987 2008年06月 [査読有り][通常論文]
     
    Background and Aim: Epidemiological studies have suggested the positive correlation between hyperlipidemia and/or hyperglycemia and colorectal cancer risk. Methods: We retrospectively examined the association between fasting blood sugar (BS) or triglycerides (TG) and the presence of colorectal adenoma, carcinoma in situ and invasive cancer in 867 patients who received total colonoscopy by medical health check. Results: An increased TG level, but not a BS level, was significantly associated with the increased risk of adenoma, although with non-independent multivariate analysis. In contrast, an elevated BS level was identified as an independent risk factor for invasive cancer in 93 patients with carcinoma lesions with an odds ratio of 1.74 (P < 0.05). Conclusion: Our data suggest that hypertriglyceridemia and hyperglycemia may correlate with the development of adenoma and invasive cancer, respectively. The effectiveness of strict BS control in patients with hypertriglyceridemia for the prevention of the invasive colorectal carcinoma deserves further studies.
  • Kensuke Otani, Joji Kitayama, Shoichi Kaisaki, Hironori Ishigami, Akio Hidemura, Mitsuhiro Fujishiro, Masao Omata, Hirokazu Nagawa
    GASTRIC CANCER 11 2 86 - 95 2008年06月 [査読有り][通常論文]
     
    Background. Visceral obesity is known to be a risk factor for diabetes and cardiovascular disease. Cancer of the gastric cardia has been shown to have a close association with obesity in Western countries. In order to examine the possible relationship between fat volume and the development of gastric cancer (GC), we quantified visceral and subcutaneous fat areas of computed tomography (CT) images of patients with early GC. Methods. A total of 210 patients who underwent endoscopic resection or surgical gastrectomy and whose disease was pathologically diagnosed as early GC were investigated for total fat area (TFA), visceral fat area (VFA), and subcutaneous fat area (SFA) with Fat Scan software, using a CT slice at the umbilical level, and the relationships of these findings with clinical and pathological data were analyzed. The same analysis was performed in 147 patients with early colorectal cancer (CRC). Results. TFA, VFA, and SFA values in GC patients were not significantly different from the values in CRC patients. These values did not differ with the location of the GC. However, patients with undifferentiated-type GC had significantly smaller VFAs and SFAs than those with differentiated-type GC. Among the patients with undifferentiated GC, TFA and SFA values in the patients with submucosal cancer were significantly smaller than those in the patients with mucosal cancer. Conclusion. GC has different associations with adipose tissue volume according to its histological type. As compared with differentiated GC, lower adipose tissue volume may be a preferential environment for the development and progression of undifferentiated GC.
  • Takeshi Tsuchiya, Nelson H. Tsuno, Masahiro Asakage, Jun Yamada, Satomi Yoneyama, Yurai Okaji, Shin Sasaki, Joji Kitayama, Takuya Osada, Koki Takahashi, Hirokazu Nagawa
    HEPATO-GASTROENTEROLOGY 55 84 930 - 935 2008年05月 [査読有り][通常論文]
     
    Background/Aims: The p38 mitogen-activated protein kinases. (p38 MAPKs) function in a wide variety,of signaling pathways. However, the role of p38s is cell type- and stimulus-dependent. The present study aimed to evaluate the effects of p38 MAPK inhibitor on human colon cancer cells. Methodology: The effect of p38 MAPK inhibitor, FR167653, on DLD-1 and SW480 was investigated related to cell proliferation, apoptosis induction and caspase activity. Additionally, the effect of FR167653 on colon cancer cell migration, MMPs production and ability to adhere to extracellular matrix was investigated. Results: Inhibitor of p38 MAPK dose-dependently suppressed the proliferative activity of both cell lines, and increased the induction of cell apoptosis. The caspase-3, 8, and 9 activities were accompanied in the pathway. Neither cell migration, MMPs production, nor the ability to adhere extracellular matrix were affected by FR167653. Conclusions: Inhibitor of p38 MAPK suppressed the proliferation of colon cancer cells by induction of cell apoptosis through the caspase activation. The present results suggest the pro-oncogenic role of p38 in colon cancer, and its inhibition would be a novel strategy for the prevention and treatment of colon cancer.
  • Yurai Okaji, Nelson H. Tsuno, Minoru Tanaka, Satomi Yoneyama, Mika Matsuhashi, Joji Kitayama, Shinsuke Saito, Yutaka Nagura, Takeshi Tsuchiya, Jun Yamada, Junichiro Tanaka, Naoyuki Yoshikawa, Takeshi Nishikawa, Yasutaka Shuno, Tomoki Todo, Nobuhito Saito, Koki Takahashi, Hirokazu Nagawa
    EUROPEAN JOURNAL OF CANCER 44 3 383 - 390 2008年02月 [査読有り][通常論文]
     
    Vaccines targeting tumour angiogenesis were recently shown to inhibit tumour growth in animal models. However, there is still a lack of information about the clinical utility of anti-angiogenic vaccination. Therefore, here, we aimed to test the clinical effects of a vaccine using glutaraldehyde-fixed human umbilical vein endothelial cells (HUVECs). Six patients with recurrent malignant brain tumours and three patients with metastatic colorectal cancer received intradermal injections of 5 x 10(7) HUVECs/dose (in total 230 vaccinations). ELISA and flow cytometry revealed immunoglobulin response against HUVECs' membrane antigens. ELISPOT and chromium-release cytotoxicity assay revealed a specific cellular immune response against HUVECs, which were lysed in an effectors:targets ratio-dependent manner. Gadolinium-contrasted MRI showed partial or complete tumour responses in three malignant brain tumour patients. Except for a DTH-like skin reaction at the injection site, no adverse effect of vaccination could be observed. our results suggest that the endothelial vaccine can overcome peripheral tolerance of self-angiogenic antigens in clinical settings, and therefore should be useful for adjuvant immunotherapy of cancer. (c) 2007 Elsevier Ltd. All rights reserved
  • Shin Sasaki, Takashi Kobunai, Joji Kitayama, Hirokazu Nagawa
    ONCOLOGY REPORTS 19 2 407 - 412 2008年02月 [査読有り][通常論文]
     
    The prediction of the cellular direction of metabolic pathways toward either DNA synthesis or DNA methylation is crucial for determining the susceptibility of cancers to antimetabolites such as fluorouracil (5-FU). We genotyped the methylenetetrahydrofolate reductase (MTHFR) gene in NCI-60 cancer cell lines, and identified the methylation status of 24 tumor suppressor genes using methylation-specific multiplex ligation-dependent probe amplification. The susceptibility of the cancer cell lines to seven antimetabolites was then determined. Cells homozygous for CC at MTHFR-A1298C were significantly more sensitive to cyclocytidine, cytarabine (AraC) and floxuridine than those with AA or AC (p=0.0215, p=0.0166, and p=0.0323, respectively), and carried more methylated tumor suppressor genes (p=0.0313). Among the 12 tumor suppressor genes which were methylated in >25% of cancer cell lines, the methylation status of TIMP3, APC and IGSF4 significantly correlated with sensitivity to pyrimidine synthesis inhibitors. In particular, cells with methylated TIMP3 had reduced mRNA levels and were significantly more sensitive to aphidicolin-glycinate, AraC and 5-FU than cells with unmethylated TIMP3. We speculate that MTHFR-A1298C homozygous CC might direct the methylation rather than the synthesis of DNA, and result in the methylation of several tumor suppressor genes such as TIMP3. These genes could be useful biological markers for predicting the efficacy of antimetabolites.
  • Satomi Yoneyama, Kazushige Kawai, Nelson H. Tsuno, Yurai Okaji, Masahiro Asakage, Takeshi Tsuchiya, Jun Yamada, Eiji Sunami, Takuya Osada, Joji Kitayama, Koki Takahashi, Hirokazu Nagawa
    JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 121 1 209 - 214 2008年01月 [査読有り][通常論文]
     
    Background: Epigallocatechin gallate (EGCG), a component of green tea catechin with the strongest biological activity, has been focused in recent years because of its anti-inflammatory and immunomodulatory activities. Dendritic cells (DCs) are professional antigen-presenting cells, capable of priming naive T cells, and play the key roles in the activation of T-cell-mediated immune responses. Objective: We aimed to investigate the effect of EGCG on human monocyte-derived DCs (MODCs) and, consequently, on the T-cell-mediated immune response. Methods: The induction of apoptosis, and the detailed phenotypic and functional changes of MODCs, generated by culture of peripheral blood monocytes in the presence of GM-CSF and IL-4, induced by EGCG was investigated and compared with the effects of dexamethasone. Results: Epigallocatechin gallate induced apoptosis and affected the phenotype of the developing DCs. The expressions of CD83, CD80, CD11c, and MHC class II, which are molecules essential for antigen presentation by DCs, were downregulated by EGCG. EGCG also suppressed the endocytotic ability of immature DCs, whereas dexamethasone-treated DCs had higher endocytotic ability than control DCs. Most importantly, mature DCs treated with EGCG inhibited stimulatory activity toward allogeneic T cells while secreting high amounts of IL-10. Conclusion: Epigallocatechin gallate induces immunosuppressive alterations on human MODCs, both by induction of apoptosis and suppression of cell surface molecules and antigen presentation.
  • Shuangta Xu, Joji Kitayama, Hiroharu Yamashita, Daisuke Souma, Hirokazu Nagawa
    JOURNAL OF SURGICAL ONCOLOGY 97 1 44 - 50 2008年01月 [査読有り][通常論文]
     
    Background: HER family is an attractive target for the treatment of esophageal cancer. The clinical relevance of HER-4 has not been yet characterized. Methods: The expression of HER-4 was immunohistochemically examined in 61 surgically resected esophageal squamous cell carcinomas (ESCC), and the prognostic significance of HER-4 in ESCC was evaluated. Results: HER-4 was positive in the cytoplasm and cell membrane of 51 (84%) tumors, with variable intensity and a heterogeneous distribution, with preferential expression in well or moderately differentiated tumors. Nuclear staining of HER-4 was observed in 37 (61%) cases as well. The membranous/cytoplasmic, but not nuclear, expression of HER-4 was positively correlated with the expression of HER-2 and HER-3. Survival of the HER-4-positive group was significantly better than that of the HER-4-negative group (P < 0.05). Multivariate analysis revealed that I extranuclear expression of HER-4 was independently correlated with increased survival. In contrast, nuclear staining of HER-4 was correlated r with increased T stage, which resulted in a significant reduction in survival in the HER-4 positive group (P < 0.05). Conclusion: Extranuclear HER-4 may have negative effects on the progression of ESCC, whereas nuclear translocation of HER-4 may elicit a tumor-promoting property. Inummohistochemical detection of HER-4 localization is clinically useful to predict the survival of the patients with ESCC.
  • S. Yoneyama, Y. Okaji, N. H. Tsuno, K. Kawai, H. Yamashita, T. Tsuchiya, J. Yamada, E. Sunami, T. Osada, J. Kitayama, K. Takahashi, H. Nagawa
    EJSO 33 10 1191 - 1198 2007年12月 [査読有り][通常論文]
     
    Aim: Historically, cancer therapy directly targeting tumor cells have yielded suboptimal clinical results, and therefore anti-angiogenic therapy that targets tumor cells indirectly through impairing tumor vasculature is now considered to be one of the novel approaches potentially effective against various types of cancer. In this study, we evaluated whether lysates of endothelium could be effectively pulsed in dendritic cells (DCs), to enhance their anti-tumor effects. Methods: For this purpose, we prepared DCs of BALB/c mouse, incubated them with lysates of autologous or xenogeneic endothelium, and tested their anti-tumor effects in two syngeneic models of colon cancer. Results: DCs pulsed with the respective endothelium lysates significantly inhibited the growth of subcutaneous tumors as well as pulmonary metastases in mice, and their anti-tumor effect was superior to that of unpulsed DCs. Immunohistopathological analysis showed significant decrease in the mean vascular density of tumors, correlating well with the extent of tumor inhibition. In vitro analysis of splenocytes isolated from immunized mice revealed an induction of cytotoxic T lymphocytes and activation of natural killer cells, with a lytic activity against activated endothelium but not tumor cells. In addition, antibodies reacting with activated endothelium, but not tumor cells, were detected in murine sera by ELISA, and their function was confirmed by complement-dependent cytotoxicity assay. Conclusions: Our present results suggest that lysates of endothelium can be effectively pulsed in DCs and enhance their anti-tumor effects through induction of anti-angiogenesis, and therefore should have important clinical implications for adjuvant cancer therapy. (c) 2007 Elsevier Ltd. All rights reserved.
  • Hashimoto T, Kitayama J, Hidemura A, Ishigami H, Kaizaki S, Fukushima N, Miyata T, Nagawa H
    Case reports in gastroenterology 1 1 184 - 189 2007年12月 [査読有り][通常論文]
  • Soichiro Ishihara, Joji Kitayama, Hirokazu Nagawa
    Gastroenterology 133 5 1412 - 1747 2007年11月 [査読有り][通常論文]
  • J. Yamada, H. Tsuno, J. Kitayama, J. Tanaka, T. Tsuchiya, S. Yoneyama, Y. Okaji, K. Takahashi, H. Nagawa
    EJC SUPPLEMENTS 5 4 113 - 114 2007年09月 [査読無し][通常論文]
  • Jun Yamada, Kazushige Kawai, Nelson H. Tsuno, Joji Kitayama, Takeshi Tsuchiya, Satomi Yoneyama, Masahiro Asakage, Yurai Okaji, Koki Takahashi, Hirokazu Nagawa
    PLANTA MEDICA 73 10 1068 - 1073 2007年08月 [査読有り][通常論文]
     
    Although some isoprenoids, such as taxans and geranylgeraniol (GGOH), have been reported to have strong anticancer activities, the effect of plaunotol, the isoprenoid extracted from the leaves of Plau-noi, on cancer has not yet been evaluated. Here, we aimed to investigate the effect of plaunotol on gastric cancer cell lines. Three gastric cancer cell lines, namely MKN-45, MKN-74 and AZ-521 were used. Plaunotol was tested at 10, 20, 30 and 40 mu mol/L. Plaunotol dose-dependently inhibited the growth of all gastric cancer cells, dependent on the induction of apoptosis. Caspases-8, -9 and -3, were found to be activated in the apoptotic cells. The expression of Bax protein was increased, but Bcl-2 and Bcl-xL protein expressions were not significantly affected. Plaunotol should be a promising new antitumor agent, and since it is already available for clinical use in Japan, its anticancer properties should be confirmed in clinical trials.
  • Hideo Kagaya, Joji Kitayama, Akio Hidemura, Shoichi Kaisaki, Hironori Ishigami, Junko Takei, Takamitsu Kanazawa, Hirokazu Nagawa
    JAPANESE JOURNAL OF CLINICAL ONCOLOGY 37 8 628 - 631 2007年08月 [査読有り][通常論文]
     
    A 55-year-old man developed progressive dysphagia 14 months after palliative colectomy and subsequent systemic chemotherapy for advanced cecal cancer with carcinomatosis peritonei. Radiologic and endoscopic examinations suggested a submucosal tumor in the lower esophagus causing a severe luminal stricture. A self-expanding metal stent was placed for palliation. The prosthesis was effective for several months, but ingrowth of the tumor caused re-stricture of the esophagus. Since his general condition was quite good without any evidence of recurrence of the cecal cancer, we performed bypass surgery for palliation. The pathological appearance of the tumor was compatible with the metastasis of cecal cancer. Our case suggests that a surgical approach can be considered as a therapeutic method for metastatic esophageal tumor, even in patients with advanced cancer, as long as the primary tumor is satisfactorily controlled.
  • Makoto Ishikawa, Joji Kitayama, Toshimasa Yamauchi, Takashi Kadowaki, Toshiyuki Maki, Hideyo Miyato, Hiroharu Yamashita, Hirokazu Nagawa
    CANCER SCIENCE 98 7 1120 - 1127 2007年07月 [査読有り][通常論文]
     
    Adiponectin, a circulating peptide hormone produced in adipose tissue, has been shown to be reduced in the plasma of patients with cancer, suggesting that this adipokine may be mechanically involved in the pathogenesis of adiposity-related carcinogenesis. In this study, we examined the expression of adiponectin receptors (AdipoR1 and AdipoR2) and assessed the function of adiponectin in gastric cancer. All of the six gastric cancer cell lines significantly expressed mRNA and protein of both receptors with variable levels. Addition of 30 mu g/mL adiponectin potently induced apoptosis and inhibited the proliferation of AZ521 and HCG27. Down-regulation of either AdipoR1 or AdipoR2 by specific siRNA significantly suppressed the growth inhibitory effects of adiponectin in both cell lines. Moreover, a local injection of adiponectin markedly inhibited the growth of AZ521 inoculated subcutaneously in nude mice. Similarly, the continuous intraperitoneal infusion of adiponectin effectively suppressed the development of peritoneal metastasis of AZ521. Adiponectin negatively regulates the progression of gastric cancer cells possibly through both AdipoR1 and AdipoR2. Although adiponectin was already reported to have antiangiogenic effects, our results suggest that the antitumor effect of adiponectin was, at least partially, dependent on the direct effects on tumor cells.
  • Ken Mori, Joji Kitayama, Junken Aoki, Yasuhiro Kishi, Dai Shida, Hiroharu Yamashita, Hiroyuki Arai, Hirokazu Nagawa
    VIRCHOWS ARCHIV 451 1 47 - 56 2007年07月 [査読有り][通常論文]
     
    Lysophosphatidic acid (LPA) is involved in a broad spectrum of biological activities, including wound healing and cancer metastasis. Autotaxin (ATX), originally isolated from a melanoma supernatant as a tumor cell motility-stimulating factor, has been shown to be molecularly identical to lysophospholipase D (lysoPLD), which is the main enzyme in the production of LPA. Although ATX/lysoPLD is known to be widely expressed in normal human tissues, the exact distribution of ATX-producing cells has not been fully investigated. In this study, we evaluated ATX/lysoPLD expression by immunohistochemical staining using a rat anti-ATX mAb in the human gastrointestinal tract and found that submucosal mast cells (MC) highly expressed this enzyme. This was confirmed by immunofluo rescent double staining using mAbs to tryptase and chymase. Then, we isolated MC from human gastric tissue by an immunomagnetic method using CD 117-microbeads and showed that a subpopulation of CD203c-positive MC showed positive staining for intracellular ATX/lysoPLD on flowcytometry. This was confirmed by Western blotting of the isolated cells. Moreover, a significant level of ATX/lysoPLD release could be detected in the culture supernatants of human MC by Western blot analysis. Our data suggest that submucosal MC play significant roles in various aspects of pathophysiology in the gastrointestinal tract by locally providing bioactive LPA through the production of ATX/lysoPLD.
  • Aoki S, Yatomi Y, Shimosawa T, Yamashita H, Kitayama J, Tsuno NH, Takahashi K, Ozaki Y
    Journal of thrombosis and haemostasis : JTH 5 6 1292 - 1301 2007年06月 [査読有り][通常論文]
  • Joji Kitayama, Hironori Ishigami, Makoto Ishikawa, Hiroharu Yamashita, Daisuke Soma, Hideyo Miyato, Hirokazu Nagawa
    SURGERY 141 6 815 - 820 2007年06月 [査読有り][通常論文]
     
    Background. We assessed whether a mixture of hyaluronic acid (HA) and dye can facilitate dye-guided sentinel node (SN) mapping in gastric surgery. Although dye-guided, SN-navigated surgery is clinically applied for the treatment of early gastric cancer, there are still some practical problems. Because dyes are carried out from the SN within 20 to 30 minutes, it is sometimes difficult to detect SNs accurately, especially when they are located in a deep area in obese patients. Methods. Patent blue or ferumoxides, superparamagnetic iron nanocolloids, with or without HA, were injected into the gastrointestinal tract of the pig, and the time course of dye transfer through the lymphatic system of the pig mesentery was assessed. Results. When a mixture of HA and patent blue at a volume ratio of 1:4 was injected into the submucosal layer, the time to stain the SN did not differ from that with patent blue alone; however, HA markedly prolonged the time the blue dye was retained in the SN. Patent blue alone stained the efferent lymphatics of the SN and spread to other lymph nodes within 20 minutes after submucosal injection. At the same time point, in contrast, blue stain was restricted to a part of the SN, and the efferent lymphatics were not stained for 2 hours when patent blue was mixed with HA. When a mixture of HA and ferumoxides was used as the tracer, the ferumoxides were still observed in the mesenteric SN even at 2 days after injection. Iron staining showed that Fe was trapped primarily in cells in the peripheral sinus of the SN, suggesting that the iron nanoparticles were mostly incorporated by phagocytic macrophages in the SN within a few hours. Conclusions. Our data indicate that a mixture with HA prolongs the stay of a dye tracer in the SN and thus enables easy and accurate detection of the SN. HA may be a useful tool to develop a more sophisticated SN mapping technique.
  • H. Yamashita, J. Kitayama, H. Ishigami, J. Yamada, H. Miyato, S. Kaisaki, H. Nagawa
    DIGESTIVE AND LIVER DISEASE 39 4 389 - 391 2007年04月 [査読無し][通常論文]
  • Hiroharu Yamashita, Joji Kitayama, Makoto Ishikawa, Hirokazu Nagawa
    JOURNAL OF SURGICAL ONCOLOGY 95 4 324 - 331 2007年03月 [査読有り][通常論文]
     
    Background and Objectives: Tissue factor (TF), which normally safeguards vascular integrity by inducing hemostasis upon injury, has received widespread attention in the pathogenesis of cancer progression and metastasis. Aberrantly expressed TF in cancer cells has been reported to be associated with advanced stages of malignancy in various cancers. Methods: The expression of TF and microvessel density (MVD) were immunohistochemically evaluated in 207 gastric cancers, and their relationship with clinicopathological features was examined. Results: TF was preferentially expressed (41.8%) in intestinal-type cancer at a significantly higher rate than that in diffuse-type cancer (12.1%, P < 0.0001). The expression of TF was associated with advanced stage of disease and showed a positive correlation with a higher rate of lymphatic and venous invasion and lymphatic metastasis in intestinal-type, but not in diffuse-type carcinoma. Moreover, TF expression was associated with high MVD in the tumor and a worse outcome only in intestinal-type carcinoma. Conclusions: TF may be critically involved in tumor progression in intestinal-type, but not in diffuse-type, gastric carcinoma. The difference in clinical features between these two histological types might be partially dependent on TF expression profile.
  • Shoichi Kaisaki, Joji Kitayama, Hironori Ishigami, Hirokazu Nagawa
    SURGERY TODAY 37 3 243 - 247 2007年03月 [査読有り][通常論文]
     
    Although locoregional recurrence is often observed in the cervicothoracic area even after an esophagectomy with three-field lymph node dissection (3FL), recurrence in the mediastinal lymph nodes is relatively rare. We experienced two cases of solitary recurrence in a posterior mediastinal node ( No 112-ao) after a curative resection for thoracic esophageal cancer. The lymph node recurrence was located in the connective tissue adjacent to the left posterior wall of the thoracic aorta, and thus could not have been removed by the conventional approach of an esophagectomy through a right thoracotomy. These two patients underwent surgical removal of the tumor through left thoracotomy, and survived for 5 years and 1 year without recurrence, respectively. Because the rate of metastasis in this area appears to be low, it is not always necessary to perform complete nodal dissection of the left side of the descending aorta at the initial surgery in cases of thoracic esophageal cancer. However, our experience suggests the importance of periodic computed tomography scans to check for any nodal recurrence in this area, since a surgical resection may be effective when the recurrence is detected as a solitary metastasis.
  • Akihiro Sako, Joji Kitayama, Makoto Ishikawa, Hiroharu Yamashita, Hirokazu Nagawa
    Gastric Cancer 9 4 295 - 302 2006年11月 [査読有り][通常論文]
     
    Background. Among various clinical and pathological findings, lymphatic invasion (Ly) is the strongest risk factor for nodal metastasis in gastric cancer. However, the diagnosis of Ly is subjective and often inaccurate because of the difficulty of detecting lymphatic vessels with conventional hematoxylin and eosin (HE) staining. Methods. The distribution of lymphatics in the normal gastric wall was immunohistochemically characterized using a new selective marker of lymphatic endothelium, D2-40, in surgical specimens resected for early gastric cancer (EGC). Then, Ly in the primary lesion was reevaluated, and the positive (PPV) and negative (NPV) predictive values for nodal metastasis were comparatively examined for Ly detected by HE staining (Ly-HE) and by immunohistochemical staining (Ly-IM) in 131 cases of EGC. Results. D2-40-positive lymphatic vessels were observed in the deep proper mucosal layer, and the lymphatic vessel density (LVD) was extremely high in the muscularis mucosa (MM) layer. The number of Ly-IM-positive cases (15/131) was higher than the Ly-HE-positive cases (10/131). In 48 cases of intestinal-type cancer, Ly-IM had a PPV of 33.3% (2/6) and anNPV of 100% (42/42), which was more accurate than the corresponding figures for Ly-HE (25% and 98%, respectively). In contrast, the accuracy of Ly-IM was similar to that of Ly-HE in 83 cases of diffuse-type cancer. Conclusion. Lymphatic vessels are most densely distributed in the MM layer in the gastric wall. Immunohistochemical identification of lymphatics is useful to increase the accuracy of diagnosing Ly in resected gastric EGCs. Ly-IM is superior to Ly-HE as a predictor of nodal metastasis, at least for intestinal-type EGC. © 2006 International and Japanese Gastric Cancer Association.
  • Makoto Ishikawa, Joji Kitayama, Hirokazu Nagawa
    WORLD JOURNAL OF GASTROENTEROLOGY 12 34 5517 - 5522 2006年09月 [査読有り][通常論文]
     
    AIM: To examine the expression of leptin and its receptor, OB-R, in normal gastric mucosa and neoplasia. METHODS: By immunohistochemical staining using specific antibodies, we evaluated the expression of leptin and OB-R in 207 gastric carcinomas (100 early and 107 advanced carcinomas) and analyzed their relationship with clinicopathological features. RESULTS: Both normal gastric epithelium and carcinoma cells expressed a significant level of leptin. In cases with OB-R staining, carcinoma cells showed OB-R-positive expression, but the intensity was weaker than that in normal mucosa. The expression of OB-R showed a significant correlation with the level of leptin expression. The expression levels of both leptin and OB-R tended to increase as the depth of tumor invasion or TMN stage increased (P< 0.01). Lymph node metastasis was detected in 49.5% (47/95) of leptin-strong cases and in 50.5% (48/95) of OB-R-positive cases, and the rate was 33% (37/112) in leptin-weak cases and 17% (19/112) in OB-R-negative cases. Both venous and lymphatic invasion also tended to be observed frequently in positive tumors as compared with negative tumors. Interestingly, in the 96 leptin- or OB-R-positive tumors, hematogenous metastasis was detected preoperatively in 3 (3.1%) patients. In contrast, none of the carcinomas that lacked expression of leptin and OB-R showed hematogenous metastasis. CONCLUSION: Overexpression of leptin and expression of OB-R may play a positive role in the process of progression in gastric cancer. Functional upregulation of leptin/OB-R may have a positive role in the development and initial phase of progression in gastric cancer. (C) 2006 The WJG Press. All rights reserved.
  • J Kitayama, T Morota, S Kaisaki, H Nakayama, H Ishigami, H Yamashita, M Ishikawa, K Shibata, S Takamoto, H Nagawa
    AMERICAN JOURNAL OF SURGERY 192 1 130 - 134 2006年07月 [査読有り][通常論文]
     
    Aortoesophageal fistula secondary to a thoracic aortic aneurysm is usually a fatal disease with few survivors reported previously. We encountered 2 consecutive patients who were treated successfully with esophagectomy and in situ aorta reconstruction using cryopreserved homograft that was wrapped completely with omental pedicle flap. For the construction of omental flap, the right gastroepiploic artery was resected at the root and all the vessels entering the greater curvature and the transverse colon were resected at the adherent edges. Because the gastroepiploic arcade is totally preserved, large amounts of omental tissue could be obtained, with an excellent blood supply mainly from the left gastroepiploic artery. This type of omental flap is highly mobile, easily transferred to the left hemithorax, and has enough volume to cover the in situ aortic graft completely including anastomosis lines. Thus, our omental coverage appears to be the most reliable method to prevent postoperative graft infection. (c) 2006 Excerpta Medica Inc. All rights reserved.
  • M Asakage, NH Tsuno, J Kitayama, K Kawai, Y Okaji, K Yazawa, S Kaisaki, T Osada, T Watanabe, K Takahashi, H Nagawa
    CANCER IMMUNOLOGY IMMUNOTHERAPY 55 6 708 - 716 2006年06月 [査読有り][通常論文]
     
    Endothelial progenitor cells (EPCs) have been recently found to exist circulating in peripheral blood of adults, and home to sites of neovascularization in peripheral tissues. They can also be differentiated from peripheral blood mononuclear cells (PBMNCs). In tumor tissues, EPCs are found in highly vascularized lesions. Few reports exist in the literature concerning the characteristics of EPCs, especially related to their surface antigen expressions, except for endothelial markers. Here, we aimed to investigate the surface expression of differentiation markers, and the functional activities of early-outgrowth of EPCs (EO-EPCs), especially focusing on their antigen-presenting ability. EO-EPCs were generated from PBMNCs, by culture in the presence of angiogenic factors. These EO-EPCs had the morphological and functional features of endothelial cells and, additionally, they shared antigen-presenting ability. They induced the proliferation of allogeneic lymphocytes in a mixed-lymphocyte reaction, and could generate cytotoxic lymphocytes, with the ability to lyze tumor cells in an antigen-specific manner. The antigen-presenting ability of EO-EPCs, however, was weaker than that of monocyte-derived dendritic cells, but stronger than peripheral blood monocytes. Since EO-EPCs play an important role in the development of tumor angiogenesis, targeting EPCs would be an effective anti-angiogenic strategy. Alternatively, due to their antigen-presenting ability, EO-EPCs can be used as the effectors of anti-tumor immunotherapy. Since they share endothelial antigens, the activation of a cellular immunity against angiogenic vessels can be expected. In conclusion, EO-EPCs should be an interesting alternative for the development of new therapeutic strategies to combat cancer, either as the effectors or as the targets of cancer immunotherapy.
  • Y Kishi, S Okudaira, M Tanaka, K Hama, D Shida, J Kitayama, T Yamori, J Aoki, T Fujimaki, H Arai
    JOURNAL OF BIOLOGICAL CHEMISTRY 281 25 17492 - 17500 2006年06月 [査読有り][通常論文]
     
    Autotaxin (ATX) is a multifunctional phosphodiesterase originally isolated from melanoma cells as a potent cell motility-stimulating factor. ATX is identical to lysophospholipase D, which produces a bioactive phospholipid, lysophosphatidic acid (LPA), from lysophosphatidylcholine (LPC). Although enhanced expression of ATX in various tumor tissues has been repeatedly demonstrated, and thus, ATX is implicated in progression of tumor, the precise role of ATX expressed by tumor cells was unclear. In this study, we found that ATX is highly expressed in glioblastoma multiforme (GBM), the most malignant glioma due to its high infiltration into the normal brain parenchyma, but not in tissues from other brain tumors. In addition, LPA(1), an LPA receptor responsible for LPA-driven cell motility, is predominantly expressed in GBM. One of the glioblastomas that showed the highest ATX expression (SNB-78), as well as ATX-stable transfectants, showed LPA(1)-dependent cell migration in response to LPA in both Boyden chamber and wound healing assays. Interestingly these ATX-expressing cells also showed chemotactic response to LPC. In addition, knockdown of the ATX level using small interfering RNA technique in SNB-78 cells suppressed their migratory response to LPC. These results suggest that the autocrine production of LPA by cancer cell-derived ATX and exogenously supplied LPC contribute to the invasiveness of cancer cells and that LPA(1), ATX, and LPC-producing enzymes are potential targets for cancer therapy, including GBM.
  • Hiroharu Yamashita, Joji Kitayama, Nobuko Kanno, Yutaka Yatomi, Hirokazu Nagawa
    BMC CANCER 6 147  2006年06月 [査読有り][通常論文]
     
    Background: Abnormal hemostasis in cancer patients has previously been described, however the correlation between the plasma fibrinogen level and cancer metastasis and prognosis has not been reported in a large-scale clinical study. Methods: Preoperative plasma fibrinogen levels were retrospectively examined in 405 patients who underwent surgery for advanced gastric cancer. The association of fibrinogen levels with clinical/pathological findings and clinical outcome was evaluated. Results: There was a positive correlation between plasma fibrinogen levels and the depth of invasion ( p < 0.05). Hyperfibrinogenemia (> 310 mg/dl) was independently associated with lymph node ( Odds Ratio; 2.342, P = 0.0032) and liver ( Odds Ratio; 2.933, P = 0.0147) metastasis, not with peritoneal metastasis in this series. Patients with hyperfibrinogenemia showed worse clinical outcome in T2 gastric cancer, however, there was no correlation of plasma fibrinogen level with prognosis in T3/T4 gastric cancer. Conclusion: Our results might support the idea that hyperfibrinogenemia can augment lymphatic and hematogeneous metastasis of advanced gastric cancer, which is major determinant of the prognosis in T2 gastric cancer. Therefore, in the situation without peritoneal involvement, hyperfibrinogenemia is a useful biomarker to predict the possible metastasis and worse clinical outcome in T2 gastric cancer.
  • Masahiro Asakage, Nelson H. Tsuno, Joji Kitayama, Takeshi Tsuchiya, Satomi Yoneyama, Jun Yamada, Yurai Okaji, Shoichi Kaisaki, Takuya Osada, Koki Takahashi, Hirokazu Nagawa
    Angiogenesis 9 2 83 - 91 2006年06月 [査読有り][通常論文]
     
    Sulforaphane (SUL), one of the isothiocyanates (ITCs), has recently been focused due to its inhibitory effects on tumor cell growth in vitro and in vivo, which is dependent on the direct effect on cancer cells. In the present study, we aimed to investigate the potential anti-angiogenic effect of SUL and its mechanism of action. Using the human umbilical vein endothelial cells (HUVECs) as a model of angiogenesis, we investigated the effect of SUL on the various steps of angiogenesis, including the proliferation of endothelial cells, tubular formation, and matrix metalloproteinase (MMP) production. Sulforaphane induced a dose-dependent decrease in the proliferative activity of endothelial cells, which was dependent on cell apoptosis. Also SUL inhibited tube formation on matrigel, but did not affect MMP production. The present results demonstrate the anti-angiogenic activity of SUL and its potential use as an anti-cancer drug is suggested. © Springer Science+Business Media B.V. 2006.
  • T Konishi, S Sasaki, T Watanabe, J Kitayama, H Nagawa
    ONCOGENE 25 22 3160 - 3169 2006年05月 [査読有り][通常論文]
     
    Resistance to apoptosis is one of the important determinants of resistance to 5-fluorouracil (5-FU) in colorectal cancer cells. Human Ring-Finger homologous to Inhibitor of apoptosis protein type (hRFI) is a newly discovered gene that has been shown to inhibit death receptor-mediated apoptosis in colorectal cancer cells. However, the molecular mechanism of the inhibition of apoptosis is presently unknown. In order to investigate the molecular function of hRFI in the regulation of 5-FU-induced apoptosis in colorectal cancer cells, HCT116 cells were stably transfected with hRFI or LacZ as a control. hRFI overexpression resulted in cellular resistance to 5-FU through an inhibition of the mitochondrial apoptotic pathway and specific upregulation of Bcl-2 and Bcl-XL. Futhermore, hRFI overexpression resulted in the activation of nuclear factor-kappa B (NF-kappa B). Inhibition of NF-kappa B effectively reversed the resistance to apoptosis as well as the upregulation of Bcl-2 and Bcl-XL in the hRFI transfectant, indicating that the activation of NF-kappa B is the key mechanism for all these findings. Overexpression of hRFI in SW480 and COLO320 colorectal cancer cells similarly resulted in resistance to 5-FU with the activation of NF-kappa B and up regulation of Bcl-2 and Bcl-XL. hRFI might be a novel therapeutic target for gene therapy in colorectal cancer.
  • K Mori, J Kitayama, D Shida, H Yamashita, T Watanabe, H Nagawa
    JOURNAL OF SURGICAL RESEARCH 132 1 56 - 61 2006年05月 [査読有り][通常論文]
     
    Background. Lysophosphatidic acid (LPA) is a lipid mediator of diverse effects on various cells. LPA is well known to induce phosphorylation of the epidermal growth factor receptor (EGFR), which is termed transactivation, in some cell types. In this study, we investigated the contribution of EGFR transactivation in LPA-induced responses in colon cancer DLD1 cells. Materials and methods. Immunoprecipitation was performed to investigate whether LPA induced EGFR phosphorylation. Then, we investigated LPA-induced migration and IL-8 secretion in DLD1 cells. Migration was measured in a modified Boyden chamber and IL-8 secretion was measured by ELISA. In these experiments we used an EGFR inhibitor, AG1478 or matrix metalloproteinase (MMP) inhibitor, GM6001. Results. Immunoprecipitation analysis revealed that LPA induced a significant level of tyrosine phosphorylation of EGFR in DLD1 cells. The LPA-induced phosphorylation of EGFR was almost completely abrogated by either AG1478 or GM6001. LPA induced significant migration and IL-8 secretion in DLD1, both of which were significantly inhibited by AG1478 or GM6001. However, the inhibitory effects were only partial (migration; 29% +/- 2%, 32 +/- 13% inhibition, IL-8 secretion; 33% +/- 1%, 26% +/- 5% inhibition, respectively). Conclusion. These results clearly indicate that LPA acts upstream of EGFR and compensates the EGF signal and antagonism of the EGF signal cannot completely block tumor progression in colon cancer cells. Blockade of the LPA signal may have clinical significance in the treatment of colon cancer. (c) 2005 Elsevier Inc. All rights reserved.
  • Tsuyoshi Konishi, Toshiaki Watanabe, Keita Morikane, Kazuhiko Fukatsu, Joji Kitayama, Naoyuki Umetani, Junji Kishimoto, Hirokazu Nagawa
    INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY 27 5 526 - 528 2006年05月 [査読有り][通常論文]
     
    At a university hospital in Japan, the introduction of prospective surveillance and subsequent interventions was effective in reducing the rate of surgical site infection associated with elective colorectal surgery from 27.5% to 17.8% of surgeries. Japan should both recognize the importance of broader surveillance for surgical site infection and establish its own nationwide surveillance database.
  • Masafumi Tabuchi, Joji Kitayama, Yoh Kato
    GASTROINTESTINAL ENDOSCOPY 63 5 AB221 - AB221 2006年04月 [査読無し][通常論文]
  • H Yamashita, J Kitayama, H Ishigami, H Yamaguchi, D Souma, R Nagano, H Nagawa
    DIGESTIVE AND LIVER DISEASE 38 3 214 - 215 2006年03月 [査読無し][通常論文]
  • Y Okaji, NH Tsuno, J Kitayama, D Sakurai, N Tsuchiya, S Saito, K Takegami, T Tsuchiya, K Kawai, K Yazawa, M Asakage, S Yoneyama, J Yamada, K Tokunaga, K Takahashi, H Nagawa
    EUROPEAN JOURNAL OF CANCER 42 5 668 - 673 2006年03月 [査読有り][通常論文]
     
    Id genes (inhibitor of DNA binding/differentiation) play important roles in tumour growth. We have previously described crucial roles of Id gene over-expression in endothelial cells for tumour angiogenesis. Here, we have evaluated direct effects of Id gene down-regulation on tumour cells, namely on cell proliferation, motility, and adhesion to lung microvasculature during haematogenous metastasis. For this purpose, Id genes were stably down-regulated by RNA interference in human colorectal cancer cells. These cells showed delayed proliferation, inhibited motility and decreased expression of integrin alpha 6 and consequently reduced adhesion to lung microvasculature in mice. Static adhesion assays and laminar flow assays revealed decreased laminin binding capacity of these cells, and blocking experiments confirmed that it could be attributed to decreased expression of integrin alpha 6. The present results indicate important roles of Id genes in tumour cells during early steps of haematogenous metastasis and suggest dual effects from their therapeutic inhibition. (c) 2005 Elsevier Ltd. All rights reserved.
  • Hiroharu Yamashita, Masahiro Ishimaru, Hironori Yamaguchi, Haruo Yamauchi, Arishige Sugiura, Joji Kitayama, Hirokazu Nagawa
    Journal of Anesthesia 20 1 36 - 39 2006年02月 [査読有り][通常論文]
     
    Massive postoperative polyuria is rare, except in neurosurgery patients. Here we report excessive polyuria in a 59-year-old woman following total gastrectomy for advanced gastric cancer. The etiology of the patient's polyuria was unknown. Urine output was measured hourly and replaced with Ringer's lactate solution at 80% of measured volume. The rate of urine output during 9 postoperative days ranged from 900 to 2700 ml·h-1. Several administrations of an antidiuretic hormone (ADH) analogue were ineffective in reducing urine output, suggesting a possible relationship of the massive polyuria to nephrogenic diabetes insipidus. Following oral administration of a thiazide diuretic, known to exert an antidiuretic action in nephrogenic diabetes insipidus, urine output was dramatically reduced. We conclude that this case of massive polyuria probably resulted from postoperative nephrogenic diabetes insipidus. © JSA 2006.
  • Masafumi Tabuchi, Joji Kitayama, Hirokazu Nagawa
    WORLD JOURNAL OF GASTROENTEROLOGY 12 8 1261 - 1264 2006年02月 [査読有り][通常論文]
     
    AIM: To determine the real association between serum lipid levels and colonic polyp formation. METHODS: We performed a large scale retrospective study to analyze the correlation between the incidence of colorectal adenoma or carcinoma and the fasting serum levels of total cholesterol (TC) and triglycericles; (TG) in patients who underwent total colonoscopy for screening for colon cancer. RESULTS: Both levels were significantly elevated in patients with adenomas as compared with patients without any neoplastic lesion (TC 207.6 +/- 29.5 vs 199.5 +/- 34.3, n = 4883, p < 0.001; TG 135.0 +/- 82.2 vs 108.7 +/- 71.5, n = 4874, p < 0.001). The difference was significant in patients with tubular adenoma but not in those with villous or serrated adenoma. Multiple logistic regression analysis including age and sex revealed that TG was an independent correlation factor in male (p < 0.01), but not in female patients. The level of TG in patients with invasive carcinoma did not show a significant elevation from that in patients with adenoma. These findings suggest that hypertriglyceridemia is an independent risk factor for colonic adenoma in men. CONCLUSION: Although a high level of serum triglyceride does not appear to be mechanically involved in the development of carcinoma, reduction of serum TG and intensive surveillance with total colonoscopy may have benefit in men with hypertriglyceridemia. (c) 2006 The WJG Press. All rights reserved.
  • A Sako, J Kitayama, D Shida, R Suzuki, T Sakai, H Ohta, H Nagawa
    JOURNAL OF SURGICAL RESEARCH 130 1 94 - 101 2006年01月 [査読有り][通常論文]
     
    Background. Lysophosphatidic acid (LPA) is a lipid mediator with multiple biological activities that may affect the progression of various cancers. Malignant ascites contains high levels of LPA as well as vascular endothelial growth factor (VEGF). Although LPA receptors are widely expressed in normal as well as cancer cells, little is known about the effect of LPA on host cells. Therefore, we evaluated the effect of LPA specifically on peritoneal mesothelial cells (PMC), and assessed another aspect of LPA in tumor biology mediated through the host cells. Materials and methods. The effect of LPA on the production of VEGF was evaluated by ELISA and northern blotting. Next, we quantified human- and mouse-VEGF separately in ascitic fluid of nude mice inoculated intraperitoneally with a human gastric cancer, MKN45, and thus evaluated the ratio of host-derived VEGF in malignant ascites. Results. Addition of 10 to 80 mu m LPA enhanced VEGF production by PMC through gene activation. The effect was strongly inhibited by pre-treatment with PTX or Ki16425, indicating that the effect was mainly dependent on the LPA1 signal. Of the VEGF in ascitic fluid at 3 weeks after tumor inoculation, 12.8% was derived from mouse cells. At 6 weeks, however, the ratio of host-derived VEGF was reduced to 5.0%, suggesting that the ratio of host-derived VEGF may be higher in the earlier phase. Conclusion. Because tumor growth is often associated with an increase of LPA concentration in ascites, stimulation of VEGF production in PMC might have an important role in the growth of cancer cells disseminated in the peritoneal cavity. (c) 2006 Elsevier Inc. All rights reserved.
  • H Yamashita, J Kitayama, D Shida, H Yamaguchi, K Mori, M Osada, S Aoki, Y Yatomi, Y Takuwa, H Nagawa
    JOURNAL OF SURGICAL RESEARCH 130 1 80 - 87 2006年01月 [査読有り][通常論文]
     
    Introduction. Sphingosine 1-phosphate (S1P) is a bioactive lysophospholipid, derived from activated platelet, that is known to induce diverse cellular responses through at least five G-protein-coupled receptors on various cell types. Abnormal platelet and coagulation activation is often seen in patients with gastric cancer. However, neither the effects of this platelet-derived mediator S1P nor the distribution of S1P receptors on the gastric cancer cell are fully understood. The aim of this study was to examine the possible role of S1P and its receptors in the progression of gastric cancer. Materials and methods. We characterized the expression profiles of S1P receptors in nine human gastric cancer cell lines and evaluated the relationship between the responses to S1P and its receptor expression on cell migration by modified Boyden chamber and cell proliferation by MTS assay. Results. Northern blotting analysis has revealed that S1P2 was expressed in all gastric cancer cell lines to varying degrees, and S1P3 was expressed in four cell lines. S1P1 expression was weak, and no significant expression of either S1P4 or S1P5 was detected. The addition of S1P markedly stimulated the migration of MKN1 and HCG-27 that dominantly expressed S1P3, and the effect was potently inhibited by pertussis toxin or wortmannin. In contrast, S1P significantly inhibited the migration of AZ-521 that expressed S1P2 exclusively. This indicates that the balance between S1P2- and S1P3-mediated signals might be critical in determining the metastatic response of gastric cancer cells to S1P. S1P elicited weak but significant antiproliferative effects on all of the three cell lines, although the effects were not major. In these cells, S1P induced extracellular signal-regulated kinase (ERK) phosphorylation with transient Akt dephosphorylation that may cause the weak effects on proliferation. Conclusions. Our results suggest that the S1P receptor expression may critically determine the biological behavior of gastric cancers and thus therapeutic interventions directed at each S1P receptor might be clinically effective in preventing metastasis in gastric cancer. (c) 2006 Elsevier Inc. All rights reserved.
  • H Yamashita, J Kitayama, D Shida, M Ishikawa, K Hama, J Aoki, H Arai, H Nagawa
    JOURNAL OF SURGICAL ONCOLOGY 93 1 30 - 35 2006年01月 [査読有り][通常論文]
     
    Background and Objectives: Lysophosphatidic acid (LPA), a natural phospholipid, can modulate diverse cellular responses through LPA receptor, LPA(1-4). Although LPA, is known to be widely expressed in human tissues, the distribution of other LPA receptors is not characterized in malignant tissues. Recently, it was reported that malignant transformation resulted in aberrant expression of LPA(2) in a various type of cancer, suggesting the positive role of LPA2 in tumor development. Methods: We investigated the expression of the LPA2 receptor immunohistochemically in 204 gastric cancers and analyzed the relationship between the expression of LPA2 and clinicopathological features. Results: LPA(2) was preferentially expressed (67%) in intestinal-type cancer that was significantly higher than that in diffuse-type cancer (32%, P < 0.0001). The expression of LPA2 showed correlation with a higher rate of lymphatic and venous invasion, lymphatic metastasis, and resultingly tumor stage in diffuse-type cancer, but not in intestinal-type cancer. Conclusions: Our results highlight the possibility that LPA2 expression is an important process in the carcinogenesis of gastric cancer, especially in intestinal-type cancer. Since LPA can transactivate HGF receptor (c-Met) as well as EGF-receptor, LPA may promote the progression of gastric cancer in diffuse-type with high expression of c-Met. The development of LPA(2)-specific antagonists might have future therapeutic relevance in the treatment as well as prevention of gastric cancer.
  • Makoto Ishikawa, Joji Kitayama, Shoichi Kaisaki, Hiroyuki Okamoto, Tetsuro Miyata, Masaaki Akahane, Hirokazu Nagawa
    Gastroenterology 130 1 7  2006年 [査読有り][通常論文]
  • M Ishikawa, J Kitayama, S Kaizaki, H Nakayama, H Ishigami, S Fujii, H Suzuki, T Inoue, A Sako, M Asakage, H Yamashita, K Hatono, H Nagawa
    WORLD JOURNAL OF SURGERY 29 11 1415 - 1421 2005年11月 [査読有り][通常論文]
     
    To determine the clinical efficacy of Roux-en-Y reconstruction (RY) after distal gastrectomy, we compared postoperative outcomes of patients who underwent RY or conventional Billroth I reconstruction (B-I). A total of 50 patients were prospectively randomized to either B-I or RY reconstruction, and complications, postoperative course, and nutritional status were compared. Bile reflux and inflammation in the remnant stomach and lower esophagus were evaluated by postoperative follow-up endoscopy at 6 months. Operative time and blood loss as well as postoperative nutrition did not show significant differences between the two groups. As anticipated, 5 of 24 patients with RY reconstruction developed gastrojejunal stasis in the early postoperative period, which led to a longer postoperative hospital stay as compared with the B-I group (mean +/- S.D; B-I; 19.0 +/- 6.2, RY; 31.8 +/- 21.7 days) (P < 0.05). Endoscopic examination revealed that the frequency of bile reflux (P < 0.01) and degree of inflammation in the remnant stomach (P < 0.05) were less in the RY group than in the B-I group. However, inflammatory findings in the lower esophagus were observed in 7 (27%) of B-I, and 8 (35%) of the RY group, suggesting that late phase esophagitis was not improved in the RY group. Roux-en-Y reconstruction was effective in preventing duodenogastric reflux and resulting gastritis, but it did not prevent esophagitis. Because RY reconstruction induces the frequent complication of Roux-en-Y stasis, causing longer postoperative hospital stay, this method has limited advantages over B-I anastomosis after distal gastrectomy.
  • T Tsuchiya, Y Okaji, NH Tsuno, D Sakurai, N Tsuchiya, K Kawai, K Yazawa, M Asakage, J Yamada, S Yoneyama, J Kitayama, T Osada, T Watanabe, K Tokunaga, K Takahashi, H Nagawa
    CANCER SCIENCE 96 11 784 - 790 2005年11月 [査読有り][通常論文]
     
    Inhibitor of DNA binding (Id) proteins are essential for cell differentiation, proliferation, migration, invasion and angiogenesis. Recently, they have been shown to correlate with less differentiated phenotypes, high malignant potential and poor clinical outcome in various kinds of tumors. In an attempt to develop new strategies for the treatment of peritoneal metastasis of gastric cancer, we prepared an Id1, 3 double-knockdown gastric cancer cell line, MKN45, by RNA interference and investigated its effects on the development of metastatic nodules in the peritoneal cavity. Both cell proliferation and migration capabilities were decreased in Id1, 3 double-knockdown cells, as was their ability to bind to laminin, which could be explained by the decreased expression of integrin alpha 6. These are important steps in the metastatic process. In a mouse model, the number of peritoneal metastatic nodules formed by Id1, 3 double-knockdown cells was reduced compared to mock-transfected control cells, as was the size of individual tumors. In this study, we clearly demonstrated that Id1, 3 double-knockdown significantly impaired the ability of gastric cancer cells to form peritoneal metastasis. Id should be considered an ideal target for the treatment and prevention of gastric cancer, and RNA interference is an attractive and promising strategy to achieve it.
  • H Yamashita, J Kitayama, H Nagawa
    JAPANESE JOURNAL OF CLINICAL ONCOLOGY 35 10 595 - 600 2005年10月 [査読有り][通常論文]
     
    Background: Although abnormal hemostasis has been described in cancer patients, the precise association between the plasma fibrinogen level and lymphatic metastasis has not been reported in a large-scale clinical study. Methods: Preoperative plasma levels of fibrinogen as well as C-reactive protein (CRP) and carcinoembryonic antigen (CEA) were retrospectively examined in 649 patients who underwent surgery for gastric cancer, and the correlation between these factors and nodal status was evaluated. Results: Plasma fibrinogen level in patients with gastric cancer showed a positive association with nodal classification (P < 0.0001). Hyperfibrinogenemia (> 310 mg/dl) as well as high CEA (> 5 ng/ml) and CRP (> 0.3 mg/dl) showed a significant association with nodal metastasis in univariate analysis. Multivariate analysis revealed that hyperfibrinogenemia had an independent association with nodal metastasis (odds ratio, 2.004 (1.140-3.521); P = 0.0157), whereas CEA and CRP were not independent factors. Hyperfibrinogenemia showed an independent association even in advanced cancer [odds ratio 2.611 (1.404-4.854), P = 0.0024, n = 319]. When the 649 gastric cancers were classified into intestinal-type and gastric-type adenocarcinomas, plasma fibrinogen level was correlated with nodal metastasis only in the intestinal-type. Conclusions: Our results suggest that hyperfibrinogenemia may provide favorable circumstances for cancer cells to metastasize via the lymphatic system. Preoperative plasma fibrinogen level is a useful predictor of lymphatic metastasis in intestinal-type gastric cancer.
  • D Shida, J Kitayama, K Mori, T Watanabe, H Nagawa
    CANCER RESEARCH 65 20 9159 - 9163 2005年10月 [査読有り][通常論文]
     
    Leptin is known to act as a growth factor through the Janus-activated kinase (JAK)/signal transducer and activator of transcription signaling pathway as well as the mitogen-activated protein kinase pathway. In this study, we showed a novel signal transduction pathway using two human gastric cancer cell lines, MKN28 and MKN74. Both gastric cancer cells expressed leptin and its receptors (Ob-R) at the protein level. We found that leptin, even at as low as 0.1 ng/mL, induced significant tyrosine phosphorylation of epidermal growth factor receptor (EGFR). Time-course experiments revealed that phosphorylation was maximal after 5 minutes of stimulation and declined thereafter. We also revealed that tyrosine phosphorylation of EGFR induced by leptin was significantly attenuated by two inhibitors, an EGFR tyrosine kinase inhibitor, AG1478, and a broad-spectrum matrix metalloproteinase inhibitor, GM6001. This indicates that the pathway of EGFR transactivation induced by leptin is dependent on proteolytically released EGFR ligands. Leptin induced JAK2 activation and extracellular signal-regulated kinase (ERK) 1/2 activation in these gastric cancer cells, both of which occurred after the peak of EGFR transactivation. Pretreatment of gastric cancer cells with AG1478 significantly reduced the degree of phosphorylation of both JAK2 and ERK1/2. These findings indicate the involvement of EGFR transactivation in the activation of JAK2 and ERK1/2. Our results reveal that EGFR transactivation is involved in the leptin signaling pathway in gastric cancer cells, which extends the physiologic action of leptin beyond its central effects in the hypothalamus to regulate body weight.
  • Asakage M, Tsuno NH, Kitayama J, Yamada J, Tsuchiya T, Yoneyama S, Takahashi K, Nagawa H
    Gan to kagaku ryoho. Cancer & chemotherapy 32 11 1576 - 1577 2005年10月 [査読有り][通常論文]
  • S Sasaki, T Watanabe, T Kobunai, T Konishi, J Kitayama, H Nagawa
    JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH 24 3 397 - 403 2005年09月 [査読有り][通常論文]
     
    We previously reported that the over-expression of hRFI, a protein preferentially expressed in the digestive tract regions of several cancers, exhibited a tendency to inhibit TNF-alpha induced apoptosis. In this study, we sought to determine the potential effect of hRFI expression on the sensitivity to 5-fluorouracil (5-FU) and/or other fluoropyrimidines. For the whole lysates of 8 colon cancer cell lines, we performed Western blotting with anti-hRFI antibody and analyzed the correlations between the expression level of hRFI and the cell lines' sensitivity to 5-FU induced apoptosis. Furthermore, for a tissue microarray consisting of 32 xenograft derived human cancer cell lines, we examined the expression levels of hRFI and survivin by immunohistochemical staining, and analyzed the correlations between the expression of each protein and the sensitivity to several chemotherapeutic agents in the xenografts examined. Both in colon cancer cell lines and in xenografts, the expression level of hRFI was correlated with resistance to 5-FU and its derivatives. This evidence suggests that hRFI may be a marker predicting the response to fluorouracil derived chemotherapeutic agents and that the reduction of the expression level of hRFI might improve the outcome of chemotherapy.
  • M Ishikawa, J Kitayama, S Kaizaki, A Sako, K Nakao, M Sugawara, H Nagawa
    ACTA OTO-LARYNGOLOGICA 125 9 1014 - 1017 2005年09月 [査読有り][通常論文]
     
    We report the case of a patient with nasopharyngeal carcinoma who was diagnosed as having metastasis in mediastinal lymph nodes and successfully underwent systemic chemotherapy without surgery. A 61- year- old male with a history of nasopharyngeal carcinoma presented with odynophagia. Examination revealed two palpable lymph nodes in the right neck. Pharyngoscopy showed a mass in the left inferior pharyngeal mucosa, and upper gastrointestinal endoscopy showed only chronic gastritis, with no sign of esophageal disease. Chest CT confirmed the presence of a non- enhancing 20- mm soft tissue mass in the paraesophageal area, with increased attenuation compared with the adjacent esophagus. To evaluate this lesion we applied endoscopic ultrasonography- guided fine- needle aspiration biopsy ( EUS- FNA). Two passes were made with a 21- gauge fine needle and the patient tolerated the procedure well, without complications. Cytological findings were compatible with metastatic squamous cell carcinoma from a nasopharyngeal tumor, and the clinical stage was determined as T3N2bM1 ( stage IVC) because of mediastinal lymph node metastasis. We thus determined the nodal status of a head and neck tumor by means of EUS- FNA. In conclusion, EUS- FNA is a safe and reliable technique for evaluation of mediastinal lymphadenopathy, and is especially valuable for head and neck tumors with suspected metastasis.
  • Dai Shida, Joji Kitayama, Hironori Yamaguchi, Hiroharu Yamashita, Ken Mori, Toshiaki Watanabe, Hirokazu Nagawa
    WORLD JOURNAL OF GASTROENTEROLOGY 11 36 5638 - 5643 2005年09月 [査読有り][通常論文]
     
    AIM: To examine whether lysophosphatidic acid (LPA) induces phosphorylation of c-Met and epidermal growth factor receptor (EGFR), both of which have been proposed as prognostic markers of colorectal cancer, and whether LPA induces cyclooxygenase-2 (COX-2) expression in human colon cancer cells. METHODS: Using a human colon cancer cell line, LoVo cells, we performed immunoprecipitation analysis, followed by Western blot analysis. We also examined whether LPA induced COX-2 expression, by Western blot analysis. RESULTS: Immunoprecipitation analysis revealed that 10 mu mol/L LPA induced tyrosine phosphorylation of c-Met and EGFR in LoVo cells within a few minutes. We found that c-Met tyrosine phosphorylation induced by LPA was not attenuated by pertussis toxin or a matrix metalloproteinase inhibitor, in marked contrast to the results for EGFR. In addition, 0.2-40 mu mol/L LPA induced COX-2 expression in a dose-dependent manner. CONCLUSION: Our results suggest that LPA acts upstream of various receptor tyrosine kinases (RTKs) and COX-2, and thus may act as a potent stimulator of colorectal cancer. (C) 2005 The WJG Press and Elsevier Inc. All rights reserved.
  • K Kawai, NH Tsuno, M Matsuhashi, J Kitayama, T Osada, J Yamada, T Tsuchiya, S Yoneyama, T Watanabe, K Takahashi, H Nagawa
    JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 116 1 192 - 197 2005年07月 [査読有り][通常論文]
     
    Background: CD11b belongs to the integrin family and is expressed on neutrophils, monocytes, natural killer cells, and a subset of lymphocytes. Although CD11b expressed on neutrophils and monocytes has been extensively investigated and has been reported to play an important role in the migration of these subsets of leukocytes, the function of CD11b expressed on a subset of B cells has not yet been clarified. Objective: To elucidate the functional activity of CD11b expressed on B cells, we characterized the CD11b-expressing cells among the B-cell population and investigated their migratory ability. Methods: Isolated peripheral blood CD19(+) B cells were analyzed by flow cytometry. The migratory ability of B cells was evaluated by the transwell assay, and the contribution of CD11b to this ability was investigated by using an anti-CD11b blocking mAb. Results: The majority of CD27(-)IgD(+) naive B cells were CD11b(-), whereas most CD27(+) memory cells were CD11b(+). Among the CD27(+) memory cells, expression of CD11b was stronger on the IgD(-) cells than on the IgD(+) cells. In the transwell assay, the migrating cells were predominantly CD27(+)IgD(-) cells, most of which expressed CD11b. The addition of an anti-CD11b blocking mAb resulted in the significant reduction of the number of migrating B cells. Conclusion: Memory B cells express CD11b and, in contrast with naive B cells, have high migratory ability. CD11b plays an essential role in the homing process of memory cells.
  • T Konishi, S Sasaki, T Watanabe, J Kitayama, H Nagawa
    ANTICANCER RESEARCH 25 4 2737 - 2741 2005年07月 [査読有り][通常論文]
     
    Background: hRFI is a newly discovered gene encoding a Ring Finger domain highly homologous to that of the X-chromosome-linked inhibitor of apoptosis protein, which is among the most potent inhibitors of apoptosis. The hRFI protein is preferentially expressed in colorectal cancers, although its actual function is unknown. The aim of this study was to determine whether hRFI possesses an anti-apoptotic function in colorectal cancer cells against chemotherapeutic agents. Materials and Methods: HCT116 colorectal cancer cells were exogenously transfected with hRFI or LacZ as a control. After exposure to either cisplatin, irinotecan or 5-fluorouracil, apoptosis and caspase-3 activity were evaluated by flow cytometry analysis. Results: The hRFI transfectant exhibited significant resistance to apoptosis induced by each of the three agents, along with inactivation of caspase-3. Growth in the normal medium was not altered. Conclusion: hRFI plays an important role in the resistance to chemotherapeutic agent-induced apoptosis in colorectal cancer cells.
  • T Konishi, S Sasaki, T Watanabe, J Kitayama, H Nagawa
    MOLECULAR CANCER THERAPEUTICS 4 5 743 - 750 2005年05月 [査読有り][通常論文]
     
    The acquisition of antiapoptotic properties is one of the essential mechanistic steps in colorectal carcinogenesis and is closely correlated with a loss of chemosensitivity and radiosensitivity. Human ring finger homologous to inhibitor of apoptosis protein type (hRFI) is a newly discovered gene encoding a ring finger domain highly homologous to that of X chromosome-linked inhibitor of apoptosis protein. Immunohistochemistry has revealed that the expression of hRFI increased in transition from normal colorectal mucosas to adenomas and from adenomas to carcinomas, suggesting an essential role in the early stage of colorectal carcinogenesis. However, the function role of hRFI in colorectal carcinoma has not been elucidated. To determine whether hRFI possesses an antiapoptotic function in colorectal cancer cells, HCT116 colorectal cancer cells stably overexpressing hRFI were established. The hRFI transfectant exhibited significant resistance to apoptosis induced by tumor necrosis factor-ex or tumor necrosis factor-related apoptosis-inducing ligand compared with control. This antiapoptotic response was associated with decreased activity of caspase-3, -8, and -9. We also established an antisense down-regulation of hRFI, which effectively reversed the antiapoptotic activity of the hRFI transfectant. This confirmed that the antiapoptotic property of the hRFI transfectant was not due to the clonal effect but in fact dependent on hRFI function. In conclusion, hRFI possesses an antiapoptotic function in HCT116 colorectal cancer cells. Considering the progressive increase of hRFI expression in the advance of the colorectal adenoma-carcinoma sequence, hRFI is one of the important players in colorectal carcinogenesis through its effect on apoptosis regulation.
  • M Asakage, J Kitayama, NH Tsuno, Y Komuro, S Kaisaki, N Hori, H Nagawa, NH Tsuno, N Hori, K Takahashi
    JOURNAL OF GASTROENTEROLOGY 40 5 545 - 546 2005年05月 [査読有り][通常論文]
  • K Kawai, NH Tsuno, J Kitayama, Y Okaji, K Yazawa, M Asakage, H Yamashita, T Watanabe, K Takahashi, H Nagawa
    ANTI-CANCER DRUGS 16 4 401 - 407 2005年04月 [査読有り][通常論文]
     
    We have investigated a potential anti-angiogenic effect of plaunotol, an extract from the leaves of Plau-noi, in an angiogenesis model consisting of human umbilical vein endothelial cells (HUVECs). Plaunotol inhibited the proliferative activity of HUVECs in a dose-dependent manner. In addition, it caused a remarkable decrease of the ability of HUVECs to adhere and spread on gelatin and vitronectin, but not fibronectin. Tube-like formation in Matrigel was also inhibited in a dose-dependent way. These results strongly suggest the specific inhibition of integrin alpha(v)beta(3) to be the main event of plaunotol-induced suppression of angiogenesis. The alpha(v)beta(3) antagonists are known to be potent inhibitors of tumor angiogenesis and plaunotol, by causing the functional inhibition of alpha(v)beta(3), should be considered a promising new anti-angiogenic drug. (c) 2005 Lippincott Williams W Wilkins.
  • M Ishikawa, J Kitayama, S Fujii, H Ishigami, S Kaizaki, H Nagawa
    AMERICAN SURGEON 71 4 366 - 368 2005年04月 [査読有り][通常論文]
     
    The occurrence of early gastric carcinoma with invasion to the duodenum is supposed to be very low, although advanced cancers arising in the antrum can often invade the duodenal area. Generally, malignant invasion of the duodenum is difficult to diagnose preoperatively, as spread of gastric cancer to the duodenum is often infiltrative and invades through the submucosal or subserosal layer. We report an unusual case of an intramucosal gastric carcinoma with extensive duodenal invasion that was preoperatively diagnosed by endoscopy.
  • A Sako, J Kitayama, T Inoue, S Kaizaki, H Nagawa, H Suzuki
    GUT 54 2 192 - + 2005年02月 [査読無し][通常論文]
  • K Yazawa, NH Tsuno, J Kitayama, K Kawai, Y Okaji, M Asakage, E Sunami, S Kaisaki, N Hori, T Watanabe, K Takahashi, H Nagawa
    INTERNATIONAL JOURNAL OF CANCER 113 4 541 - 548 2005年02月 [査読有り][通常論文]
     
    High-level expression of cyclooxygenase (COX)-2 is reported in 80-90% of colorectal adenocarcinomas. Selective inhibition of COX-2 was shown to reduce colorectal tumorigenesis in different models of carcinogenesis and to prevent metastasis in xenograft tumor models, as well as to suppress in vitro induced angiogenesis. Recently, COX-2 was reported to be expressed not only in malignant epithelial cells, but also in the neovasculature that feeds the tumor in a variety of solid human cancers. Thus, one of the possible mechanisms by which selective COX-2 inhibitor reduces tumor growth and metastasis is through inhibition of tumor angiogenesis. Although a report suggested a possible role of endothelial COX-I in the process of angiogenesis, in a recent study, the selective inhibition of COX-2 was shown to strongly inhibit angiogenesis by inducing endothelial cell (EC) apoptosis. In the present study, using human umbilical vein endothelial cells (HUVECs) as a model of angiogenesis, we investigated the potential antiangiogenic effect of the selective COX-2 inhibitor and its mechanism of action, and clearly demonstrated that selective inhibition of COX-2 caused a dose-dependent decrease in the proliferative activity of ECs, as well as an inhibition of capillary-like tube formation. The inhibitory effect on EC proliferation was dependent on the cell cycle arrest to the G1 phase and not on cell apoptosis. (C) 2004 Wiley-Liss, Inc.
  • D Shida, J Kitayama, H Yamaguchi, H Yamashita, K Mori, T Watanabe, H Nagawa
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 327 3 907 - 914 2005年02月 [査読有り][通常論文]
     
    The ligand-less receptor HER2/neu (erbB-2) has been proposed as a prognostic marker of gastric cancer that correlates with poor clinical outcome, indicating that HER2 signals play an important role in gastric cancer progression. This study demonstrated that two Major natural lysophospholipids, lysophosphatidic acid (LPA) and sphingosine I-phosphate (SIP), induce rapid and transient phosphorylation of HER2 in two human gastric cancer cell lines, MKN28 and MKN74 cells. We also revealed that tyrosine phosphorylation of HER2 induced by both lysophospholipids was significantly attenuated by two inhibitors, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, AG1478, and a broad-spectrum matrix metalloproteinase inhibitor, GM6001. This suggests that the pathway of HER2 transactivation induced by these lysophospholipids is dependent on the proteolytically released EGFR ligands. Our results indicate that LPA and SIP act upstream of HER2 in gastric cancer cells, and thus may act as potent stimulators of gastric cancer. (C) 2004 Elsevier Inc. All rights reserved.
  • K Yazawa, NH Tsuno, J Kitayama, K Kawai, Y Okaji, M Asakage, E Sunami, S Kaisaki, N Hori, T Watanabe, K Takahashi, H Nagawa
    CANCER SCIENCE 96 2 93 - 99 2005年02月 [査読有り][通常論文]
     
    High level expression of cyclooxygenase (COX)-2 is reported in 80-90% of colorectal adenocarcinomas. In the recent years, selective inhibitors of COX-2 have been developed, and are shown to effectively protect against cancer development and progression. Colon cancer cells, as well as the epithelial cells in general, are dependent on appropriate interactions with the extracellular matrix (ECM) proteins to achieve a number of important functions, such as proliferation, differentiation, invasion and survival. These interactions are mediated via a family of cell-surface receptors called integrins, which interact with cytoskeletal proteins on the cytoplasmic side of the plasma membrane and thereby provide a link between the ECM and the cytoskeleton. In the present study, a high-COX-2 (high level COX-2 expression) colon cancer cell line, HT-29, and a low-COX-2 (low level COX-2 expression), DLD-1, were used to investigate the anticolon cancer effect of the selective COX-2 inhibitor, JTE-522. Moreover, to clarify its mechanisms of action, we focused especially on the ability to adhere to and to migrate on ECM. We could clearly demonstrate that, in addition to the decrease of the proliferative activity, JTE-522 caused a dose-dependent decrease in both the ability of colon cancer cells to adhere to and to migrate on ECM. These effects were, at least in part, dependent on the down-regulation of beta 1-integrin expression, which was evident in HT-29, the high-COX-2 colon cancer cells, but not the low-COX-2, DLD-1. In addition, prostaglandin E2 almost completely reversed the effect of JTE-522, strongly suggesting the involvement of a COX-2-dependent pathway. In conclusion, for the first time, we could demonstrate the down-regulation of beta 1 integrin caused by COX-2 inhibition, with consequent impairment of the ability of cancer cells to adhere to and to migrate on ECM, which are crucial steps for cancer metastases to develop.
  • Makoto Ishikawa, Joji Kitayama, Shinsuke Kazama, Hirokazu Nagawa
    World Journal of Surgical Oncology 3 1 2  2005年01月 [査読有り][通常論文]
     
    Background: Vascular endothelial growth factor (VEGF)-C is implicated in lymphangiogenesis, however the exact role of VEGF-C in promoting lymphatic spread of cancer cells remains largely unknown. Methods: The expression of VEGF-C was immunohistochemically determined in 97 endoscopic biopsy specimens from 46 patients with submucosal gastric carcinoma (SGC). Nodal metastases including micrometastasis and isolated tumor cells (ITC) were evaluated by immunohistochemical staining for cytokeratin in 1650 lymph nodes, and tumor cells in these metastatic nodes were also examined for VEGF-C expression. Results: In biopsy samples, VEGF-C was positively detected in 21 (47%) patients. Metastases were identified in 46 (2.8%) nodes from 15 (33%) patients. Metastases were detected in 39 nodes by hematoxylin-eosin (H& E) staining and in additional 7 nodes as ITC by immunohistochemical staining. The rate of lymph node metastases was significantly correlated with VEGF-C expression in biopsy samples (p < 0.05). The positive and negative predictive values of VEGF-C in biopsy specimens for nodal metastasis were 44 %(10/21) and 80% (20/25), respectively. Among the 46 metastatic nodes, tumor cells in 29 (63%) nodes positive patients expressed VEGF-C, whereas those in 17 (37%) nodes did not. VEGF-C expression was high in macronodular foci in medullary areas, whereas more than half of ITC or micrometastasis located in peripheral sinus lacked the expression of VEGF-C. Conclusions: Despite the significant correlation, immunodetcetion of VEGF-C in endoscopic biopsy specimens could not accurately predict the nodal status, and thus cannot be applied for the decision of the treatment for SGC. VEGF-C may not be essential for lymphatic transport, but rather important to develop the macronodular lesion in metastatic nodes. © 2005 Ishikawa et al licensee BioMed Central Ltd.
  • T Konishi, T Watanabe, J Kitayama, J Shibahara, H Nagawa
    GASTROINTESTINAL ENDOSCOPY 61 1 161 - 164 2005年01月 [査読有り][通常論文]
  • J Kitayama, D Shida, A Sako, M Ishikawa, H Yamashita, H Nagawa
    Proceedings of the 6th International Gastric Cancer Congress 277 - 281 2005年 [査読有り][通常論文]
     
    Lysophosphatidic acid (LPA), which interacts with at least three G protein-coupled receptors, LPA1/Edg-2, LPA2/Edg-4, and LPA3/Edg-7, is a lipid mediator with diverse effects on various cells. Nothernblot analysis showed that MKN1, NUGC-3, AZ521, HGC-27, and GCIY, preferentially expressed LPA1, whereas MKN28, MKN45, MKN74 and KATO III expressed LPA2 exclusively. Using a Boyden chamber assay, LPA markedly increased cell migration of LPA1 expressing cells, but not of LPA2 expressing cells. However, when hepatocyte growth factor (HGF) was placed with LPA in the lower chamber, LPA strongly augmented migration of LPA2 expressing cells. Immunoprecipitation revealed LPA induce transient tyrosine phosphorylation of the c-met in MKN28, suggesting the transactivation of c-met by LPA. Our results indicate that LPA regulates migration and metastatic potential of gastric cancer in receptor specific manner.
  • K Kawai, NH Tsuno, J Kitayama, Y Okaji, K Yazawa, M Asakage, S Sasaki, T Watanabe, K Takahashi, H Nagawa
    JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 115 1 186 - 191 2005年01月 [査読有り][通常論文]
     
    Background: Monocytes are the main effector cells of the immune system, and the regulation of their survival and apoptosis is essential for monocyte-involved immune responses. Green tea polyphenol catechin has been reported to have antiallergic and antiinflammatory activities, but its effect on monocytes has not yet been explored. Objective: To elucidate the mechanisms of the anti-inflammatory effect of catechin, we studied the effect of catechin, especially epigallocatechin gallate (EGCG), on the apoptosis of monocytes. Methods: Isolated peripheral blood monocytes were incubated without or with catechin, and apoptosis was evaluated by annexin V and propidium iodide double-staining or terminal deoxynucleotidyl assay. The activation of caspases 3, 8, and 9 was also evaluated by flow cytometry. The influence of GMCSF or LPS, the known monocyte survival factors, on the EGCG-induced apoptosis of monocytes was investigated. Results: Among the 4 catechin derivatives tested, EGCG and epicatechin gallate induced apoptosis of monocytes. Caspases 3, 8, and 9, which play a central role in the apoptotic cascade, were dose-dependently activated by EGCG treatment. The EGCG-induced apoptosis of monocytes was not affected by GM-CSF or LPS. Conclusion: Catechin, especially EGCG, by promoting monocytic apoptosis, may be a new promising antiinflammatory agent, and should be tested in clinical trials.
  • T Konishi, T Watanabe, J Kitayama, J Shibahara, H Nagawa
    GASTROINTESTINAL ENDOSCOPY 61 1 161 - 164 2005年01月 [査読有り][通常論文]
  • M Ishikawa, J Kitayama, S Kazama, T Hiramatsu, K Hatano, H Nagawa
    CLINICAL CANCER RESEARCH 11 2 466 - 472 2005年01月 [査読有り][通常論文]
     
    Background. Recently, increased body weight has been associated with an increased risk of cancers at multiple specific sites, including gastric cancer. Adiponectin is a peptide hormone secreted by adipose tissue, affecting the proliferation and insulin sensitivity of various types of cells. Moreover, the circulating level of adiponectin has been reported to be inversely related to body mass index. Methods: Fasting plasma levels of adiponectin were determined in 75 patients with gastric cancer and 52 healthy controls using an ELISA. In these patients, we analyzed the association between plasma adiponectin level and gastric cancer risk as well as various clinicopathologic characteristics. Results: Plasma adiponectin level was significantly lower in patients with gastric cancer than in healthy controls (9.1 +/- 6.2 versus 13.3 +/- 9.4 ng/mL, P < 0.01) and showed a significant modest inverse relation with the gastric cancer (odds ratio, 0.92; 95% confidence interval, 0.85-0.97; adjusted odds ratio, 0.89; 95% confidence interval, 0.84-0.95], although body mass index was not different. In addition, adiponectin level was extremely low in patients with upper gastric cancers (upper, 5.5 +/- 4.1 ng/mL; middle, 9.7 +/- 6.4 ng/mL; lower, 10.7 +/- 4.1 ng/mL; P = 0.012). Furthermore, adiponectin level tended to decrease as the tumor stage increased (stage I, 9.9 +/- 6.9 ng/mL; stage II, 8.7 +/- 5.5 ng/mL; stage III, 8.6 +/- 4.1 ng/mL; stage IV, 5.2 +/- 6.2 ng/mL; P = 0.34). Interestingly, in 32 patients with undifferentiated cancer, serum adiponectin showed a negative correlation with pathologic findings such as tumor size, depth of invasion, as well as tumor stage (P < 0.05), but no correlation in the remaining 43 patients with differentiated cancer. Conclusions: Our results suggest that a low plasma adiponectin level is associated with an increased risk for gastric cancer and raise the possibility that adiponectin has a potential role in the progression of gastric cancer, especially in undifferentiated type cancers in the upper stomach.
  • M Ishikawa, J Kitayama, K Kohno, H Nagawa
    PATHOBIOLOGY 72 3 139 - 145 2005年 [査読有り][通常論文]
     
    Objective: UDP-N-acetyl-alpha-D- galactosamine-polypeptide N-acetylgalactosaminyl transferase-3 (GalNAc-T3) regulates the initial glycosylation of mucin-type O-linked proteins. Although a different expression of GalNAc-T3 has been reported in various cancers, the expression has not been characterized in squamous cell carcinoma (SCC) of the esophagus. Methods: We have also evaluated the expression of this enzyme in surgically resected esophageal mucosa. By immunohistochemical staining using a specific antibody, we evaluated the expression of GalNAc-T3 in 66 esophageal SCC and 28 dysplasia samples, and analyzed the relationship between the expression of GalNAc-T3 and clinicopathological features. Results: GalNAc-T3 was positively detected in the majority of the cases of SCC, but not in dysplasia as well as the normal counterparts in resected esophagus. GalNAc-T3 was determined to be positive in 37 cases (68.5%) of differentiated carcinomas, but only in 4 cases (33.3%) of undifferentiated carcinomas ( p < 0.05). Hematogeneous metastasis was observed in 13 of 41 (31.7%) GalNAc-T3-positive tumors, which was significantly more frequent than in negative tumors (2/25, 8%; p < 0.05). The number of metastatic nodes was significantly higher in tumors with GalNAc-T3-positive than GalNAc-negative expression (4.2 +/- 3.2 vs. 2.8 +/- 1.3, p < 0.05). The survival rate tended to be lower for patients with GalNAc-T3-positive tumors, although the difference was not statistically significant ( p = 0.18). Conclusion: GalNAc-T3 may play a positive role in the process of carcinogenesis and progression in esophageal SCC. Functional inhibition of GalNAc- T3 may be effective for the prevention and treatment of esophageal SCC. Copyright (C) 2005 S. Karger AG, Basel.
  • D Shida, J Kitayama, H Yamaguchi, K Hama, J Aoki, H Arai, H Yamashita, K Mori, A Sako, T Konishi, T Watanabe, T Sakai, R Suzuki, H Ohta, Y Takuwa, H Nagawa
    EXPERIMENTAL CELL RESEARCH 301 2 168 - 178 2004年12月 [査読有り][通常論文]
     
    Lysophosphatidic acid (LPA), which interacts with at least three G protein-coupled receptors (GPCRs), LPA I /Edg-2, LPA2/Edg-4, and LPA3/Edg-7, is a lipid mediator with diverse effects on various cells. Here, we investigated the expression profiles of LPA receptors and patterns of LPA-induced migration in gastric cancer cells. Northern blot analysis revealed that various gastric cancer cells expressed variable levels of LPA1, LPA2, and LPA3 without a consistent pattern. Using a Boyden chamber assay, LPA markedly increased cell migration of LPA1-expressing cells, the effects of which were almost totally abrogated by Kil6425, anLPA antagonist against LPA1 and LPA3. In contrast, LPA by itself did not significantly induce migration in MKN28 and MKN74 cells, which exclusively expressed LPA2. However, when hepatocyte growth factor (HGF) was placed with LPA in the lower chamber, LPA induced migration of these cells in a dose-dependent manner. Inummoprecipitation analysis revealed that LPA induced transient tyrosine phosphorylation of c-Met in LPA2-expressing cells, which suggests that the transactivation of c-Met by LPA causes a cooperative migratory response with HGF to these cells. Our results indicate that LPA regulates the migration of gastric cancer cells in a receptor-specific manner and suggest that the expression pattern of LPA receptors may affect the metastatic behavior of gastric cancer. (C) 2004 Elsevier Inc. All rights reserved.
  • Y Okaji, NH Tsuno, J Kitayama, S Saito, T Takahashi, K Kawai, K Yazawa, M Asakage, T Tsuchiya, D Sakurai, N Tsuchiya, K Tokunaga, K Takahashi, H Nagawa
    JOURNAL OF IMMUNOLOGICAL METHODS 295 1-2 183 - 193 2004年12月 [査読有り][通常論文]
     
    Analysis of specific properties of tumor endothelium should be useful for development of novel antiangiogenic strategies. However, the isolation of pure endothelial cells from tumor tissues is still a fundamental problem. In this study, we have attempted to develop a reliable method for the isolation of endothelial cells from murine tumors. We found that the labeling with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate-acetylated-low density lipoprotein (Dil-Ac-LDL), commonly used for this purpose, can result in the contamination of isolated endothelium by macrophages due to the overlapping staining patterns of these two distinct cell types. Therefore, we chose the CD16, which is expressed on macrophages but not endothelial cells, to better distinguish them when labeled with Dil-Ac-LDL. By using this method, we obtained pure populations of endothelial cells and macrophages from murine colorectal cancer tissues, showing characteristic morphological and functional properties of the either cell type. The endothelial cells were long spindle-shaped, spread on gelatin, formed tube-like structures on Matrigel and expressed MECA-32 but not CD68. In contrast, the macrophages were round-shaped, partially spread on gelatin, formed unorganized aggregates on Matrigel and expressed CD68 but not MECA-32. The additional analysis of normal and tumor tissues revealed a positive correlation between the relative numbers of tumor endothelial cells and macrophages, calculated as % total cells, as well as the respective relative number and tumor weight. The present method is hoped to be useful for the evaluation of tumor angiogenesis and antitumor immunity. (C) 2004 Elsevier B.V. All rights reserved.
  • D Shida, J Kitayama, H Yamaguchi, H Yamashita, K Mori, T Watanabe, Y Yatomi, H Nagawa
    FEBS LETTERS 577 3 333 - 338 2004年11月 [査読有り][通常論文]
     
    Receptor tyrosine kinases (RTKs) are transactivated by the stimulation of G protein-coupled receptors (GPCRs). Sphingosine I-phosphate (SIP), a ligand of GPCR, is known as a tumor-promoting lipid, but its signaling pathways are not fully understood. We here demonstrated that SIP induces rapid and transient tyrosine phosphorylation of epidermal growth factor receptor (EGFR) and c-Met in gastric cancer cells, both of which have been proposed as prognostic markers of gastric cancers. The pathway of SIP-induced c-Met transactivation is Gi-independent and matrix metalloproteinase-independent, which differs from that of EGFR transactivation. Our results indicate that SIP acts upstream of various RTKs and thus may act as a potent stimulator of gastric cancer. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
  • D Shida, T Watanabe, J Aoki, K Hama, J Kitayama, H Sonoda, Y Kishi, H Yamaguchi, S Sasaki, A Sako, T Konishi, H Arai, H Nagawa
    LABORATORY INVESTIGATION 84 10 1352 - 1362 2004年10月 [査読有り][通常論文]
     
    Lysophosphatidic acid (LPA) is a simple bioactive phospholipid with diverse effects on various cells, that interacts with three G protein-coupled transmembrane receptors, LPA1, LPA2, and LPA3. The expression pattern and functions of these LPA receptors in various tumors have not been fully examined, except in ovarian cancer. To evaluate the LPA receptor expression profile in human colorectal cancer and in normal mucosa, we used real-time reverse transcription-polymerase chain reaction (RT-PCR) and measured the expression levels of LPA1, LPA2, and LPA3 messenger RNA (mRNA) in 26 colorectal cancers and 16 corresponding normal tissue samples. Normal epithelium expressed both LPA1 and LPA2 mRNA at similar levels. In comparison, colorectal cancers expressed LPA1 mRNA at a significantly lower level (0.3-fold; P<0.05), and LPA2 mRNA at a significantly higher level (three-fold; P<0.05), as compared with normal tissues. Thus, the ratio of LPA2/LPA1 increased markedly during malignant transformation (18-fold increase). LPA3 mRNA was expressed at only a low level in both normal and cancer tissues. We also assessed LPA2 expression immunohistochemically using a rat anti-LPA2 monoclonal antibody, and confirmed high expression of LPA2 in colorectal cancer at the protein level. As for LPA1, we examined Western blot analysis for 16 matched normal and cancer tissues. It revealed a significant decrease in the expression of LPA1 protein in cancer tissues compared to normal mucosa in nine of 16 cases, and in the remaining seven cases the expression levels was much the same. These results suggested that alteration of LPA receptor expression might be an important event in the development of colorectal cancer, and therefore, LPA and its receptors could be a chemopreventive target against colorectal cancer.
  • S Sasaki, J Kitayama, T Watanabe, T Konishi, H Nagawa
    JAPANESE JOURNAL OF CLINICAL ONCOLOGY 34 10 584 - 587 2004年10月 [査読有り][通常論文]
     
    Background: hRFI, which has a relatively high homology to XIAP, is preferentially expressed in esophageal and colorectal carcinomas, and is involved in the initial tumor formation in the colorectal adenoma-carcinoma sequence. Furthermore, its diffuse expression is associated with colorectal carcinogenesis. However, hRFI expression in gastric carcinomas has not been evaluated so far. Methods: We performed immunohistochemical staining on 76 gastric carcinoma samples using the antibody to hRFI and also analyzed the correlation between the staining pattern of hRFI and the clinico-pathological characteristics. Results: All of the samples were stained focally (31 cases, 40.8%) or diffusely (45 cases, 59.2%) in the cancerous region. On the contrary, most of the normal gastric region showed no staining, except for a few cases that showed slight immunoreactivity in speckles. Furthermore, the proportion of blood vessel involvement was significantly higher in carcinomas with diffuse hRFI expression (28/45, 62.2%) than in carcinomas with focal expression (7/31, 22.6%) (P < 0.001). Liver metastasis was consistently observed in five cases (11.1%) in diffuse, but only one (3.3%) in focal type during the average follow up period of 5 years. However, the 3-year survival rate did not show significant difference between these different staining patterns of hRFI. Conclusions: These results suggest that the detection of the expression pattern of hRFI in gastric carcinomas can be another useful predictor of liver recurrence, especially when combined with other factors.
  • S Sasaki, T Watanabe, T Konishi, J Kitayama, H Nagawa
    JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH 23 3 507 - 512 2004年09月 [査読有り][通常論文]
     
    For colorectal carcinomas as well as colonic polyps we investigated the expression of a newly discovered gene, hRFI, which is isolated by the yeast two-hybrid screening using hTid as a bait and expressed highly in esophageal carcinomas. Immunohistochemical staining was performed on 48 colorectal carcinomas and 77 colorectal polyps consisting of 70 adenomas and 7 hyperplastic polyps using the antibody of hRFI. We analyzed the expression of hRFI and the correlation between the percentage of staining of each and their clinico-pathological characteristics. Protein coding by hRFI was specifically and diffusely expressed in most of the cancerous regions of the colorectum. Also, in the early stage of colorectal adenomas, staining of hRFI was focal, and the percentage area of diffuse staining increased as the degree of dysplasia progressed. Although all normal colorectal glands and most hyperplastic polyps (71.4%) showed no staining of hRFI, most colorectal adenomas and carcinomas (93.2%) showed a focal or diffuse staining (P<0.001). Furthermore, the percentage of diffuse staining in carcinomas (81.3%) was significantly higher than in adenomas (5.7%) (P<0.001). hRFI is highly expressed in colorectal carcinomas. In the adenoma-carcinoma sequence, hRFI is involved at the initial tumor formation and its diffuse expression is associated with colorectal carcinogenesis. This evidence suggests that hRFI may act as an oncogenic molecule affecting the apoptotic pathway.
  • M Ishikawa, J Kitayama, S Kazama, H Nagawa
    HEPATO-GASTROENTEROLOGY 51 59 1319 - 1322 2004年09月 [査読有り][通常論文]
     
    Background/Aims: Vascular endothelial. growth factor C (VEGF-C) and D (VEGF-D) are considered to be potentially lymphangiogenic and can selectively induce hyperplasia of the lymphatic vasculature. In this study, we examined the expression of VEGFC and -D in esophageal carcinoma. Methodology: With immunohistochemical staining using specific antibodies, we classified 26 esophageal carcinoma cases and 11 dysplasia cases. Results: All esophageal carcinomas clearly expressed VEGF-C. In esophageal dysplasia, 9 (82%) cases were positive for VEGF-C, and 2 (18%) were negative. In contrast, none of the normal esophageal mucosa expressed VEGF-C. Seventeen (65%) of 26 cases of esophageal carcinoma were positively stained for VEGF-D and 7 (35%) were negative. VEGF-D was also positive in 2 (18%) cases of esophageal dysplasia, but in no cases of normal tissue. VEGF-C was detected in all carcinomas and dysplastic lesions that expressed VEGF-D. Conclusions: Active production of VEGF-C and -D was observed not only in esophageal carcinomas but also in some dysplastic lesions. This finding raises the possibility that VEGF-C and -D might play positive roles in the early stage of esophageal carcinogenesis.
  • H Nozawa, T Watanabe, T Ohnishi, T Tada, G Tsurita, S Sasaki, J Kitayama, H Nagawa
    JOURNAL OF CLINICAL ONCOLOGY 22 14 276S - 276S 2004年07月 [査読無し][通常論文]
  • M Asakage, NH Tsuno, J Kitayama, K Kawai, Y Okaji, K Yazawa, S Kaisaki, K Takahashi, H Nagawa
    ANTI-CANCER DRUGS 15 6 625 - 632 2004年07月 [査読有り][通常論文]
     
    3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors have been developed as lipid-lowering drugs, and are well recognized to reduce morbidity and mortality from coronary artery disease. Several recent experimental studies have focused on the inhibitory effects of HMG-CoA reductase inhibitor on tumor cell growth in vitro and in vivo, dependent on a direct effect on cancer cells. In the present study, we aimed to investigate the potential anti-angiogenic effect of pravastatin and its mechanism of action. Using human umbilical vein endothelial cells (HUVECs) as a model of angiogenesis, we investigated the effect of pravastatin on the various steps of angiogenesis, including endothelial cell proliferation and adhesion to extracellular matrix proteins. Pravastatin induced a dose-dependent decrease in the proliferative activity of endothelial cells, which was dependent on the cell cycle arrest to the G(1) phase and not on cell apoptosis. G(1) arrest was due to the decrease of cyclin D, cyclin E and cyclin-dependent kinase 2 levels. In addition, pravastatin inhibited tube formation on Matrigel and adhesion to extracellular matrix, but did not affect matrix metalloproteinase production. The present results demonstrate the anti-angiogenic activity of pravastatin and its potential use as an anticancer drug is suggested. (C) 2004 Lippincott Williams Wilkins.
  • M Ishikawa, J Kitayama, H Nagawa
    CLINICAL CANCER RESEARCH 10 13 4325 - 4331 2004年07月 [査読有り][通常論文]
     
    Purpose: To evaluate leptin and leptin receptor (OB-R) expression in human breast cancer and determine whether it could be effective for the prevention and treatment of breast cancer. Experimental Design: Immunohistochemical staining using specific antibodies was used to evaluate the protein expression of leptin and OB-R in 76 invasive ductal carcinomas and 32 samples of corresponding normal mammary gland, and the relationship between the expression of OB-R and leptin and clinicopathological features was analyzed. Results: Normal mammary epithelial cells did not express a significant level of Ob-R, whereas carcinoma cells showed positive staining for OB-R. in 63 (83%) cases. Both normal epithelial cells and carcinoma cells expressed a significant level of leptin. However, overexpression of leptin, as determined by staining intensity, was observed in 70 cancers (92%) but in no normal epithelium. The expression of OB-R showed a significant correlation with the level of leptin expression. Interestingly, distant metastasis was detected in 21 (34%) of 61 OB-R-positive tumors with leptin overexpression, but in none of the 15 tumors that lacked OB-R expression or leptin overexpression (P < 0.05). Consequently, patients with the former tumors showed significantly lower survival than those with the latter. Conclusions: Leptin may have a promoting effect on the carcinogenesis and metastasis of breast cancer, possibly in an autocrine manner. Functional inhibition of leptin may be effective for the prevention and treatment of breast cancer.
  • T Konishi, T Watanabe, J Kitayama, H Nagawa
    DISEASES OF THE COLON & RECTUM 47 6 1032 - 1032 2004年06月 [査読無し][通常論文]
  • K Kawai, NH Tsuno, J Kitayama, Y Okaji, K Yazawa, M Asakage, N Hori, T Watanabe, K Takahashi, H Nagawa
    JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 113 6 1211 - 1217 2004年06月 [査読有り][通常論文]
     
    Background: Although green tea polyphenol catechin has been reported to have antiallergic and anti-inflammatory activities, the precise mechanisms of its effect on the immune system have been poorly investigated. Objective: In this study, we aimed to elucidate the mechanisms of the anti-inflammatory effect of catechin. For this purpose, we studied the effect of 2 kinds of catechin, epigallocatechin gallate (EGCG) and epicatechin gallate, on peripheral blood CD8(+) T cells, which play the key role in immune responses. Methods: Isolated peripheral blood mononuclear cells or CD8(+) T cells were incubated without or with catechin, and the changes in the surface expression of integrin molecules were investigated by flow cytometry and the direct binding of catechin to CD11b molecule by competitive ELISA. Also, the effect of catechin on the ability of CD8(+) T cells to bind intracellular adhesion molecule 1 and to migrate in response to chemokines was evaluated by using the adhesion and migration assays. Results: The 2 catechins directly bound to CD11b expressed on CD8(+) T cells, which caused a consequent decrease of flow-cytometric CD11b expression. The effect was more prominent with EGCG than epicatechin gallate, and the impaired expression of CD11b induced by EGCG resulted in decreased ability of CD8(+) T cells to adhere intercellular adhesion molecule 1, and consequently decreased migration in response to chemokines. Conclusion: We concluded that catechin, especially EGCG, by downregulating CD11b expression on CD8(+) T cells and, in consequence, inhibiting infiltration of these cells into the sites of inflammation, is a promising new potent anti-inflammatory agent.
  • A Sako, J Kitayama, S Kaisaki, H Nagawa
    CANCER LETTERS 208 1 43 - 49 2004年05月 [査読有り][通常論文]
     
    Although increased dietary fat or cholesterol has been reported to be a risk factor for the development of certain cancers, the effect of the serum lipid level on tumor metastasis has not been well documented. Fasting serum levels of total cholesterol (TC) and triglycerides (TG) were examined in 54 patients with superficial esophageal cancer (SEC) invading lamia musucularis or submucosal layer who underwent esophagectomy with classical lymphadenectomy. The association between lymph node metastasis and the preoperative serum lipid levels as well as the pathological findings was retrospectively analyzed. The levels of TC and TG were significantly higher in 18 node-positive than in 36 node-negative patients (TC: 205.4 +/- 38.9 vs. 174.5 +/- 26.8 mg/dl, P < 0.01; TG: 152.0 +/- 68.5 vs. 88.7 +/- 28.6 mg/dl, P < 0.001). Patients with hypercholesterolemia (TC greater than or equal to 220 mg/dl) and hypertriglyceridemia (TG greater than or equal to 150 mg/dl) showed extremely high rates of nodal metastasis (80 and 91 %, respectively), that were significantly higher than those of patients with normal lipid levels (P < 0.01 and P < 0.001). When hyperlipidemia was defined as the presence of either hypertriglyceridemia or hypercholesterolemia, hyperlipidemia was an independent risk factor for nodal metastasis in SEC. Elevated serum lipid levels might bring favorable circumstances for the development of lymph node metastasis in the early stage of EC. Hyperlipidemia might prompt us to perform more studies to investigate possible metastasis. (C) 2003 Elsevier Ireland Ltd. All rights reserved.
  • A Sako, J Kitayama, H Koyama, H Ueno, H Uchida, H Hamada, H Nagawa
    CANCER RESEARCH 64 10 3624 - 3628 2004年05月 [査読有り][通常論文]
     
    The prognosis of gastric cancer with peritoneal metastasis has not improved. Despite many promising studies, gene therapy has limited clinical application because of the lack of suitable vector systems to enable selective gene transduction to tumor cells. The aim of this study was to clarify whether gene therapy targeted to peritoneal mesothelial cells (PMCs) can inhibit peritoneal dissemination of gastric cancer. In vitro experiments showed that adenovirus expressing LacZ infected human omental tissue-derived PMCs more efficiently than human gastric cancer cell lines MKN1 and MKN45. When adenovirus expressing LacZ was injected into the peritoneal cavity of nude mice, the expression was detected in the peritoneum for at least 4 weeks. Furthermore, when adenovirus expressing soluble Flt-1 (Ad-sFLT-1) was i.p. administered in vivo, a high level of sFlt-1 protein could be detected in peritoneal lavage for 8 weeks. When MKN45 cells were i.p. inoculated 3 days after adeno-viral vector injection, Ad-sFLT-1 markedly reduced the number of metastatic nodules larger than I mm in diameter on the peritoneal surface, and significantly prolonged the survival of nude mice without any significant side effects. Thus, peritoneal dissemination was significantly suppressed by a single i.p. injection of Ad-sFlt-1. Anti-angiogenic gene therapy targeted to PMCs could be a novel and practical strategy against peritoneal dissemination of gastric cancer, because it does not require tumor-specific gene transfer.
  • T Konishi, T Watanabe, J Kitayama, J Shibahara, T Hiramatsu, K Hara, K Kuriki, H Nagawa
    JOURNAL OF GASTROENTEROLOGY 39 5 484 - 489 2004年05月 [査読有り][通常論文]
     
    Colon perforation (CP) is still a critical complication after renal transplantation (RT), and idiopathic perforation is extremely rare. Here we describe a successfully treated case of idiopathic rectosigmoid perforation that occurred 7 years after RT. In our research this is the tenth reported case of idiopathic CP after RT and the second case that has occurred in the rectosigmoid. The patient was a 51-year-old Japanese male RT recipient still receiving immunosuppressive medication. He was admitted to the hospital for sudden onset of abdominal pain during defecation. Emergency laparotomy was performed 5 h after the onset, and a longitudinal 1.5 cm perforation with a clear margin was observed in the rectosigmoid, 8 cm above the peritoneal reflection. Hartmann's operation was performed. Macroscopic and histological examination did not reveal any specific findings that may have caused perforation, so the case was diagnosed as idiopathic rectosigmoid perforation.
  • M Ishikawa, J Kitayama, H Nariko, K Kohno, H Nagawa
    JOURNAL OF SURGICAL ONCOLOGY 86 1 28 - 33 2004年04月 [査読有り][通常論文]
     
    Background and Objectives: Tumor development usually is accompanied by alterations of O-glycosylation. Initial glycosylation of mucin-type O-linked proteins is regulated by UDP-N-acetyl-alpha-D-galactosamine: polypeptide N-acetylgalactosaminyl transferase-3 (GalNAc-T3). Although the expression of GalNAc-T3 has been examined in various cancers, the expression has not been characterized in early stages of cancer. Methods: Using the specific antibody, we evaluated the expression of GaINAc-T3 in 125 early gastric cancers that were treated as classical gastrectomy with lymphadenectomy, and analyzed the relationship between the expression of GaINAc-T3 and clinicopathological features. Results: GalNac-T3 was positively expressed in 40 cases (76%) in differentiated carcinomas, whereas in only six cases (8%) in undifferentiated carcinomas (P < 0.001). Positive staining was observed in 17 (26%) intramucosal and in 29 (48%) submucosal carcinomas, indicating that GalNac-T3 tended to be highly expressed as the depth of invasion increased (P < 0.05). Lymph node metastasis tended to be observed more frequently in GalNac-T3 positive than negative cases, and the difference was significant in undifferentiated type cancer (P < 0.05). Conclusions: GaINAc-T3 expression was a useful indicator of tumor differentiation in early gastric cancer, and the expression had positive correlation with depth of tumor invasion and lymph node metastasis. This suggests that the overexpression of GalNAc-T3 may have a role in invasion and metastasis in early stages of gastric cancer. (C) 2004 Wiley-Liss, Inc.
  • S Kazama, J Kitayama, T Watanabe, H Nagawa
    HEPATO-GASTROENTEROLOGY 51 56 391 - 395 2004年03月 [査読有り][通常論文]
     
    Background/Aims: Vascular endothelial growth factor-C (VEGF-C) is a potent growth factor stimulating lymphangiogenesis. Methodology: We examined the expression of VEGF-C immunohistochemically in neoplastic as well as normal mucosa of colorectal tissues, and evaluated the significance of VEGF-C in colorectal carcinogenesis and as a marker to predict the outcome of colorectal cancer. Results: VEGF-C was strongly stained in 70/79 adenomas (89%), but the staining was focal in all cases, and the expression pattern in adenomas was not significantly related to either dysplasia or size of the adenoma. In the 8/8 intramucosal carcinomas within adenomas, both the carcinomatous and adenomatous lesions were stained focally, but in 6 cases (75%), the VEGF-C-positive area was larger in the carcinomatous lesion than in the adenomatous lesion. In most invasive adenocarcinomas, VEGF-C was clearly stained (83/85; 98%), with both a focal (40%) and diffuse (60%) staining pattern. In invasive carcinomas, the expression of VEGF-C was significantly correlated with lymphatic involvement, lymph node metastasis and tumor size, but not with venous involvement or liver metastasis. Survival rate tended to be lower in the high VEGF-C group than in the low group, although statistical significance was not observed. Conclusions: These results suggest that VEGF-C plays a positive role in lymphatic spread in colorectal carcinomas.
  • J Kitayama, K Hatano, S Kaisaki, H Suzuki, S Fujii, H Nagawa
    BRITISH JOURNAL OF SURGERY 91 2 191 - 198 2004年02月 [査読有り][通常論文]
     
    Background: Although increased dietary fat or cholesterol has been reported to be a risk factor for the development of certain cancers, the effect of serum lipid levels on turnout metastasis is not clearly understood. Methods: The association between lymph node metastasis and preoperative serum levels of total cholesterol (TC) and triglyceride (TG) as well as various pathological findings for tumours was examined in 353 patients with early gastric cancer who underwent gastrectomy with classical lymphadenectomy. Results: The rate of lymph node metastasis was significantly higher in patients with early gastric cancer who had hypercholesterolaemia (TC 220 mg/dl or greater) or hypertriglyceridaemia (TG 150 mg/dl or greater). The tendency was more prominent in men, and multivariate analysis showed that hypertriglyceridaemia was an independent risk factor for nodal metastasis in men, in addition to pathological invasion to the submucosal layer or to lymphatic vessels. In contrast, neither hypercholesterolaemia nor hypertriglyceridaemia showed a significant association with nodal status in women with early gastric cancer. Conclusion: Raised serum lipid levels might favour the development of lymph node metastasis in men with early-stage gastric cancer. In patients with early gastric cancer serum lipid levels should be checked before operation, and the use of minimal local treatments must be considered carefully in male patients with hyperlipidaemia.
  • Y Okaji, NH Tsuno, J Kitayama, S Saito, T Takahashi, K Kawai, K Yazawa, M Asakage, N Hori, T Watanabe, Y Shibata, K Takahashi, H Nagawa
    CANCER SCIENCE 95 1 85 - 90 2004年01月 [査読有り][通常論文]
     
    Overcoming immune tolerance of tumor angiogenesis should be useful for adjuvant therapy of cancer. we hypothesized that vaccination with autologous endothelium would induce an autoimmune response targeting tumor angiogenesis. To test this concept, we immunized BALB/c mice with a vaccine of glutaraldehyde-fixed murine hepatic sinusoidal endothelial cells (HSEs) in a lung metastasis model of Colon-26 cancer. Vaccination with autologous HSEs induced both preventive and therapeutic anti-tumor immunity that significantly inhibited the development of metastases. ELISA revealed an immunoglobulin response involving IgM and IgG subclasses. These antibodies had a strong affinity for antigens of both murine and human endothelium, and lyzed endothelial cells in the CDC assay. Flow-cytometry and chromium-release cytotoxicity assay revealed a specific CTL response against endothelial cells, which were lyzed in an effector: target ratio-dependent manner. Neither antibodies nor CTLs reacted with Colon-26. The effect of autologous HSEs was more pronounced than that of xenogeneic human umbilical vein endothelial cells (HUVECs), which were tested in the same experimental setting. Our results suggest that vaccination with autologous endothelium can overcome peripheral tolerance of self-angiogenic antigens and therefore should be useful for adjuvant immunotherapy of cancer.
  • J Kitayama, D Shida, A Sako, M Ishikawa, K Hama, J Aoki, H Arai, H Nagawa
    BREAST CANCER RESEARCH 6 6 R640 - R646 2004年 [査読有り][通常論文]
     
    Introduction Lysophosphatidic acid (LPA) is a bioactive phospholipid with diverse effects on various cells. It interacts with at least three G-protein-coupled transmembrane receptors, namely LPA1, LPA2 and LPA3, whose expression in various tumours has not been fully characterized. In the present study we characterized the expression profile of LPA receptors in human breast cancer tissue and assessed the possible roles of each receptor. Methods The relative expression levels of each receptor's mRNA against - actin mRNA was examined in surgically resected invasive ductal carcinomas and normal gland tissue using real-time RT-PCR. LPA2 expression was also examined immunohistochemically using a rat anti-LPA2 monoclonal antibody. Results In 25 cases normal and cancer tissue contained LPA1 mRNA at similar levels, whereas the expression level of LPA2 mRNA was significantly increased in cancer tissue as compared with its normal counterpart (3479.0 +/- 426.6 versus 1287.3 +/- 466.8; P < 0.05). LPA3 was weakly expressed in both cancer and normal gland tissue. In 48 (57%) out of 84 cases, enhanced expression of LPA2 protein was confirmed in carcinoma cells as compared with normal mammary epithelium by immunohistochemistry. Over-expression of LPA2 was detected in 17 (45%) out of 38 premenopausal women, as compared with 31 (67%) out of 46 postmenopausal women, and the difference was statistically significant ( P < 0.05). Conclusion These findings suggest that upregulation of LPA2 may play a role in carcinogenesis, particularly in postmenopausal breast cancer.
  • A Sako, J Kitayama, H Yamaguchi, S Kaisaki, H Suzuki, K Fukatsu, S Fujii, H Nagawa
    JOURNAL OF SURGICAL RESEARCH 115 1 113 - 120 2003年11月 [査読有り][通常論文]
     
    Although peritoneal metastasis is an important factor determining the prognosis of patients with gastrointestinal cancer, the mechanisms have not yet been clearly defined. Human peritoneal mesothelial cells (HPMC) are the first line against disseminated tumor cells. Recent reports have shown that mesothelial cells are capable of secreting various cytokines and growth factors. In this study, we isolated human mesothelial cells from surgically resected omental tissue and examined the production and interaction of two major angiogenic factors, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF-2). Quiescent HPMC produced a considerable amount of VEGF at almost the same level as tumor cells. Interestingly, addition of FGF-2 to the culture significantly increased the mRNA synthesis and protein secretion of VEGF in a dose-dependent manner, as determined by Northern blot and ELISA. The addition of 0.5 ng/mL FGF-2 was enough to stimulate VEGF production, and the effect reached a plateau at 5 ng/mL. Reverse-transcribed polymerase chain reaction (RT-PCR) method clarified that the HPMC-derived VEGF consisted mostly of VEGF(121) and VEGF(165), which are both predominantly soluble forms. These data suggest that HPMC contribute to the development of metastases and the accumulation of malignant ascites due to the production of VEGF, especially in cancers that do not express enough amount of VEGF. (C) 2003 Elsevier Inc. All rights reserved.
  • K Kawai, NH Tsuno, J Kitayama, Y Okaji, K Yazawa, M Asakage, N Hori, T Watanabe, K Takahashi, H Nagawa
    JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 112 5 951 - 957 2003年11月 [査読有り][通常論文]
     
    Background: Epigallocatechin gallate (EGCG), the major component of tea polyphenol, has been reported to have various physiologic modulatory activities. Several reports also have shown that catechin has a protective effect against HIV infection, part of which is mediated by inhibiting virions to bind to the target cell surface. Objective: We investigated the effect of EGCG on the expression of CD4 molecules and on its ability to bind gp120, an envelope protein of HIV-1. Methods: Peripheral blood CD4(+) T cells were incubated in the presence of EGCG, and the expression of CD4 was evaluated by means of flow cytometry. The effect of EGCG on the antibody binding to CD4 was investigated by using a sandwich ELISA, and the effect on the gp120 binding to CD4 was analyzed by means of flow cytometry. Results: EGCG efficiently inhibited binding of anti-CD4 antibody to its corresponding antigen. This effect was mediated by the direct binding of EGCG to the CD4 molecule, with consequent inhibition of antibody binding, as well as gp120 binding. Conclusion: The present results suggest a potential preventive effect of EGCG on HIV-1 infection by modulating binding to CD4.
  • H Nozawa, T Watanabe, T Ohnishi, T Tada, G Tsurita, S Sasaki, J Kitayama, H Nagawa
    SURGERY 134 5 791 - 798 2003年11月 [査読有り][通常論文]
     
    Background. Liver metastasis is an important factor determining prognosis in colorectal cancer. The objective of this study was to assess whether colorectal cancer cells in the drainage veins can be detected by measuring telomerase activity and its detection is correlated with liver metastasis. Methods. Telomeric repeat amplification protocol assay in combination with an immunomagnetic sorting was used for measuring telomerase activity of epithelial cells in blood samples collected from mesenteric (tumor-drainage) vein and peripheral vessels of 41 colorectal cancer patients. Telomerase activity was calculated as relative telomerase activity (RTA) against a control template and analyzed in terms of liver metastasis. Results. RTA of mesenteric blood samples was significantly higher in patients with liver metastasis. (60.8%; n = 7) than in those without metastasis (19.7%; n = 34; P = .019). The RTA of peripheral blood sample was also higher in patients with liver metastasis (26.8%) than in those without metastasis (11.1%; p = .17). Moreover, 57% of cases with liver metastasis exhibited a positive telomerase activity in mesenteric blood sample, whereas it was 18% in cases without metastasis. Conclusions. Our assay was proven to be a feasible method for detecting cancer cells in tumor-drainage veins. High telomerase activity of mesenteric blood samples reflected the existence of liver metastasis of colorectal cancer.
  • A Sako, J Kitayama, H Yamaguchi, S Kaisaki, H Suzuki, K Fukatsu, S Fujii, H Nagawa
    JOURNAL OF SURGICAL RESEARCH 115 1 113 - 120 2003年11月 [査読有り][通常論文]
     
    Although peritoneal metastasis is an important factor determining the prognosis of patients with gastrointestinal cancer, the mechanisms have not yet been clearly defined. Human peritoneal mesothelial cells (HPMC) are the first line against disseminated tumor cells. Recent reports have shown that mesothelial cells are capable of secreting various cytokines and growth factors. In this study, we isolated human mesothelial cells from surgically resected omental tissue and examined the production and interaction of two major angiogenic factors, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF-2). Quiescent HPMC produced a considerable amount of VEGF at almost the same level as tumor cells. Interestingly, addition of FGF-2 to the culture significantly increased the mRNA synthesis and protein secretion of VEGF in a dose-dependent manner, as determined by Northern blot and ELISA. The addition of 0.5 ng/mL FGF-2 was enough to stimulate VEGF production, and the effect reached a plateau at 5 ng/mL. Reverse-transcribed polymerase chain reaction (RT-PCR) method clarified that the HPMC-derived VEGF consisted mostly of VEGF(121) and VEGF(165), which are both predominantly soluble forms. These data suggest that HPMC contribute to the development of metastases and the accumulation of malignant ascites due to the production of VEGF, especially in cancers that do not express enough amount of VEGF. (C) 2003 Elsevier Inc. All rights reserved.
  • K Kawai, NH Tsuno, J Kitayama, Y Okaji, K Yazawa, M Asakage, N Hori, T Watanabe, K Takahashi, H Nagawa
    JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 112 5 951 - 957 2003年11月 [査読有り][通常論文]
     
    Background: Epigallocatechin gallate (EGCG), the major component of tea polyphenol, has been reported to have various physiologic modulatory activities. Several reports also have shown that catechin has a protective effect against HIV infection, part of which is mediated by inhibiting virions to bind to the target cell surface. Objective: We investigated the effect of EGCG on the expression of CD4 molecules and on its ability to bind gp120, an envelope protein of HIV-1. Methods: Peripheral blood CD4(+) T cells were incubated in the presence of EGCG, and the expression of CD4 was evaluated by means of flow cytometry. The effect of EGCG on the antibody binding to CD4 was investigated by using a sandwich ELISA, and the effect on the gp120 binding to CD4 was analyzed by means of flow cytometry. Results: EGCG efficiently inhibited binding of anti-CD4 antibody to its corresponding antigen. This effect was mediated by the direct binding of EGCG to the CD4 molecule, with consequent inhibition of antibody binding, as well as gp120 binding. Conclusion: The present results suggest a potential preventive effect of EGCG on HIV-1 infection by modulating binding to CD4.
  • H Nozawa, T Watanabe, T Ohnishi, T Tada, G Tsurita, S Sasaki, J Kitayama, H Nagawa
    SURGERY 134 5 791 - 798 2003年11月 [査読有り][通常論文]
     
    Background. Liver metastasis is an important factor determining prognosis in colorectal cancer. The objective of this study was to assess whether colorectal cancer cells in the drainage veins can be detected by measuring telomerase activity and its detection is correlated with liver metastasis. Methods. Telomeric repeat amplification protocol assay in combination with an immunomagnetic sorting was used for measuring telomerase activity of epithelial cells in blood samples collected from mesenteric (tumor-drainage) vein and peripheral vessels of 41 colorectal cancer patients. Telomerase activity was calculated as relative telomerase activity (RTA) against a control template and analyzed in terms of liver metastasis. Results. RTA of mesenteric blood samples was significantly higher in patients with liver metastasis. (60.8%; n = 7) than in those without metastasis (19.7%; n = 34; P = .019). The RTA of peripheral blood sample was also higher in patients with liver metastasis (26.8%) than in those without metastasis (11.1%; p = .17). Moreover, 57% of cases with liver metastasis exhibited a positive telomerase activity in mesenteric blood sample, whereas it was 18% in cases without metastasis. Conclusions. Our assay was proven to be a feasible method for detecting cancer cells in tumor-drainage veins. High telomerase activity of mesenteric blood samples reflected the existence of liver metastasis of colorectal cancer.
  • Y Komuro, T Watanabe, J Kitayama, H Yamaguchi, N Tsuno, H Nagawa
    HEPATO-GASTROENTEROLOGY 50 54 1770 - 1773 2003年11月 [査読有り][通常論文]
     
    Background/Aims: The EDG-2 (endothelial cell differentiation gene-2) has been characterized as one of the high-affinity receptors of lysophosphatidic acid: an extracellular lipid mediator which can induce tumor progression. Recent studies have revealed that EDG-2 plays an important role in various pathological events including cell proliferation and tumor development. The investigation of EDG-2 is thus considered important for eliciting the mechanism of tumorigenesis. However, in colorectal tissue, the clinical significance of EDG-2 expression remains unclear. In the current study, we examined the immunohistochemical expression of EDG-2 in colorectal mucosa and adenoma, and clarified its relation with the clinicopathological features. Methodology: One hundred and sixty-one colorectal polyps were resected endoscopically or surgically at our institute from 2000 to 2001. According to the degree of dysplasia, adenomas were grouped into two categories: low-grade (mild or moderate dysplasia) and high-grade (severe dysplasia or carcinoma in situ). We investigated EDG-2 expression by immunohistochemistry. Results: EDG-2 was expressed almost exclusively in the cytoplasm in colorectal normal mucosa and adenoma. EDG-2 expression in normal mucosa and adenoma was 8% and 76%, respectively. EDG-2 expression was increased in low-grade adenoma compared with that in normal mucosa (P < 0.001). EDG-2 expression was significantly greater in adenomas with larger diameters (P < 0.001). Conclusions: We demonstrated that EDG-2 expression was increased in the early stage of adenoma. A significant correlation between EDG-2 expression and the size - of the adenomas suggests that EDG-2 may play an important role in the growth of these adenomas.
  • S Saito, J Kitayama, ZX Jin, N Tsuno, S Kaisaki, Y Seto, H Nagawa
    JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH 22 3 453 - 459 2003年09月 [査読有り][通常論文]
     
    Chemokines have been shown to be expressed in some malignant or precancerous tissues. However, the role of these chemokines on tumor development or progression is not clear. The expression patterns of chemokines in gastric cancer tissues were examined in 86 surgically resected samples using immunohistochemistry. Macrophage inflammatory protein-1 beta (MIP-1beta) was clearly detected in many gastric carcinoma cells. In most of the differentiated carcinomas, intracellular localization of MIP-1beta was detected in more than 5% of cancer cells, although the percentages of MIP-1beta-positive cells differed among each sample. Undifferentiated carcinomas showed contrasted staining pattern between solid type and non-solid (diffuse) type. MIP-1beta was totally absent in all the poorly differentiated carcinomas with solid type growth pattern (porl). In contrast, MIP-1beta was highly expressed in all of the non-solid type of poorly differentiated carcinoma (por2) and signet-ring cell carcinoma samples. In particular, MIP-1beta was strongly stained in carcinoma cells at the front of invasive lesions. In 43 diffuse type undifferentiated cancers, tumors with high expression of MIP-1beta exhibited significantly more lymph node metastasis. Our results suggest a possibility that MIP-1beta may be related to the scattering and invasion step of gastric carcinoma cells with undifferentiated phenotype.
  • H Yamaguchi, J Kitayama, N Takuwa, K Arikawa, Inoki, I, K Takehara, H Nagawa, Y Takuwa
    BIOCHEMICAL JOURNAL 374 Pt 3 715 - 722 2003年09月 [査読有り][通常論文]
     
    We have recently reported that S1P (sphingosine-1-phosphate) differentially regulates cellular Rac activity and cell migration in either a positive or a negative direction via distinct G-protein-coupled receptor subtypes, i.e. S1P(1)/Edg1 (endothelial differentiation gene) and S1P(1)/Edg5 respectively, when each of the S1P receptor subtypes is expressed in CHO (Chinese-hamster ovary) cells. In B16F10 mouse melanoma cells, in which S1P(2), but not the other S1P-receptor subtypes, is endogenously expressed, S1P inhibited cell migration with concomitant inhibition of Rac and stimulation of RhoA in dose-dependent manners. Overexpression of S1P, in the melanoma cells resulted in potentiation of S1P inhibition of both Rac and cell migration. In contrast, overexpression of S1P(1) led to stimulation of cell migration, particularly at the lower S1P concentrations. Treatment of B16F10 cells with S1P inhibited lung metastasis 3 weeks after injection into mouse tail veins. Intriguingly, overexpression of S1P(2) greatly potentiated the inhibition of metastasis by S1P, whereas that of S1P(1) resulted in aggravation of metastasis. Suppression of cellular Rac activity by adenovirus-transduced expression of N(17)Rac, but not N(19)RhoA, strongly inhibited cell migration in vitro and lung metastasis in vivo. These results provide the first evidence that G-protein-coupled receptors could participate in the regulation of metastasis, in which ligand-dependent, subtype-specific regulation of the cellular Rac activity is probably critically involved as a mechanism.
  • K Arikawa, N Takuwa, H Yamaguchi, N Sugimoto, J Kitayama, H Nagawa, K Takehara, Y Takuwa
    JOURNAL OF BIOLOGICAL CHEMISTRY 278 35 32841 - 32851 2003年08月 [査読有り][通常論文]
     
    We investigated mechanisms for inhibition of B16 melanoma cell migration and invasion by sphingosine-1-phosphate (S1P), which is the ligand for the Edg family G protein-coupled receptors and also implicated as an intracellular second messenger. S1P, dihydro-S1P, and sphingosylphosphorylcholine inhibited B16 cell migration and invasion with the relative potencies expected as S1P(2) receptor agonists. The S1P(2)-selective antagonist JTE013 completely abolished the responses to these agonists. In addition, JTE013 abrogated the inhibition by sphingosine, which is the S1P precursor but not an agonist for S1P receptors, indicating that the sphingosine effects were mediated via S1P(2) stimulation, most likely by S1P that was converted from sphingosine. S1P induced inhibition and activation, respectively, of Rac and RhoA in B16 cells, which were abrogated by JTE013. Adenovirus-mediated expression of N(17)Rac mimicked S1P inhibition of migration, whereas C3 toxin pretreatment, but not Rho kinase inhibitors, reversed the S1P inhibition. Overexpression of S1P(2) sensitized, and that of either S1P(1) or S1P(3) desensitized, B16 cells to S1P inhibition of Rac and migration. In JTE013-pretreated, S1P(3)-overexpressing B16 cells, S1P stimulated cellular RhoA but failed to inhibit either Rac or migration, indicating that RhoA stimulation itself is not sufficient for inhibition of migration. These results provide compelling evidence that endogenously expressed S1P(2) negatively regulates cell motility and invasion through ligand dependent reciprocal regulation of cellular Rac and RhoA activities. In the presence of JTE013, S1P instead stimulated Rac and migration in B16 cells that overexpress either S1P(1) or S1P(3), unveiling counteractions between S1P(2) and S1P(1) or S1P(3) chemotactic receptor.
  • Y Komuro, T Watanabe, N Tsuno, J Kitayama, N Inagaki, M Nishida, H Nagawa
    HEPATO-GASTROENTEROLOGY 50 52 906 - 911 2003年07月 [査読有り][通常論文]
     
    Background/Aims: DPD (dihydropyrimidine. dehydrogenase) activity shows a correlation with 5-fluorouracil chemosensitivity. To quantify DPD activity is important for selection of chemosensitive cases of not only sporadic colorectal cancer but also rectal cancer with preoperative radiotherapy. However, it is not cost-effective. We investigated the relation between the immunohistochemical expression pattern of DPD and its activity in rectal cancer treated with radiotherapy, and compared the immunohistochemical. DPD expression pattern of preradiation biopsy specimens with that of resected tissues. Methodology DPD expression pattern of preradiation biopsy specimens were compared with that of resected. tissues. Eighteen colorectal cancer tissue samples were obtained after surgery from October 2000 to January 2001. DPD activity was quantified by sandwich enzyme-linked immunosorbent assay. The streptoavidin-biotin peroxidase complex technique was used for, the immunohistochemical expression pattern. Results: DPD was stained in the cytoplasm of cancer cells. There was a significant correlation between the immunohistochemical expression pattern of DPD and its activity in tumor tissue treated with or without radiotherapy. The immunohistochemical expression pattern of preradiation biopsy specimens was almost the same as that of resected tissues. Conclusions: The immunohistochemical expression pattern of DPD correlated with its activity in tumor tissue treated with preoperative radiotherapy. Immunohistochemical evaluation is considered to be an effective method of predicting the sensitivity to 5-fluorouracil of rectal cancer treated with preoperative radiotherapy.
  • Y Komuro, T Watanabe, Y Hosoi, Y Matsumoto, K Nakagawa, S Saito, S Ishihara, S Kazama, N Tsuno, J Kitayama, N Suzuki, G Tsurita, T Muto, H Nagawa
    JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH 22 2 223 - 228 2003年06月 [査読有り][通常論文]
     
    The identification of predictive indicators of radiosensitivity is extremely useful in selecting patients suited for preoperative radiotherapy and avoiding unnecessary preoperative treatment. In this study, we evaluated the possible role of the immunohistochemical expression pattern of p53 and Ku70 protein in determining tumor radiosensitivity in rectal cancer before preoperative irradiation. We examined pretreatment biopsy materials from 111 patients by immunohistochemistry. The expression pattern of p53 and Ku70 was evaluated for association with tumor radiosensitivity, which was defined according to the criteria of the Japanese Research Society for Cancer of the Colon and Rectum. There was a significant correlation between the expression pattern of p53 and tumor radiosensitivity (P=0.045); Ku70 and tumor radiosensitivity (P<0.001); and the combination of p53 and Ku70, and tumor radiosensitivity (P<0.001). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in both p53 and Ku70-positive cases for radioresistance were all superior to those of the group positive for p53 alone. In conclusion the examination of the combination of p53 and Ku70 may predict the radiosensitivity of rectal cancer before preoperative irradiation.
  • A Hidemura, H Saito, K Fukatsu, S Ikeda, J Kitayama, T Matsuda, H Nagawa
    SHOCK 19 6 497 - 502 2003年06月 [査読有り][通常論文]
     
    Appropriate polymorphonuclear neutrophil (PMN) recruitment is essential for host defense against infection. We investigated the significance of the preoperative PMN adhesion-migration process, as assessed by the flow chamber method, on postoperative infectious complications. Thirty-one consecutive patients with gastrointestinal malignancies, 21 colorectal and 10 gastric, who were undergoing elective surgery were enrolled. PMNs, isolated preoperatively from each patient's venous blood, were perfused onto a tumor necrosis factor a-stimulated human umbilical vein endothelial cell (HUVEC) monolayer through the flow chamber. We evaluated the adherent PMN number, the migrated PMN number, and the stuck PMN number by directly inspecting PMN interactions with a HUVEC monolayer under continuous shear flow simulating postcapillary venules. The expression of adhesion molecules on circulating PMNs was also measured. Patients were grouped into an infectious and a noninfectious group according to the occurrence of postoperative infectious complications defined by the Centers for Disease Control criteria. Eleven patients developed postoperative infectious complications. Although the number of preoperative in vitro adherent PMNs in patients with postoperative infection was significantly higher than in those without postoperative infection (P = 0.01), migrated PMN number was similar in both groups. Stuck PMN number tended to be higher in the infectious group than in the noninfectious group. The migrated PMN number showed a significant positive correlation with the adherent PMN number in the noninfectious group but not in the infectious group. Preoperative CD31 expression on circulating PMNs was significantly lower in the infectious group than in the noninfectious group. Preoperative in vitro derangement of the PMN adhesion-migration process is closely associated with postoperative infectious complications.
  • M Tabata, J Kitayama, H Kanemoto, T Fukasawa, H Goto, K Taniwaka
    AMERICAN SURGEON 69 5 363 - 366 2003年05月 [査読有り][通常論文]
     
    We report a case of autoimmune pancreatitis presenting as a mass in the head of the pancreas that was successfully diagnosed without pancreaticoduodenectomy. The patient was a 64-year-old man who had no complaint. A routine physical checkup unexpectedly revealed mild diabetes and a low-echoic mass in the pancreatic head. The diagnosis was made by noting irregular narrowing of the main pancreatic duct, hypergammaglobulinemia, and increased immunoglobulin G levels. An open wedge biopsy of the mass was performed; this showed a marked fibrosis with lymphocyte- or macrophage-predominant inflammatory infiltrates. Immunohistochemical study revealed that the remnant acinar cells expressed Fas (CD95) ligand and not Fas. We review some of the literature and discuss various features and diagnostic clues of autoimmune pancreatitis. Awareness of this pathologic condition may prevent confusion with pancreatic malignancy and unnecessary surgery.
  • D Shida, J Kitayama, H Yamaguchi, Y Okaji, NH Tsuno, T Watanabe, Y Takuwa, H Nagawa
    CANCER RESEARCH 63 7 1706 - 1711 2003年04月 [査読有り][通常論文]
     
    Lysophosphatidic acid (LPA) is a lipid mediator with diverse effects on various cells. Here, we investigated the effects of LPA on human colon carcinoma DLD1 cells. Northern blot analysis revealed that DLD1 highly expressed LPA1/Edg-2 but showed only low expression of LPA2/Edg-4 and no expression of LPA3/Edg-7 at the mRNA level. Western blot analysis revealed that DLD1 cells highly expressed LPA1 at the protein level. Using the Boyden chamber assay, LPA markedly increased DLD1 cell migration at concentrations as low as 10 nm, with maximum stimulation at 100 nm (3.6-fold increase). Checkerboard analysis indicated that LPA stimulated both the chemotactic and chemokinetic migration of DLD1 cells. LPA induced a dose-dependent increase in the proliferation of DLD1 cells (3.2-fold increase at 20 mum). Furthermore, LPA stimulated DLD1 cell adhesion to collagen type I (2.0-fold increase at 10 mum) and also stimulated the secretion of both vascular endothelial growth factor (1.4-fold increase at 20 mum) and interleukin 8 (19-fold increase at 20 mum) by ELISA. In contrast, as for matrix metalloproteinase, LPA had no significant effect on pro-matrix metalloproteinase-2 secretion and its activation, as measured by Western blot analysis. Thus, LPA, at concentrations that are present physiologically, enhanced DLD1 cell migration, proliferation, adhesion, and secretion of angiogenic factors, all of which are crucial for cancer metastasis. In comparison, other human colon carcinoma cells (HT29 and WiDR) exclusively expressed LPA2. LPA enhanced their proliferation and secretion of angiogenic factors, whereas LPA did not enhance migration or adhesion. Our results suggest that LPA acts as a potent stimulator of colon cancer progression, although the binding to LPA1 and LPA2 induces slightly different responses.
  • H Uchida, N Shinoura, J Kitayama, T Watanabe, H Nagawa, H Hamada
    JOURNAL OF GENE MEDICINE 5 4 287 - 299 2003年04月 [査読有り][通常論文]
     
    Background In order to develop a safe and effective gene therapy for cancer, more powerful therapeutic genes must be selected and a gene transduction methodology needs to be devised that minimizes the total dose of vector required. We investigated the combination effect of 5-fluorouracil (5-FU), a first-choice drug for the treatment of colorectal cancer and adenovirus-mediated transfer of caspase-8 in DLD-1 colon cancer cells. Methods The degree of cell death was assessed by determining the percentage of cells which had died, and the degree of DNA fragmentation. The protein expression levels and degree of activation of caspase-8 were analyzed by Western blot analysis. The degree of transgene expression was assessed using adenoviral vectors expressing lacZ and GFP. Results Combination treatment led to a significant induction of apoptosis, whereas treatment with either approach alone resulted in only minimal cytotoxicity. Caspase-8 was only activated in cells that received the combined treatment. Exposure to 5-FU increased the quantity of transgene expression per cell, 48 h post-infection. A potentiating effect of adenoviral treatment was also seen when 5-FU treatment was substituted by the overexpression of cyclin-dependent kinase inhibitors, p21(WAF1/CIP1) and p27(KIP1), suggesting that the cytostatic effect of 5-FU augmented apoptosis induced by caspase-8 gene transduction by inhibiting the dilution of gene products associated with cell division. Conclusions This combination strategy may be very useful in the treatment of 5-FU-resistant colorectal cancers and may also be more generally helpful in minimizing the dose of therapeutic vectors used in cancer gene therapy. Copyright (C) 2002 John Wiley Sons, Ltd.
  • A Hidemura, H Saito, K Fukatsu, T Matsuda, J Kitayama, S Ikeda, W Kang, H Nagawa
    NUTRITION 19 3 270 - 274 2003年03月 [査読有り][通常論文]
     
    OBJECTIVE: Dietary restriction impairs polymorphonuclear neutrophil (PMN) recruitment into the local inflammatory site, resulting in susceptibility to infection. Probiotics enhance host immunity via conditioning host intestinal microflora. Oral administration of Bifidobacterium longum culture condensate (BCC) in a diet-restricted marine peritonitis model may enhance PMN recruitment into the inflammatory site. METHODS: Male ICR mice (n = 40) were assigned in equal numbers to control or BCC groups and subjected to 75% restricted food intake for 7 d. During dietary restriction, controls received only standard mouse chow, whereas the BCC group received standard mouse chow containing 1% BCC. Mice were killed before (0 h) or after (2 or 4 h) intraperitoneal glycogen injection. Peritoneal lavage fluid and exudative cells were recovered by, peritoneal lavage. Peritoneal exudative cell number was counted. Taper necrosis factor-alpha, interleukin-6, macrophage inflammatory protein-2, and interleukin-10 concentrations in peritoneal lavage-fluid were determined by enzyme-linked immuosorbent assay. CD11b, CD18; CD31, and CD62L expressions on circulating PMNs were measured by flow cytometry. RESULTS: Oral BCC administration unregulated PMN recruitment into the peritoneal cavity and increased peritoneal fluid cytokine concentrations as well as CD18 and CD62L expressions on circulating PMNs during glycogen-induced peritonitis. CONCLUSIONS: Oral BCC administration in a diet-restricted marine peritonitis model augmented P recruitment into the inflammatory site by upregulating cytokine concentrations in the local inflammatory site and adhesion molecule expression on circulating PMNs. Oral BCC administration may be a favorable modality for improving dietary restriction-induced host immunosuppression. (C)Elsevier Science Inc. 2003.
  • A Hidemura, H Saito, K Fukatsu, T Matsuda, J Kitayama, S Ikeda, W Kang, H Nagawa
    NUTRITION 19 3 270 - 274 2003年03月 [査読有り][通常論文]
     
    OBJECTIVE: Dietary restriction impairs polymorphonuclear neutrophil (PMN) recruitment into the local inflammatory site, resulting in susceptibility to infection. Probiotics enhance host immunity via conditioning host intestinal microflora. Oral administration of Bifidobacterium longum culture condensate (BCC) in a diet-restricted marine peritonitis model may enhance PMN recruitment into the inflammatory site. METHODS: Male ICR mice (n = 40) were assigned in equal numbers to control or BCC groups and subjected to 75% restricted food intake for 7 d. During dietary restriction, controls received only standard mouse chow, whereas the BCC group received standard mouse chow containing 1% BCC. Mice were killed before (0 h) or after (2 or 4 h) intraperitoneal glycogen injection. Peritoneal lavage fluid and exudative cells were recovered by, peritoneal lavage. Peritoneal exudative cell number was counted. Taper necrosis factor-alpha, interleukin-6, macrophage inflammatory protein-2, and interleukin-10 concentrations in peritoneal lavage-fluid were determined by enzyme-linked immuosorbent assay. CD11b, CD18; CD31, and CD62L expressions on circulating PMNs were measured by flow cytometry. RESULTS: Oral BCC administration unregulated PMN recruitment into the peritoneal cavity and increased peritoneal fluid cytokine concentrations as well as CD18 and CD62L expressions on circulating PMNs during glycogen-induced peritonitis. CONCLUSIONS: Oral BCC administration in a diet-restricted marine peritonitis model augmented P recruitment into the inflammatory site by upregulating cytokine concentrations in the local inflammatory site and adhesion molecule expression on circulating PMNs. Oral BCC administration may be a favorable modality for improving dietary restriction-induced host immunosuppression. (C)Elsevier Science Inc. 2003.
  • S Saito, NH Tsuno, E Sunami, N Hori, J Kitayama, S Kazama, Y Okaji, K Kawai, T Kanazawa, T Watanabe, Y Shibata, H Nagawa
    JOURNAL OF GASTROENTEROLOGY 38 3 229 - 237 2003年03月 [査読有り][通常論文]
     
    Background. Platelet-derived endothelial cell growth factor (PD-ECGF) is reported to be highly expressed in tumors and inflammatory tissues, but its expression and role in inflammatory bowel disease (IBD) are still unclear. In this study we examined the location and tissue density of cells immunoreactive for PD-ECGF in the colonic mucosa of (IBD). Methods. Paraffin-embedded sections of colonic tissue from patients with ulcerative colitis (UC) or Crohn's disease (CD) were immunostained for PD-ECGF. As controls, noninflamed mucosa of IBD, as well as normal colonic mucosa from patients with colorectal cancer, were used. Also, cancer tissues were evaluated. In addition, changes in the expression of PD-ECGF in human umbilical vein endothelial cells (HUVEC) after treatment with inflammatory cytokines and angiogenic factors, as well as after coculture with colon cancer cell lines, were evaluated by flow cytometry. Results. In normal colonic mucosa and noninflamed mucosa of (IBD), PD-ECGF expression was negligible. In inflamed colonic mucosa, strong expression was observed, predominantly in macrophages and fibroblasts. Vascular endothelial cells of the inflamed colonic mucosa, but not of normal colonic mucosa or of neoplastic tissues, stained for PD-ECGF, and the microvessel density was significantly increased in the severely inflamed mucosa. Flow cytometry demonstrated that PD-ECGF was constitutively expressed in HUVEC. Inflammatory cytokines and vascular endothelial growth factor (VEGF) increased its expression, whereas basic fibroblast growth factor (bFGF) decreased it. Coculture with colon cancer cell lines in direct contact, but not in those without contact, also resulted in an important decrease in the expression of PD-ECGF in HUVEC. Conclusions. Autocrine production of PD-ECGF by endothelial cells may be a mechanism of inflammatory angiogenesis, but not tumor angiogenesis, and may be particularly important for the maintenance of damaged vasculature in IBD.
  • M Kato, J Kitayama, S Kazama, H Nagawa
    BREAST CANCER RESEARCH 5 5 R144 - R150 2003年 [査読無し][通常論文]
     
    Background: The stromal cell-derived factor-1/CXC chemokine receptor-4 (SDF-1/CXCR4) signal has been shown to be important in various immunological reactions. Recent studies have suggested that CXCR4 is expressed in certain cancer cells and that they use this chemokine receptor efficiently for metastasis formation. Method: The expression of CXCR4 was evaluated by immunohistochemical study in 79 surgically resected invasive ductal carcinomas, and the relation between the staining pattern and clinicopathological features was examined. Results: CXCR4 was diffusely and homogeneously expressed in 59 cancers, which were further divided into 28 high-expression and 31 low-expression cancers by their staining intensity. The other 20 cancers showed heterogeneous immunoreactivity in tumor tissue, which was defined as focal type. In comparison with the diffuse type, focal type tumors showed significantly more extensive lymph node metastasis, because the number and extent of metastatic nodes were larger in the focal than the diffuse type. In the diffuse type, the rate of node-positive cases did not show a difference in staining intensity. However, high-CXCR4 tumors showed more extensive nodal metastasis in comparison with low-expression tumors. In contrast, the expression pattern of CXCR4 did not have a significant correlation with hematogeneous metastasis. The overall survival of these patients tended to be better in the diffuse type than in the focal type, although the difference was not statistically significant. Conclusion: The expression pattern of CXCR4 was significantly correlated with the degree of lymph node metastasis in breast cancers. Our data suggest that CXCR4 might be particularly important in facilitating metastasis through the lymphatic system.
  • M Ishikawa, J Kitayama, S Kazama, H Nagawa
    JAPANESE JOURNAL OF CLINICAL ONCOLOGY 33 1 21 - 27 2003年01月 [査読有り][通常論文]
     
    Background: Vascular endothelial growth factor C (VEGF-C) and D (VEGF-D) are considered to be potentially lymphangiogenic and can selectively induce hyperplasia of the lymphatic vasculature. In this study, we aimed to clarify the relation between expression of VEGF-C and -D and lymphatic metastasis in early gastric cancers. Methods: Using the specific antibodies, we classified 105 cases which were treated as gastrectomy with standard lymphadenectomy at the First Department of Surgery, Tokyo University Hospital, between 1994 and 2001, into three groups (diffuse type, focal type and negative type) for VEGF-C and two groups (positive and negative) for VEGF-D. Results: There was a significant correlation between the expression of VEGF-C and -D and lymphatic invasion but not with venous invasion. All of the 22 cases that were negative for VEGF-C and -D were histologically classified as adenocarcinoma of undifferentiated type and showed negative lymph node metastasis and also negative lymphatic invasion. VEGF-C was positive in all tumors of differentiated type, while its expression varied in tumors of undifferentiated type. The VEGF-D positive rate is much lower than that of VEGF-C. In undifferentiated tumors in particular, VEGF-D was positive only in 4/64 (6%) and three of these four had nodal metastasis. Therefore, in tumors of differentiated type, expression of VEGF-C and -D had no clinical relevance. In tumors of undifferentiated type, the negative expression of VEGF-C suggests lack of nodal metastasis, while the positive expression of VEGF-D suggests nodal metastasis. The lymph node metastasis was significantly related to the expression of VEGF-C and -D in adenocarcinomas of undifferentiated type but not in those of differentiated tumors. Conclusions: In early gastric cancers of histologically undifferentiated type with negative expression of VEGF-C and -D, limited surgery might be safely applied because the possibility of nodal metastasis is very low. These observations are based only on retrospective analysis of a small case series and further evaluation with a larger number of cases is necessary.
  • Kato M, Kitayama J, Kazama S, Nagawa H
    Breast cancer research : BCR 5 5 R144 - 50 2003年 [査読有り][通常論文]
  • S Fujii, J Kitayama, S Kaisaki, S Sasaki, Y Seto, O Tominaga, N Tsuno, N Umetani, H Yokota, K Kitamura, T Tsuruo, H Nagawa
    JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH 21 4 547 - 553 2002年12月 [査読有り][通常論文]
     
    Peritoneal dissemination is the most frequent type of recurrence in patients with gastric cancer with serosal exposure, irrespective of whether they have undergone curative gastrectomy. The purpose of this study was to establish a method to detect micrometastatic cells in the abdominal cavity and predict peritoneal recurrence in patients with such gastric carcinomas. A total of 86 patients with gastric carcinoma, undergoing gastrectomy, were examined. Reverse transcriptase-polymerase chain reaction (RT-PCR) assay was used to detect carcinoembryonic antigen (CEA) mRNA in abdominal lavage fluid. Twenty-four cases without serosal exposure were negative, while all 13 cases with macroscopic peritoneal dissemination were positive for CEA mRNA. Among the 49 cases with macroscopic serosal invasion and without peritoneal metastasis, cancer cells were detected in 27 cases with RT-PCR while in only 6 cases with conventional cytology. All cytologically-positive cases were also positive for CEA mRNA. Among the 27 CEA-positive cases, 15 patients (56%) relapsed with peritoneal metastasis within 12 months after gastrectomy. In contrast, none of the 22 CEA-negative cases had peritoneal recurrence within 16-60 months of observation, whereas in 43 cytologically-negative cases, 10 patients relapsed with peritoneal recurrence. As compared with conventional cytological examination, this method would be clinically more beneficial for detecting free cancer cells in the peritoneal cavity and for predicting peritoneal recurrence in gastric carcinoma with serosal invasion.
  • Y Komuro, T Watanabe, Y Hosoi, Y Matsumoto, K Nakagawa, N Tsuno, S Kazama, J Kitayama, N Suzuki, H Nagawa
    CANCER 95 6 1199 - 1205 2002年09月 [査読有り][通常論文]
     
    BACKGROUND. Preoperative radiotherapy reduces the rate of local recurrence and improves the chance of survival in patients with resectable, advanced rectal carcinoma. However, because not all tumors respond similarly to radiation, sorting out suitable patients is required to irradiate tumors rationally. The authors examined the possible role of Ku protein in determining tumor radiosensitivity and disease free survival in patients with rectal carcinoma. METHODS. The authors studied 96 patients with advanced rectal carcinoma. In preradiation biopsy specimens of tumor samples, the number of cells that were stained positive for Ku protein was evaluated by immunohistochemistry. The expression pattern of Ku protein was examined for an association between tumor radiosensitivity (which was determined according to T classification downstaging, complete pathologic response, or Response Evaluation Criteria in Solid Tumors) and disease free survival. RESULTS. There was a high degree of correlation between the percentage of cells that expressed the 70-kDa Ku protein (Ku70) and the 86-kDa Ku protein (Ku86) in the tumor sections (correlation coefficient = 0.85; P < 0.001). The expression pattern of Ku protein was correlated not only with tumor radiosensitivity but also with disease free survival. Pathologic TMN classification, histopathologic grade, and Ku70 expression were significant prognostic variables for disease free survival in a multivariate analysis (P = 0.0031, P = 0.030, and P = 0.023, respectively). CONCLUSIONS. Ku70 and Ku86 raise the predictive possibility of tumor radiosensitivity. Ku may be a useful parameter for selecting patients with rectal carcinoma for preoperative radiotherapy. (C) 2002 American Cancer Society.
  • H Nakayama, J Kitayama, H Nagawa
    JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH 21 2 289 - 294 2002年06月 [査読有り][通常論文]
     
    Cancer cell adhesion to lymphatic endothelial cells (LEC) was examined under shear stress mimicking lymph flow. An established rat gastric adenocarcinoma cell line, BV9, was perfused over a primary cultured monolayer of LEC, which were explanted from the rat thoracic duct, and the adhesion pattern was observed. BV9 preferably adhered to LEC, at a level 8-fold greater than that to vascular endothelium in the unstimulated condition. When shear stress was increased after adhesion, a considerable number of BV9 on LEC withstood shear up to 50 dyn/cm(2), while BV9 attached on vascular endothelium did not remain adherent under 5 dyn/cm2. Adhesion was significantly augmented by prestimulation of LEC with 10 ng/ml IL1-beta or 500 ng/ml TNF-alpha. Our study indicates high affinity between cancer cells and LEC, and suggests the possibility that lymph node metastasis arises from cancer cells adherent to LEC, which can be augmented by an inflammatory stimulus.
  • T Osada, H Nagawa, T Takahashi, NH Tsuno, J Kitayama, Y Shibata
    JOURNAL OF IMMUNOTHERAPY 25 2 176 - 184 2002年03月 [査読有り][通常論文]
     
    The function of dendritic cells (DCs). antigen-presenting cells that can initiate and regulate cellular and humoral responses, is highly influenced by their level of maturation. Immature DCs may be harmful in anti-tumor immunotherapy, because they can induce immunotolerance rather than immunostimulation. In this study, the authors sought to determine the optimal culture conditions for obtaining fully mature DCs. When DCs were cultured in agonistic anti-CD40 monoclonal antibody-immobilized plates, they showed a higher expression of the maturation marker CD83 than DCs cultured without CD40 ligation or those cultured in medium supplemented with anti-CD40 monoclonal antibody. In addition, when interferon-gamma (IFN-gamma) was added to the medium, additive up-regulation of CD83 expression was observed. These DCs treated with both maturation signals showed a higher secretion of interleukin-12. To evaluate the capacity of antigen presentation. specific cytotoxic T lymphocytes were generated using autologous DC pulsed with a human lymphocyte antigen-A24-restricted peptide epitope derived from carcinoembryonic antigen. Interferon-gamma-secreting CD8+ T cells were analyzed by now cytometry using the cellular affinity matrix technology. Dendritic cells, matured with CD40 ligation and IFN-gamma, were more efficient at eliciting an antigen-specific T-cell response in vitro than DCs stimulated with anti-CD40 monoclonal antibody or IFN-gamma alone. A cytotoxicity assay using carcinoembryonic antigen-expressing tumor cell lines also showed that DCs matured with both signals were more efficient at inducing cytotoxic T lymphocytes. These results demonstrate that DC culture in an anti-CD40 monoclonal antibody-immobilized plate in medium supplemented with IFN-gamma has a positive impact oil DC maturation and may be optimal for eliciting an antigen-specific T-cell response without the need for CD4+ T-helper epitopes.
  • H Uchida, N Shinoura, J Kitayama, T Watanabe, H Nagawa, H Hamada
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 292 2 347 - 354 2002年03月 [査読有り][通常論文]
     
    Caspase-8 is a member of the cysteine protease family that plays a critical role in death receptor-mediated apoptosis. We previously demonstrated that adenovirally transduced caspase-8 efficiently induced apoptosis in tumor cells (Shinoura et al. (2000) Hun. Gene Ther. 11, 1123-1137). However, to ensure safety in clinical applications some devise for minimization of the dose of adenoviral vector required for sufficient antitumor effect is needed. In this study, we evaluated the proapoptotic effect in DLD-1 colon cancer cells of a combination of low-dose infection with an adenoviral vector expressing caspase-8 and X-ray irradiation. Under these conditions, X-ray irradiation strongly induced apoptosis whereas irradiation without transduction only had a trace proapoptotic effect. Overexpression of bcl-xL strongly blocked the activation of caspase-8 and induction of apoptosis, suggesting that adenovirally transduced caspase-8 was activated at a point downstream of mitochondria. This combination strategy may be a useful modality for gene therapy of colorectal cancer. (C) 2002 Elsevier Science (USA).
  • Osada T, Nagawa H, Takahashi T, Tsuno NH, Kitayama J, Shibata Y
    Journal of immunotherapy (Hagerstown, Md. : 1997) 25 2 176 - 184 2002年03月 [査読有り][通常論文]
  • E Ueda, J Kitayama, Y Seto, T Motoi, H Nagawa
    SURGERY TODAY 32 4 305 - 309 2002年 [査読有り][通常論文]
     
    Purpose. Local resection of the stomach for early gastric cancer is being performed more frequently, despite which no report focusing on the Postoperative complications has been published. The purpose of this study was to investigate the incidence and factors affecting postoperative complications after local resection of the stomach. Methods. Local resection of the stomach was performed in 37 patients with gastric cancers, submucosal tumors (SMT), or bleeding gastric ulcers, 24 of whom underwent gastroscopy at least once after their operation. We retrospectively examined the complications and background relating to the operations performed in those 24 patients. Results. Postoperative hemorrhage occurred in 2 patients, an open ulcer developed on the suture line in 2 and leakage developed in 1. The hemorrhage and open ulcer were observed only when wide resection with regional lymph node dissection was performed for early gastric cancers in the middle third of the stomach. Conclusion. These findings show that the possibility of postoperative hemorrhage and open ulcers on the suture line should be borne in mind, especially when wide local resection with lymph node dissection is performed for cancers in the middle part of the stomach.
  • E Sunami, NH Tsuno, J Kitayama, S Saito, T Osada, H Yamaguchi, S Tomozawa, T Tsuruo, Y Shibata, H Nagawa
    SURGERY TODAY 32 4 343 - 350 2002年 [査読有り][通常論文]
     
    Purpose. In the present study, we investigated the effect of troglitazone, a selective ligand and agonist of PPAR-gamma on the metastatic potential of human colon cancer cells. Methods. High- and low-PPAR-gamma expression clones of the colon cancer cell line, HT29, namely clones 21 and 3 respectively, were used. We investigated the effect of troglitazone on the proliferation, on the adhesion to extracellular matrix proteins and on the synthesis of matrix metalloproteinases (MMPs) of colon cancer cells. Results. Troglitazone inhibited the proliferation of both subclones, in a dose-dependent manner, and the inhibitory effect correlated with the level of PPAR-gamma expression. Troglitazone strongly inhibited the production of MMP-7, an enzyme associated with invasiveness of cancer cells, by both subclones. In addition, troglitazone caused a strong decrease in the adhesion of clone 21 to extracellular matrix (ECM) proteins, laminin and type IV collagen. This effect was independent of beta1-integrins expression. Conclusion. In addition to inhibition of cancer cell growth, troglitazone had an inhibitory effect on two important events associated with the metastatic potential of cancer cells, production of MMPs and adhesion to ECM proteins. Consequently, troglitazone is a promising agent for the treatment and prevention of colon cancer metastasis.
  • T Osada, J Kitayama, H Nagawa
    SURGERY TODAY 32 11 981 - 984 2002年 [査読有り][通常論文]
     
    Cholesterol granuloma of the breast is a rare benign condition which is often clinically and radiologically indistinguishable from breast carcinoma. We herein report the case of a 62-year-old asymptomatic woman who was found on a routine breast examination to have an elastic hard mass, measuring 0.9 cm in diameter, in the upper outer quadrant of the left breast. Physical examination and ultrasonography strongly suggested a carcinomatous lesion. A cytological examination of a fine-needle aspiration biopsy specimen was inconclusive because of the paucity of epithelial cells. A histological examination of excisional biopsy materials showed scattered cholesterol crystals arranged in irregular, parallel arrays, surrounded by histiocytes and giant cells, which were consistent with a diagnosis of cholesterol granuloma. This case report indicates the importance of performing a histological examination to establish the final diagnosis of cholesterol granuloma. We believe that a better awareness of this breast disease might help to prevent both a misdiagnosis and unnecessary surgery.
  • T Osada, H Nagawa, J Kitayama, NH Tsuno, S Ishihara, M Takamizawa, Y Shibata
    CELLULAR IMMUNOLOGY 213 1 14 - 23 2001年10月 [査読有り][通常論文]
     
    Dendritic cells (DCs) are essential antigen-presenting cells with a wide variety of functions relating to both adaptive and innate immunity. Recently, interactions of DCs with natural killer (NK) cells and NK1.1-positive T cells have been reported in mice. However, in humans, this interaction is not well understood. Here we report the use of a coculture method to analyze the modulation of NK cell function in antitumor immunity by DCs. We found that peripheral blood DCs (PDCs) enhanced NK cell activity in cytotoxicity assay, even without direct contact between DC and NK cells. In contrast, neither monocyte-derived DCs (MoDCs), nor TNF-alpha-treated MoDCs, stimulated NK lytic activity. Secretion of IL-12 and TNF-alpha into the PDC-NK coculture supernatant was increased. However, blocking antibodies against these cytokines could not completely abolish the upregulation of NK activity, suggesting the presence of other soluble factor(s) that affect DC-NK cell interaction. To summarize, this study demonstrates for the first time the direct activation of human NK cells by DC-NK cell interaction in vitro, suggesting that DCs may have a central role linking the innate and adaptive immune responses. Moreover, in stimulating NK cell function, PDCs appear to have a different potential from MoDCs. (C) 2001 Elsevier Science.
  • H Yano, J Kitayama, K Hatano, N Tsuno, T Osada, T Watanabe, T Tsuruo, T Muto, H Nagawa
    JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH 20 3 407 - 412 2001年09月 [査読有り][通常論文]
     
    It remains a question whether hematogeneous metastasis arises from a single cancer cell attached to the local endothelium or from a cluster of cancer cells trapped in the vascular bed in the target organ. Adhesive interaction of the single cell form and the clustered form of cancer cells was examined under flow conditions, using two subclones of mouse colon adenocarcinoma Colon 26. A subclone NL17, but not NL14, formed many clusters composed of tumor cells and platelets just after the addition of platelet rich plasma (PRP). Under the shear of 1.0 dyn/cm(3), the clustered form of NL17 tethered on laminin or mouse endothelial cell line in hepatic sinusoids (HSE) more frequently than the single cell form of NL17 and NL14. However, all of the clusters showed only transient attachment and never underwent stable arrest on coated laminin, while the single cell form of NL14 and NL17 underwent immediate arrest under shear conditions. On HSE stimulated with TNF-alpha, a small number of NL17 clusters made stable adhesion, although all the clusters detached if the shear stress was increased above 4.0 dyn/cm(2). In contrast, the single form of arrested NL17 as well as NL14 remained adherent even at shear of 8.0 dyn/cm(2). Compared with single cell, binding of cancer cell clusters to laminin and HSE showed lower resistance to shear stress, although they had adhesive interactions more frequently inflow condition. Since NL17 cells form significantly more metastases by intravenous injection in vivo, our data suggest that "stable adhesion" observed in our flow assay system is not always a prerequisite for clustered cancer cells to develop into metastatic lesions.
  • Furukawa Y, Kawasoe T, Daigo Y, Nishiwaki T, Ishiguro H, Takahashi M, Kitayama J, Nakamura Y
    Biochemical and Biophysical Research Communications 284 3 643 - 649 2001年 [査読有り][通常論文]
  • Hata K, Kitayama J, Shinozaki M, Komuro Y, Watanabe T, Takano T, Iwase S, Nagawa H
    Jpn J Clin Oncol 31 162 - 164 2001年 [査読有り][通常論文]
  • T Osada, Nagashima, I, NH Tsuno, J Kitayama, H Nagawa
    JOURNAL OF HEPATOLOGY 33 2 247 - 253 2000年08月 [査読有り][通常論文]
     
    Background/Aims: Glutamine synthetase (GS) catalyzes the synthesis of glutamine, a major energy source of cells, and is upregulated in a subset of human hepatocellular carcinomas (HCCs), GS expression may be related to tumor recurrence, since GS-expressing tumors have a growth advantage in that they are independent of the extracellular glutamine supply, However, there are no studies concerning the prognostic value of GS expression in patients with HCC. Methods: Seventy-three patients with a single advanced HCC nodule who underwent curative hepatectomy were included in the study. GS expression in the HCC nodules was analyzed immunohistochemically and was compared with clinicopathologic features and the behavior of the tumors. Survival curves were assessed according to the Kaplan-Meier product-limit method and multivariate analysis based on the Cox regression model was performed. Results: GS expression was strong in 26 cases (35.6%, high-GS group) and weak or absent in 47 cases (64.4%, low-GS group), Univariate analysis showed that the high-GS group had a significantly shorter disease-free survival time than the low-GS group (p=0.042). Multivariate analysis revealed that GS expression (p=0.021), as well as Child's classification (p=0.005) and portal invasion (p=0.039), was a significant and independent prognostic parameter that affected tumor recurrence. Conclusion: The results of this study indicate that GS expression may enhance the metastatic potential in HCC, and GS immunostaining may be helpful in identifying HCC patients at high risk for disease recurrence.
  • S Tomozawa, NH Tsuno, E Sunami, K Hatano, J Kitayama, T Osada, S Saito, T Tsuruo, Y Shibata, H Nagawa
    BRITISH JOURNAL OF CANCER 83 3 324 - 328 2000年08月 [査読有り][通常論文]
     
    Epidemiological studies have demonstrated that nonsteroidal anti-inflammatory drugs (NSAIDs), known to inhibit cyclooxygenase (COX), reduce the risk of colorectal cancer. COX is a key enzyme in prostaglandin biosynthesis, and two isoforms of COX, COX-1 and COX-2, have been identified. Recently COX-2 has been reported to frequently overexpress in colorectal neoplasms and to play a role in colorectal tumorigenesis and tumour progression. In this study, using immunohistochemistry, we examined COX-2 expression in advanced human colorectal cancer and its correlation with clinicopathological features. COX-2 expression was observed mainly in the cytoplasm of cancer cells in all the specimens examined, but some stromal cells and endothetial cells were also stained. According to the grade of COX-2 expression of the cancer cells, patients were divided into high- and low-COX-2 expression groups. High-COX-2 expression significantly correlated with tumour recurrence, especially haematogenous metastasis. These results suggest that a selective COX-2 inhibitor can be a novel class of therapeutic agents not only for tumorigenesis but also for haematogenous metastasis of cololectal cancer. To our knowledge, this is the first report on the correlation between COX-2 overexpression and recurrence of colorectal cancer. (C) 2000 Cancer Research Campaign.
  • S Ishihara, M Nieda, J Kitayama, T Osada, T Yabe, A Kikuchi, Y Koezuka, SA Porcelli, K Tadokoro, H Nagawa, T Juji
    JOURNAL OF IMMUNOLOGY 165 3 1659 - 1664 2000年08月 [査読有り][通常論文]
     
    alpha-Glycosylceramides, such as alpha-galactosylceramide and alpha-glucosylceramide, induce antitumor immunity in various murine cancer models. In the murine hepatic metastasis model, V alpha 14 TCR(+)NK1.1(+) T cells, which accumulate preferentially in the liver, are considered to play a key role in the induction of antitumor immunity by alpha-glycosylceramides. We recently reported that V alpha 24 TCR+ NKT cells, the human homologues of murine V alpha 14 TCR(+)NK1.1(+)cells, are rarely seen among freshly isolated human hepatic lymphocytes, Therefore, it is important to examine whether alpha-glycosylceramides also enhance the antitumor cytotoxicity of human hepatic lymphocytes, as they have been shown to do in murine systems, to determine the usefulness of alpha-glycosylceramides in cancer immunotherapy in humans. Here, we show that alpha-glycosylceramides greatly enhance the cytotoxicity of human hepatic lymphocytes obtained from cancer patients against the tumor cell lines, K562 and Colo201, in vitro, The direct effector cells of the elicited cytotoxicity were CD3(-)CD56(+) NK cells. Even though V alpha 24 TCR+NKT cells proliferated remarkably in response to alpha-glycosylceramides, they did not contribute directly to the cytotoxicity. Our observations strongly suggest the potential usefulness of alpha-glycosylceramides for immunotherapy of liver cancer in humans based on their ability to activate CD3-CD56+ NK cells in the liver.
  • J Kitayama, A Hidemura, H Saito, H Nagawa
    CELLULAR IMMUNOLOGY 203 1 39 - 46 2000年07月 [査読有り][通常論文]
     
    Polymorphonuclear cell (PMN) transmigration across the TNF-alpha-stimulated endothelial cell (HUVEC) monolayer in the presence of shear flow was monitored with time-lapse videotapes. More than half of the PMN that arrested on HUVEC transmigrated through endothelial cell junctions within the following 15 min. The kinetics of transmigration was significantly faster than that of PMN placed under static conditions. Once PMN crept into the subendothelial space, they showed random migration beneath the HUVEC monolayer. PMN that did not transmigrate moved on the apical surface of HUVEC in the direction of flow down stream. Anti-beta 1 integrin mAb (4B4) and RGD peptide inhibited the transmigration more effectively than anti-beta 2 integrin mAb (TS1/18) and almost totally abrogated transmigration. When HUVEC were cultured on fibronectin or laminin, the transmigration was significantly inhibited by anti-alpha 5 or alpha 6 integrin mAbs, respectively. Our data clearly indicate that shear stress affects the migration behavior of PMN arrested on endothelium and suggest that binding to subendothelial extracellular matrix via beta 1 integrins is another essential step in leukocyte extravasation. (C) 2000 Academic Press.
  • H Nakayama, J Kitayama, T Muto, H Nagawa
    JAPANESE JOURNAL OF CLINICAL ONCOLOGY 30 7 301 - 305 2000年07月 [査読有り][通常論文]
     
    Background: Analysis of serum cytokine levels has shown that cancer-bearing hosts have lower levels of IL-2 and IFN-gamma, suggesting that Th1-type immunity is impaired by cancer. However, the mechanisms of the Th1 dysfunction are not clearly understood. Method: The frequencies of Th1 cells in CD4(+) helper T cells were evaluated with an intracytoplasmic cytokine staining method in peripheral blood lymphocytes (PBL) and lymph node lymphocytes (LNL) of patients with gastrointestinal cancer. Results: Activation of lymphocytes with PMA + lonomycin induced the expression of IL-2 and IFN-gamma in each lymphocyte population. Compared with PBL of non-malignant donors, PBL in cancer patients contained significantly lower frequencies of CD4(+) T cells that produced IL-2 and IFN-gamma. LNL in cancer patients also contained lower levels of IL-2- and IFN-gamma-producing CD4(+) T cells, although the percentages did not show significant differences from those of PBL in the same patients. Conclusion: Our data suggest that suppression of Th1 cytokine in cancer patients is,at least in part, due to the decreased frequency of Th1 cells with CD4(+) phenotype.
  • T Takenoue, H Nagawa, K Matsuda, S Fujii, ME Nita, K Hatano, J Kitayama, T Tsuruo, T Muto
    ANNALS OF SURGICAL ONCOLOGY 7 3 193 - 198 2000年04月 [査読無し][通常論文]
     
    Background: Thymidylate synthase (TS) is regarded as a parameter of 5-fluorouracil (5-FU) chemosensitivity for colorectal carcinoma. Recent researchers indicate that the chemosensitivity of 5-FU for colorectal carcinoma with low expression of TS is better than tumors with high expression of TS. But the relation between TS expression and overall survival of curatively resected colorectal cancer patients has been less studied. Methods: Specimens of curatively resected colon carcinoma from 148 patients were included in this study. TS expression in the tumor was assessed by immunohistochemical staining technique, and the patients were categorized into TS-(+) and TS-(-) groups. First, the relation between TS expression and survival of patients was examined. Next, for each group, we compared survival between the chemotherapy-(+) and the chemotherapy-(-) subgroup. Results: Overall survival was significantly better in the TS-(-) group (n = 107) than in the TS-(+) group (n = 41) (P = .0003). In the TS-(-) group, there was Little difference between the chemotherapy-(+) and the chemotherapy-(-) subgroup. In the TS-(+) group, the survival of the chemotherapy-(+) subgroup was significantly better than the chemotherapy-(-) subgroup (P = .0439). Conclusions: TS, itself, may be a prognostic factor for colon carcinoma; and 5-FU adjuvant chemotherapy may be appropriate for colon carcinoma with high expression of TS.
  • T Takenoue, J Kitayama, Y Takei, N Umetani, K Matsuda, ME Nita, K Hatano, T Tsuruo, H Nagawa
    ANNALS OF ONCOLOGY 11 3 273 - 279 2000年03月 [査読有り][通常論文]
     
    Background: Dihydropyrimidine dehydrogenase (DPD) is the first enzyme that metabolizes 5-fluorouracil (5-FU). Until now, enzymatic activity or mRNA expression of DPD has been investigated. However, there are no papers on immunohistochemical evaluation of DPD. We investigated DPD staining on immunohistochemistry, and examined the relationship among immunohistochemical score, protein level and mRNA expression of DPD. Materials and methods: Forty-seven resected colon cancer specimens, four colon cancer cell lines, two xenografts by colon cancer cell lines, and human mononuclear cells were used. Immunohistochemistry was performed using DPD monoclonal antibody. Protein levels were determined by Western blot analysis. And mRNA levels were calculated by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). Results: DPD was strongly expressed in the cytoplasm of cancer cells, and in the cytoplasm of macrophage and plasma cells. The immunohistochemical score was more correlated with protein levels (P = 0.0054) than mRNA expression (P = 0.9028). Conclusions: We investigated the characterization of DPD immunohistochemically, and showed that immunohistochemical expression of DPD can be used to predict the sensitivity of colorectal carcinomas to 5-FU.
  • B Zhao, W Kimura, N Futakawa, H Abe, J Kitayama, H Nagawa, M Makuuchi
    JAPANESE JOURNAL OF CANCER RESEARCH 91 3 331 - 336 2000年03月 [査読有り][通常論文]
     
    The expression of thymidine phosphorylase (TP) in carcinoma of the papilla of Vater was studied to clarify its significance in tumor progression and in determining prognosis. Fifty-nine cases of surgically resected carcinoma of the papilla of Vater were studied. Immunohistochemical staining was performed to evaluate the expression of TP, microvessel count and p53 overexpression. TP expression was demonstrated in tumor cells in 62.7% (37/59) of the cases. A higher frequency of regional lymph node metastasis was found in TP-positive tumors than in TP-negative tumors (P=0.006). TP-positive tumors were more advanced than TP-negative tumors with regard to clinical stage (P=0.035). TP-positive tumors had significantly higher microvessel density (27.6+/-10.1) than TP-negative tumors (20.4+/-10.0, P=0.01). Moreover, TP expression was significantly correlated with a poor prognosis (P=0.02). These suggest that in carcinoma of the papilla of Vater, TP production by tumor cells is correlated with tumor progression through its regulatory effect on neovascularization.
  • J Kitayama, S Ikeda, K Kumagai, H Saito, H Nagawa
    CELLULAR IMMUNOLOGY 199 2 97 - 103 2000年02月 [査読有り][通常論文]
     
    Polymorphonuclear leukocytes (PMN) were perfused over extracellular matrix protein substrates under laminar shear flow. Under shear below 1.5 dyn/cm(2), many PMN tethered to immobilized laminin but not to fibronectin or vitronectin, Almost all the tethered PMN immediately arrested on laminin. The number of tethered PMN was mostly abrogated by mAbs to integrin alpha 6 Or beta 1 chains at concentrations of more than 5 mu g/ml. Addition of the two mAbs together produced no further inhibition compared with each mAb alone. In contrast, none of the mAbs to alpha 2, alpha 3, and beta 4 chains showed significant inhibition, indicating that PMN tethering to laminin is mostly dependent on alpha 6 beta 1 integrin. The addition of 10-100 ng/ml IL-8 in the assay medium before perfusion partially reduced PMN tethering to laminin. Stimulation with IL-8 also induced detachment of some tethered PMN within 30 s. Thus, IL-8 partially weakens the adhesiveness of alpha 6 beta 1 integrin on PMN in how conditions. (C) 2000 Academic Press.
  • Eiji Sunami, Nelson Tsuno, Takuya Osada, Shinsuke Saito, Joji Kitayama, Shigeru Tomozawa, Takashi Tsuruo, Yoichi Shibata, Tetsuichiro Muto, Hirokazu Nagawa
    Oncologist 5 2 108 - 114 2000年 [査読有り][通常論文]
     
    Background. Degradation of basement membrane and extracellular matrix by matrix metalloproteinases (MMPs) is believed to be an essential step in the complicated process of hematogenous metastasis. MMP-1 is a member of collagenases, a family of MMPs that degrades collagens type I, II, and III, main components of the interstitial stroma. The purpose of this study was to investigate the expression of MMP-1 in colorectal cancer and its correlation with hematogenous metastasis. Patients and Methods. We examined 133 cases of colorectal cancer (Dukes A: 72 Dukes B: 26 Dukes C: 23 Dukes D: 12). Sections were cut from formalin-fixed, paraffin-embedded samples containing the deepest site of cancer invasion and stained immunohistochemically with a monoclonal antibody to MMP-1. According to the area of the tumor that was stained, patients were divided into high- and low-MMP-1 expression groups. Results. MMP-1 expression was observed in the cytoplasm of cancer cells, some stromal cells, and a few normal epithelial cells of colonic mucosa. High MMP- 1 expression was found in 47 (35.3%) cases and low in 86 (64.7%). Hematogenous metastasis was identified in 14 (29.8%) of high-MMP-1 groups and 12 (13.9%) of low-MMP-1 groups. MMP-1 expression significantly correlated with hematogenous metastasis of colorectal cancer, but no correlation was found between MMP-1 expression and the other clinicopathological features investigated. Conclusions. MMP-1 expression may be a novel marker for hematogenous metastasis of colorectal cancer, and its inhibition may be a strategy for prevention of metastasis.
  • S Saito, N Tsuno, H Nagawa, E Sunami, J Zhengxi, O Takuya, J Kitayama, Y Shibata, T Tsuruo, T Muto
    CANCER 88 1 42 - 49 2000年01月 [査読有り][通常論文]
     
    BACKGROUND. Platelet-derived endothelial cell growth factor (PD-ECGF) is an angiogenic factor that has potent chemotactic activity for endothelial cells. Although it is expressed in the majority of colorectal tumors, and some reports suggest that its high expression is related to poor prognosis, to the authors' knowledge there is yet no consensus regarding whether PD-ECGF expression is a prognostic factor. To investigate the prognostic value of PD-ECGF and its role in tumor angiogenesis, an immunohistochemical study of PD-ECGF expression and tumor vasculature was performed and their relation with the clinicopathologic factors in patients with advanced colorectal carcinoma was evaluated. METHODS. Formalin fixed, paraffin embedded specimens from 86 colorectal carcinoma patients (40 cases in the muscularis propria and 46 cases in the subserosa) were immunostained for PD-ECGF and CD31 as a marker for vascular endothelial cells and expression of PD-ECGF was evaluated using an image analysis system. Patients were divided into high expression and low expression groups based on PD-ECGF expression, and were divided into high vascular grade and low vascular grade groups based on the microvessel density. Correlations between PD-ECGF expression and vascular grade and between PD-ECGF: expression,vascular grade, and the clinicopathologic features of the patients were evaluated statistically. RESULTS. PD-ECGF expression was observed predominantly in the turner stroma and not in tumor cells. The cells that stained strongly for PD-ECGF were confirmed to be macrophages infiltrating the interstitial tissue of the tumor. High PD-ECGF expression was found in 56 cases (65.1%) and low expression was detected in 30 cases (34.9%). Thirty-one of 86 tumors (36.0%) showed high vascular grade and 55 (64.0%) showed lo iv vascular grade. No correlation between PD-ECGF expression and vascular grade was found, but there was an inverse correlation between PD-ECGF expression and the rate of incidence of lymph node and hematogenous metastasis. These correlations were statistically significant. Vascular grade was not found to correlate with the clinicopathologic features, CONCLUSIONS. Patients with high PD-ECGF expression had a lower rate of incidence of lymphatic and hematogenous metastasis, with a consequently better prognosis than patients with low PD-ECGF expression. PD-ECGF expression did not correlate with vascular grade, suggesting that PD-ECGF plays little role in tumor angiogenesis of colorectal carcinoma. Based on these data, the authors conclude that macrophages infiltrating the tumor stroma produce PD-ECGF and play important roles in the immune reaction against the tumor rather than in tumor angiogenesis. Cancer 2000;88:42-9, (C) 2000 American Cancer Society.
  • J Kitayama, N Tsuno, E Sunami, T Osada, T Muto, H Nagawa
    EUROPEAN JOURNAL OF CANCER 36 1 121 - 127 2000年01月 [査読有り][通常論文]
     
    The aim of this study was to determine whether colon cancer cells flowing in blood exhibit the same adhesion pattern to the vascular bed as leucocytes using a flow adhesion system. In shear flow conditions, five colon cancer cell lines showed less tethering to E-selectin substrates than polymorphonuclear cells (PMN). However, some of the Colo201 cells formed complete arrest on E-selectin in continuous shear flow which was never observed in PMN cells. Colo201 cells expressed both sialyl Le-x and sialyl Le-a at similar levels in flow cytometry. However, the staining pattern showed marked contrast under the fluorescein microscope. The cell membrane of Colo201 cells was uniformly stained with anti-salyl Le-a MAb, whereas anti-sialyl Le-x MAb only stained in the patchy areas. Pretreatment of Colo201 cells with anti-ale-a decreased tethering, while anti-sle-x significantly inhibited the arrest formation. Our data suggest that E-selectin alone can mediate colon cancer cell lodgement and subsequent metastasis without the contribution of integrin molecules and that the different distribution of E-selectin ligands may affect the adhesion behaviour of colon cancer cells in flow conditions. (C) 2000 Elsevier Science Ltd. All rights reserved.
  • J Kitayama, H Nagawa, N Tsuno, T Osada, K Hatano, E Sunami, H Salto, T Muto
    BRITISH JOURNAL OF CANCER 80 12 1927 - 1934 1999年08月 [査読有り][通常論文]
     
    Under the physiological shear condition, cultured colon cancer cells bound to laminin (LM), but not to fibronectin or vitronectin. Most of the tethered cells did not roll, but arrested immediately and spread within 10-30 min on LM under the continuous presence of shear flow. The tethering of Colo201 was partially inhibited by monoclonal antibodies (mAbs) to alpha 6 integrin and a combination of mAbs to beta 1 and beta 4 integrins, but not by mAb to 67KD laminin receptor. Some Colo201 cells still tethered at 4 degrees C. This suggests that alpha 6 beta 1 and alpha 6 beta 4 integrins participate in Colo201 tethering on LM, although other non-integrin molecules play roles. In contrast, the spread of Colo201 was effectively inhibited by the mAbs to integrin alpha 2, alpha 6 and beta 1 chains. The effect of anti-alpha 2 plus anti-alpha 6 mAbs was almost equal to anti-beta 1, suggesting that Colo201 cells mainly use alpha 2 beta 1 and alpha 6 beta 1 integrins for spreading on LM. When the cells were perfused on subconfluent endothelial cells (HUVEC) cultured on LM, they did not tether on HUVEC but did on coated LM exposed at intercellular gap area. Immunohistochemistry revealed that LM abundantly existed in the cytosol of human portal and hepatic vein endothelial cells. These data suggest that LM can mediate from tethering to spreading of colon cancer cells under the blood flow and plays an essential role in haematogeneous metastasis.
  • S Ishihara, M Nieda, J Kitayama, T Osada, T Yabe, Y Ishikawa, H Nagawa, T Muto, T Juji
    EUROPEAN JOURNAL OF IMMUNOLOGY 29 8 2406 - 2413 1999年08月 [査読有り][通常論文]
     
    A unique subset of T cells that co-express NKR-P1, which is a lectin type of NK receptor and is thought to have a major role in triggering NK activity, has been identified. In mice, NK1.1 (mouse NKR-P1C)(+) T cells, called NKT cells, preferentially accumulate in the liver and bone marrow. They predominantly use invariant V alpha 14 chain VCR and phenotypically are CD4(+)CD8(-) or CD4(-)CD8(-) T cells. In this study, we analyzed, phenotypically and functionally, the NKR-P1A (analogue of murine NKR-P1C)(+) T cells resident: in the human liver. Here, we show that in complete contrast to the NKT cells in the mouse liver, the majority of NKR-P1A(+) T cells in the human liver are CD8(+) and their TCR repertoire is not skewed to V alpha 24 TCR, the homologue of murine V alpha 14 TCR. Almost all of the NKR-P1A(+) T cells in the human liver expressed CD69, suggesting that they were activated. Furthermore, the NKR-P1A(+) T cells in the human liver exhibited strong cytotoxicity against a variety of tumor cell lines including K562, Molt4 and some colonic adenocarcinoma cell lines.
  • J Kitayama, N Tuno, H Nakayama, Y Shibata, T Muto, H Nagawa
    ANNALS OF SURGICAL ONCOLOGY 6 5 500 - 506 1999年07月 [査読有り][通常論文]
     
    Integrins play an important role in various lymphocyte functions. In this study, we isolated lamina propria lymphocytes (LPL) and tumor-infiltrating lymphocytes (Tn) from normal and malignant tissues in patients with colorectal cancer, and examined the expression of beta 1 and beta 2 integrins on these lymphocytes quantitatively with two-color flow cytometry, Both LPL and Tn expressed a lower level of common beta 1 chain (CD29) in CD4 and CD8 subpopulations than did peripheral blood lymphocytes (PBL). Among the associated alpha chains, the expression levels of alpha 1 (CD49a) and alpha 2 (CD49b) were slightly higher, whereas those of alpha 4 (CD49d) and alpha 6 (CD49f) were markedly reduced in LPL and Tn. No significant differences were observed in expressions of any beta 1 integrin chains between these two lymphocytes populations. Similarly, both alpha L (CD11a) and beta 2 (CD18) were down-regulated in TIL and LPL with CD8(+) cytotoxic phenotype, but not in these with CD4 phenotype. CD8(+) TIL expressed a slightly but significantly higher level of alpha L beta 2 than did CD8 LPL. CD8(+) LPL and CD8(+) TIL consistently showed significantly decreased binding to purified ICAM-1, VCAM-1 and HT29 colon cancer cells as compared with CD8(+) PBL. Although CD8(+) TIL showed a slightly higher level of adhesion to these substrates than did CD8(+) LPL, the level was much lower than that in PBL. The expression pattern and functional down-regulation of these integrins may be one of the reasons why TIL cannot eradicate the cancer cells in colorectal cancer.
  • ME Nita, H Nagawa, O Tominaga, N Tsuno, K Hatano, J Kitayama, T Tsuruo, CE Domene, T Muto
    ANNALS OF SURGICAL ONCOLOGY 6 5 481 - 488 1999年07月 [査読有り][通常論文]
     
    Background: p21Waf1/Cip1 (p21), p27Kip1 (p27), p53, and Rb play critical roles in cell cycle regulation and may influence the clinical behavior of tumors. We examined whether their expression is useful to predict survival of patients with esophageal squamous cell carcinoma (ESC). Methods: Expression of p21, p27, p53, and Rb was studied by the immunohistochemical method in specimens from 62 patients with curatively resected ESC tumors and scored by a computerized image analysis system. Results: The median expression scores of p21, p27, p53, and Rb (14, 12, 27, and 50, respectively) were used as cut-off points to define low and high expression groups for each protein. The 5-year survival rate for the high p21 expression group was 68%; that for the low expression group was 31% (P = .0062). p27, p53, and Rb were not correlated with overall survival. When patients were categorized into four groups based on p21 expression level and lymph node involvement (pN), the survival curves were significantly different (P = .0017). Thus, patients without lymph node involvement but with low p21 expression had survival similar to that of patients with lymph node involvement and high p21 expression. Multivariate analysis showed that age (P = .0102), lymph node involvement (P = .0076), and p21 (P = .0276) were independent prognostic factors, Conclusions: Expression of p21 is an independent prognostic factor in curatively resected ESC. Definition of new subgroups of patients based on p21 expression may help to enhance the stratification of stage.
  • J Kitayama, H Nagawa, H Nakayama, N Tuno, Y Shibata, T Muto
    JOURNAL OF GASTROENTEROLOGY 34 3 327 - 333 1999年06月 [査読有り][通常論文]
     
    Integrins play an important role in various lymphocyte functions. In this study, tumor-infiltrating lymphocytes (TIL) were isolated from colorectal cancer tissues and the expression of beta 1 and beta 2 integrins on the TIL was quantitatively examined with two-color flow cytometry. In comparison with peripheral blood lymphocytes (PBL), TIL expressed a lower level of common beta 1 chain (CD29) in both CD4 and CD8 subpopulations. Among the associated a chains, the expressions of alpha 1 (CD49a) and alpha 2 (CD49b) were slightly higher in TIL than in PBL, whereas alpha 4 (CD-49d) and alpha 6 (CD49f) were markedly downregulated in TIL. Both alpha L (CD11a) and beta 2 (CD18) were reduced in CD8(+) TIL but not in CD4(+) TIL, TIL with the CD8(+) cytotoxic phenotype showed significantly decreased binding to purified intracellular adhesion molecules (ICAM)-1, and vascular adhesion cell molecule (VCAM)-1, and HT29 colon cancer cells, compared with the in counterparts in PBL, The peculiar expression pattern and functional down regulation of these integrins may explain why TIL in colorectal cancer cannot eradicate the malignant cells.
  • ME Nita, H Nagawa, O Tominaga, N Tsuno, J Kitayama, T Takenoue, T Tsuruo, T Muto
    GASTROENTEROLOGY 116 4 A475 - A475 1999年04月 [査読無し][通常論文]
  • ME Nita, H Nagawa, O Tominaga, N Tsuno, K Hatano, T Takenoue, J Kitayama, CE Domene, T Tsuruo, T Muto
    GASTROENTEROLOGY 116 4 A475 - A475 1999年04月 [査読無し][通常論文]
  • Y Seto, H Nagawa, Y Muto, S Kaizaki, J Kitayama, T Muto
    BRITISH JOURNAL OF SURGERY 86 4 526 - 528 1999年04月 [査読無し][通常論文]
     
    Background: The frequency of lymph node metastasis in mucosal gastric cancers 2-4 cm in diameter was low (three (1.3 per cent) of 234) in patients treated in this unit between 1966 and 1995. This study was a prospective report on local resection with lymphadenectomy for early gastric cancer. Methods: Eight patients with a single early gastric cancer underwent local resection with lymphadenectomy. The tumour was excised with a non-cancerous rim of approximately 2 cm. The extent of lymphadenectomy depended on tumour location. Intraoperative endoscopic examination and frozen-section analysis of the dissected nodes were used to determine the resection line and evaluate nodal status. Results: Mean operating time, blood loss and number of dissected nodes were 171 min, 87 ml and 8 respectively. There were no operative complications. Cancer invasion was confined to the mucosa in six tumours but two patients had minute submucosal invasion. The maximum diameter of the resected specimens was 10 cm and no nodal involvement was detected. No patient developed postgastrectomy syndrome. Conclusion: For selected patients with early gastric cancer, local resection with lymphadenectomy can provide a good quality of life without compromising cure rate.
  • S Sameshima, K Sakai, H Nagawa, N Tsuno, J Kitayama, T Muto
    SURGERY TODAY-THE JAPANESE JOURNAL OF SURGERY 29 1 55 - 62 1999年 [査読有り][通常論文]
     
    It has been established that lymphocytes obtained from tumor-draining lymph nodes (DLN) are sensitized to the tumor antigen in vivo. Moreover, after being activated in vitro, these cells can be utilized for adoptive immunotherapy. In the present study, DLN cells, obtained from C57BL/6 mice with fibrosarcoma (MC-1), were activated and expanded with anti-CD3 monoclonal antibody followed by culture with recombinant interleukin-2 (rIL-2), These CD4(-) CD8(+) CD25(+) CD44(+) T-cells shelved specific antitumor efficacy to the pulmonary micrometastases of an autologous tumor, against which lymphokine-activated killer cells were ineffective; however, they did not show cytolytic activity in vitro. The supernatant, obtained by coculturing the activated DLN cells with MC-1 cells, exhibited the specific production of interferon-gamma (IFN-gamma) which was enhanced by rIL-2, The therapeutic effect of the activated DLN cells correlated with the specific IFN-gamma production better than with the cytolytic activity.
  • Y Seto, H Nagawa, J Kitayama, T Muto
    SURGERY TODAY-THE JAPANESE JOURNAL OF SURGERY 29 11 1229 - 1230 1999年 [査読有り][通常論文]
     
    A technique, by which the root of the right gastric artery can be clearly exposed and the area of the right gastric artery can thus be completely dissected, is presented herein, In conventional procedures, the approach to the right gastric artery is performed from the lessor omentum, and a lymphadenectomy along the common hepatic artery is carried out after the division of the right gastric artery. Using the present technique, the common hepatic artery is exposed before the exposure of the right gastric artery and lymph node dissection is thus continued peripherally to the proper hepatic artery, During these procedures, the root of the right gastric artery arising from the hepatic artery can be easily identified. The lymphatic flow from the area of the right gastric artery to that of the common hepatic artery is transected using the conventional procedure, but not with the present technique. In addition, an en bloc dissection of the regional lymph nodes is also possible when using this procedure.
  • H Shinkai, J Kitayama, W Kimura, T Muto, Y Shibata
    CANCER 78 8 1677 - 1685 1996年10月 [査読有り][通常論文]
     
    BACKGROUND. To evaluate the immunologic activity of regional lymph nodes, the phenotype of lymphocytes and the functional expression of cell adhesion molecules (CAMs) on lymph node lymphocytes (LNL-: uninvolved, LNL+: involved) were investigated in patients with gastrointestinal carcinoma. METHODS. The lymphocyte subpopulation and the expression of CD11a, CD44, and CD29 on CD4+ and CD8+ cells in peripheral blood lymphocytes (PBL), LNL-, and LNL+ derived from 37 patients with gastrointestinal carcinoma were studied. In addition, the adherence of CD8+ cells to ICAM-1 which reflects the adhesive function of CD11a, was examined, and changes in this adherence were studied by experimental coculture with cancer cells (DLD-1). RESULTS. Although there were no differences in the overall proportion of T cells between the groups, CD8+ cells and CD16+ cells were considerably diminished in LNL+. The expression of CD11a and CD29 on CD4+ and CD8+ cells was significantly lower in LNL than in PBL, whereas the expression of CD44 showed no significant differences. The expression levels of these CAMs were almost the same in LNL- and LNL+. Only CD11a expression on CD8+ cells in LNL+ was significantly lower than that in LNL- (P < 0.005). The adherence of CD8+ cells in LNL+ to ICAM-1 was lower than that in PBL and LNL-, and was extremely enhanced by experimental coculture with cancer cells (DLD-1). CONCLUSIONS. These data indicate that the functional expression of CD11a (LFA-1) on CD8+ T cells is suppressed in cancer-involved regional lymph nodes in patients with gastrointestinal carcinoma. (C) 1996 American Cancer Society.
  • C Weber, J Kitayama, TA Springer
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 93 20 10939 - 10944 1996年10月 [査読有り][通常論文]
     
    The CC chemokines regulated on activation normal T expressed and secreted (RANTES) and monocyte chemotactic protein 3 (MCP-3), and the anaphylatoxin C5a, induce activation, degranulation, chemotaxis, and transendothelial migration of eosinophils. Adhesion assays on purified ligands showed differential regulation of beta 1 and beta 2 integrin avidity in eosinophils. Adhesiveness of VLA-4 (alpha 4 beta 1, CD29/CD49d) for vascular cell adhesion molecule 1 or fibronectin was rapidly increased but subsequently reduced by RANTES, MCP-3, or C5a. The deactivation of VLA-4 lead to cell detachment, whereas phorbol 12-myristate 13-acetate in duced sustained activation of VLA-4. In contrast, chemoattractants stimulated a prolonged increase in the adhesiveness of Mac-1 (alpha M beta 2, CD11b/CD18) for intercellular adhesion molecule 1, Inhibition by pertussis toxin confirmed signaling via G protein-coupled receptors, Chemoattractants induced transient, while phorbol 12-myristate 13-acetate induced sustained actin polymerization, Disruption of actin filaments by cytochalasins inhibited increases in avidity of VLA-4 but not of Mac-1, Chemoattractants did not upregulate a Mn2+-inducible beta 1 neoepitope defined by the mAb 9EG7, but induced prolonged expression of a Mac-1 activation epitope recognized by the mAb CBRM1/5. This mAb inhibited chemoattractant stimulated adhesion of eosinophils to intercellular adhesion molecule 1, Thus, regulation of VLA-4 was dependent on the actin cytoskeleton, whereas conformational changes appeared to be crucial for activation of Mac-1, To our knowledge, this is the first demonstration that physiological agonists, such as chemoattractants, can differentially regulate the avidity of a beta 1 and a beta 2 integrin expressed on the same leukocyte.
  • N TSUNO, M SHINOZAKI, J KITAYAMA, H NAGAWA, T WATANABE, S SAMESHIMA, M UCHIYAMA, Y SAITO, T SAWADA, T MUTO
    GASTROENTEROLOGY 108 4 A931 - A931 1995年04月 [査読無し][通常論文]
  • S SAMESHIMA, K SAKAI, H NAGAWA, N TSUNO, J KITAYAMA, Y SAITO, T SAWADA, T MUTO
    GASTROENTEROLOGY 108 4 A533 - A533 1995年04月 [査読無し][通常論文]
  • T FUKAGAWA, H NAGAWA, J KITAYAMA, N TSUNO, O TOMINAGA, H TSUKUI, R FUKUSHIMA, Y SETO, Y MUTO, S KAISAKI, H SUZUKI, K HATANO, T MUTO
    1ST INTERNATIONAL GASTRIC CANCER CONGRESS, VOL 1-2 437 - 442 1995年 [査読有り][通常論文]
  • J KITAYAMA, H NAGAWA, H YASUHARA, N TSUNO, W KIMURA, Y SHIBATA, T MUTO
    CANCER RESEARCH 54 17 4729 - 4733 1994年09月 [査読有り][通常論文]
     
    The effect of basic fibroblast growth factor (b-FGF), one of the commonest angiogenic factors in various cancer types, on lymphocyte adhesion and transmigration across the endothelial cell monolayer was investigated using human umbilical vein-derived endothelial cells (HUVEC) and type I collagen gel. Forty-eight h exposure of HUVEC with 2 ng/ml b-FGF significantly decreased the basal adhesion of lymphocytes to endothelial cells. The decrease ratio is further enhanced by the addition of shear stress in this assay system. When HUVEC was stimulated for the last 24 h with optimal conditions of recombinant interleukin 1 beta, the percentages of transmigration as well as adhesion were also decreased significantly by the presence of b-FGF. The expression of intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 was downregulated by b-FGF exposure in both resting and activated conditions by recombinant interleukin 1 beta, supposedly the main reason for this phenomenon. The migrating cells across b-FGF-stimulated HUVEC contained a markedly lower percentage of CD4(+) T-cells than those across nontreated HUVEC, although the 4B4(+)/2H4(+) ratio in CD4(+) T-cell populations did not differ significantly. These facts suggest that the presence of b-FGF in the angiogenic area suppresses lymphocyte emigration, especially that of CD4(c) T-cells, and thus causes insufficient helper function in local immune response. This effect of b-FGF was possibly one of the critical mechanisms by which cancer cells escape from the host immune reactions in the angiogenic stage of tumor development.
  • M FURUE, N YAMADA, T TAKAHASHI, K KIKUCHI, T TSUCHIDA, Y ISHIBASHI, O KOBORI, A IHARA, J KITAYAMA, M MINAMI
    JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY 30 5 899 - 903 1994年05月 [査読無し][通常論文]
     
    We describe a 56-year-old woman with Stewart-Treves syndrome who had severe dyspnea from a pleural effusion caused by metastatic angiosarcoma in the right lung. Tumorinfiltrating lymphocytes (TIL) in the pleural effusion were cultured and expanded in vitro in the continuous presence of recombinant interleukin 2 with periodic stimulation by CD3 antibody. The expanded TIL were administered intrapleurally seven times at 1- to 4-week intervals in combination with intravenous infusion of recombinant interleukin 2. A panel of T-cell clones was also obtained from TIL. Immunotherapy dramatically improved the patient's dyspnea and pleural effusion. A CD4(+) T-cell clone and a CD8(+) T-cell clone established from TIL had specific cytotoxicity to the tumor cells.
  • J KITAYAMA, N TSUNO, H YASUHARA, H NAGAWA, W KIMURA, A KURODA, Y SHIBATA, T JUJI, T MUTO
    CANCER IMMUNOLOGY IMMUNOTHERAPY 38 5 317 - 322 1994年05月 [査読有り][通常論文]
     
    The mechanisms of lysis of endothelial cells derived from human umbilical vein (HUVEC) by autologous lymphokine-activated killer (LAK) cells, generated from cord blood lymphocytes of the same donor, were investigated. Freshly isolated HUVEC as well as HUVEC cultured for several passages were efficiently lysed by autologous LAK cells, and their susceptibility to the LAK cells was almost the some as that of allogenic HUVEC. Complement-depletion experiments revealed that the lysis was mainly dependent on CD16(+) natural killer (NK) LAK cells. Pretreatment of HUVEC with recombinant interferon gamma (rIFN gamma) for 24 h made them resistant to lysis by autologous LAK cells, while pretreatment with either rIL-1 beta. rTNF alpha or acidic or basic fibroblast growth factor did not alter the lyric sensitivity of HUVEC. The resistance of rIFN gamma-treated HUVEC was specific to lysis by CD16(+) NK LAK cells, and their lysis by CD3(+) T-LAK cells was not significantly altered. Moreover, in comparison with control HUVEC or rIL-1 beta-treated HUVEC, rlFN beta-treated HUVEC had a significantly less potent inhibitory effect on the lysis of untreated HUVEC, when used as an unlabeled target. This suggests that rIFN gamma treatment may down-regulate the recognition of some molecules on HUVEC by rIL-2-activated NK cells. These data suggest that damage of the endothelium during LAK therapy is mainly dependent on LAK cells with a NK phenotype that can specifically recognize a certain molecule on autologous endothelial cells.
  • J KITAYAMA, N TSUNO, T FUKAGAWA, H SHINKAI, M SHINOZAKI, H NAGAWA, W KIMURA, T SAWADA, Y SHIBATA, T MUTO
    GASTROENTEROLOGY 106 4 A711 - A711 1994年04月 [査読無し][通常論文]
  • J KITAYAMA, Y ATOMI, H NAGAWA, A KURODA, T MUTOH, M MINAMI, T JUJI
    CLINICAL AND EXPERIMENTAL IMMUNOLOGY 93 3 442 - 447 1993年09月 [査読有り][通常論文]
     
    In six patients with advanced pancreatic carcinoma, TIL and tumour-draining lymphocytes (TDL) were isolated from primary pancreatic tumour and regional lymph nodes. In comparison with TDL and peripheral blood lymphocytes (PBL), TIL contained a comparatively higher percentage of TCR gammadelta+ cells, although they were still a small fraction. By 2 weeks culture with rIL-2 and immobilized OKT-3 antibody, the TCR gammadelta + cells in TIL were preferentially expanded at the early culture periods, although it was temporary. In four cases, the TCR gammadelta+ and CD8+ TCR alphabeta+ TIL were separated by negative sorting using flowcytometry. All the TCR gammadelta+ TIL were CD4-, CD8- (double negative), and one of the TIL lines was mostly composed of deltaTCS1+ cells, while the others were deltaTCS1-. In comparison with CD8+ TCR alphabeta+ TIL, all the TCR gammadelta+ TIL exhibited much stronger lytic activity against freshly isolated autologous pancreatic cancer cells. However, all the gammadelta+ TIL also exhibited a strong non-MHC-restricted cytotoxicity, and there was no correlation between the lytic pattern and the percentage of deltaTCS1+ cells. These data suggest that the TCR gammadelta+ T cells can proliferate vigorously in a certain condition, and if successfully expanded in vitro they might be helpful material for effective adoptive immunotherapy.
  • J KITAYAMA, N TSUNO, M SHINOZAKI, T SAWADA, Y KUBOTA, H NAGAWA, W KIMURA, A KURODA, T JUJI, T MUTO
    GASTROENTEROLOGY 104 4 A416 - A416 1993年04月 [査読無し][通常論文]

講演・口頭発表等

  • 膵内多発腫瘤の1例
    森嶋 計, 下平 健太郎, 青木 裕一, 目黒 由行, 宮戸 秀世, 遠藤 和洋, 笹沼 英紀, 松原 大祐, 佐久間 康成, 北山 丈二, 佐田 尚宏
    膵臓 2021年08月 (一社)日本膵臓学会
  • Flow cytometryを用いた胃癌患者腹腔内遊離癌細胞・免疫細胞の解析
    高橋 和也, 大澤 英之, 金丸 理人, 倉科 憲太郎, 齋藤 心, 山口 博紀, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2021年07月 (一社)日本消化器外科学会
  • Stage IV胃癌に対するConversion surgeryの課題と展望 IP-PTX+SOX療法に奏功を認めた腹膜播種陽性胃癌症例に対するconversoin surgeryの適応と成績
    金丸 理人, 山口 博紀, 齋藤 心, 倉科 憲太郎, 大澤 英之, 高橋 和也, 金子 勇貴, 細谷 好則, 佐田 尚宏, 北山 丈二
    日本消化器外科学会総会 2021年07月 (一社)日本消化器外科学会
  • コロナ感染症対策下のおける当科の臨床実習について
    鯉沼 広治, 川平 洋, 倉科 憲太郎, 遠藤 和洋, 原尾 美智子, 笹沼 英紀, 佐久間 康成, 山口 博紀, 味村 俊樹, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    医学教育 2021年07月 (一社)日本医学教育学会
  • 自治医科大学附属病院における、初期臨床研修医に対する外科研修
    遠藤 和洋, 倉科 憲太郎, 鯉沼 広治, 原尾 美智子, 笹沼 英紀, 佐久間 康成, 川平 洋, 山口 博紀, 味村 俊樹, 堀江 久永, 細谷 好則, アラン・レフォー, 北山 丈二, 佐田 尚宏
    医学教育 2021年07月 (一社)日本医学教育学会
  • コロナ禍における外科臨床実習での医学生の意識変容調査報告
    川平 洋, 鈴木 義彦, 前田 佳孝, 淺田 義和, 倉科 憲太郎, 原尾 美智子, 遠藤 和洋, 笹沼 英紀, 鯉沼 広治, 山口 博紀, 佐久間 康成, 堀江 久永, 細谷 好則, 味村 俊樹, 北山 丈二, アラン・レフォー, 松山 泰, 佐田 尚宏
    医学教育 2021年07月 (一社)日本医学教育学会
  • 消化器癌患者の術直後末梢血中の低比重好中球の割合は侵襲度と相関し、術後再発の予測因子となりうる
    熊谷 祐子, 宮戸 秀世, 大澤 英之, 山口 博紀, 川平 洋, 堀江 久永, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2021年07月 (一社)日本消化器外科学会
  • 直腸癌における縫合不全防止の取り組み 腹腔鏡下低位前方切除術における縫合不全予防の取り組み
    佐田友 藍, 堀江 久永, 鯉沼 広治, 井上 賢之, 直井 大志, 太白 健一, 太田 学, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2021年07月 (一社)日本消化器外科学会
  • 側方リンパ節転移陽性直腸癌に対する治療戦略 臨床的側方リンパ節転移陽性症例に対する術前化学放射線療法と選択的側方リンパ節郭清の治療成績
    堀江 久永, 鯉沼 広治, 直井 大志, 井上 賢之, 佐田友 藍, 太田 学, 太白 健一, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2021年07月 (一社)日本消化器外科学会
  • Stage IV胃癌に対するConversion surgeryの課題と展望 腹膜播種陽性胃癌に対する全身・腹腔内併用化学療法奏効後のconversion surgeryについて
    山下 裕玄, 石神 浩徳, 大森 健, 深川 剛生, 川崎 普司, 岸 健太郎, 上田 修吾, 竹野 淳, 畑 啓昭, 北山 丈二
    日本消化器外科学会総会 2021年07月 (一社)日本消化器外科学会
  • 肝嚢胞性腫瘍の臨床病理学的検討
    下平 健太郎, 青木 裕一, 目黒 由行, 森嶋 計, 遠藤 和洋, 笹沼 英紀, 佐久間 康成, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2021年07月 (一社)日本消化器外科学会
  • 糖尿病治療薬メトホルミンが大腸癌患者の予後に与える影響に関する臨床的検討
    齋藤 晶, 大澤 英之, 山口 博紀, 佐久間 康成, 川平 洋, 堀江 久永, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2021年07月 (一社)日本消化器外科学会
  • 横行結腸癌手術におけるアプローチ法と至適郭清範囲 術者教育と臨床的安全性の両立を目指した腹腔鏡下横行結腸癌手術の定型化
    鯉沼 広治, 堀江 久永, 佐田友 藍, 直井 大志, 井上 賢之, 太白 健一, 太田 学, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2021年07月 (一社)日本消化器外科学会
  • Ta-TMEの現状と展望 下部直腸癌に対するtaTMEの短期治療成績と今後の展望
    井上 賢之, 堀江 久永, 太田 学, 太白 健一, 佐田友 藍, 直井 大志, 鯉沼 広治, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2021年07月 (一社)日本消化器外科学会
  • 消化器外科における医工連携の現状と展望 外科医が主導する医療機器開発と医工連携・知財化の重要性 膵断端処置具開発(Class IV)の経験を通して
    兼田 裕司, 木村 有希, 齋藤 晶, 小泉 大, 笹沼 英紀, 川平 洋, 細谷 好則, 北山 丈二, Lefor Alan, 佐田 尚宏
    日本消化器外科学会総会 2021年07月 (一社)日本消化器外科学会
  • 経口糖尿病薬メトホルミン加療歴を有する乳癌患者の特徴
    芝 聡美, 原尾 美智子, 丸藤 琴音, 扇原 香澄, 佐々木 裕美子, 西田 紗季, 櫻木 雅子, 水沼 洋文, 北山 丈二, 佐田 尚宏
    日本乳癌学会総会プログラム抄録集 2021年07月 (一社)日本乳癌学会
  • 超高齢者乳癌患者にいかに適切な治療を選択するか
    原尾 美智子, 丸藤 琴音, 佐々木 裕美子, 西田 紗季, 芝 聡美, 櫻木 雅子, 塩澤 幹雄, 北山 丈二, 佐田 尚宏
    日本乳癌学会総会プログラム抄録集 2021年07月 (一社)日本乳癌学会
  • 1型糖尿病を合併した原発性乳癌の2症例
    西田 紗季, 原尾 美智子, 丸藤 琴音, 佐々木 裕美子, 芝 聡美, 櫻木 雅子, 北山 丈二, 佐田 尚宏
    日本乳癌学会総会プログラム抄録集 2021年07月 (一社)日本乳癌学会
  • 超音波検査で検出できない石灰化病変の乳房温存手術 誰にでもできる切除範囲の決定
    櫻木 雅子, 原尾 美智子, 佐々木 裕美子, 西田 紗季, 芝 聡美, 塩澤 幹夫, 宮崎 千絵子, 扇原 香澄, 水沼 洋文, 北山 丈二, 佐田 尚宏
    日本乳癌学会総会プログラム抄録集 2021年07月 (一社)日本乳癌学会
  • 温存乳房内再発に対する再度のセンチネルリンパ節生検についての検討
    佐々木 裕美子, 原尾 美智子, 相良 由佳, 芝 聡美, 西田 紗季, 宮崎 千絵子, 塩澤 幹雄, 櫻木 雅子, 藤田 崇史, 北山 丈二, 佐田 尚宏
    日本乳癌学会総会プログラム抄録集 2021年07月 (一社)日本乳癌学会
  • マンモグラフィー閲覧ソフトと学習管理システム(Learning Management System)を応用した診断学習について
    塩澤 幹雄, 櫻木 雅子, 丸藤 琴音, 扇原 香澄, 佐々木 裕美子, 西田 紗季, 芝 聡美, 原尾 美智子, 竹原 めぐみ, 北山 丈二
    日本乳癌学会総会プログラム抄録集 2021年07月 (一社)日本乳癌学会
  • イマチニブにより縮小を得て根治切除し得た胃GISTの1例
    及川 修平, 森嶋 計, 下平 健太郎, 青木 裕一, 目黒 由行, 宮戸 秀世, 遠藤 和洋, 笹沼 英紀, 佐久間 康成, 北山 丈二, 佐田 尚宏
    日本消化器病学会関東支部例会プログラム・抄録集 2021年07月 日本消化器病学会-関東支部
  • 癌腹膜播種治療のガイドライン 大量癌性腹水に対する治療戦略
    松崎 圭祐, 有留 邦明, 江本 成伸, 梶本 広明, 北山 丈二, 高垣 伸匡, 高橋 孝郎, 鍔本 浩志, 長尾 昌二, 渡邊 昭博
    日本外科系連合学会誌 2021年05月 日本外科系連合学会
  • 癌腹膜播種治療のガイドライン 腹膜播種治療のガイドライン 腹膜偽粘液腫編
    五井 孝憲, 石原 聡一郎, 大澤 英之, 合田 良政, 小島 康志, 谷口 浩也, 森川 充洋, 室野 浩司, 島田 英昭, 北山 丈二
    日本外科系連合学会誌 2021年05月 日本外科系連合学会
  • 癌腹膜播種治療のガイドライン 膵癌腹膜播種診療ガイドライン
    山口 博紀, 里井 壯平, 伊佐山 浩通, 高原 楠昊, 辻 靖, 藤井 努, 宮戸 秀世, 山田 豪, 島田 英昭, 北山 丈二
    日本外科系連合学会誌 2021年05月 日本外科系連合学会
  • 癌腹膜播種治療のガイドライン 胃癌腹膜播種に対するガイドライン
    藤原 義之, 北山 丈二
    日本外科系連合学会誌 2021年05月 日本外科系連合学会
  • 癌腹膜播種治療のガイドライン 腹膜播種診療ガイドラインの作成に当たって
    北山 丈二
    日本外科系連合学会誌 2021年05月 日本外科系連合学会
  • 内視鏡観察下、急速増大傾向となりLECSによる根治的手術を行った胃平滑筋肉腫の1例
    高木 徹, 齋藤 心, 細谷 好則, 金丸 理人, 倉科 憲太郎, 山口 博紀, 北山 丈二, 河田 浩敏, 大澤 博之, 佐田 尚宏
    日本胃癌学会総会記事 2021年03月 (一社)日本胃癌学会
  • 当院における大腸NET治療成績の検討
    佐田友 藍, 堀江 久永, 太田 学, 本間 祐子, 直井 大志, 田原 真紀子, 巷野 佳彦, 伊藤 誉, 井上 賢之, 鯉沼 広治, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本大腸肛門病学会雑誌 2021年02月 (一社)日本大腸肛門病学会
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    千葉 小夜, 千葉 蒔七, 金丸 理人, 倉科 憲太郎, 齋藤 心, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化器病学会関東支部例会プログラム・抄録集 2021年02月 日本消化器病学会-関東支部
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    竹野 淳, 石神 浩徳, 大森 健, 小寺 泰弘, 藪崎 裕, 福島 亮治, 今野 元博, 伊藤 誠二, 富田 寿彦, 北山 丈二
    日本消化器外科学会総会 2020年12月 (一社)日本消化器外科学会
  • 非反回下喉頭神経を伴う食道癌に対しNIM併用鏡視下食道亜全摘術を施行した1例
    金子 勇貴, 齋藤 心, 春田 英律, 倉科 憲太郎, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本食道学会学術集会プログラム・抄録集 2020年12月 (NPO)日本食道学会
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    高木 徹, 齋藤 心, 細谷 好則, 高橋 和也, 金丸 理人, 倉科 憲太郎, 山口 博紀, 北山 丈二, 二木 利郎, 佐田 尚宏
    日本食道学会学術集会プログラム・抄録集 2020年12月 (NPO)日本食道学会
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    倉科 憲太郎, 細谷 好則, 山口 博紀, 齋藤 心, 春田 英律, 金丸 理人, 高橋 和也, 大澤 英之, 北山 丈二, 佐田 尚宏
    日本食道学会学術集会プログラム・抄録集 2020年12月 (NPO)日本食道学会
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    熊谷 祐子, 大澤 英之, 山口 博紀, 佐久間 康成, 川平 洋, 堀江 久永, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2020年12月 (一社)日本消化器外科学会
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    清水 敦, 野田 泰子, 佐久間 康成, 山口 博紀, 川平 洋, 堀江 久永, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2020年12月 (一社)日本消化器外科学会
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    齋藤 晶, 大澤 英之, 山口 博紀, 佐久間 康成, 川平 洋, 堀江 久永, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2020年12月 (一社)日本消化器外科学会
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    本間 祐子, 味村 俊樹, 佐田友 藍, 直井 大志, 巷野 佳彦, 鯉沼 広治, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2020年12月 (一社)日本消化器外科学会
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    田原 真紀子, 堀江 久永, 佐田友 藍, 直井 大志, 巷野 佳彦, 鯉沼 広治, 味村 俊樹, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2020年12月 (一社)日本消化器外科学会
  • 腹腔内液中エクソソームマイクロRNAを用いた胃癌腹膜播種のバイオマーカー研究
    大澤 英之, 木村 有希, 齋藤 晶, 山口 博紀, 佐久間 康成, 堀江 久永, 細谷 好則, 佐田 尚宏, 北山 丈二
    日本消化器外科学会総会 2020年12月 (一社)日本消化器外科学会
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    高橋 和也, 大澤 英之, 山口 博紀, 佐久間 康成, 川平 洋, 堀江 久永, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2020年12月 (一社)日本消化器外科学会
  • 正常膵に対する連続した膵体尾部切除22例の定型化膵離断
    笹沼 英紀, 佐久間 康成, 下平 健太郎, 宮戸 秀世, 森嶋 計, 遠藤 和洋, 吉田 淳, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2020年12月 (一社)日本消化器外科学会
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    佐田友 藍, 堀江 久永, 鯉沼 広治, 直井 大志, 巷野 佳彦, 佐久間 康成, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2020年12月 (一社)日本消化器外科学会
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    堀江 久永, 鯉沼 広治, 巷野 佳彦, 佐田友 藍, 直井 大志, 佐久間 康成, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2020年12月 (一社)日本消化器外科学会
  • [胃]高度進行胃癌に対するConversion surgery 腹膜播種陽性胃癌に対する全身・腹腔内併用化学療法奏効後の胃切除
    竹野 淳, 石神 浩徳, 大森 健, 小寺 泰弘, 藪崎 裕, 福島 亮治, 今野 元博, 伊藤 誠二, 富田 寿彦, 北山 丈二
    日本消化器外科学会総会 2020年12月 (一社)日本消化器外科学会
  • [胃]高度進行胃癌に対するConversion surgery IP-PTX+SOX療法に奏功を認めた腹膜播種陽性胃癌症例に対するconversion surgeryの適応と成績
    齋藤 心, 山口 博紀, 倉科 憲太郎, 春田 英律, 川平 洋, 佐久間 康成, 堀江 久永, 細谷 好則, 佐田 尚宏, 北山 丈二
    日本消化器外科学会総会 2020年12月 (一社)日本消化器外科学会
  • 直腸原発Goblet cell carcinoidの1例
    小林 龍ノ介, 太田 学, 本間 祐子, 熊谷 祐子, 東條 峰之, 太白 健一, 佐田友 藍, 直井 大志, 井上 賢之, 鯉沼 広治, 笹沼 英紀, 山口 博紀, 佐久間 康成, 川平 洋, 堀江 久永, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本消化器病学会関東支部例会プログラム・抄録集 2020年12月 日本消化器病学会-関東支部
  • 遠隔診療と遠隔教育 学習管理・ウェブ会議システム併用による遠隔型外科臨床実習の実施報告
    川平 洋, 前田 佳孝, 淺田 義和, 鈴木 義彦, 山口 博紀, 佐久間 康成, 堀江 久永, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本コンピュータ外科学会誌 2020年11月 (一社)日本コンピュータ外科学会
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    利府 数馬, 鯉沼 広治, 直井 大志, 佐田友 藍, 本間 祐子, 太田 学, 山口 博紀, 佐久間 康成, 川平 洋, 堀江 久永, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本消化器外科学会雑誌 2020年11月 (一社)日本消化器外科学会
  • 食道癌術後再発に対する化学療法中に発症したWernicke脳症の一例
    倉科 憲太郎, 松本 志郎, 細谷 好則, 春田 英律, 高木 徹, 千葉 蒔七, 山口 博紀, 北山 丈二, 佐田 尚宏
    学会誌JSPEN 2020年11月 (一社)日本臨床栄養代謝学会
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    齋藤 晶, 大澤 英之, 金子 勇貴, 風當 ゆりえ, 田村 昂平, 高橋 和也, 木村 有希, 東條 峰之, 熊谷 祐子, 佐田 尚宏, 北山 丈二
    日本癌治療学会学術集会抄録集 2020年10月 (一社)日本癌治療学会
  • 胃癌腹膜転移に対する診断と治療の工夫 腹膜播種を伴う進行胃癌に対して腹腔内及び全身化学療法後に手術を行う治療戦略
    深川 剛生, 石神 浩徳, 福島 亮治, 清川 貴志, 堀川 昌宏, 熊田 宜真, 添田 成美, 五十嵐 裕一, 鈴木 悠介, 緑川 裕紀, 金城 信哉, 小寺 泰弘, 北山 丈二
    日本癌治療学会学術集会抄録集 2020年10月 (一社)日本癌治療学会
  • 4型胃癌に対する術後/周術期化学療法としての腹腔内化学療法を検証する第III相試験
    石神 浩徳, 山下 裕玄, 小寺 泰弘, 今野 元博, 福島 亮治, 深川 剛生, 藪崎 裕, 伊藤 誠二, 北山 丈二, 山口 博紀, 瀬戸 泰之
    日本癌治療学会学術集会抄録集 2020年10月 (一社)日本癌治療学会
  • 腹膜播種に対する治療戦略 腹膜播種を伴う胃癌に対する全身・腹腔内投与併用化学療法の治療成績
    太田 光彦, 石神 浩徳, 小寺 泰弘, 小林 大介, 福島 亮治, 深川 剛生, 門脇 重憲, 秀村 晃生, 竹野 淳, 吉川 幸造, 山口 博紀, 北山 丈二
    日本臨床外科学会雑誌 2020年10月 日本臨床外科学会
  • 骨髄間葉系幹細胞由来エクソソーム内包miR-29bは腹膜中皮細胞への影響を介して胃癌腹膜播種を抑止する
    木村 有希, 大澤 英之, 齋藤 晶, 高橋 和也, 東條 峰之, 熊谷 祐子, 佐田 尚宏, 北山 丈二
    日本癌学会総会記事 2020年10月 (一社)日本癌学会
  • 腹腔内液中エクソソームmiRNAを用いた胃癌腹膜播種関連バイオマーカーの探索
    大澤 英之, 木村 有希, 齋藤 晶, 山口 博紀, 細谷 好則, 佐田 尚宏, 北山 丈二
    日本癌学会総会記事 2020年10月 (一社)日本癌学会
  • 腫瘍免疫微小環境に対するメトホルミンの効果
    齋藤 晶, 大澤 英之, 高橋 和也, 木村 有希, 東條 峰之, 熊谷 祐子, 佐田 尚宏, 北山 丈二
    日本癌学会総会記事 2020年10月 (一社)日本癌学会
  • マウス胃癌腹膜播種モデルにおける抗PD-1抗体の効果と腹腔内免疫細胞の動態について
    熊谷 祐子, 宮戸 秀世, 大澤 英之, 佐久間 康成, 堀江 久永, 細谷 好則, 佐田 尚宏, 北山 丈二
    日本癌学会総会記事 2020年10月 (一社)日本癌学会
  • 大腸癌細胞株LuM1肺転移モデルにおけるMetformin併用放射線治療
    東條 峰之, 津久井 秀則, 齋藤 晶, 高橋 和也, 木村 有希, 熊谷 祐子, 宮戸 秀世, 大澤 英之, 鯉沼 広治, 堀江 久永, 佐田 尚宏, 北山 丈二
    日本癌学会総会記事 2020年10月 (一社)日本癌学会
  • Neutrophil extracellular trapsは胃癌細胞の浸潤能を促進する
    高橋 和也, 大澤 英之, 木村 有希, 齋藤 晶, 東條 峰之, 熊谷 祐子, 北山 丈二, 佐田 尚宏
    日本癌学会総会記事 2020年10月 (一社)日本癌学会
  • Flowcytometryを用いた胃癌患者腹腔内免疫細胞の解析
    高橋 和也, 大澤 英之, 金丸 理人, 倉科 憲太郎, 齋藤 心, 山口 博紀, 細谷 好則, 佐田 尚宏, 北山 丈二
    日本癌治療学会学術集会抄録集 2020年10月 (一社)日本癌治療学会
  • 腹膜播種に対する治療戦略 腹膜播種を伴う胃癌に対する全身・腹腔内投与併用化学療法の治療成績
    太田 光彦, 石神 浩徳, 小寺 泰弘, 小林 大介, 福島 亮治, 深川 剛生, 門脇 重憲, 秀村 晃生, 竹野 淳, 吉川 幸造, 山口 博紀, 北山 丈二
    日本臨床外科学会雑誌 2020年10月 日本臨床外科学会
  • 当科におけるエリブリン投与患者の末梢好中球リンパ球比と予後の相関についての検討
    西田 紗季, 原尾 美智子, 扇原 香澄, 櫻木 雅子, 北山 丈二, 佐田 尚宏
    日本乳癌学会総会プログラム抄録集 2020年10月 (一社)日本乳癌学会
  • 術後1ヵ月で再発したG-CSF産生を疑うMyoepithelial carcinomaの一例
    扇原 香澄, 原尾 美智子, 櫻木 雅子, 西田 紗季, 北山 丈二, 佐田 尚宏
    日本乳癌学会総会プログラム抄録集 2020年10月 (一社)日本乳癌学会
  • 働き方改革 ワーク・ライフ・バランスを意識してのりこえる 短時間業務者との連携プレー
    櫻木 雅子, 原尾 美智子, 扇原 香澄, 相良 由佳, 西田 紗季, 芝 聡美, 佐々木 裕美子, 宮崎 千絵子, 大澤 英之, 竹原 めぐみ, 塩澤 幹雄, 水沼 洋文, 北山 丈二, 佐田 尚宏
    日本乳癌学会総会プログラム抄録集 2020年10月 (一社)日本乳癌学会
  • 当院におけるBRCAnalysisの現状と今後の課題
    原尾 美智子, 扇原 香澄, 西田 紗季, 櫻木 雅子, 北山 丈二, 佐田 尚宏
    日本乳癌学会総会プログラム抄録集 2020年10月 (一社)日本乳癌学会
  • 回腸原発悪性黒色腫の一例
    篠原 翔一, 直井 大志, 太田 学, 本間 祐子, 佐田 友藍, 巷野 佳彦, 鯉沼 広治, 山口 博紀, 佐久間 康成, 川平 洋, 堀江 久永, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本臨床外科学会雑誌 2020年10月 日本臨床外科学会
  • 術前CT検査による3D血管構築が腹腔鏡手術に有用であった腸回転異常に伴う上行結腸癌の1例
    直井 大志, 鯉沼 広治, 太田 学, 本間 祐子, 佐田 友藍, 巷野 佳彦, 山口 博紀, 佐久間 康成, 川平 洋, 堀江 久永, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本臨床外科学会雑誌 2020年10月 日本臨床外科学会
  • 高度進行胃癌、再発胃癌に対する治療戦略-薬物療法と手術との融合- 腹膜播種陽性初発胃癌に対するタキサン系抗癌剤による腹腔内化学療法後の手術加療の意義
    廣野 靖夫, 石神 浩徳, 大森 健, 藪崎 裕, 松木 淳, 今野 元博, 新海 政幸, 富田 寿彦, 有上 貴明, 藤本 大裕, 山下 直行, 松村 卓樹, 北山 丈二
    日本臨床外科学会雑誌 2020年10月 日本臨床外科学会
  • 腹膜播種に対する治療戦略 腹膜播種を伴う胃癌に対する全身・腹腔内投与併用化学療法の治療成績
    太田 光彦, 石神 浩徳, 小寺 泰弘, 小林 大介, 福島 亮治, 深川 剛生, 門脇 重憲, 秀村 晃生, 竹野 淳, 吉川 幸造, 山口 博紀, 北山 丈二
    日本臨床外科学会雑誌 2020年10月 日本臨床外科学会
  • 低位前方切除後症候群診療における進歩と課題 低位前方切除後症候群に対する経肛門的洗腸療法の有用性に関する検討
    本間 祐子, 味村 俊樹, 村橋 賢, 太田 学, 太白 健一, 熊谷 祐子, 東條 峰之, 佐田友 藍, 直井 大志, 鯉沼 広治, 堀江 久永, 北山 丈二, 佐田 尚宏
    日本大腸肛門病学会雑誌 2020年09月 (一社)日本大腸肛門病学会
  • Growing teratoma syndromeの診断で外科的切除を行った1例
    篠田 祐之, 吉田 淳, 篠原 翔一, 窪木 大悟, 宮戸 秀世, 森嶋 計, 遠藤 和洋, 笹沼 英紀, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本臨床外科学会雑誌 2020年09月 日本臨床外科学会
  • 膵内副脾に発生した類表皮嚢胞の1例
    小堀 篤也, 森嶋 計, 下平 健太郎, 青木 裕一, 目黒 由行, 宮戸 秀世, 遠藤 和洋, 笹沼 英紀, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化器病学会関東支部例会プログラム・抄録集 2020年09月 日本消化器病学会-関東支部
  • 芝 聡美, 原尾 美智子, 西田 紗季, 櫻木 雅子, 水沼 洋文, 北山 丈二, 佐田 尚宏
    乳腺甲状腺超音波医学 2020年09月 (一社)日本乳腺甲状腺超音波医学会
  • 腹腔鏡下膵体尾部切除術における定型化膵離断20例の治療成績
    笹沼 英紀, 佐久間 康成, 下平 健太郎, 森嶋 計, 宮戸 秀世, 吉田 淳, 北山 丈二, 佐田 尚宏
    日本外科学会定期学術集会抄録集 2020年08月 (一社)日本外科学会
  • Flowcytometryを用いた大腸癌組織における細胞別PD-L1、PD-L2の発現解析の試み
    齋藤 晶, 東条 峰之, 高橋 和也, 木村 有希, 熊谷 祐子, 津久井 秀則, 金丸 理人, 山口 博紀, 佐久間 康成, 川平 洋, 堀江 久永, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本外科学会定期学術集会抄録集 2020年08月 (一社)日本外科学会
  • Flowcytometryを用いた胃癌腹膜播種患者の腹腔内遊離細胞の解析
    金丸 理人, 大澤 英之, 高橋 和也, 松本 志郎, 春田 英律, 倉科 憲太郎, 齋藤 心, 山口 博紀, 佐久間 康成, 川平 洋, 堀江 久永, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本外科学会定期学術集会抄録集 2020年08月 (一社)日本外科学会
  • 食道癌術前DCF療法の予後に関わる因子の検討
    松本 志郎, 高橋 和也, 金丸 理人, 宇井 崇, 春田 英律, 倉科 憲太郎, 斎藤 心, 山口 博紀, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本外科学会定期学術集会抄録集 2020年08月 (一社)日本外科学会
  • 医学生対象内視鏡外科手術トレーニングの報告と縫合結紮手技解析の初回報告
    川平 洋, 前田 佳孝, 松本 志郎, 鈴木 義彦, 淺田 義和, 山口 博紀, 佐久間 康成, 堀江 久永, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本外科学会定期学術集会抄録集 2020年08月 (一社)日本外科学会
  • 外科医の服装は患者・家族による診療の評価に影響するのか? 自治医科大学附属病院消化器一般移植外科病棟におけるアンケート調査
    清水 敦, Lefor Alan, 山口 博紀, 佐久間 康成, 堀江 久永, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本外科学会定期学術集会抄録集 2020年08月 (一社)日本外科学会
  • 胃全摘後の体重減少・食欲不振に対する六君子湯の治療効果 新規治療ターゲットと新規作用機序の解明を目指したパイロット試験
    田口 昌延, 倉科 憲太郎, 出崎 克也, 松本 志郎, 春田 英律, 山口 博紀, 佐久間 康成, 川平 洋, 堀江 久永, 細谷 好則, 味村 俊樹, 北山 丈二, 矢田 俊彦, 佐田 尚宏
    日本外科学会定期学術集会抄録集 2020年08月 (一社)日本外科学会
  • 肝門部領域胆管癌における切除断端と再発形態についての検討
    森嶋 計, 下平 健太郎, 青木 裕一, 三木 厚, 宮戸 英世, 遠藤 和洋, 吉田 淳, 笹沼 英紀, 山口 博紀, 佐久間 康成, 川平 洋, 堀江 久永, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本外科学会定期学術集会抄録集 2020年08月 (一社)日本外科学会
  • 消化器外科用新規接着剤の開発
    佐久間 康成, 田口 哲志, 三木 厚, 斉藤 晶, 芝 聡美, 堀江 久永, 細谷 好則, 山口 博紀, 川平 洋, 北山 丈二, 佐田 尚宏
    日本外科学会定期学術集会抄録集 2020年08月 (一社)日本外科学会
  • クローン病腸管病変に対する内科外科連携に基づく治療戦略
    太田 学, 伊藤 誉, 津久井 秀則, 本間 祐子, 熊谷 祐子, 東條 峰之, 佐田友 藍, 直井 大志, 田原 真紀子, 巷野 佳彦, 鯉沼 広治, 山口 博紀, 佐久間 康成, 川平 洋, 堀江 久永, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本外科学会定期学術集会抄録集 2020年08月 (一社)日本外科学会
  • CD73を標的とした治療による直腸癌に対する放射線治療の増強効果(CD73 targeting therapy enhances the antitumor effect of radiotherapy in rectal cancer)
    津久井 秀則, 堀江 久永, 大澤 英之, 山口 博紀, 佐久間 康成, 川平 洋, 細谷 好則, 味村 俊樹, 吉村 浩太郎, Alan Lefor, 佐田 尚宏, 北山 丈二
    日本外科学会定期学術集会抄録集 2020年08月 (一社)日本外科学会
  • 術後膵液瘻ゼロを目指した膵断端処置具の新規開発
    兼田 裕司, 木村 有希, 齋藤 晶, 青木 裕一, 目黒 由行, 森嶋 計, 宮戸 英世, 大澤 英之, 遠藤 和洋, 吉田 淳, 小泉 大, 笹沼 英紀, 山口 博紀, 佐久間 康成, 川平 洋, 堀江 久永, 味村 俊樹, 北山 丈二, Alan Lefor, 佐田 尚宏
    日本外科学会定期学術集会抄録集 2020年08月 (一社)日本外科学会
  • 腹腔内液中エクソソームを用いた腹膜播種関連バイオマーカーの探索
    大澤 英之, 木村 有希, 齋藤 晶, 山口 博紀, 佐久間 康成, 堀江 久永, 細谷 好則, 佐田 尚宏, 北山 丈二
    日本外科学会定期学術集会抄録集 2020年08月 (一社)日本外科学会
  • 器械縫合において粘膜縫合の欠損が腸管吻合部の強度に与える影響
    直井 大志, 堀江 久永, 熊谷 祐子, 太田 学, 東條 峰之, 兼田 裕司, 斎藤 晶, 木村 有希, 津久井 秀則, 本間 祐子, 佐田友 藍, 田原 真紀子, 巷野 佳彦, 鯉沼 広治, 菱川 修司, 佐久間 康成, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本外科学会定期学術集会抄録集 2020年08月 (一社)日本外科学会
  • 十二指腸乳頭部癌切除例の長期成績
    小泉 大, 下平 健太郎, 木村 有希, 斉藤 晶, 森嶋 計, 兼田 裕司, 宮戸 秀世, 遠藤 和洋, 笹沼 英紀, 山口 博紀, 川平 洋, 佐久間 康成, 堀江 久永, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本外科学会定期学術集会抄録集 2020年08月 (一社)日本外科学会
  • 外科的侵襲・炎症と癌の転移再発 手術侵襲は末梢血中低比重好中球を増加させ遠隔転移を促進する
    熊谷 祐子, 金丸 理人, 大澤 英之, 山口 博紀, 佐久間 康成, 川平 洋, 堀江 久永, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本外科学会定期学術集会抄録集 2020年08月 (一社)日本外科学会
  • 初診時切除不能胃癌に対するconversion surgeryの意義【International】腹膜播種を伴う進行胃癌症例に対する腹腔内投与を伴う全身化学療法後の外科手術の成績(Surgical outcomes for advanced gastric cancer with peritoneal metastases after intraperitoneal and systemic chemotherapy)
    深川 剛生, 石神 浩徳, 大森 健, 小寺 泰弘, 藪崎 裕, 福島 亮治, 今野 元博, 三澤 一成, 富田 寿彦, 秀村 晃生, 有上 貴明, 天貝 賢二, 辻 靖, 楠本 哲也, 岸 健太郎, 上田 修吾, 伏田 幸夫, 今村 和弘, 緒方 杏一, 北山 丈二
    日本外科学会定期学術集会抄録集 2020年08月 (一社)日本外科学会
  • 術前CRT施行直腸癌症例に対する側方リンパ節郭清の適応
    井上 賢之, 堀江 久永, 鯉沼 広治, 田原 真紀子, 巷野 佳彦, 清水 徹一郎, 本間 祐子, 津久井 秀則, 熊谷 祐子, 東條 峰之, 佐田友 藍, 直井 大志, 伊藤 誉, 佐久間 康成, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本大腸肛門病学会雑誌 2020年07月 (一社)日本大腸肛門病学会
  • 当院における内視鏡摘除後のT1直腸癌追加腸切除適応症例についての検討
    巷野 佳彦, 堀江 久永, 津久井 秀則, 本間 祐子, 熊谷 祐子, 東條 峰之, 佐田友 藍, 清水 徹一郎, 直井 大志, 田原 真紀子, 伊藤 誉, 井上 賢之, 鯉沼 広治, 佐久間 康成, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本大腸肛門病学会雑誌 2020年07月 (一社)日本大腸肛門病学会
  • クラインフェルター症候群合併の高度肥満症に対しBariatric surgeryが奏功した1例
    千葉 蒔七, 春田 英律, 齋藤 心, 細谷 好則, 岡田 健太, 松本 志郎, 金丸 理人, 高橋 和也, 北山 丈二, 佐田 尚宏
    日本消化器病学会関東支部例会プログラム・抄録集 2020年07月 日本消化器病学会-関東支部
  • Heidelberg大学病院の膵頭十二指腸切除術
    田口 昌延, 佐久間 康成, 小泉 大, 笹沼 英紀, 下平 健太郎, 齋藤 晶, 木村 有希, 青木 裕一, 目黒 由行, 笠原 尚哉, 森嶋 計, 兼田 裕司, 三木 厚, 宮戸 英世, 遠藤 和洋, 吉田 淳, 清水 敦, 山口 博紀, 北山 丈二, 佐田 尚宏
    膵臓 2020年07月 (一社)日本膵臓学会
  • 急性膵炎に対する局所合併症治療 左側感染性Walled-off necrosis(WON)に対する小切開Videoscope補助下ネクロセクトミー
    笹沼 英紀, 佐田 尚宏, 下平 健太郎, 森嶋 計, 宮戸 秀世, 遠藤 和洋, 吉田 淳, 佐久間 康成, 北山 丈二
    膵臓 2020年07月 (一社)日本膵臓学会
  • 膵全摘術の現状と展望 膵全摘の治療成績と周術期血糖・栄養管理に関する検討と今後の課題
    笹沼 英紀, 佐田 尚宏, 下平 健太郎, 森嶋 計, 宮戸 秀世, 遠藤 和洋, 吉田 淳, 佐久間 康成, 北山 丈二
    膵臓 2020年07月 (一社)日本膵臓学会
  • Conversion症例に対する治療戦略 腹膜播種陽性初発胃癌に対するIP療法後の手術加療の意義(Treatment strategy for down-staged cases from stage IV Gastrectomy after intraperitoneal/systemic chemotherapy in gastric cancer with peritoneal metastasis)
    廣野 靖夫, 石神 浩徳, 大森 健, 藪崎 裕, 松木 淳, 今野 元博, 新海 政幸, 富田 寿彦, 有上 貴明, 藤本 大裕, 山下 直行, 松村 卓樹, 北山 丈二
    日本胃癌学会総会記事 2020年03月 (一社)日本胃癌学会
  • 当院でのABTHERドレッシングキットの使用経験と工夫について
    篠原 翔一, 笹沼 英紀, 篠田 祐之, 窪木 大悟, 宮戸 秀世, 森嶋 計, 吉田 淳, 遠藤 和洋, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本腹部救急医学会雑誌 2020年02月 (一社)日本腹部救急医学会
  • 大豆生田 尚彦, 森嶋 計, 宮戸 秀世, 片野 匠, 篠原 翔一, 兼田 裕司, 遠藤 和洋, 三木 厚, 吉田 淳, 笹沼 英紀, 山口 博紀, 佐久間 康成, 川平 洋, 堀江 久永, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本内分泌学会雑誌 2020年02月 (一社)日本内分泌学会
  • 切除可能進行食道癌における体重と予後との関連
    倉科 憲太郎, 細谷 好則, 北山 丈二, 山口 博紀, 齋藤 心, 春田 英律, 松本 志郎, 宇井 崇, 金丸 理人, 高橋 和也, 大澤 英之, 川平 洋, 堀江 久永, 佐久間 康成, 佐田 尚宏
    日本成人病(生活習慣病)学会会誌 2020年01月 日本成人病(生活習慣病)学会
  • 腹腔鏡下スリーブ状胃切除術における高血圧症改善因子の検討
    金丸 理人, 春田 英律, 細谷 好則, 倉科 憲太郎, 齋藤 心, 宇井 崇, 松本 志郎, 高橋 和也, 山口 博紀, 佐久間 康成, 堀江 久永, 北山 丈二, 佐田 尚宏
    日本成人病(生活習慣病)学会会誌 2020年01月 日本成人病(生活習慣病)学会
  • 消化器癌治癒切除術後患者の予後解析 メトホルミン内服群とDPP-4阻害薬内服群の比較検討
    齋藤 晶, 大澤 英之, 高橋 和也, 木村 有希, 東條 峰之, 熊谷 祐子, 金丸 理人, 津久井 秀則, 佐田 尚宏, 北山 丈二
    日本成人病(生活習慣病)学会会誌 2020年01月 日本成人病(生活習慣病)学会
  • 食道癌とS状結腸癌に対し、鏡視下食道亜全摘術と腹腔鏡下S状結腸切除術を施行した一例
    窪木 大悟, 春田 英律, 松本 志郎, 倉科 憲太郎, 細谷 好則, 佐久間 康成, 川平 洋, 堀江 久永, 北山 丈二, 佐田 尚宏
    日本内視鏡外科学会雑誌 2019年12月 (一社)日本内視鏡外科学会
  • 肝内胆管癌疑いの症例に対して腹腔鏡下肝切除を行い肝類上皮細胞肉芽腫と診断された1例
    吉田 淳, 佐久間 康成, 宮戸 英世, 森嶋 計, 三木 厚, 兼田 裕司, 遠藤 和洋, 笹沼 英紀, 川平 洋, 堀江 久永, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本内視鏡外科学会雑誌 2019年12月 (一社)日本内視鏡外科学会
  • 胃癌・大腸癌に対して腹腔鏡下に同時切除を行った9症例の検討
    倉科 憲太郎, 細谷 好則, 春田 英律, 松本 志郎, 齋藤 心, 宇井 崇, 金丸 理人, 高橋 和也, 佐久間 康成, 堀江 久永, 味村 俊樹, 川平 洋, 北山 丈二, 佐田 尚宏
    日本内視鏡外科学会雑誌 2019年12月 (一社)日本内視鏡外科学会
  • 内視鏡手術手技の初学者にとって3次元内視鏡のアドバンテージはあるか?
    松本 志郎, 遠藤 和宏, 川平 洋, 細谷 好則, 佐久間 康成, 堀江 久永, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本内視鏡外科学会雑誌 2019年12月 (一社)日本内視鏡外科学会
  • 腹腔鏡下直腸切断術におけるインターシードの使用経験
    田原 真紀子, 堀江 久永, 太田 学, 本間 祐子, 熊谷 祐子, 佐田友 藍, 直井 大志, 巷野 佳彦, 伊藤 誉, 鯉沼 広治, 佐久間 康成, 味村 俊樹, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本内視鏡外科学会雑誌 2019年12月 (一社)日本内視鏡外科学会
  • 予防的人工肛門造設からみた直腸癌術後の縫合不全対策
    佐田友 藍, 鯉沼 広治, 太田 学, 本間 祐子, 田原 真紀子, 巷野 佳彦, 伊藤 誉, 佐久間 康成, 川平 洋, 堀江 久永, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本内視鏡外科学会雑誌 2019年12月 (一社)日本内視鏡外科学会
  • 直腸癌術前化学放射線治療実施症例に対する腹腔鏡下側方リンパ節郭清の適応について
    堀江 久永, 鯉沼 広治, 伊藤 誉, 田原 真紀子, 佐田友 藍, 巷野 佳彦, 本間 祐子, 太田 学, 佐久間 康成, 川平 洋, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本内視鏡外科学会雑誌 2019年12月 (一社)日本内視鏡外科学会
  • 当科における直腸癌に対するTaTMEの導入と短期治療成績
    巷野 佳彦, 堀江 久永, 田原 真紀子, 太田 学, 本間 祐子, 佐田友 藍, 伊藤 誉, 鯉沼 広治, 佐久間 康成, 川平 洋, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本内視鏡外科学会雑誌 2019年12月 (一社)日本内視鏡外科学会
  • スリーブ状胃切除術の問題点 当院の肥満外科手術の治療成績と今後の課題
    春田 英律, 細谷 好則, 倉科 憲太郎, 松本 志郎, 齋藤 心, 宇井 崇, 金丸 理人, 高橋 和也, 川平 洋, 佐久間 康成, 堀江 久永, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本内視鏡外科学会雑誌 2019年12月 (一社)日本内視鏡外科学会
  • サイトメガロウイルス胃炎による幽門狭窄に胃癌を合併した一例
    松本 志郎, 高橋 和也, 金丸 理人, 春田 英律, 倉科 憲太郎, 細谷 好則, 伊藤 淳史, 天野 雄介, 河田 浩敏, 佐久間 康成, 堀江 久永, 北山 丈二, 佐田 尚宏
    日本消化器外科学会雑誌 2019年11月 (一社)日本消化器外科学会
  • 胃癌・大腸癌切除例における術前CTで指摘された膵嚢胞性病変の検討
    小泉 大, 斉藤 晶, 青木 裕一, 森嶋 計, 田口 昌延, 三木 厚, 遠藤 和洋, 笹沼 英紀, 吉田 淳, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化器外科学会雑誌 2019年11月 (一社)日本消化器外科学会
  • 膵十二指腸動脈瘤を併発した正中弓状靱帯症候群に対し、腹腔鏡下胃切除術中に靱帯切離を行った一例
    窪木 大悟, 倉科 憲太郎, 松本 志郎, 春田 英律, 細谷 好則, 山口 博紀, 斎藤 心, 川平 洋, 味村 俊樹, 堀江 久永, 佐久間 康成, 北山 丈二, 佐田 尚宏
    日本臨床外科学会雑誌 2019年10月 日本臨床外科学会
  • 潰瘍形成により穿通を来した腸間膜脂肪腫を伴うLipomatosisの1例
    太田 学, 伊藤 誉, 崎尾 亮太郎, 本間 祐子, 佐田友 藍, 田原 真紀子, 巷野 佳彦, 山口 博紀, 佐久間 康成, 川平 洋, 堀江 久永, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本臨床外科学会雑誌 2019年10月 日本臨床外科学会
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    崎尾 亮太郎, 伊藤 誉, 太田 学, 本間 祐子, 佐田友 藍, 田原 真紀子, 巷野 佳彦, 山口 博紀, 佐久間 康成, 川平 洋, 堀江 久永, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本臨床外科学会雑誌 2019年10月 日本臨床外科学会
  • 腫瘍出血による褐色細胞腫クリーゼに対して体外循環補助下に副腎摘出術を施行し救命し得た1例
    片野 匠, 森嶋 計, 青木 裕一, 山口 博紀, 佐久間 康成, 川平 洋, 堀江 久永, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本臨床外科学会雑誌 2019年10月 日本臨床外科学会
  • 大学病院初期研修医に対する、魅力的な外科研修環境の構築
    遠藤 和洋, 塩澤 幹雄, 川平 洋, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本臨床外科学会雑誌 2019年10月 日本臨床外科学会
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    本間 祐子, 味村 俊樹, 太田 学, 佐田友 藍, 田原 真紀子, 伊藤 誉, 巷野 佳彦, 山口 博紀, 佐久間 康成, 川平 洋, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本臨床外科学会雑誌 2019年10月 日本臨床外科学会
  • 外科臨床におけるAIの利用 Deep Learningによる早期大腸癌病変における内視鏡診断支援の試み ESD/EMRか手術か?
    川平 洋, 中島 寛隆, 上里 昌也, 宮内 英聡, 山口 博紀, 佐久間 康成, 堀江 久永, 細谷 好則, 味村 俊樹, 北山 丈二, 松原 久裕, 佐田 尚宏
    日本臨床外科学会雑誌 2019年10月 日本臨床外科学会
  • 新しい医療機器の開発と臨床応用 外科医用ウェアラブルチェア「アルケリス」の開発と臨床使用の経験
    川平 洋, 中村 亮一, 下村 義弘, 大城 崇司, 岡住 慎一, 山口 博紀, 佐久間 康成, 堀江 久永, 細谷 好則, 味村 俊樹, 北山 丈二, アラン・レフォー, 佐田 尚宏
    日本臨床外科学会雑誌 2019年10月 日本臨床外科学会
  • 寺谷 工, 笠原 尚哉, 浦橋 泰然, 藤本 康弘, 小林 英司, 後藤 昌史, 佐田 尚宏, 北山 丈二
    Organ Biology 2019年10月 (一社)日本臓器保存生物医学会
  • 篠田 祐之, 春田 英律, 細谷 好則, 岡田 健太, 倉科 憲太郎, 齋藤 心, 松本 志郎, 金丸 理人, 高橋 和也, 山口 博紀, 笹沼 英紀, 堀江 久永, 北山 丈二, 佐田 尚宏
    肥満研究 2019年10月 (一社)日本肥満学会
  • 千葉 蒔七, 春田 英律, 細谷 好則, 岡田 健太, 倉科 憲太郎, 齋藤 心, 松本 志郎, 金丸 理人, 高橋 和也, 山口 博紀, 笹沼 英紀, 佐久間 康成, 堀江 久永, 北山 丈二, 佐田 尚宏
    肥満研究 2019年10月 (一社)日本肥満学会
  • リウマチに対してメトトレキサート内服中に発症した、肝原発悪性リンパ腫の一例  [通常講演]
    大豆生田 尚彦, 森嶋 計, 宮戸 秀世, 遠藤 和洋, 三木 厚, 吉田 厚, 笹沼 英紀, 山口 博紀, 佐久間 康成, 川平 洋, 堀江 久永, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本臨床外科学会雑誌 2019年10月 日本臨床外科学会
  • 切除不能膵頭部腫瘍による総胆管閉塞に対し、胃空腸バイパス術と胆道ステント留置を併施した一例  [通常講演]
    窪木 大悟, 笹沼 英紀, 橋本 雄介, 三木 厚, 吉田 淳, 森嶋 計, 遠藤 和洋, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    胆道 2019年10月 日本胆道学会
  • 白血病治療中に発症した胆嚢炎の治療方針と転帰  [通常講演]
    篠原 翔一, 笹沼 英紀, 宮戸 英世, 森嶋 計, 三木 厚, 遠藤 和洋, 吉田 淳, 佐久間 康成, 北山 丈二, 佐田 尚宏
    胆道 2019年10月 日本胆道学会
  • Bardet-Biedle症候群に先天性胆道拡張症を合併し、肝外胆管切除術を施行した1例  [通常講演]
    吉田 淳, 笹沼 英紀, 片野 匠, 篠原 翔一, 森嶋 計, 三木 厚, 宮戸 英世, 遠藤 和洋, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    胆道 2019年10月 日本胆道学会
  • 春田 英律, 細谷 好則, 岡田 健太, 倉科 憲太郎, 齋藤 心, 松本 志郎, 金丸 理人, 高橋 和也, 山口 博紀, 堀江 久永, 北山 丈二, 佐田 尚宏
    肥満研究 2019年10月 (一社)日本肥満学会
  • 篠田 祐之, 春田 英律, 細谷 好則, 岡田 健太, 倉科 憲太郎, 齋藤 心, 松本 志郎, 金丸 理人, 高橋 和也, 山口 博紀, 笹沼 英紀, 堀江 久永, 北山 丈二, 佐田 尚宏
    肥満研究 2019年10月 (一社)日本肥満学会
  • 佐久間 康成, 寺谷 工, 笠原 尚哉, 三木 厚, 春田 英律, 細谷 好則, 北山 丈二, 佐田 尚宏
    肥満研究 2019年10月 (一社)日本肥満学会
  • 千葉 蒔七, 春田 英律, 細谷 好則, 岡田 健太, 倉科 憲太郎, 齋藤 心, 松本 志郎, 金丸 理人, 高橋 和也, 山口 博紀, 笹沼 英紀, 佐久間 康成, 堀江 久永, 北山 丈二, 佐田 尚宏
    肥満研究 2019年10月 (一社)日本肥満学会
  • 春田 英律, 細谷 好則, 岡田 健太, 倉科 憲太郎, 齋藤 心, 松本 志郎, 金丸 理人, 高橋 和也, 山口 博紀, 堀江 久永, 北山 丈二, 佐田 尚宏
    肥満研究 2019年10月 (一社)日本肥満学会
  • 腹膜播種陽性胃癌に対するSOX+PTX腹腔内投与併用療法
    宮戸 秀世, 山口 博紀, 齋藤 心, 細谷 好則, 春田 英律, 倉科 憲太郎, 堀江 久永, 佐久間 康成, 北山 丈二, 佐田 尚宏
    日本癌治療学会学術集会抄録集 2019年10月 (一社)日本癌治療学会
  • 腹腔内液中エクソソームマイクロRNAを用いた胃癌腹膜播種症例のリキッドバイオプシー
    大澤 英之, 木村 有希, 齊籐 晶, 山口 博紀, 細谷 好則, 佐田 尚宏, 北山 丈二
    日本癌治療学会学術集会抄録集 2019年10月 (一社)日本癌治療学会
  • 胃癌Up to Date 腹膜播種陽性胃癌に対する腹腔内化学療法 腹腔内化学療法研究会の臨床試験
    石神 浩徳, 小寺 泰弘, 今野 元博, 福島 亮治, 藪崎 裕, 大森 健, 門脇 重憲, 富田 寿彦, 有上 貴明, 秀村 晃生, 廣野 靖夫, 辻 靖, 天貝 賢二, 山口 博紀, 北山 丈二
    日本癌治療学会学術集会抄録集 2019年10月 (一社)日本癌治療学会
  • 難治性排便障害に対する経肛門的洗腸療法の治療成績
    本間 祐子, 味村 俊樹, 田原 真紀子, 巷野 佳彦, 清水 徹一郎, 太田 学, 太白 健一, 津久井 秀則, 熊谷 祐子, 東條 峰之, 伊藤 誉, 佐田友 藍, 直井 大志, 鯉沼 広治, 堀江 久永, 北山 丈二, 佐田 尚宏
    日本大腸肛門病学会雑誌 2019年09月 (一社)日本大腸肛門病学会
  • Flowcytometryを用いた大腸癌組織における細胞別PD-L1、PD-L2の発現解析の試み
    齋藤 晶, 東條 峰之, 大澤 英之, 佐久間 康成, 細谷 好則, 堀江 久永, 佐田 尚宏, 北山 丈二
    日本大腸肛門病学会雑誌 2019年09月 (一社)日本大腸肛門病学会
  • 術前化学放射線治療実施症例に対する側方リンパ節郭清の適応について
    堀江 久永, 鯉沼 広治, 井上 賢之, 田原 真紀子, 巷野 佳彦, 清水 徹一郎, 本間 祐子, 太田 学, 太白 健一, 津久井 秀則, 熊谷 祐子, 東條 峰之, 伊藤 誉, 佐田 藍, 直井 大志, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本大腸肛門病学会雑誌 2019年09月 (一社)日本大腸肛門病学会
  • 進行大腸癌所属リンパ節におけるPD-1/PD-L1分子の発現解析
    津久井 秀則, 斎藤 晶, 東條 峰之, 田原 真紀子, 巷野 佳彦, 清水 徹一郎, 本間 祐子, 太田 学, 太白 健一, 熊谷 祐子, 伊藤 誉, 佐田友 藍, 直井 大志, 鯉沼 広治, 大澤 英之, 味村 俊樹, 堀江 久永, 佐田 尚宏, 北山 丈二
    日本大腸肛門病学会雑誌 2019年09月 (一社)日本大腸肛門病学会
  • 排便障害診療におけるチーム医療の問題点と対策
    本間 祐子, 味村 俊樹, 清水 徹一郎, 田原 真紀子, 巷野 佳彦, 太田 学, 津久井 秀則, 太白 健一, 熊谷 祐子, 東條 峰之, 伊藤 誉, 佐田友 藍, 直井 大志, 鯉沼 広治, 堀江 久永, 北山 丈二, 佐田 尚宏
    日本大腸肛門病学会雑誌 2019年09月 (一社)日本大腸肛門病学会
  • 専門領域の連携による炎症性腸疾患の治療 クローン病腸管狭窄に対するKono-S吻合の短期成績
    佐田友 藍, 堀江 久永, 本間 祐子, 直井 大志, 清水 徹一郎, 田原 真紀子, 巷野 佳彦, 伊藤 誉, 井上 賢之, 鯉沼 広治, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本大腸肛門病学会雑誌 2019年09月 (一社)日本大腸肛門病学会
  • 通過障害を伴う進行胃癌に対し、PTEG造設後に腹腔内化学療法を行い奏功した1例  [通常講演]
    佐藤 孝弘, 高橋 和也, 春田 英律, 山口 博紀, 金丸 理人, 松本 志郎, 宇井 崇, 倉科 憲太郎, 齋藤 心, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本臨床外科学会雑誌 2019年08月
  • 腹腔鏡下直腸切断術を施行した難治性cap polyposisの1例  [通常講演]
    関口 和正, 田原 真紀子, 堀江 久永, 宮原 悠三, 本間 祐子, 清水 徹一郎, 巷野 佳彦, 井上 賢之, 鯉沼 広治, 佐久間 康成, 味村 俊樹, 細谷 好則, 北山 丈二, 佐田 尚宏, 小林 泰俊
    日本臨床外科学会雑誌 2019年07月
  • 医学部生からレジデントまでを対象とした内視鏡外科手術トレーニングの初回報告  [通常講演]
    川平 洋, 前田 佳孝, 鈴木 義彦, 淺田 義和, 遠藤 和洋, 山本 真一, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2019年07月
  • 右側結腸手術における術前機械的前処置省略の効果  [通常講演]
    直井 大志, 堀江 久永, 巷野 佳彦, 井上 賢之, 鯉沼 広治, 佐久間 康成, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2019年07月
  • 腹腔内液中エクソソームを用いた胃癌腹膜播種症例のリキッドバイオプシー  [通常講演]
    大澤 英之, 齋藤 晶, 熊谷 祐子, 山口 博紀, 細谷 好則, 佐田 尚宏, 北山 丈二
    日本消化器外科学会総会 2019年07月
  • 術前CRTと側方郭清による側方リンパ節転移の制御  [通常講演]
    堀江 久永, 鯉沼 広治, 井上 賢之, 田原 真紀子, 巷野 佳彦, 佐久間 康成, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2019年07月
  • 腎細胞癌膵転移切除症例の検討  [通常講演]
    吉田 淳, 佐久間 康成, 森嶋 計, 三木 厚, 遠藤 和洋, 笹沼 英紀, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2019年07月
  • 開腹術後腹腔内滲出好中球上のPD-L1発現  [通常講演]
    金丸 理人, 大澤 英之, 高橋 和也, 松本 志郎, 春田 英律, 倉科 健太郎, 山口 博紀, 細谷 好則, 佐田 尚宏, 北山 丈二
    日本消化器外科学会総会 2019年07月
  • 当院における肥満外科手術の減量効果と代謝改善効果の中長期成績  [通常講演]
    春田 英律, 細谷 好則, 岡田 健太, 齋藤 心, 倉科 憲太郎, 金丸 理人, 石橋 俊, 山口 博紀, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2019年07月
  • 大腸癌所属リンパ節内のTリンパ球におけるPD-1の発現について  [通常講演]
    津久井 秀則, 齋藤 晶, 東條 峰之, 大澤 英之, 佐久間 康成, 細谷 好則, 堀江 久永, 佐田 尚宏, 北山 丈二
    日本消化器外科学会総会 2019年07月
  • 潰瘍性大腸炎のため内服していたメサラジン腸溶錠が狭窄腸管に停留しイレウスをきたした腹膜癌の一例  [通常講演]
    清水 敦, 堀江 久永, 佐久間 康成, 細谷 好則, 北山 丈二, 伊藤 千紗, 内田 真一郎, 藤原 寛行, 丹波 嘉一郎, 佐田 尚宏
    日本消化器外科学会総会 2019年07月
  • Flowcytometryを用いた大腸癌組織における細胞別PD-L1、PD-L2の発現解析の試み  [通常講演]
    齋藤 晶, 東條 峰之, 大澤 英之, 佐久間 康成, 細谷 好則, 堀江 久永, 佐田 尚宏, 北山 丈二
    日本消化器外科学会総会 2019年07月
  • 【胃】胃癌腹膜播種に対する治療戦略 胃癌腹膜播種に対する全身・腹腔内投与併用化学療法  [通常講演]
    石神 浩徳, 藪崎 裕, 大森 健, 小寺 泰弘, 福島 亮治, 今野 元博, 有上 貴明, 富田 寿彦, 山口 博紀, 北山 丈二
    日本消化器外科学会総会 2019年07月
  • 【胃】胃癌腹膜播種に対する治療戦略 腹膜播種陽性胃癌に対するSOX+PTX腹腔内投与併用療法  [通常講演]
    齋藤 心, 山口 博紀, 細谷 好則, 金丸 理人, 春田 英律, 倉科 憲太郎, 堀江 久永, 佐久間 康成, 佐田 尚宏, 北山 丈二
    日本消化器外科学会総会 2019年07月
  • 在宅での看取りを考える 自宅で最期をむかえた癌患者の検討  [通常講演]
    櫻木 雅子, 藤田 崇史, 佐々木 裕美子, 西田 紗季, 芝 聡美, 宮崎 千絵子, 塩澤 幹雄, 水沼 洋文, 北山 丈二, 佐田 尚宏
    日本乳癌学会総会プログラム抄録集 2019年07月
  • 自家組織移植による乳房再建施行後、再建乳房内に局所再発を認めた2例  [通常講演]
    西田 紗季, 藤田 崇史, 佐々木 裕美子, 芝 聡美, 櫻木 雅子, 塩澤 幹雄, 宇田 宏一, 吉村 浩太郎, 北山 丈二, 佐田 尚宏
    日本乳癌学会総会プログラム抄録集 2019年07月
  • 食道神経内分泌癌(NEC)7例の検討  [通常講演]
    金子 勇貴, 齋藤 心, 山口 博紀, 春田 英律, 松本 四郎, 倉科 憲太郎, 細谷 好則, 北山 丈二, 仁木 利郎, 佐田 尚宏
    日本食道学会学術集会プログラム・抄録集 2019年06月
  • 腎細胞癌膵転移切除症例の診断、手術、経過に関して  [通常講演]
    吉田 淳, 佐久間 康成, 森嶋 計, 遠藤 和洋, 三木 厚, 笹沼 英紀, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    膵臓 2019年06月
  • 低肺機能症例に対する縦隔鏡併用非開胸食道切除術の導入  [通常講演]
    倉科 憲太郎, 細谷 好則, 愛甲 丞, 瀬戸 泰之, 齋藤 心, 春田 英律, 松本 志郎, 宇井 崇, 北山 丈二, 佐田 尚宏
    日本食道学会学術集会プログラム・抄録集 2019年06月
  • 術前DCF療法の治療効果に係る因子の検討  [通常講演]
    松本 志郎, 細谷 好則, 宇井 崇, 高橋 和也, 金丸 理人, 春田 英律, 倉科 憲太郎, 齋藤 心, 山口 博紀, 北山 丈二
    日本食道学会学術集会プログラム・抄録集 2019年06月
  • 小腸癌に対する外科治療の意義 原発性小腸癌24例の臨床病理学的検討  [通常講演]
    井上 賢之, 堀江 久永, 鯉沼 広治, 田原 真紀子, 巷野 佳彦, 本間 祐子, 佐田友 藍, 清水 徹一郎, 伊藤 誉, 直井 大志, 熊谷 祐子, 津久井 秀則, 東條 峰之, 佐久間 康成, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本大腸肛門病学会雑誌 2019年05月
  • 高度膀胱浸潤を伴う直腸・S状結腸癌に対する治療戦略と当科における手術成績  [通常講演]
    田原 真紀子, 堀江 久永, 本間 祐子, 熊谷 祐子, 佐田友 藍, 直井 大志, 清水 徹一郎, 伊藤 誉, 巷野 佳彦, 井上 賢之, 鯉沼 広治, 佐久間 康成, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本外科学会定期学術集会抄録集 2019年04月
  • 大腸内視鏡検査により発症した脾損傷の1例  [通常講演]
    本間 祐子, 井上 賢之, 清水 徹一郎, 巷野 佳彦, 田原 真紀子, 佐久間 康成, 堀江 久永, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本大腸検査学会雑誌 2019年04月
  • 12年の長期経過観察中に悪性化したと考えられる膵粘液嚢胞性腫瘍の一例  [通常講演]
    高橋 礼, 笹沼 英紀, 三木 厚, 森嶋 計, 吉田 淳, 遠藤 和洋, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏, 池田 恵理子, 福島 敬宜
    日本消化器病学会関東支部例会プログラム・抄録集 2019年04月
  • 胃管癌8例の臨床病理学的検討  [通常講演]
    齋藤 心, 細谷 好則, 松原 大祐, 春田 英律, 倉科 憲太郎, 松本 志郎, 北山 丈二, 山口 博紀, 佐久間 康成, 堀江 久永, 佐田 尚宏
    日本外科学会定期学術集会抄録集 2019年04月
  • 当院における直腸癌内視鏡切除後の追加切除適応症例についての検討  [通常講演]
    巷野 佳彦, 堀江 久永, 津久井 秀則, 本間 祐子, 熊谷 祐子, 東條 峰之, 佐田友 藍, 清水 徹一郎, 直井 大志, 田原 真紀子, 伊藤 誉, 森 和亮, 井上 賢之, 鯉沼 広治, 佐久間 康成, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本外科学会定期学術集会抄録集 2019年04月
  • 十二指腸乳頭部腫瘍に対する外科的乳頭切除術による段階的治療戦略  [通常講演]
    小泉 大, 斎藤 晶, 青木 裕一, 森嶋 計, 兼田 裕司, 三木 厚, 遠藤 和洋, 笹沼 英紀, 吉田 淳, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本外科学会定期学術集会抄録集 2019年04月
  • 開腹術後腹腔内滲出好中球の臨床的意義  [通常講演]
    金丸 理人, 大澤 英之, 松本 志郎, 春田 英律, 倉科 憲太郎, 山口 博紀, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本外科学会定期学術集会抄録集 2019年04月
  • 術前CRTが施行された直腸癌症例に対する側方郭清の適応について  [通常講演]
    堀江 久永, 鯉沼 広治, 井上 賢之, 田原 真紀子, 巷野 佳彦, 清水 徹一郎, 本間 祐子, 津久井 秀則, 熊谷 祐子, 東條 峰之, 伊藤 誉, 佐田友 藍, 直井 大志, 佐久間 康成, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本外科学会定期学術集会抄録集 2019年04月
  • 消化器癌手術患者における末梢血中低比重好中球の術中推移  [通常講演]
    熊谷 祐子, 金丸 理人, 大澤 英之, 山口 博紀, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本外科学会定期学術集会抄録集 2019年04月
  • クローン病腸管病変に対する内科外科連携に基づく治療戦略  [通常講演]
    伊藤 誉, 堀江 久永, 津久井 秀則, 本間 祐子, 熊谷 祐子, 東條 峰之, 佐田友 藍, 直井 大志, 清水 徹一郎, 田原 真紀子, 巷野 佳彦, 井上 賢之, 鯉沼 広治, 佐久間 康成, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本外科学会定期学術集会抄録集 2019年04月
  • 放射線照射が癌細胞におけるアデノシン産生酵素CD73に与える影響について  [通常講演]
    津久井 秀則, 大澤 英之, 山口 博紀, 佐久間 康成, 細谷 好則, 堀江 久永, 藤井 博文, 北山 丈二, 佐田 尚宏
    日本外科学会定期学術集会抄録集 2019年04月
  • 腹腔内液中エクソソームを用いた胃癌腹膜播種治療におけるバイオマーカー探索  [通常講演]
    大澤 英之, 齋藤 晶, 熊谷 祐子, 佐久間 康成, 山口 博紀, 堀江 久永, 細谷 好則, 佐田 尚宏, 北山 丈二
    日本外科学会定期学術集会抄録集 2019年04月
  • 脾彎曲部結腸癌に対する腹腔鏡下手術の工夫  [通常講演]
    鯉沼 広治, 堀江 久永, 田原 真紀子, 清水 徹一郎, 巷野 佳彦, 井上 賢之, 本間 祐子, 伊藤 誉, 佐田友 藍, 直井 大志, 佐久間 康成, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本外科学会定期学術集会抄録集 2019年04月
  • 胃癌における周術期化学療法の最先端 根治切除可能な漿膜浸潤陽性胃癌に対する腹腔内投与併用の周術期化学療法を検証する第II相試験(GAPS試験)  [通常講演]
    會澤 雅樹, 今野 元博, 藪崎 裕, 伊藤 誠二, 上之園 芳一, 廣野 靖夫, 上田 修吾, 松村 卓樹, 千葉 康敬, 千葉 佐知, 松木 淳, 有上 貴明, 伊藤 友一, 藤本 大裕, 石神 浩徳, 山口 博紀, 安田 卓司, 北山 丈二, 古河 洋
    日本外科学会定期学術集会抄録集 2019年04月
  • 上部消化管癌集学的治療における手術のタイミング 腹膜転移を伴う胃癌患者に対するtaxanesによる腹腔内(IP)化学療法後の転換手術(Conversion surgery for gastric cancer patients with peritoneal metastasis after intraperitoneal(IP) chemotherapy with taxanes)  [通常講演]
    福島 亮治, 石神 浩徳, 藪崎 裕, 大森 健, 小寺 泰弘, 今野 元博, 有上 貴明, 富田 寿彦, 岸 健太郎, 北山 丈二
    日本外科学会定期学術集会抄録集 2019年04月
  • 左乳房腺様嚢胞癌の術後に肺転移を認めた一例  [通常講演]
    西田 紗季, 藤田 崇史, 扇原 香澄, 田中 裕美子, 芝 聡美, 宮崎 千絵子, 櫻木 雅子, 塩澤 幹雄, 北山 丈二, 佐田 尚宏
    日本臨床外科学会雑誌 2019年03月
  • 腹腔動脈狭窄を伴う特発性下膵十二指腸動脈破裂の1例  [通常講演]
    小泉 恵, 吉田 淳, 高橋 和也, 青木 裕一, 田口 昌延, 森嶋 計, 三木 厚, 遠藤 和洋, 笹沼 英紀, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本臨床外科学会雑誌 2019年03月
  • 膵十二指腸動脈瘤の3例  [通常講演]
    渡部 晃佑, 吉田 淳, 高橋 和也, 青木 裕一, 田口 昌延, 森嶋 計, 三木 厚, 兼田 裕司, 遠藤 和洋, 笹沼 英紀, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本腹部救急医学会雑誌 2019年02月
  • 鼠径部ヘルニア嵌頓症例における経過時間と腸切除の検討  [通常講演]
    小泉 大, 斎藤 晶, 青木 裕一, 森嶋 計, 兼田 裕司, 三木 厚, 遠藤 和洋, 笹沼 英紀, 吉田 淳, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本腹部救急医学会雑誌 2019年02月
  • 術前診断しえた特発性大網出血の1例  [通常講演]
    高橋 和也, 笹沼 英紀, 青木 裕一, 森嶋 計, 兼田 裕司, 遠藤 和洋, 吉田 淳, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本腹部救急医学会雑誌 2019年02月
  • 部分的脾動脈塞栓後に残胃血流を考慮し幽門側胃切除術および脾臓摘出術を施行したITP合併胃癌  [通常講演]
    金子 勇貴, 齋藤 心, 高橋 大二郎, 松本 志郎, 宇井 崇, 春田 英律, 倉科 憲太郎, 宮戸 秀世, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本胃癌学会総会記事 2019年02月
  • 横隔膜上憩室を伴う食道平滑筋腫の1例  [通常講演]
    倉科 憲太郎, 細谷 好則, 春田 英律, 松本 志郎, 齋藤 心, 宇井 崇, 金丸 理人, 高橋 和也, 佐久間 康成, 堀江 久永, 北山 丈二, 佐田 尚宏
    日本消化器病学会関東支部例会プログラム・抄録集 2019年02月
  • 會澤雅樹, 今野元博, 藪崎裕, 伊藤誠二, 上之園芳一, 廣野靖夫, 上田修吾, 松村卓樹, 千葉康敬, 千葉佐知, 松木淳, 有上貴明, 伊藤友一, 藤本大裕, 石神浩徳, 山口博紀, 安田卓司, 北山丈二, 古河洋
    日本外科学会定期学術集会(Web) 2019年
  • 福島亮治, 石神浩徳, 藪崎裕, 大森健, 小寺泰弘, 今野元博, 有上貴明, 富田寿彦, 岸健太郎, 北山丈二
    日本外科学会定期学術集会(Web) 2019年
  • 当科における高度肥満症に対する腹腔鏡下スリーブ状胃切除術の取り組みと治療成績  [通常講演]
    春田 英律, 細谷 好則, 倉科 憲太郎, 斎藤 心, 宇井 崇, 松本 志郎, 金丸 理人, 高橋 和也, 山口 博紀, 佐久間 康成, 堀江 久永, 北山 丈二, 佐田 尚宏
    日本成人病(生活習慣病)学会会誌 2019年01月
  • 治癒切除を受けた消化器癌患者のメトホルミン内服による生存率改善について  [通常講演]
    熊谷 祐子, 大澤 英之, 山口 博紀, 佐久間 康成, 堀江 久永, 細谷 好則, 佐田 尚宏, 北山 丈二
    日本成人病(生活習慣病)学会会誌 2019年01月
  • 直腸穿通をきたした卵巣成熟嚢胞性奇形腫の1例  [通常講演]
    松本 健司, 井上 賢之, 坂口 美織, 森 和亮, 鯉沼 広治, 堀江 久永, アラン K.・レフォー, 北山 丈二, 佐田 尚宏
    日本外科系連合学会誌 2018年12月 日本外科系連合学会
     
    症例は48歳,女性.数日前からの血便を主訴に当院を受診した.腹部造影CTでは,腹腔内に腹水貯留やfree airは認められなかった.両側の卵巣には嚢胞成分を含む腫瘤性病変を認め,特に右卵巣は内部に高吸収域を有し直腸に近接していた.卵巣腫瘍による直腸浸潤もしくは直腸腫瘍による卵巣浸潤が疑われ,精査目的に同日緊急入院となった.下部消化管内視鏡を施行したところ,直腸Raに毛髪が付着した腫瘤が穿通している所見を認めた.卵巣奇形腫の直腸穿通が疑われたが腹膜炎所見を認めなかったため,待機的手術の方針とした.良悪性の鑑別が困難であったため,術中迅速病理所見により切除範囲を検討する方針とし,入院第9日目に手術を施行した.術中所見では両側の卵巣・直腸・子宮が一塊となっており両側附属器切除術・低位前方切除術・子宮全摘術を施行した.迅速病理では卵巣成熟嚢胞性奇形腫の診断であり,リンパ節郭清は行わず,手術終了とした.経過良好で術後10日目に退院となった.卵巣成熟嚢胞性奇形腫による消化管穿通例の報告は比較的稀である.良性症例だけでなく悪性症例も存在し,手術対応が異なるため,正確な術前術中診断が必要である.(著者抄録)
  • 腹腔鏡下肝切除とRFAを併用して治療した肝細胞癌5例の検討  [通常講演]
    森嶋 計, 青木 裕一, 田口 昌延, 遠藤 和洋, 笹沼 英紀, 吉田 淳, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本内視鏡外科学会雑誌 2018年12月
  • 内視鏡補助下に切除した膵内分泌腫瘍術後の異時性転移性副腎腫瘍の1例  [通常講演]
    吉田 淳, 佐久間 康成, 青木 裕一, 田口 昌延, 森嶋 計, 遠藤 和洋, 笹沼 英紀, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本内視鏡外科学会雑誌 2018年12月
  • 当科の後腹膜鏡下副腎摘出術の手術成績の検討  [通常講演]
    小泉 大, 田口 昌延, 森嶋 計, 遠藤 和洋, 笹沼 英紀, 吉田 淳, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本内視鏡外科学会雑誌 2018年12月
  • 当科で施行した縦隔鏡併用非開胸食道切除術3症例の経験  [通常講演]
    倉科 憲太郎, 細谷 好則, 愛甲 丞, 瀬戸 泰之, 齋藤 心, 春田 英律, 松本 志郎, 宇井 崇, 金丸 理人, 高橋 和也, 堀江 久永, 佐久間 康成, 北山 丈二, 佐田 尚宏
    日本内視鏡外科学会雑誌 2018年12月
  • 腹腔鏡下右側結腸手術に対するERASプロトコル導入の短期成績  [通常講演]
    直井 大志, 堀江 久永, 鯉沼 広治, 井上 賢之, 伊藤 誉, 巷野 佳彦, 田原 真紀子, 清水 徹一郎, 佐田友 藍, 佐久間 康成, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本内視鏡外科学会雑誌 2018年12月
  • 腹腔鏡下低位前方切除術後に発症した下肢コンパートメント症候群の2例  [通常講演]
    田原 真紀子, 堀江 久永, 津久井 秀則, 熊谷 祐子, 佐田友 藍, 清水 徹一郎, 直井 大志, 巷野 佳彦, 伊藤 誉, 井上 賢之, 鯉沼 広治, 佐久間 康成, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本内視鏡外科学会雑誌 2018年12月
  • 自治医科大学附属病院「鏡視下手術部」の役割  [通常講演]
    細谷 好則, 佐久間 康成, 堀江 久永, 北山 丈二, 佐田 尚宏
    日本内視鏡外科学会雑誌 2018年12月
  • 腹腔鏡下膵体尾部切除(Lap-DP)における定型化膵離断 膵臓の厚みとカートリッジに関する検討  [通常講演]
    笹沼 英紀, 佐久間 康成, 木村 有希, 青木 裕一, 田口 昌延, 森嶋 計, 遠藤 和洋, 吉田 淳, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本内視鏡外科学会雑誌 2018年12月
  • 抗血栓薬内服患者に対する腹腔鏡下大腸手術の安全性について  [通常講演]
    清水 徹一郎, 堀江 久永, 熊谷 祐子, 佐田友 藍, 直井 大志, 田原 真紀子, 巷野 佳彦, 井上 賢之, 鯉沼 広治, 佐久間 康成, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本内視鏡外科学会雑誌 2018年12月
  • 腹腔鏡下右半結腸切除における腸管引き出し操作による副右結腸静脈からの出血の1例  [通常講演]
    佐田友 藍, 堀江 久永, 直井 大志, 清水 徹一郎, 田原 真紀子, 伊藤 誉, 巷野 佳彦, 井上 賢之, 鯉沼 広治, 佐久間 康成, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本内視鏡外科学会雑誌 2018年12月
  • 術前シミュレーションと3D内視鏡を用いた安全な腹腔鏡下側方リンパ節郭清の導入  [通常講演]
    堀江 久永, 鯉沼 広治, 井上 賢之, 田原 真紀子, 巷野 佳彦, 清水 徹一郎, 伊藤 誉, 佐田友 藍, 直井 大志, 佐久間 康成, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本内視鏡外科学会雑誌 2018年12月
  • ウェアラブルチェア「アルケリス」の使用経験 内視鏡外科手術の負担軽減を目指して  [通常講演]
    井上 賢之, 川平 洋, 清水 徹一郎, 田原 真紀子, 巷野 佳彦, 遠藤 和洋, 佐久間 康成, 堀江 久永, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本内視鏡外科学会雑誌 2018年12月
  • 下行結腸進行癌に対する腹腔鏡下手術の工夫  [通常講演]
    鯉沼 広治, 堀江 久永, 佐田友 藍, 直井 大志, 田原 真紀子, 伊藤 誉, 清水 徹一郎, 井上 賢之, 巷野 佳彦, 佐久間 康成, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本内視鏡外科学会雑誌 2018年12月
  • 肥満外科手術のコツ 腹腔鏡下スリーブ状胃切除術における周術期管理と手技の工夫  [通常講演]
    春田 英律, 細谷 好則, 斎藤 心, 倉科 憲太郎, 宇井 崇, 松本 志郎, 高橋 和也, 佐久間 康成, 堀江 久永, 北山 丈二, 佐田 尚宏
    日本内視鏡外科学会雑誌 2018年12月
  • 肥満外科治療の現状と展望 当科における腹腔鏡下スリーブ状胃切除術の取組みと今後の展望  [通常講演]
    春田 英律, 細谷 好則, 斎藤 心, 倉科 憲太郎, 宇井 崇, 松本 志郎, 高橋 和也, 佐久間 康成, 堀江 久永, 北山 丈二, 佐田 尚宏
    日本内視鏡外科学会雑誌 2018年12月
  • 食道癌治療後再燃に対して縦隔鏡併用非開胸食道切除術を施行した1例  [通常講演]
    塚本 恵, 倉科 憲太郎, 細谷 好則, 愛甲 丞, 瀬戸 泰之, 松本 志郎, 春田 英律, 北山 丈二, 佐田 尚宏
    日本胸部外科学会関東甲信越地方会要旨集 2018年11月
  • ホルモン受容体陽性HER2陰性乳癌における転移・再発後の薬物療法の治療期間の検討  [通常講演]
    田中 裕美子, 藤田 崇史, 芝 聡美, 西田 紗季, 宮崎 千絵子, 櫻木 雅子, 塩澤 幹雄, 北山 丈二, 佐田 尚宏
    日本癌治療学会学術集会抄録集 2018年10月
  • 経口摂取困難な腹膜播種陽性胃癌症例に対するmFOLFOX6+paclitaxel腹腔内投与併用療法  [通常講演]
    廣野 靖夫, 石神 浩徳, 室 圭, 門脇 重憲, 吉田 俊太郎, 富田 寿彦, 藪崎 裕, 楠本 哲也, 太田 光彦, 小寺 泰弘, 辻 靖, 秀村 晃生, 蜂谷 修, 大庭 幸治, 北山 丈二, 腹腔内化学療法研究会
    日本癌治療学会学術集会抄録集 2018年10月
  • 胃癌腹膜播種に対するSOX+PTX腹腔内投与併用化学療法の新規導入施設における治療成績  [通常講演]
    山口 博紀, 金丸 理人, 大澤 英之, 松本 志郎, 倉科 憲太郎, 春田 英律, 細谷 好則, 藤井 博文, 北山 丈二, 佐田 尚宏
    日本癌治療学会学術集会抄録集 2018年10月
  • 胃癌腹膜播種に対する全身化学療法と腹腔内化学療法および胃切除術による集学的治療  [通常講演]
    小林 大介, 石神 浩徳, 藪崎 裕, 大森 健, 小寺 泰弘, 福島 亮治, 今野 元博, 有上 貴明, 富田 寿彦, 岸 健太郎, 松村 卓樹, 三澤 一成, 廣野 靖夫, 山口 博紀, 北山 丈二, 腹腔内化学療法研究会
    日本癌治療学会学術集会抄録集 2018年10月
  • 腹膜播種を伴う胃癌に対するS-1/CDDP+パクリタキセル腹腔内投与併用の第II相臨床試験  [通常講演]
    小林 大介, 太田 光彦, 福島 亮治, 伏田 幸夫, 上田 修吾, 楠本 哲也, 秀村 晃生, 山下 直行, 藪崎 裕, 大森 健, 有上 貴明, 石神 浩徳, 北山 丈二, 小寺 泰弘, 腹腔内化学療法研究会
    日本癌治療学会学術集会抄録集 2018年10月
  • 複雑な部分内臓逆位症を伴う総胆管結石症に対し手術を行った1例  [通常講演]
    丸藤 琴音, 吉田 淳, 笹沼 英紀, 宮戸 秀世, 目黒 由行, 森嶋 計, 三木 厚, 遠藤 和洋, 小泉 大, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本臨床外科学会雑誌 2018年10月
  • 慢性膵炎急性増悪を契機に脾膿瘍を合併した1例  [通常講演]
    寺田 茉位子, 吉田 淳, 佐久間 康成, 木村 有希, 青木 裕一, 森嶋 計, 遠藤 和洋, 笹沼 英紀, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本臨床外科学会雑誌 2018年10月
  • 急速な経過をたどった乳房領域の壊死性筋膜炎の一例  [通常講演]
    扇原 香澄, 塩澤 幹雄, 西田 紗季, 田中 裕美子, 芝 聡美, 櫻木 雅子, 藤田 崇史, 北山 丈二, 佐田 尚宏, 秋根 大, 富永 経一郎
    日本臨床外科学会雑誌 2018年10月
  • 乳房腺様嚢胞癌の術後に肺転移を認めた一例  [通常講演]
    西田 紗季, 藤田 崇史, 櫻木 雅子, 塩澤 幹雄, 芝 聡美, 田中 裕美子, 扇原 香澄, 北山 丈二, 佐田 尚宏
    日本臨床外科学会雑誌 2018年10月
  • 75歳以上高齢者大腸癌症例における腹腔鏡下手術の検討  [通常講演]
    高橋 礼, 田原 真紀子, 本間 祐子, 佐田友 藍, 清水 徹一郎, 井上 賢之, 巷野 佳彦, 鯉沼 広治, 佐久間 康成, 味村 俊樹, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本臨床外科学会雑誌 2018年10月
  • 膵頭部癌に対して膵頭十二指腸切除術を施行し膵尾側断端閉鎖を行った一例  [通常講演]
    倉田 佳彦, 木村 有希, 青木 裕一, 森嶋 計, 遠藤 和洋, 笹沼 英紀, 吉田 淳, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本臨床外科学会雑誌 2018年10月
  • 腹痛にて発症した乳癌小腸転移の一例  [通常講演]
    窪木 大悟, 堀江 久永, 森島 計, 本間 祐子, 田原 真紀子, 井上 賢之, 櫻木 雅子, 藤田 崇史, 佐久間 康成, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本臨床外科学会雑誌 2018年10月
  • 根治切除可能であったTrousseau症候群を合併した進行胃癌の1例  [通常講演]
    齋藤 匠, 倉科 憲太郎, 細谷 好則, 山口 博紀, 益子 貴史, 春田 英律, 齋藤 心, 宇井 崇, 松本 志郎, 金丸 理人, 高橋 和也, 堀江 久永, 佐久間 康成, 北山 丈二, 佐田 尚宏
    日本臨床外科学会雑誌 2018年10月
  • 3D-CT angiographyによる術前シミュレーションと2方向間膜アプローチ法を組み合わせた腹腔鏡下右側大腸癌手術の定型化への試み  [通常講演]
    田原 真紀子, 鯉沼 広治, 津久井 秀則, 熊谷 祐子, 清水 徹一郎, 直井 大志, 巷野 佳彦, 伊藤 誉, 井上 賢之, 佐久間 康成, 細谷 好則, 味村 俊樹, 堀江 久永, 北山 丈二, 佐田 尚宏
    日本臨床外科学会雑誌 2018年10月
  • 外科の緩和ケア バランス麻酔のアプローチに学ぶ外科医のtotal distressマネジメント  [通常講演]
    清水 敦, 佐久間 康成, 細谷 好則, 堀江 久永, 藤田 崇史, 山口 博紀, 北山 丈二, 佐田 尚宏
    日本臨床外科学会雑誌 2018年10月
  • 肥満に対する外科治療の最前線 当院における肥満外科手術の取り組みと治療成績  [通常講演]
    春田 英律, 細谷 好則, 倉科 憲太郎, 斎藤 心, 宇井 崇, 松本 志郎, 金丸 理人, 高橋 和也, 山口 博紀, 佐久間 康成, 堀江 久永, 北山 丈二, 佐田 尚宏
    日本臨床外科学会雑誌 2018年10月
  • 「地域医療の実践」と「医師のキャリア形成」の両立 自治医科大学の取り組み  [通常講演]
    深井 晴成, 遠藤 和洋, 小泉 大, 笹沼 英紀, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏, 山本 真一, 遠藤 俊輔
    日本臨床外科学会雑誌 2018年10月
  • 当院における腹腔鏡下スリーブ状胃切除術の治療成績  [通常講演]
    細谷 好則, 春田 英律, 松本 志郎, 倉科 憲太郎, 斎藤 心, 岡田 健太, 海老原 健, 石橋 俊, 矢田 俊彦, 北山 丈二, 佐田 尚宏
    肥満研究 2018年09月
  • 当院における腹腔鏡下スリーブ状胃切除術の治療成績  [通常講演]
    細谷 好則, 春田 英律, 松本 志郎, 倉科 憲太郎, 斎藤 心, 岡田 健太, 海老原 健, 石橋 俊, 矢田 俊彦, 北山 丈二, 佐田 尚宏
    肥満研究 2018年09月
  • 腹腔鏡下直腸切断術における人工肛門造設の工夫  [通常講演]
    巷野 佳彦, 堀江 久永, 太田 学, 宮原 悠三, 津久井 秀則, 本間 祐子, 太白 健一, 熊谷 祐子, 東條 峰之, 佐田友 藍, 清水 徹一郎, 直井 大志, 田原 真紀子, 伊藤 誉, 井上 賢之, 丸山 博行, 鯉沼 広治, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本大腸肛門病学会雑誌 2018年09月
  • 直腸原発Goblet cell carcinoidに対し腹腔鏡下直腸切断術を施行した1例  [通常講演]
    井上 賢之, 堀江 久永, 本間 祐子, 佐田友 藍, 清水 徹一郎, 田原 真紀子, 森 和亮, 伊藤 誉, 巷野 佳彦, 鯉沼 広治, 佐久間 康成, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本大腸肛門病学会雑誌 2018年09月
  • 残尿測定による直腸癌術後排尿障害の評価  [通常講演]
    東條 峰之, 堀江 久永, 太田 学, 宮原 悠三, 津久井 秀則, 本間 祐子, 太白 健一, 熊谷 祐子, 佐田友 藍, 清水 徹一郎, 直井 大志, 巷野 佳彦, 田原 真紀子, 伊藤 誉, 井上 賢之, 丸山 博行, 鯉沼 広治, 味村 俊樹, 北山 丈二, 佐田 尚宏
    日本大腸肛門病学会雑誌 2018年09月
  • IBD治療における内科・外科・肛門科の連携 クローン病腸管病変に対する内科外科連携に基づく治療戦略  [通常講演]
    伊藤 誉, 堀江 久永, 本間 祐子, 直井 大志, 清水 徹一郎, 田原 真紀子, 巷野 佳彦, 井上 賢之, 鯉沼 広治, 佐久間 康成, 細谷 好則, 味村 俊樹, 北山 丈二, 佐田 尚宏, 矢野 智則, 砂田 圭二郎, 山本 博徳
    日本大腸肛門病学会雑誌 2018年09月
  • 原発性十二指腸癌におけるムチンタンパク発現と悪性化機序解明(Functional blockade of MUC1 can inhibit the progression of duodenum adenocarcinoma)  [通常講演]
    芝 聡美, 三木 厚, 大澤 英之, 寺谷 工, 佐久間 康成, アラン・レフォー, 北山 丈二, 佐田 尚宏
    日本癌学会総会記事 2018年09月
  • 消化器癌手術患者の末梢血中低比重好中球と術後転移再発との関連について(Low density neutrophils(LDN) in postoperative peripheral blood may assist the recurrence of gastrointestinal cancer)  [通常講演]
    熊谷 祐子, 金丸 理人, 大澤 英之, 山口 博紀, 佐久間 康成, 堀江 久永, 細谷 好則, 佐田 尚宏, 北山 丈二
    日本癌学会総会記事 2018年09月
  • 胃癌腹膜播種治療における腹腔内液中エクソソームマイクロRNA解析(Exosomal microRNA profiles in peritoneal fluids as a therapeutic biomarker for peritoneal metastasis of gastric cancer)  [通常講演]
    大澤 英之, 熊谷 祐子, 山口 博紀, 北山 丈二
    日本癌学会総会記事 2018年09月
  • 好中球細胞外トラップ(NETs)による開腹術後腹膜再発促進機構(Neutrophil extracellular traps(NETs) on postoperative peritoneal surface may support the tumor recurrence on peritoneum)  [通常講演]
    金丸 理人, 大澤 英之, 高橋 和也, 松本 志郎, 春田 英律, 倉科 憲太郎, 山口 博紀, 佐久間 康成, 堀江 久永, 細谷 好則, 佐田 尚宏, 北山 丈二
    日本癌学会総会記事 2018年09月
  • 担癌マウスリンパ節におけるアデノシン脱リン酸化酵素(CD39,CD73)発現についての解析(Expression of adenosine generating ecto-enzymes, CD39 and CD73, in lymphocytes in tumor bearing mouse)  [通常講演]
    津久井 秀則, 大澤 英之, 山口 博紀, 佐久間 康成, 細谷 好則, 堀江 久永, 藤井 博文, 佐田 尚宏, 北山 丈二
    日本癌学会総会記事 2018年09月
  • 腹腔環境の特殊性に基づいた新規腹膜播種治療(Treatment of peritoneal dissemination based on the unique microenvironment in peritoneal cavity)  [通常講演]
    北山 丈二, 金丸 理人, 大澤 英之, 熊谷 祐子, 山口 博紀, 細谷 好則, 松崎 圭祐, 佐田 尚宏
    日本癌学会総会記事 2018年09月
  • 開腹手術後の末梢血低比重好中球の臨床的意義
    熊谷 祐子, 大澤 英之, 金丸 理人, 佐久間 康成, 堀江 久永, 細谷 好則, 山口 博紀, 佐田 尚宏, 北山 丈二
    日本がん免疫学会総会プログラム・抄録集 2018年07月 日本がん免疫学会
  • 腹腔鏡下左側結腸癌切除に対する肥満の影響  [通常講演]
    田原 真紀子, 堀江 久永, 森 和亮, 井上 賢之, 鯉沼 広治, 笹沼 英紀, 佐久間 康成, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2018年07月
  • 膵体尾部切除術における膵断端処理と術後膵液瘻の検討  [通常講演]
    木村 有希, 小泉 大, 三木 厚, 遠藤 和洋, 笹沼 英紀, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2018年07月
  • 腹膜播種の診断と治療の工夫 腹膜播種に対するパクリタキセル腹腔内化学療法におけるドラッグデリバリー向上の工夫  [通常講演]
    江本 成伸, 北山 丈二, 山口 博紀, 石神 浩徳, 室野 浩司, 田中 敏明, 畑 啓介, 川合 一茂, 野澤 宏彰
    日本消化器外科学会総会 2018年07月
  • 腹膜播種の診断と治療の工夫 腹膜播種陽性胃癌に対するSOX+PTX腹腔内投与併用化学療法の新規導入施設における治療成績  [通常講演]
    齋藤 心, 山口 博紀, 松本 志郎, 倉科 憲太郎, 佐久間 康成, 春田 英律, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2018年07月
  • 開腹手術後の腹腔内滲出好中球由来細胞外トラップ(NETs)の臨床的意義  [通常講演]
    金丸 理人, 大澤 英之, 松本 志郎, 春田 英律, 倉科 憲太郎, 宮戸 秀世, 山口 博紀, 細谷 好則, 佐田 尚宏, 北山 丈二
    日本消化器外科学会総会 2018年07月
  • 当院における腹腔鏡下直腸切断術症例人工肛門造設の工夫  [通常講演]
    巷野 佳彦, 堀江 久永, 田原 真紀子, 森 和亮, 井上 賢之, 鯉沼 広治, 佐久間 康成, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2018年07月
  • 集学的治療は微小転移を制御できるか? 胃癌腹膜微小転移に対するパクリタキセル腹腔内反復化学療法の有用性  [通常講演]
    北山 丈二, 石神 浩徳, 山口 博紀, 腹腔内化学療法研究会
    日本消化器外科学会総会 2018年07月
  • 消化器外科手術における術前血清total cholesterol値と術後感染症との関連について  [通常講演]
    森本 光昭, 堀江 久永, 井上 賢之, 伊藤 誉, 森 和亮, 田原 真紀子, 鯉沼 広治, 北山 丈二, 細谷 好則, 佐田 尚宏
    日本消化器外科学会総会 2018年07月
  • 放射線化学療法(CRT)後の直腸癌組織におけるCD73の発現  [通常講演]
    津久井 秀則, 大澤 英之, 山口 博紀, 佐久間 康成, 細谷 好則, 堀江 久永, 藤井 博文, 若月 優, 佐田 尚宏, 北山 丈二
    日本消化器外科学会総会 2018年07月
  • 治癒切除を受けた消化器癌術後患者へのメトホルミン内服による生存率改善について  [通常講演]
    熊谷 祐子, 大澤 英之, 津久井 秀則, 金丸 理人, 芝 聡美, 堀江 久永, 細谷 好則, 佐久間 康成, 佐田 尚宏, 北山 丈二
    日本消化器外科学会総会 2018年07月
  • 骨盤内臓全摘術後の骨盤死腔炎の予防には有茎大網充填が有用である  [通常講演]
    伊藤 誉, 堀江 久永, 田原 真紀子, 森 和亮, 井上 賢之, 鯉沼 広治, 佐久間 康成, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2018年07月
  • 術後膵液瘻ゼロを目指した膵空腸吻合の工夫 Blumgart変法自治医大方式  [通常講演]
    小泉 大, 田口 昌延, 三木 厚, 遠藤 和洋, 笹沼 英紀, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2018年07月
  • 腹腔鏡下横行結腸癌手術においてSurgical trunkの郭清を安全に行うための工夫  [通常講演]
    鯉沼 広治, 堀江 久永, 井上 賢之, 田原 真紀子, 森 和亮, 巷野 佳彦, 佐久間 康成, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2018年07月
  • 当院における腹腔鏡下スリーブ状胃切除術の周術期管理と手技の工夫  [通常講演]
    春田 英律, 細谷 好則, 岡田 健太, 齋藤 心, 倉科 憲太郎, 松本 志郎, 石橋 俊, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2018年07月
  • 上行結腸Neuroendocrine carcinomaの一例  [通常講演]
    齋藤 匠, 鯉沼 広治, 田原 真紀子, 森 和亮, 井上 賢之, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2018年07月
  • 胃癌腹膜播種手術症例における予後因子としての腹腔洗浄液中CEA mRNA定量値  [通常講演]
    山口 博紀, 石神 浩徳, 松本 志郎, 宇井 崇, 春田 英律, 倉科 憲太郎, 齋藤 心, 細谷 好則, 佐田 尚宏, 北山 丈二
    日本消化器外科学会総会 2018年07月
  • 腹腔内液中エクソソームマイクロRNAを用いた胃癌腹膜播種症例のリキッドバイオプシー  [通常講演]
    大澤 英之, 熊谷 祐子, 山口 博紀, 佐久間 康成, 堀江 久永, 細谷 好則, 佐田 尚宏, 北山 丈二
    日本消化器外科学会総会 2018年07月
  • 転移巣の切除を行い長期生存が得られている直腸癌甲状腺転移の1例  [通常講演]
    森 和亮, 鯉沼 広治, 堀江 久永, 田原 真紀子, 巷野 佳彦, 井上 賢之, 佐久間 康成, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2018年07月
  • 早期胃癌ESD非治癒切除症例274例の検討  [通常講演]
    松本 志郎, 宇井 崇, 春田 英律, 倉科 憲太郎, 斎藤 心, 堀江 久永, 佐久間 康成, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2018年07月
  • 下行結腸癌異時性孤立性脾転移の1例  [通常講演]
    松宮 美沙希, 三木 厚, 川口 英之, 兼田 裕司, 遠藤 和洋, 小泉 大, 笹沼 英紀, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本臨床外科学会雑誌 2018年07月
  • 腹腔鏡下左側結腸癌切除に対する肥満の影響  [通常講演]
    田原 真紀子, 堀江 久永, 森 和亮, 井上 賢之, 鯉沼 広治, 笹沼 英紀, 佐久間 康成, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2018年07月
  • 膵体尾部切除術における膵断端処理と術後膵液瘻の検討  [通常講演]
    木村 有希, 小泉 大, 三木 厚, 遠藤 和洋, 笹沼 英紀, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2018年07月
  • 腹膜播種の診断と治療の工夫 腹膜播種に対するパクリタキセル腹腔内化学療法におけるドラッグデリバリー向上の工夫  [通常講演]
    江本 成伸, 北山 丈二, 山口 博紀, 石神 浩徳, 室野 浩司, 田中 敏明, 畑 啓介, 川合 一茂, 野澤 宏彰
    日本消化器外科学会総会 2018年07月
  • 腹膜播種の診断と治療の工夫 腹膜播種陽性胃癌に対するSOX+PTX腹腔内投与併用化学療法の新規導入施設における治療成績  [通常講演]
    齋藤 心, 山口 博紀, 松本 志郎, 倉科 憲太郎, 佐久間 康成, 春田 英律, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2018年07月
  • 開腹手術後の腹腔内滲出好中球由来細胞外トラップ(NETs)の臨床的意義  [通常講演]
    金丸 理人, 大澤 英之, 松本 志郎, 春田 英律, 倉科 憲太郎, 宮戸 秀世, 山口 博紀, 細谷 好則, 佐田 尚宏, 北山 丈二
    日本消化器外科学会総会 2018年07月
  • 当院における腹腔鏡下直腸切断術症例人工肛門造設の工夫  [通常講演]
    巷野 佳彦, 堀江 久永, 田原 真紀子, 森 和亮, 井上 賢之, 鯉沼 広治, 佐久間 康成, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2018年07月
  • 集学的治療は微小転移を制御できるか? 胃癌腹膜微小転移に対するパクリタキセル腹腔内反復化学療法の有用性  [通常講演]
    北山 丈二, 石神 浩徳, 山口 博紀, 腹腔内化学療法研究会
    日本消化器外科学会総会 2018年07月
  • 消化器外科手術における術前血清total cholesterol値と術後感染症との関連について  [通常講演]
    森本 光昭, 堀江 久永, 井上 賢之, 伊藤 誉, 森 和亮, 田原 真紀子, 鯉沼 広治, 北山 丈二, 細谷 好則, 佐田 尚宏
    日本消化器外科学会総会 2018年07月
  • 放射線化学療法(CRT)後の直腸癌組織におけるCD73の発現  [通常講演]
    津久井 秀則, 大澤 英之, 山口 博紀, 佐久間 康成, 細谷 好則, 堀江 久永, 藤井 博文, 若月 優, 佐田 尚宏, 北山 丈二
    日本消化器外科学会総会 2018年07月
  • 術後膵液瘻ゼロを目指した膵空腸吻合の工夫 Blumgart変法自治医大方式  [通常講演]
    小泉 大, 田口 昌延, 三木 厚, 遠藤 和洋, 笹沼 英紀, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2018年07月
  • 腹腔鏡下横行結腸癌手術においてSurgical trunkの郭清を安全に行うための工夫  [通常講演]
    鯉沼 広治, 堀江 久永, 井上 賢之, 田原 真紀子, 森 和亮, 巷野 佳彦, 佐久間 康成, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2018年07月
  • 当院における腹腔鏡下スリーブ状胃切除術の周術期管理と手技の工夫  [通常講演]
    春田 英律, 細谷 好則, 岡田 健太, 齋藤 心, 倉科 憲太郎, 松本 志郎, 石橋 俊, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2018年07月
  • 治癒切除を受けた消化器癌術後患者へのメトホルミン内服による生存率改善について  [通常講演]
    熊谷 祐子, 大澤 英之, 津久井 秀則, 金丸 理人, 芝 聡美, 堀江 久永, 細谷 好則, 佐久間 康成, 佐田 尚宏, 北山 丈二
    日本消化器外科学会総会 2018年07月
  • 上行結腸Neuroendocrine carcinomaの一例  [通常講演]
    齋藤 匠, 鯉沼 広治, 田原 真紀子, 森 和亮, 井上 賢之, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2018年07月
  • 胃癌腹膜播種手術症例における予後因子としての腹腔洗浄液中CEA mRNA定量値  [通常講演]
    山口 博紀, 石神 浩徳, 松本 志郎, 宇井 崇, 春田 英律, 倉科 憲太郎, 齋藤 心, 細谷 好則, 佐田 尚宏, 北山 丈二
    日本消化器外科学会総会 2018年07月
  • 腹腔内液中エクソソームマイクロRNAを用いた胃癌腹膜播種症例のリキッドバイオプシー  [通常講演]
    大澤 英之, 熊谷 祐子, 山口 博紀, 佐久間 康成, 堀江 久永, 細谷 好則, 佐田 尚宏, 北山 丈二
    日本消化器外科学会総会 2018年07月
  • 転移巣の切除を行い長期生存が得られている直腸癌甲状腺転移の1例  [通常講演]
    森 和亮, 鯉沼 広治, 堀江 久永, 田原 真紀子, 巷野 佳彦, 井上 賢之, 佐久間 康成, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2018年07月
  • 早期胃癌ESD非治癒切除症例274例の検討  [通常講演]
    松本 志郎, 宇井 崇, 春田 英律, 倉科 憲太郎, 斎藤 心, 堀江 久永, 佐久間 康成, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2018年07月
  • 下行結腸癌異時性孤立性脾転移の1例  [通常講演]
    松宮 美沙希, 三木 厚, 川口 英之, 兼田 裕司, 遠藤 和洋, 小泉 大, 笹沼 英紀, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本臨床外科学会雑誌 2018年07月
  • 骨盤内臓全摘術後の骨盤死腔炎の予防には有茎大網充填が有用である  [通常講演]
    伊藤 誉, 堀江 久永, 田原 真紀子, 森 和亮, 井上 賢之, 鯉沼 広治, 佐久間 康成, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2018年07月
  • 上行結腸が後腹膜に固定されていない腸回転異常症を伴う絞扼性イレウスの1例  [通常講演]
    吉田 陽, 下平 健太郎, 斎藤 心, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本臨床外科学会雑誌 2018年06月
  • 原発性副甲状腺機能亢進症に併発した重症急性膵炎後の感染性被包化壊死の1例  [通常講演]
    辻 賢太郎, 笠原 尚哉, 三木 厚, 遠藤 和洋, 小泉 大, 笹沼 英紀, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本臨床外科学会雑誌 2018年06月
  • 当院における腹腔鏡下スリーブ状胃切除術の治療成績  [通常講演]
    春田 英律, 細谷 好則, 岡田 健太, 倉科 憲太郎, 齋藤 心, 宇井 崇, 松本 志郎, 金丸 理人, 高橋 和也, 山口 博紀, 佐久間 康成, 堀江 久永, 北山 丈二, 佐田 尚宏
    日本肥満症治療学会学術集会プログラム・抄録集 2018年06月
  • StageII・III食道癌の治療前BMIと術前化学療法中の体重減少は予後不良と関連する  [通常講演]
    倉科 憲太郎, 細谷 好則, 大澤 英之, 齋藤 心, 春田 英律, 松本 志郎, 山口 博紀, 藤井 博文, 北山 丈二, 佐田 尚宏
    日本食道学会学術集会プログラム・抄録集 2018年06月
  • 食道に穿破した神経鞘腫の一例  [通常講演]
    松本 志郎, 細谷 好則, 金丸 理人, 宇井 崇, 春田 英律, 倉科 憲太郎, 佐久間 康成, 堀江 久永, 北山 丈二, 佐田 尚宏
    日本食道学会学術集会プログラム・抄録集 2018年06月
  • 困難例に対する手術の工夫 胃全摘術後の総胆管結石に対し、腹腔鏡下胆管切石術(経胆嚢管法)を施行した2例  [通常講演]
    春田 英律, 齋藤 心, 倉科 憲太郎, 宇井 崇, 松本 志郎, 金丸 理人, 高橋 和也, 山口 博紀, 細谷 好則, 佐久間 康成, 北山 丈二, 佐田 尚宏
    小切開・鏡視外科学会雑誌 2018年06月
  • 当院における腹腔鏡下スリーブ状胃切除術の治療成績  [通常講演]
    春田 英律, 細谷 好則, 岡田 健太, 倉科 憲太郎, 齋藤 心, 宇井 崇, 松本 志郎, 金丸 理人, 高橋 和也, 山口 博紀, 佐久間 康成, 堀江 久永, 北山 丈二, 佐田 尚宏
    日本肥満症治療学会学術集会プログラム・抄録集 2018年06月
  • 慢性特発性偽性腸閉塞症に発症した結腸二重癌の1例  [通常講演]
    関口 裕美, 太白 健一, 堀江 久永, 直井 大志, 巷野 佳彦, 田原 真紀子, 森本 光昭, 鯉沼 広治, 佐久間 康成, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本臨床外科学会雑誌 2018年05月
  • 急性膵炎を繰り返した多発性膵漿液性嚢胞腫瘍の1例  [通常講演]
    齋藤 匠, 笹沼 英紀, 田口 昌延, 三木 厚, 遠藤 和洋, 小泉 大, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    膵臓 2018年05月
  • 膵頭部残膵再発に対して、初回左胃動脈温存が有用であった膵内分泌癌の再手術例  [通常講演]
    泉 遼, 遠藤 和洋, 斉藤 晶, 田口 昌延, 三木 厚, 小泉 大, 笹沼 英紀, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    膵臓 2018年05月
  • 切除可能膵癌に対する術前放射線化学療法の有用性  [通常講演]
    三木 厚, 佐久間 康成, 斉藤 晶, 目黒 由行, 遠藤 和洋, 小泉 大, 笹沼 英紀, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    膵臓 2018年05月
  • 切除可能膵癌に対する術前放射線化学療法の有用性  [通常講演]
    三木 厚, 佐久間 康成, 斉藤 晶, 目黒 由行, 遠藤 和洋, 小泉 大, 笹沼 英紀, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    膵臓 2018年05月
  • 膵頭部残膵再発に対して、初回左胃動脈温存が有用であった膵内分泌癌の再手術例  [通常講演]
    泉 遼, 遠藤 和洋, 斉藤 晶, 田口 昌延, 三木 厚, 小泉 大, 笹沼 英紀, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    膵臓 2018年05月
  • 急性膵炎を繰り返した多発性膵漿液性嚢胞腫瘍の1例  [通常講演]
    齋藤 匠, 笹沼 英紀, 田口 昌延, 三木 厚, 遠藤 和洋, 小泉 大, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    膵臓 2018年05月
  • 胃癌腹膜播種治療における腹腔内液中エクソソームマイクロRNA解析  [通常講演]
    大澤 英之, 熊谷 裕子, 山口 博紀, 佐久間 康成, 堀江 久永, 細谷 好則, 佐田 尚宏, 北山 丈二
    日本消化器病学会雑誌 2018年04月
  • 実臨床に即した切除不能・進行再発消化管がんに対する最適な治療戦略 消化器癌腹膜播種に対するタキサン腹腔内反復化学療法の可能性  [通常講演]
    北山 丈二, 石神 浩徳, 山口 博紀
    日本消化器病学会雑誌 2018年04月
  • 膵頭十二指腸切除術を施行した十二指腸乳頭部癌の長期成績  [通常講演]
    小泉 大, 斎藤 晶, 横田 真一郎, 兼田 裕司, 三木 厚, 遠藤 和洋, 笹沼 英紀, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本外科学会定期学術集会抄録集 2018年04月
  • 腸重積症手術例の検討  [通常講演]
    松本 健司, 小泉 大, 佐久間 康成, 細谷 好則, 堀江 久永, 北山 丈二, 佐田 尚宏
    日本外科学会定期学術集会抄録集 2018年04月
  • 当院におけるCrohn病に対するKono-S吻合の短期成績  [通常講演]
    森 和亮, 堀江 久永, 太田 学, 宮原 悠三, 津久井 秀則, 太白 健一, 熊谷 祐子, 東條 峰之, 佐田友 藍, 直井 大志, 田原 真紀子, 巷野 佳彦, 伊藤 誉, 森本 光昭, 井上 賢之, 丸山 博行, 鯉沼 広治, 佐久間 康成, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本外科学会定期学術集会抄録集 2018年04月
  • 直腸癌術前化学放射線療法における治療前後末梢血好中球リンパ球による治療効果予測  [通常講演]
    津久井 秀則, 北山 丈二, 森本 光昭, 熊谷 祐子, 佐田友 藍, 清水 徹一郎, 直井 大志, 田原 真紀子, 巷野 佳彦, 森 和亮, 伊藤 誉, 井上 賢之, 鯉沼 広治, 佐久間 康成, 細谷 好則, 堀江 久永, Lefor Alan, 佐田 尚宏
    日本外科学会定期学術集会抄録集 2018年04月
  • 消化器癌手術患者における末梢血中低比重好中球(Low Density Granulocyte)の術中推移  [通常講演]
    熊谷 祐子, 金丸 理人, 津久井 秀則, 大澤 英之, 倉科 憲太郎, 鯉沼 広治, 佐久間 康成, 堀江 久永, 細谷 好則, 佐田 尚宏, 北山 丈二
    日本外科学会定期学術集会抄録集 2018年04月
  • 拡大肝切除後合併症のリスクファクターの検討  [通常講演]
    三木 厚, 佐久間 康成, 遠藤 和洋, 小泉 大, 笹沼 英紀, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本外科学会定期学術集会抄録集 2018年04月
  • 待機的直腸癌前方切除症例におけるERAS導入の効果  [通常講演]
    巷野 佳彦, 堀江 久永, 津久井 秀則, 熊谷 祐子, 佐田友 藍, 直井 大志, 田原 真紀子, 伊藤 誉, 井上 賢之, 森本 光昭, 鯉沼 広治, 佐久間 康成, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本外科学会定期学術集会抄録集 2018年04月
  • 肝肺転移を伴う大腸癌における転移出現時期からみた外科治療の意義  [通常講演]
    佐田友 藍, 鯉沼 広治, 堀江 久永, 熊谷 祐子, 田原 真紀子, 森 和亮, 井上 賢之, 佐久間 康成, 細谷 好則, 北山 丈二, 手塚 憲志, 遠藤 俊輔, 佐田 尚宏
    日本外科学会定期学術集会抄録集 2018年04月
  • 待機的腹部手術後肺合併症の予測因子の検討(単施設前向きコホート研究) 簡易問診及び身体所見は肺機能検査を越えられるか?  [通常講演]
    横田 真一郎, 小泉 大, 森本 光昭, 冨樫 一智, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 安田 是和, Lefor Alan, 佐田 尚宏
    日本外科学会定期学術集会抄録集 2018年04月
  • 胃癌腹膜播種治療におけるバイオマーカーとしての腹水中エクソソームマイクロRNA  [通常講演]
    大澤 英之, 熊谷 祐子, 山口 博紀, 佐久間 康成, 堀江 久永, 細谷 好則, 佐田 尚宏, 北山 丈二
    日本外科学会定期学術集会抄録集 2018年04月
  • 女性外科医の働き方と当科の取り組み  [通常講演]
    田原 真紀子, 堀江 久永, 熊谷 祐子, 佐田友 藍, 森 和亮, 井上 賢之, 小泉 大, 鯉沼 広治, 笹沼 英紀, 佐久間 康成, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本外科学会定期学術集会抄録集 2018年04月
  • 胃癌腹膜播種に対する腹腔内化学療法における腹腔洗浄液中CEA mRNA定量 手術適応決定のバイオマーカーとしての意義  [通常講演]
    山口 博紀, 石神 浩徳, 金丸 理人, 大澤 英之, 松本 志郎, 倉科 憲太郎, 春田 英律, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本外科学会定期学術集会抄録集 2018年04月
  • 高度進行胃癌に対する集学的治療 腹膜播種陽性または腹腔細胞診陽性胃癌に対する集学的治療  [通常講演]
    石神 浩徳, 山口 博紀, 山下 裕玄, 朝蔭 正宏, 北山 丈二
    日本外科学会定期学術集会抄録集 2018年04月
  • 上部空腸憩室穿孔による急性汎発性腹膜炎の1例  [通常講演]
    齋藤 俊祐, 利府 数馬, 三木 厚, 遠藤 和洋, 小泉 大, 笹沼 英紀, 佐久間 康成, 細谷 好則, 堀江 久永, 北山 丈二, 佐田 尚宏
    日本臨床外科学会雑誌 2018年03月
  • 胃癌切除症例における術前D-dimer値と病期・転帰の検討  [通常講演]
    倉科 憲太郎, 細谷 好則, 清水 徹一郎, 太田 学, 齋藤 心, 春田 英律, 宇井 崇, 松本 志郎, 金丸 理人, 三木 厚, 山口 博紀, 堀江 久永, 佐久間 康成, 北山 丈二, 佐田 尚宏
    日本胃癌学会総会記事 2018年03月
  • 当院における漿膜浸潤胃癌R0切除症例における術中出血量と生命予後の関係  [通常講演]
    金丸 理人, 大澤 英之, 高橋 和也, 松本 志郎, 宇井 崇, 春田 英律, 倉科 憲太郎, 宮戸 秀世, 斉藤 心, 山口 博紀, 佐久間 康成, 堀江 久永, 細谷 好則, 佐田 尚宏, 北山 丈二
    日本胃癌学会総会記事 2018年03月
  • 腹腔内投与併用化学療法により病理学的完全奏功を得た腹膜播種陽性胃癌の2例(pCR in P1 gastric cancer using intraperitoneal and systemic chemotherapy: Report of two patients)  [通常講演]
    目黒 由行, 山口 博紀, 北山 丈二, 石神 浩徳, 奥野 貴之, 金丸 理人, 松本 志郎, 宇井 崇, 春田 英律, 倉科 憲太郎, 齋藤 心, 細谷 好則, 佐田 尚宏
    日本胃癌学会総会記事 2018年03月
  • 胃切除後胆道結石症の検討(Biliary tract stone after gastrectomy)  [通常講演]
    木村 有希, 細谷 好則, 小泉 大, 金丸 理人, 松本 史郎, 春田 英律, 宇井 崇, 倉科 健太郎, 宮戸 秀世, 齋藤 心, 佐久間 康成, 山口 博紀, 堀江 久永, 北山 丈二, アラン・レフォー, 佐田 尚宏
    日本胃癌学会総会記事 2018年03月
  • 胃癌切除症例における術前D-dimer値と病期・転帰の検討  [通常講演]
    倉科 憲太郎, 細谷 好則, 清水 徹一郎, 太田 学, 齋藤 心, 春田 英律, 宇井 崇, 松本 志郎, 金丸 理人, 三木 厚, 山口 博紀, 堀江 久永, 佐久間 康成, 北山 丈二, 佐田 尚宏
    日本胃癌学会総会記事 2018年03月
  • 当院における漿膜浸潤胃癌R0切除症例における術中出血量と生命予後の関係  [通常講演]
    金丸 理人, 大澤 英之, 高橋 和也, 松本 志郎, 宇井 崇, 春田 英律, 倉科 憲太郎, 宮戸 秀世, 斉藤 心, 山口 博紀, 佐久間 康成, 堀江 久永, 細谷 好則, 佐田 尚宏, 北山 丈二
    日本胃癌学会総会記事 2018年03月
  • 腹腔内投与併用化学療法により病理学的完全奏功を得た腹膜播種陽性胃癌の2例(pCR in P1 gastric cancer using intraperitoneal and systemic chemotherapy: Report of two patients)  [通常講演]
    目黒 由行, 山口 博紀, 北山 丈二, 石神 浩徳, 奥野 貴之, 金丸 理人, 松本 志郎, 宇井 崇, 春田 英律, 倉科 憲太郎, 齋藤 心, 細谷 好則, 佐田 尚宏
    日本胃癌学会総会記事 2018年03月
  • 胃切除後胆道結石症の検討(Biliary tract stone after gastrectomy)  [通常講演]
    木村 有希, 細谷 好則, 小泉 大, 金丸 理人, 松本 史郎, 春田 英律, 宇井 崇, 倉科 健太郎, 宮戸 秀世, 齋藤 心, 佐久間 康成, 山口 博紀, 堀江 久永, 北山 丈二, アラン・レフォー, 佐田 尚宏
    日本胃癌学会総会記事 2018年03月
  • 胃癌腹膜播種治療における腹腔内液中エクソソームマイクロRNA解析  [通常講演]
    大澤 英之, 熊谷 裕子, 山口 博紀, 佐久間 康成, 堀江 久永, 細谷 好則, 佐田 尚宏, 北山 丈二
    日本消化器病学会雑誌 2018年03月
  • 実臨床に即した切除不能・進行再発消化管がんに対する最適な治療戦略 消化器癌腹膜播種に対するタキサン腹腔内反復化学療法の可能性  [通常講演]
    北山 丈二, 石神 浩徳, 山口 博紀
    日本消化器病学会雑誌 2018年03月
  • 大腿ヘルニア嵌頓から胃壁内気腫症を来たし、4回の開腹手術により救命した1例  [通常講演]
    松本 健司, 森 和亮, 松本 志郎, 春田 英律, 倉科 憲太郎, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化管学会雑誌 2018年02月
  • 当科で経験した特発性上腸間膜静脈血栓症(SMVT)の7例  [通常講演]
    森 和亮, 宮戸 英世, 斉藤 匠, 鯉沼 広治, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本腹部救急医学会雑誌 2018年02月
  • 保存的治療で軽快した特発性気腹症・腸管気腫症の1例  [通常講演]
    小泉 大, 扇原 香澄, 下平 健太郎, 田中 裕美子, 櫻木 雅子, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本腹部救急医学会雑誌 2018年02月
  • 当院における高度肥満症に対する腹腔鏡下スリーブ状胃切除術の治療成績  [通常講演]
    春田 英律, 細谷 好則, 岡田 健太, 倉科 憲太郎, 齋藤 心, 宇井 崇, 松本 志郎, 高橋 和也, 佐久間 康成, 堀江 久永, 北山 丈二, 佐田 尚宏
    日本成人病(生活習慣病)学会会誌 2018年01月
  • 大学病院における経皮内視鏡的胃瘻造設術の適応と早期合併症  [通常講演]
    倉科 憲太郎, 細谷 好則, 齋藤 心, 春田 英律, 宇井 崇, 松本 志郎, 金丸 理人, 安部 望, 高橋 和也, 山口 博紀, 堀江 久永, 佐久間 康成, 北山 丈二, 佐田 尚宏
    日本成人病(生活習慣病)学会会誌 2018年01月
  • 画像上、類似の所見を示した胃平滑筋腫と腹壁顆粒細胞腫を合併した1症例  [通常講演]
    齋藤 心, 春田 英律, 松本 志郎, 倉科 憲太郎, 宇井 崇, 細谷 好則, 佐久間 康成, 堀江 久永, 北山 丈二, 佐田 尚宏
    日本内視鏡外科学会雑誌 2017年12月
  • 腹腔鏡下胃全摘術におけるEEA Orvilを用いた食道空腸吻合の工夫  [通常講演]
    倉科 憲太郎, 細谷 好則, 春田 英律, 松本 志郎, 齋藤 心, 宇井 崇, 宮戸 秀世, 堀江 久永, 佐久間 康成, 北山 丈二, 佐田 尚宏
    日本内視鏡外科学会雑誌 2017年12月
  • 腹腔鏡下側方リンパ節郭清を安全に導入するための工夫  [通常講演]
    堀江 久永, 鯉沼 広治, 伊藤 誉, 直井 大志, 井上 賢之, 森 克亮, 東條 峰之, 佐田友 藍, 森本 光昭, 田原 真紀子, 巷野 佳彦, 佐久間 康成, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本内視鏡外科学会雑誌 2017年12月
  • 腹腔鏡下膵体尾部切除における電動式自動縫合器を使った膵離断定型化の試み  [通常講演]
    笹沼 英紀, 佐久間 康成, 兼田 裕司, 三木 厚, 遠藤 和洋, 小泉 大, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本内視鏡外科学会雑誌 2017年12月
  • 小児GISTに対し、非穿孔式内視鏡的胃壁内反切除術を行った一例  [通常講演]
    松本 志郎, 細谷 好則, 春田 英律, 宇井 崇, 倉科 憲太郎, 宮戸 英世, 齋藤 心, 佐久間 康成, 堀江 久永, 北山 丈二, 佐田 尚宏
    日本内視鏡外科学会雑誌 2017年12月
  • 腹腔鏡下直腸切断術症例の合併症予防の工夫  [通常講演]
    巷野 佳彦, 堀江 久永, 佐田友 藍, 森 和亮, 井上 賢之, 田原 真紀子, 伊藤 誉, 森本 光昭, 直井 大志, 鯉沼 広治, 佐久間 康成, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本内視鏡外科学会雑誌 2017年12月
  • 当科における腹腔鏡下スリーブ状胃切除術の手技の定型化と工夫  [通常講演]
    春田 英律, 細谷 好則, 倉科 憲太郎, 齋藤 心, 宇井 崇, 松本 志郎, 佐久間 康成, 堀江 久永, 北山 丈二, 佐田 尚宏
    日本内視鏡外科学会雑誌 2017年12月
  • 当施設における腹腔鏡補助下低位前方切除術時の解剖の理解と解説  [通常講演]
    森本 光昭, 堀江 久永, 伊藤 誉, 森 和亮, 田原 真紀子, 巷野 佳彦, 直井 大志, 井上 賢之, 鯉沼 広治, 佐久間 康成, 北山 丈二, 細谷 好則, 佐田 尚宏
    日本内視鏡外科学会雑誌 2017年12月
  • 仮想モデル、3次元プリンターモデル、高質感臓器モデルを用いた段階的手術シミュレーション教育  [通常講演]
    遠藤 和洋, 太白 健一, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本内視鏡外科学会雑誌 2017年12月
  • 手術既往のある腹腔鏡下肝切除術症例に対する妥当性の検討  [通常講演]
    谷口 理丈, 佐久間 康成, 小泉 大, 笹沼 英紀, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本内視鏡外科学会雑誌 2017年12月
  • 当科における腹腔鏡下直腸切断術の術後短期成績の検討  [通常講演]
    田原 真紀子, 堀江 久永, 佐田友 藍, 直井 大志, 巷野 佳彦, 森 和亮, 伊藤 誉, 井上 賢之, 森本 光昭, 鯉沼 広治, 佐久間 康成, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本内視鏡外科学会雑誌 2017年12月
  • 安全な横行結腸癌に対する腹腔鏡下手術に向けての工夫  [通常講演]
    鯉沼 広治, 堀江 久永, 井上 賢之, 森 和亮, 田原 真紀子, 直井 大志, 森本 光昭, 巷野 佳彦, 東條 峰之, 佐久間 康成, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本内視鏡外科学会雑誌 2017年12月
  • 腹腔鏡補助下S状結腸切除術後腸間膜欠損部への内ヘルニアによる絞扼性イレウスの1例  [通常講演]
    直井 大志, 堀江 久永, 鯉沼 広治, 佐田友 藍, 田原 真紀子, 巷野 佳彦, 森 和亮, 伊藤 誉, 井上 賢之, 森本 光昭, 佐久間 康成, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本内視鏡外科学会雑誌 2017年12月
  • 小腸3DCTにより器質的小腸狭窄を診断した、亜急性上腸間膜静脈血栓症の一例
    松宮 美沙希, 川口 英之, 笠原 尚哉, 遠藤 和洋, 三木 厚, 小泉 大, 笹沼 英紀, 佐久間 康成, 堀江 久永, 北山 丈二, 細谷 好則, 佐田 尚宏
    日本消化器外科学会雑誌 2017年10月 (一社)日本消化器外科学会
  • 当院における皮膚筋炎に合併した胃癌症例の検討
    下平 健太郎, 斎藤 心, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化器外科学会雑誌 2017年10月 (一社)日本消化器外科学会
  • 胃全摘および食道亜全摘を施行した患者に対する術後QOLと機能障害の評価
    齋藤 心, 中村 美鈴, Lefor A., 倉科 憲太郎, 松本 志郎, 細谷 好則, 高橋 和也, 金丸 理人, 春田 英律, 佐久間 康成, 堀江 久永, 北山 丈二, 佐田 尚宏
    日本消化器外科学会雑誌 2017年10月 (一社)日本消化器外科学会
  • Stage IV胃癌への新たな治療戦略 腹膜播種陽性胃癌に対する腹腔内化学療法と手術を組み合わせた治療戦略
    山口 博紀, 石神 浩徳, 北山 丈二
    日本消化器外科学会雑誌 2017年10月 (一社)日本消化器外科学会
  • Stage IV胃癌への新たな治療戦略 腹膜播種陽性胃癌に対する腹腔内化学療法と手術を組み合わせた治療戦略
    山口 博紀, 石神 浩徳, 北山 丈二
    日本消化器外科学会雑誌 2017年10月 (一社)日本消化器外科学会
  • 潰瘍性大腸炎を背景とした神経内分泌腫瘍成分を伴うS状結腸癌の1例
    利府 数馬, 鯉沼 広治, 直井 大志, 田原 真紀子, 巷野 佳彦, 森 和亮, 井上 賢之, 森本 光昭, 丸山 博行, 堀江 久永, 佐久間 康成, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化器外科学会雑誌 2017年10月 (一社)日本消化器外科学会
  • 腹膜播種陽性胃癌に対するCape/CDDP+docetaxel腹腔内投与併用療法の第II相試験  [通常講演]
    戸澤 勝之, 石神 浩徳, 福島 亮治, 今野 元博, 小林 大介, 辻 靖, 秀村 晃生, 楠本 哲也, 大森 健, 藪崎 裕, 大橋 紀文, 太田 光彦, 山口 博紀, 北山 丈二, 腹腔内化学療法研究会
    日本癌治療学会学術集会抄録集 2017年10月
  • 「それぞれの癌」最善の治療とは? 腹膜播種治療の今 胃癌腹膜播種に対する全身・腹腔内投与併用化学療法  [通常講演]
    石神 浩徳, 山口 博紀, 北山 丈二
    日本癌治療学会学術集会抄録集 2017年10月
  • 食道癌の副腎転移と鑑別を要した副腎black adenomaの一例  [通常講演]
    吉田 陽, 松本 志郎, 春田 英律, 倉科 憲太郎, 山口 博紀, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本臨床外科学会雑誌 2017年10月
  • 食道癌の脳転移再発に対して手術および放射線療法で長期生存が得られた一例  [通常講演]
    松本 志郎, 細谷 好則, 春田 英律, 倉科 憲太郎, 宮戸 英世, 山口 博紀, 佐久間 康成, 堀江 久永, 北山 丈二, 佐田 尚宏
    日本臨床外科学会雑誌 2017年10月
  • 術前(化学)放射線療法が直腸切断術の術後短期成績に与える影響  [通常講演]
    田原 真紀子, 堀江 久永, 津久井 秀則, 清水 徹一郎, 直井 大志, 巷野 佳彦, 丸山 博之, 伊藤 誉, 井上 賢之, 森本 光昭, 鯉沼 広治, 佐久間 康成, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本臨床外科学会雑誌 2017年10月
  • 腹腔鏡下胃全摘術におけるEEA Orvilを用いた食道空腸吻合の工夫  [通常講演]
    倉科 憲太郎, 細谷 好則, 春田 英律, 松本 志郎, 齋藤 心, 宇井 崇, 宮戸 秀世, 堀江 久永, 佐久間 康成, 山口 博紀, 北山 丈二, 佐田 尚宏
    日本臨床外科学会雑誌 2017年10月
  • 膵頭十二指腸切除での再建の工夫 Blumgart変法(自治医大方式)による膵空腸吻合の成績  [通常講演]
    小泉 大, 斎藤 晶, 兼田 裕司, 三木 厚, 遠藤 和洋, 笹沼 英紀, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本臨床外科学会雑誌 2017年10月
  • 胃癌・大腸癌の腹膜播種に対する治療戦略 腹膜播種を伴う胃癌に対する腹腔内投与併用化学療法  [通常講演]
    石神 浩徳, 山口 博紀, 北山 丈二
    日本臨床外科学会雑誌 2017年10月
  • 胃癌Conversion surgery 腹膜播種を伴う胃癌に対する化学療法奏効後胃切除  [通常講演]
    石神 浩徳, 山口 博紀, 山下 裕玄, 朝蔭 正宏, 北山 丈二
    日本臨床外科学会雑誌 2017年10月
  • 当科における直腸切断術症例の術後合併症について  [通常講演]
    巷野 佳彦, 堀江 久永, 津久井 秀則, 佐田友 藍, 森 和亮, 東條 峰之, 井上 賢之, 熊谷 祐子, 宮原 悠三, 太白 健一, 田原 真紀子, 伊藤 誉, 清水 徹一郎, 丸山 博行, 森本 光昭, 直井 大志, 鯉沼 広治, 北山 丈二, 佐田 尚宏
    日本大腸肛門病学会雑誌 2017年09月
  • 直腸癌超低位前方切除5年後に発症した直腸腟瘻に対しMartius flap法にて修復した1例  [通常講演]
    井上 賢之, 堀江 久永, 浜畑 幸弘, 太白 健一, 熊谷 祐子, 東條 峰之, 佐田友 藍, 清水 徹一郎, 直井 大志, 田原 真紀子, 森 和亮, 巷野 佳彦, 伊藤 誉, 森本 光昭, 丸山 博行, 鯉沼 広治, 佐久間 康成, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本大腸肛門病学会雑誌 2017年09月
  • 直腸癌術後に孤発性の右拇指中手骨転移を来した1例  [通常講演]
    伊藤 誉, 堀江 久永, 直井 大志, 井上 賢之, 森本 光昭, 鯉沼 広治, 佐久間 康成, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本大腸肛門病学会雑誌 2017年09月
  • 当院におけるCrohn病に対するKono-S吻合の短期成績  [通常講演]
    森 和亮, 直井 大志, 鯉沼 広治, 堀江 久永, 津久井 秀則, 太白 健一, 熊谷 祐子, 東條 峰之, 佐田友 藍, 清水 徹一郎, 田原 真紀子, 巷野 佳彦, 伊藤 誉, 森本 光昭, 井上 賢之, 丸山 博行, 佐久間 康成, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本大腸肛門病学会雑誌 2017年09月
  • 当科における小腸ストーマ造設後high-output stoma症例の検討  [通常講演]
    直井 大志, 堀江 久永, 鯉沼 広治, 津久井 秀則, 太白 健一, 宮原 悠三, 熊谷 祐子, 東條 峰之, 佐田友 藍, 清水 徹一郎, 巷野 佳彦, 森 和亮, 伊藤 誉, 田原 真紀子, 森本 光昭, 井上 賢之, 丸山 博之, 北山 丈二, 佐田 尚宏
    日本大腸肛門病学会雑誌 2017年09月
  • 消化器癌腹膜播種に対する新たなアプローチ 腹膜播種を伴う胃癌に対する腹腔内化学療法  [通常講演]
    石神 浩徳, 山口 博紀, 北山 丈二
    Gastroenterological Endoscopy 2017年09月
  • Stage IV胃癌への新たな治療戦略《アンサーパッド》 腹膜播種陽性胃癌に対する腹腔内化学療法と手術を組み合わせた治療戦略  [通常講演]
    山口 博紀, 石神 浩徳, 北山 丈二
    Gastroenterological Endoscopy 2017年09月
  • 当院における腹腔鏡下スリーブ状胃切除術の治療成績  [通常講演]
    細谷 好則, 春田 英律, 田口 昌延, 斉藤 心, 倉科 憲太郎, 松本 志郎, 岡田 健太, 海老原 健, 石橋 俊, 矢田 俊彦, 北山 丈二, 佐田 尚宏
    肥満研究 2017年09月
  • 消化器癌腹膜播種に対する新たなアプローチ 腹膜播種を伴う胃癌に対する腹腔内化学療法  [通常講演]
    石神 浩徳, 山口 博紀, 北山 丈二
    日本消化器病学会雑誌 2017年09月
  • Stage IV胃癌への新たな治療戦略《アンサーパッド》 腹膜播種陽性胃癌に対する腹腔内化学療法と手術を組み合わせた治療戦略  [通常講演]
    山口 博紀, 石神 浩徳, 北山 丈二
    日本消化器病学会雑誌 2017年09月
  • 胃癌腹膜播種治療におけるバイオマーカーとしての腹水中エクソソームマイクロRNA解析  [通常講演]
    大澤 英之, 三木 厚, 山口 博紀, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本癌学会総会記事 2017年09月
  • 開腹術後の腹膜再発における腹腔滲出性低比重好中球の意義  [通常講演]
    北山 丈二, 金丸 理人, 津久井 秀則, 大澤 英之, 山口 博紀, 松本 志朗, 倉科 憲太郎, 宮戸 秀世, 細谷 好則, 佐田 尚宏
    日本癌学会総会記事 2017年09月
  • 消化器外科の診断・手技・治療に役立つ先進技術 腹腔鏡下側方リンパ節郭清に役立つ術前シミュレーション  [通常講演]
    堀江 久永, 鯉沼 広治, 伊藤 誉, 直井 大志, 井上 賢之, Lefor Alan, 佐久間 康成, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2017年07月
  • 左側大腸癌イレウスに対する経肛門イレウス管の適応と限界  [通常講演]
    井上 賢之, 堀江 久永, 直井 大志, 伊藤 誉, 森本 光昭, 鯉沼 広治, 細谷 好則, 北山 丈二, Lefor Alan, 佐田 尚宏
    日本消化器外科学会総会 2017年07月
  • 十二指腸腫瘍性病変に対する膵温存十二指腸切除術の治療成績  [通常講演]
    齋藤 晶, 小泉 大, 三木 厚, 遠藤 和洋, 笹沼 英紀, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2017年07月
  • 高度進行胃癌でのresectable metastasisに対する治療戦略 胃癌腹膜播種、腹腔内投与併用化学療法奏効例におけるConversion Surgery  [通常講演]
    山口 博紀, 石神 浩徳, 齋藤 心, 倉科 憲太郎, 大澤 英之, 松本 志郎, 藤井 博文, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2017年07月
  • 消化器癌の診断・治療を含めた新規分子腫瘍マーカーの意義と展望 胃癌腹膜播種治療における腹腔内液中バイオマーカーの意義  [通常講演]
    北山 丈二, 山口 博紀, 石神 浩則, 大澤 英之, 細谷 好則, 山下 裕玄, 瀬戸 泰之, 佐田 尚宏
    日本消化器外科学会総会 2017年07月
  • 周術期を支える漢方を科学する! その基礎と臨床 胃全摘後の摂食低下・体重減少とTJ-43六君子湯による改善及び新規メカニズムの発見  [通常講演]
    田口 昌延, 出崎 克也, 小泉 大, 倉科 憲太郎, 細谷 好則, Lefor Alan, 堀江 久永, 北山 丈二, 佐田 尚宏, 矢田 俊彦
    日本消化器外科学会総会 2017年07月
  • 閉鎖孔ヘルニア嵌頓症例の臨床的検討  [通常講演]
    金子 勇貴, 小泉 大, 下平 健太郎, 井上 賢之, 齋藤 心, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2017年07月
  • Blumgart-dumpling法(Blumgart変法 自治医大方式)による膵空腸吻合の工夫  [通常講演]
    小泉 大, 笠原 尚哉, 三木 厚, 遠藤 和洋, 笹沼 英紀, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2017年07月
  • 局所進行直腸癌に対する集学的治療戦略 術前化学放射線療法(CRT)を行った下部進行直腸癌症例の術後3ヵ月内のCEA値は予後を予測しうるか  [通常講演]
    森本 光昭, 堀江 久永, 直井 大志, 鯉沼 広治, 仲澤 聖則, 佐久間 康成, 細谷 好則, 北山 丈二, Lefor Alan, 佐田 尚宏
    日本消化器外科学会総会 2017年07月
  • 消化器外科における術後回復促進策(ERAS) 直腸癌待機的前方切除症例におけるERAS導入の効果  [通常講演]
    巷野 佳彦, 堀江 久永, 直井 大志, 井上 賢之, 森本 光昭, 鯉沼 広治, 細谷 好則, Lefor Alan, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2017年07月
  • 消化器外科の診断・手技・治療に役立つ先進技術 非視覚的主体情報の統合した、マクロ・ミクロをカバーする4K/8K対応・内視鏡手術システムの開発  [通常講演]
    遠藤 和洋, 太白 健一, 直井 大志, 佐久間 康成, 堀江 久永, 細谷 好則, アラン・レフォー, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2017年07月
  • 切除可能膵癌に対する術前治療戦略の意義 切除可能膵癌に対する術前化学放射線治療の有用性  [通常講演]
    三木 厚, 佐久間 康成, 笠原 尚哉, 遠藤 和洋, 小泉 大, 笹沼 英紀, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2017年07月
  • 横行結腸癌に対する安全な腹腔鏡下Complete Mesocolic Excisionの工夫  [通常講演]
    鯉沼 広治, 堀江 久永, 直井 大志, 井上 賢之, 田原 真紀子, 森本 光昭, 佐久間 康成, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2017年07月
  • 当科における虫垂腫瘍の臨床病理学的検討  [通常講演]
    谷口 理丈, 鯉沼 広治, 堀江 久永, 直井 大志, 井上 賢之, 森本 光昭, 佐久間 康成, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2017年07月
  • 消化器癌腹膜播種の病態解明と新たな治療戦略 腹膜播種に対するタキサン反復腹腔内化学療法の展望  [通常講演]
    北山 丈二, 石神 浩徳, 山口 博紀
    日本消化器外科学会総会 2017年07月
  • 退形成性膵管癌の6切除例  [通常講演]
    風當 ゆりえ, 三木 厚, 遠藤 和洋, 小泉 大, 笹沼 英紀, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2017年07月
  • 胃切除後の胆道結石症の検討  [通常講演]
    木村 有希, 小泉 大, 三木 厚, 遠藤 和洋, 笹沼 英紀, 佐久間 康成, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2017年07月
  • 当科における膵IPMNの縮小手術の検討  [通常講演]
    齋藤 匠, 三木 厚, 遠藤 和洋, 小泉 大, 笹沼 英紀, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2017年07月
  • 胃癌術後腹腔内Neutrophil Extracellular Traps(NETs)の腹膜播種再発の関与について  [通常講演]
    金丸 理人, 津久井 秀則, 斉藤 心, 倉科 憲太郎, 松本 志郎, 山口 博紀, 堀江 久永, 細谷 好則, 佐田 尚宏, 北山 丈二
    日本消化器外科学会総会 2017年07月
  • 漏斗胸を伴う胸部下部食道癌に対して食道亜全摘、胸骨前胃管再建術を施行した1例  [通常講演]
    高橋 大二郎, 斎藤 心, 宇井 崇, 倉科 憲太郎, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本食道学会学術集会プログラム・抄録集 2017年06月
  • 当院における腹腔鏡下スリーブ状胃切除術の治療成績  [通常講演]
    春田 英律, 細谷 好則, 松本 志郎, 齋藤 心, 倉科 憲太郎, 宇井 崇, 安部 望, 金丸 理人, 高橋 和也, 北山 丈二, 佐久間 康成, 堀江 久永, 海老原 健, 石橋 俊, 佐田 尚宏
    日本肥満症治療学会学術集会プログラム・抄録集 2017年06月
  • IPMNの手術適応と術式を再考する 当科における膵IPMNの手術術式の検討  [通常講演]
    齋藤 匠, 三木 厚, 笠原 尚哉, 遠藤 和洋, 小泉 大, 笹沼 英紀, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    膵臓 2017年05月
  • 胆嚢管合流部隔壁構造に着目した胆嚢管アプローチによる総胆管結石採石法 その解剖学的基盤と実践  [通常講演]
    清水 敦, 野田 泰子, 安田 是和, 佐久間 康成, 細谷 好則, 堀江 久永, 北山 丈二, 佐田 尚宏
    日本外科学会定期学術集会抄録集 2017年04月
  • 若手外科医に対する腹腔鏡下大腸切除トレーニングシステム  [通常講演]
    堀江 久永, 鯉沼 広治, 津久井 秀則, 熊谷 祐子, 佐田友 藍, 清水 徹一郎, 直井 大志, 田原 真紀子, 巷野 佳彦, 森 和亮, 伊藤 誉, 井上 賢之, 森本 光昭, 佐久間 康成, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本外科学会定期学術集会抄録集 2017年04月
  • 家族性大腸腺腫症に合併した十二指腸病変の検討  [通常講演]
    木村 有希, 小泉 大, 笠原 尚哉, 三木 厚, 遠藤 和洋, 笹沼 英紀, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本外科学会定期学術集会抄録集 2017年04月
  • IPMN国際診療ガイドラインからみた当院でのIPMN手術例の検討  [通常講演]
    齋藤 匠, 三木 厚, 笠原 尚哉, 遠藤 和洋, 小泉 大, 笹沼 英紀, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本外科学会定期学術集会抄録集 2017年04月
  • 膵空腸吻合Blumgart変法(自治医大方式)に適した膵臓の検討  [通常講演]
    小泉 大, 笠原 尚哉, 三木 厚, 遠藤 和洋, 笹沼 英紀, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, Lefor Alan, 佐田 尚宏
    日本外科学会定期学術集会抄録集 2017年04月
  • 当院における局所進行下部直腸癌に対する術前化学放射線療法の有用性と課題について  [通常講演]
    森本 光昭, 津久井 秀則, 熊谷 祐子, 佐田友 藍, 清水 徹一郎, 直井 大志, 田原 真紀子, 巷野 佳彦, 森 和亮, 伊藤 誉, 井上 賢之, 鯉沼 広治, 佐久間 康成, 細谷 好則, 北山 丈二, 堀江 久永, Lefor Alan, 佐田 尚宏
    日本外科学会定期学術集会抄録集 2017年04月
  • クローン病に対する腸管吻合におけるKono-S吻合導入後の短期成績  [通常講演]
    直井 大志, 堀江 久永, 鯉沼 広治, 津久井 秀則, 宮原 悠三, 太白 健一, 熊谷 祐子, 東條 峰之, 佐田友 藍, 清水 徹一郎, 巷野 佳彦, 森 和亮, 丸山 博行, 伊藤 誉, 森本 光昭, 井上 賢之, 田原 真紀子, 佐久間 康成, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本外科学会定期学術集会抄録集 2017年04月
  • 質感と人体解剖を忠実に再現した、高難度手術教育のための臓器モデル 鏡視下手術の教育効果を高めるために必要な技術トレーニング  [通常講演]
    遠藤 和洋, 太白 健一, 笠原 尚哉, 三木 厚, 小泉 大, 笹沼 英紀, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本外科学会定期学術集会抄録集 2017年04月
  • 胃癌腹膜再発における開腹術後の腹腔内滲出液中low density granulocytes(LDG)の意義  [通常講演]
    金丸 理人, 津久井 秀則, 斉藤 心, 倉科 憲太郎, 宇井 崇, 春田 英律, 松本 志郎, 安部 望, 高橋 和也, 山口 博紀, 佐久間 康成, 堀江 久永, 細谷 好則, 佐田 尚宏, 北山 丈二
    日本外科学会定期学術集会抄録集 2017年04月
  • 腹腔鏡下横行結腸癌手術における難易度克服への工夫  [通常講演]
    鯉沼 広治, 堀江 久永, 森本 光昭, 井上 賢之, 直井 大志, 田原 真紀子, 巷野 佳彦, 佐久間 康成, 細谷 好則, 北山 丈二, Lefor Alan, 佐田 尚宏
    日本外科学会定期学術集会抄録集 2017年04月
  • 高度進行胃癌に対するNeoadjuvant chemotherapyとConversion surgery 腹膜播種陽性胃癌に対するConversion surgery  [通常講演]
    石神 浩徳, 山口 博紀, 北山 丈二
    日本外科学会定期学術集会抄録集 2017年04月
  • 胃癌術後補助化学療法の新たな選択 漿膜浸潤陽性胃癌に対する補助療法としてのPaclitaxel腹腔内反復投与の可能性  [通常講演]
    北山 丈二, 石神 浩徳, 山口 博紀, 金丸 理人, 松本 志郎, 倉科 憲太郎, 斎藤 心, 細谷 好則, 佐田 尚宏
    日本外科学会定期学術集会抄録集 2017年04月
  • 下部直腸癌に対する鏡視下括約筋間切除術の治療成績  [通常講演]
    石原 聡一郎, 大谷 研介, 安田 幸嗣, 西川 武司, 田中 敏明, 田中 潤一郎, 清松 知充, 川合 一茂, 野澤 宏彰, 風間 伸介, 山口 博紀, 須並 英二, 北山 丈二, 渡邉 聡明
    日本大腸肛門病学会雑誌 2017年04月
  • 腹腔内洗浄細胞診陽性症例に対するパクリタキセル腹腔内投与+S-1/パクリタキセル静脈投与法の第II相臨床試験(Phase II study of ip paclitaxel plus S-1/iv paclitaxel in GC pts. with positive peritoneal cytology)  [通常講演]
    今野 元博, 石神 浩徳, 梨本 篤, 藪崎 裕, 今本 治彦, 山下 裕玄, 岸 健太郎, 小寺 泰弘, 上之園 芳一, 藤原 義之, 秀村 晃生, 田村 茂行, 福島 亮治, 山口 博紀, 北山 丈二
    日本胃癌学会総会記事 2017年03月
  • 腹腔内化学療法の経験のない施設における新規導入(Introduction of intraperitoneal chemotherapy at a hospital with inexperienced staff)  [通常講演]
    山口 博紀, 北山 丈二, 大澤 英之, 金丸 理人, 松本 志郎, 森 美鈴, 齋藤 心, 倉科 憲太郎, 上田 真寿, 細谷 好則, 藤井 博文, 佐田 尚宏
    日本胃癌学会総会記事 2017年03月
  • 腹膜播種を伴う胃癌に対するS-1+パクリタキセル経静脈・腹腔内併用療法/S-1+シスプラチン併用療法による第III相臨床試験(PHOENIX-GC traial)(IP PTX plus S-1/PTX compared with SP in gastric cancer with peritoneal metastasis: PHOENIX-GC trial)  [通常講演]
    小林 大介, 石神 浩徳, 藤原 義之, 福島 亮治, 梨本 篤, 藪崎 裕, 今本 治彦, 今野 元博, 小寺 泰弘, 上之園 芳一, 天貝 賢二, 門脇 重憲, 三輪 洋人, 山口 博紀, 山口 拓洋, 北山 丈二, 腹腔内化学療法研究会
    日本胃癌学会総会記事 2017年03月
  • 胃癌腹膜再発における開腹術後の腹腔内滲出液中low density granulocytes(LDG)の意義(Low density granulocytes in peritoneal exudates may assist peritoneal recurrence after gastrectomy)  [通常講演]
    北山 丈二, 金丸 理人, 津久井 秀則, 松本 志郎, 倉科 憲太郎, 斎藤 心, 細谷 好則, 山口 博紀, 石神 浩徳, 佐田 尚宏
    日本胃癌学会総会記事 2017年03月
  • 胃過形成ポリープに発生した低分化型腺癌の1例(Poorly differentiated adenocarcinoma arising in hyperplastic polyp of the stomach: A report of case)  [通常講演]
    高橋 和也, 齋藤 心, 金丸 理人, 安部 望, 松本 志郎, 宇井 崇, 春田 英律, 倉科 憲太郎, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本胃癌学会総会記事 2017年03月
  • 進行胃癌治療の最前線 PHOENIX-GC試験を中心としたパクリタキセルの腹腔内投与療法の治療成績と今後の展望  [通常講演]
    藪崎 裕, 石神 浩徳, 北山 丈二
    日本消化器病学会雑誌 2017年03月
  • 糖尿病合併大腸癌の特徴と治療成績  [通常講演]
    太田 善子, 石原 聡一郎, 金子 学, 室野 浩司, 佐々木 和人, 安田 幸嗣, 大谷 研介, 西川 武司, 田中 敏明, 清松 知充, 畑 啓介, 川合 一茂, 野澤 宏彰, 北山 丈二, 渡邉 聡明
    日本成人病(生活習慣病)学会会誌 2017年01月
  • 肺気腫、低肺機能を併存した食道癌症例に対する縦隔鏡下食道切除術の1経験  [通常講演]
    齋藤 心, 細谷 好則, 宇井 崇, 倉科 憲太郎, 春田 英律, 松本 志郎, 金丸 理人, 安部 望, 高橋 和也, 北山 丈二, 佐田 尚宏, 愛甲 丞, 瀬戸 泰之
    日本内視鏡外科学会雑誌 2016年12月
  • 癒着性腸閉塞に対する気腹CTによる術前評価が有用であった2例  [通常講演]
    直井 大志, 堀江 久永, 鯉沼 広治, 清水 徹一郎, 巷野 佳彦, 森 和亮, 丸山 博行, 伊藤 誉, 森本 光昭, 井上 賢之, 田原 真紀子, 佐久間 康成, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本内視鏡外科学会雑誌 2016年12月
  • 当科の腹腔鏡補助下低位前方切除術の出血時の対応と手術手技について  [通常講演]
    森本 光昭, 堀江 久永, 津久井 秀則, 東條 峰之, 直井 大志, 井上 賢之, 田原 真紀子, 巷野 佳彦, 森 和亮, 伊藤 誉, 鯉沼 広治, 佐久間 康成, 北山 丈二, 細谷 義則, 佐田 尚宏
    日本内視鏡外科学会雑誌 2016年12月
  • 腹腔鏡下側方リンパ節郭清を安全に導入するための工夫  [通常講演]
    堀江 久永, 鯉沼 広治, 伊藤 誉, 直井 大志, 田原 真紀子, 井上 賢之, 巷野 佳彦, 津久井 秀則, 佐田友 藍, 森 和亮, 森本 光昭, 佐久間 康成, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本内視鏡外科学会雑誌 2016年12月
  • 医工連携による革新的内視鏡手術トレーニングシステムの開発 外科教育の新たな手法確立に向けて  [通常講演]
    遠藤 和洋, 太白 健一, 笠原 直哉, 三木 厚, 小泉 大, 笹沼 英紀, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本内視鏡外科学会雑誌 2016年12月
  • 腹腔鏡下直腸前方切除術症例における早期経口摂取の検討  [通常講演]
    巷野 佳彦, 堀江 久永, 熊谷 祐子, 清水 徹一郎, 直井 大志, 田原 真紀子, 伊藤 誉, 森 和亮, 森本 光昭, 鯉沼 広治, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本内視鏡外科学会雑誌 2016年12月
  • 腹腔鏡下横行結腸癌手術における空間認識能向上への工夫  [通常講演]
    鯉沼 広治, 堀江 久永, 直井 大志, 田原 真紀子, 井上 賢之, 巷野 佳彦, 森本 光昭, 丸山 博行, 森 和亮, 伊藤 誉, 佐田友 藍, 佐久間 康成, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本内視鏡外科学会雑誌 2016年12月
  • 胸骨後経路胃管癌に対して胸壁吊り上げ式鏡視下胃管切除・空腸再建を行なった3例の経験
    齋藤 心, 宇井 崇, 倉科 憲太郎, 金丸 理人, 松本 志郎, 堀江 久永, 佐久間 康成, 細谷 好則, 北山 丈二, 佐田 尚宏, 永井 秀雄, 福嶋 敬宜
    日本消化器外科学会雑誌 2016年11月 (一社)日本消化器外科学会
  • Paraduodenal hernia type腸回転異常症を伴う上行結腸癌の1例
    岸田 杏子, 木村 有希, 森本 光昭, 田原 真紀子, 巷野 佳彦, 鯉沼 広治, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化器外科学会雑誌 2016年11月 (一社)日本消化器外科学会
  • 粘膜下層への高度浸潤とリンパ節転移を来した小型大腸癌の2症例  [通常講演]
    品川 貴秀, 石原 聡一郎, 野澤 宏彰, 室野 浩司, 大谷 研介, 西川 武司, 安田 幸嗣, 田中 潤一郎, 田中 敏明, 清松 知充, 畑 啓介, 川合 一茂, 山口 博紀, 北山 丈二, 渡邉 聡明
    日本臨床外科学会雑誌 2016年11月
  • 大腸、胃、食道など多彩な原発巣を認めた異時性10多重癌の一例  [通常講演]
    横溝 悠里子, 川合 一茂, 園田 洋史, 大谷 研介, 安田 幸嗣, 田中 敏明, 田中 潤一郎, 清松 知充, 畑 啓介, 野澤 宏彰, 風間 伸介, 石原 聡一郎, 山口 博紀, 須並 英二, 北山 丈二, 渡邉 聡明
    日本臨床外科学会雑誌 2016年11月
  • 木村有希, 小泉大, 笠原尚哉, 三木厚, 遠藤和洋, 笹沼英紀, 佐久間康成, 堀江久永, 細谷好則, 北山丈二, 佐田尚宏
    日本臨床外科学会雑誌 2016年10月
  • 遠藤和洋, 太白健一, 笠原直哉, 三木厚, 小泉大, 笹沼英紀, 佐久間康成, 堀江久永, 細谷好則, 北山丈二, 佐田尚宏
    日本臨床外科学会雑誌 2016年10月
  • 横行結腸癌手術における中結腸動脈主リンパ節のCTサイズと病理学的転移および予後との関連について  [通常講演]
    丸山 博行, 鯉沼 広治, 堀江 久永, 太白 健一, 宮原 悠三, 津久井 秀則, 熊谷 祐子, 東條 峰之, 佐田友 藍, 清水 徹一郎, 直井 大志, 井上 賢之, 田原 真紀子, 巷野 佳彦, 森 和亮, 伊藤 誉, 森本 光昭, 北山 丈二, 佐田 尚宏
    日本大腸肛門病学会雑誌 2016年10月
  • 大腸内視鏡が左鼠径ヘルニアに嵌頓し挿入困難となった2例  [通常講演]
    伊藤 誉, 堀江 久永, 直井 大志, 田原 真紀子, 巷野 佳彦, 森本 光昭, 鯉沼 広治, 北山 丈二, 佐田 尚宏
    日本大腸肛門病学会雑誌 2016年10月
  • 家族性大腸腺腫症(FAP)に対する結腸全摘・回腸直腸吻合術(IRA)の適応について  [通常講演]
    堀江 久永, 鯉沼 広治, 津久井 秀則, 太白 健一, 宮原 悠三, 熊谷 祐子, 東條 峰之, 佐田友 藍, 清水 徹一郎, 直井 大志, 巷野 佳彦, 森 和亮, 丸山 博行, 伊藤 誉, 森本 光昭, 井上 賢之, 田原 真紀子, 北山 丈二, 佐田 尚宏
    日本大腸肛門病学会雑誌 2016年10月
  • クローン病腸管狭窄に対する内科外科連携に基づく治療戦略  [通常講演]
    伊藤 誉, 堀江 久永, 直井 大志, 田原 真紀子, 巷野 佳彦, 森本 光昭, 鯉沼 広治, 北山 丈二, 佐田 尚宏, 矢野 智則, 砂田 圭二郎, 山本 博徳
    日本大腸肛門病学会雑誌 2016年10月
  • 当科の腹腔鏡補助下低位前方切除術の標準化に向けた取り組みと短期成績、手術手技について  [通常講演]
    森本 光昭, 堀江 久永, 太白 健一, 宮原 悠三, 津久井 秀則, 熊谷 祐子, 東條 峰之, 佐田友 藍, 清水 徹一郎, 直井 大志, 井上 賢之, 田原 真紀子, 巷野 佳彦, 森 和亮, 伊藤 誉, 鯉沼 広治, 北山 丈二, 佐田 尚宏
    日本大腸肛門病学会雑誌 2016年10月
  • Ra、Rb進行直腸癌に対する腹腔鏡下低位前方切除術の短期成績  [通常講演]
    津久井 秀則, 堀江 久永, 森本 光昭, 太白 健一, 宮原 悠三, 熊谷 祐子, 東條 峰之, 佐田友 藍, 清水 徹一郎, 直井 大志, 井上 賢之, 田原 真紀子, 巷野 佳彦, 森 和亮, 丸山 博行, 伊藤 誉, 鯉沼 広治, 北山 丈二, 佐田 尚宏
    日本大腸肛門病学会雑誌 2016年10月
  • 直腸癌低位前方切除術における縫合不全発生リスク因子の検討  [通常講演]
    太白 健一, 鯉沼 広治, 堀江 久永, 宮原 悠三, 津久井 秀則, 東條 峰之, 佐田友 藍, 清水 徹一郎, 直井 大志, 井上 賢之, 田原 真紀子, 巷野 佳彦, 森 和亮, 伊藤 誉, 森本 光昭, 丸山 博行, 北山 丈二, 佐田 尚宏
    日本大腸肛門病学会雑誌 2016年10月
  • 大腸外科における手術部位感染対策 当科における周術期SSI対策変更による術後SSIへの影響  [通常講演]
    直井 大志, 堀江 久永, 鯉沼 広治, 津久井 秀則, 太白 健一, 宮原 悠三, 熊谷 祐子, 東條 峰之, 佐田友 藍, 清水 徹一郎, 巷野 佳彦, 森 和亮, 丸山 博行, 伊藤 誉, 森本 光昭, 井上 賢之, 田原 真紀子, 北山 丈二, 佐田 尚宏
    日本大腸肛門病学会雑誌 2016年10月
  • 胃 胃がんに対する腹腔内化学療法の効果 腹膜播種陽性胃癌に対するパクリタキセル腹腔内投与併用療法を検証する第III相臨床試験  [通常講演]
    福島 亮治, 石神 浩徳, 藤原 義之, 梨本 篤, 藪崎 裕, 今本 治彦, 今野 元博, 小寺 泰弘, 上之園 芳一, 天貝 賢二, 門脇 重憲, 三輪 洋人, 山口 拓洋, 山口 博紀, 北山 丈二, 腹腔内化学療法研究会
    日本癌治療学会学術集会抄録集 2016年10月
  • 胃 胃がんに対する腹腔内化学療法の効果 腹膜播種陽性胃癌に対するS-1/oxaliplatin+paclitaxel腹腔内投与併用療法の第II相試験  [通常講演]
    富田 寿彦, 石神 浩徳, 藤原 義之, 門脇 重憲, 小寺 泰弘, 今本 治彦, 今野 元博, 福島 亮治, 秀村 晃生, 上田 修吾, 梨本 篤, 藪崎 裕, 楠本 哲也, 上之園 芳一, 北山 丈二, 腹腔内化学療法研究会
    日本癌治療学会学術集会抄録集 2016年10月
  • 消化器外科手術における術後遠隔部位感染症の検討  [通常講演]
    川口 英之, 小泉 大, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本外科感染症学会雑誌 2016年10月
  • 胃癌腹膜転移の成立における腹腔内間葉系細胞の意義  [通常講演]
    北山 丈二
    日本癌学会総会記事 2016年10月
  • 子宮摘出術3ヵ月後に腟断端離開、小腸脱出した一例  [通常講演]
    扇原 香澄, 遠藤 和洋, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本臨床外科学会雑誌 2016年10月
  • 十二指腸乳頭部腫瘍に対する乳頭切除術  [通常講演]
    小泉 大, 木村 有希, 笠原 尚哉, 三木 厚, 遠藤 和洋, 笹沼 英紀, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本臨床外科学会雑誌 2016年10月
  • シナリオベースの低侵襲手術training systemの開発と活用 technical skillとnon technical skillの習得  [通常講演]
    遠藤 和洋, 太白 健一, 笠原 直哉, 三木 厚, 小泉 大, 笹沼 英紀, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本臨床外科学会雑誌 2016年10月
  • 膵体尾部切除における膵断端処理の工夫 膵体尾部切除における水平マットレス法による膵断端処理と術後膵液瘻の検討  [通常講演]
    木村 有希, 小泉 大, 笠原 尚哉, 三木 厚, 遠藤 和洋, 笹沼 英紀, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本臨床外科学会雑誌 2016年10月
  • 切除不能から可能へ Conversion Therapy(食道・胃) 腹膜播種陽性胃癌に対する化学療法奏効後胃切除  [通常講演]
    石神 浩徳, 山口 博紀, 北山 丈二
    日本臨床外科学会雑誌 2016年10月
  • 胃癌腹膜播種にPTX腹腔内投与を施行し3年間無再発生存ののち骨髄癌腫症を発症した1例  [通常講演]
    奥野 貴之, 山口 博紀, 石原 聡一郎, 石神 浩徳, 須並 英二, 北山 丈二, 渡邉 聡明
    日本臨床外科学会雑誌 2016年09月
  • 胃癌・大腸癌切除例の術前CT検査で指摘された膵嚢胞性病変の検討  [通常講演]
    小泉 大, 木村 有希, 田口 昌延, 三木 広, 遠藤 和洋, 笹沼 英紀, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化器病学会雑誌 2016年09月
  • TRC法を用いた腹腔内洗浄液CEA mRNA定量検査の治療効果判定における有用性  [通常講演]
    佐藤 優実子, 山口 博紀, 高井 大哉, 北山 丈二, 大久保 滋夫, 矢冨 裕
    日本臨床検査自動化学会会誌 2016年08月
  • MIKI Atsushi, SAKUMA Yasunaru, ENDO Kazuhiro, KOIZUMI Masaru, SASANUMA Hideki, HORIE Hisanaga, HOSOYA Yoshinori, KITAYAMA Joji, SATA Naohiro
    すい臓 2016年07月
  • OTA Gaku, MIKI Atsushi, ENDO Kazuhiro, KOIZUMI Masaru, SASANUMA Hideki, SAKUMA Yasunaru, HORIE Hisanaga, HOSOYA Yoshinori, KITAYAMA Joji, SATA Naohiro
    すい臓 2016年07月
  • 進行大腸癌に対するイメージガイド腹腔鏡手術  [通常講演]
    堀江 久永, 伊藤 誉, 佐々木 崇洋, 森本 光昭, 鯉沼 広治, 佐久間 康成, 細谷 好則, Lefor Alan, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2016年07月
  • 右側結腸手術に対するERASプロトコル導入の効果  [通常講演]
    直井 大志, 堀江 久永, 田原 真紀子, 巷野 佳彦, 森本 光昭, 鯉沼 広治, 佐久間 康成, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2016年07月
  • 直腸癌前方切除後患者におけるERASプロトコール導入に向けての検討  [通常講演]
    巷野 佳彦, 堀江 久永, 田原 真紀子, 森本 光昭, 鯉沼 広治, 佐久間 康成, 細谷 好則, Lefor Alan, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2016年07月
  • 腹部予定手術後肺合併症の予測における術前肺機能検査の有用性の検討  [通常講演]
    横田 真一郎, 富樫 一智, アラン・レフォー, 小泉 大, 中村 好一, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏, 安田 是和
    日本消化器外科学会総会 2016年07月
  • 扁平上皮癌を合併した直腸肛門部尖圭コンジローマの1例  [通常講演]
    伊藤 誉, 堀江 久永, 高橋 大二郎, 清水 徹一郎, 森本 光昭, 鯉沼 広治, 佐久間 康成, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2016年07月
  • 腹腔鏡補助下低位前方切除術における縫合不全ゼロへの取り組みと、予防的回腸瘻造設基準の評価  [通常講演]
    鯉沼 広治, 堀江 久永, 森本 光昭, 巷野 佳彦, 田原 真紀子, 丸山 博行, 佐久間 康成, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2016年07月
  • 胃切除後の食道再建術式 食道切除後の血管吻合付加を伴う胸骨前Roux-en Y型空腸再建の検討  [通常講演]
    細谷 好則, 斉藤 心, 倉科 憲太郎, 去川 俊二, 中村 美鈴, 佐久間 康成, 堀江 久永, アラン・レフォー, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2016年07月
  • Blumgart-dumpling法による膵空腸吻合の工夫  [通常講演]
    小泉 大, 三木 厚, 遠藤 和洋, 笹沼 英紀, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, Lefor Alan, 佐田 尚宏
    日本消化器外科学会総会 2016年07月
  • 当院における直腸癌に対する術前放射線療法の功罪  [通常講演]
    森本 光昭, 堀江 久永, 鯉沼 広治, 巷野 佳彦, 藤井 博文, 佐久間 康成, 細谷 好則, Lefor Alan, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2016年07月
  • 腹膜播種を伴う胃癌に対するS-1/シスプラチン+パクリタキセル腹腔内投与併用療法  [通常講演]
    小林 大介, 石神 浩徳, 神田 光郎, 田中 千恵, 山口 博紀, 北山 丈二, 小寺 泰弘
    日本消化器外科学会総会 2016年07月
  • 胃癌腹膜播種の新規バイオマーカーとしての腹腔洗浄液中CEA mRNA定量値の有用性  [通常講演]
    山口 博紀, 石神 浩徳, 北山 丈二, 渡邉 聡明
    日本消化器外科学会総会 2016年07月
  • 胃癌腹膜播種の基礎と臨床 新たなエビデンスの創出に向けて 腹膜播種陽性胃癌に対する腹腔内化学療法  [通常講演]
    石神 浩徳, 山口 博紀, 北山 丈二, 渡邉 聡明
    日本消化器外科学会総会 2016年07月
  • 胃癌腹膜播種の基礎と臨床 新たなエビデンスの創出に向けて 胃癌腹膜再発予測のための腹腔内遊離癌細胞白血球比(Tumor leukocyte Ratio)の可能性  [通常講演]
    山下 裕玄, 北山 丈二, 山口 博紀, 八木 浩一, 愛甲 丞, 西田 正人, 竹中 芳治, 野村 幸世, 渡邉 聡明, 瀬戸 泰之
    日本消化器外科学会総会 2016年07月
  • 若手外科医育成のための工夫 自治医科大学での外科医教育 解剖学教室、先端医療技術開発センター、シミュレーションセンターとの連携  [通常講演]
    清水 敦, 菱川 俊司, 野田 泰子, 笹沼 英紀, 佐久間 康成, 堀江 久永, 細谷 好則, アラン・レフォー, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 2016年07月
  • 食道胃接合部癌に認めた内分泌神経細胞癌と中分化型腺癌の1例  [通常講演]
    金丸 理人, 斎藤 心, 宇井 崇, 倉科 憲太郎, 細谷 好則, 北山 丈二, 佐田 尚宏, 天野 雄介, 仁木 利郎
    日本食道学会学術集会プログラム・抄録集 2016年07月
  • 当院における胃管癌の治療経験  [通常講演]
    齋藤 心, 倉科 憲太郎, 宇井 崇, 松本 志郎, 金丸 理人, 春田 英律, 細谷 好則, 北山 丈二, 三浦 義正, 佐田 尚宏
    日本食道学会学術集会プログラム・抄録集 2016年07月
  • 胃壁筋層内へ穿破し出血を生じた膵粘液性嚢胞腫瘍の1例  [通常講演]
    太田 学, 三木 厚, 遠藤 和洋, 小泉 大, 笹沼 英紀, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本肝胆膵外科学会・学術集会プログラム・抄録集 2016年06月
  • 大腸癌肝転移に対する化学療法・拡大右肝切除後に脾動脈瘤のコイル塞栓術を施行し脾摘を回避しえた1例  [通常講演]
    清水 敦, 眞田 幸弘, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本肝胆膵外科学会・学術集会プログラム・抄録集 2016年06月
  • 転移性肝癌との鑑別に苦慮した肝柵状肉芽腫の一例  [通常講演]
    森本 光昭, 佐久間 康成, 笹沼 秀紀, 小泉 大, 遠藤 和洋, 三木 厚, 北山 丈二, アラン・レフォー, 佐田 尚宏
    日本肝胆膵外科学会・学術集会プログラム・抄録集 2016年06月
  • 十二指腸乳頭部神経内分泌癌の一例  [通常講演]
    加賀谷 丈紘, 三木 厚, 遠藤 和洋, 小泉 大, 笹沼 英紀, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本肝胆膵外科学会・学術集会プログラム・抄録集 2016年06月
  • 膵硬化度・主膵管拡張に注目した膵空腸吻合法の選択と術後膵液瘻の検討  [通常講演]
    小泉 大, 田口 昌延, 三木 厚, 遠藤 和洋, 笹沼 英紀, 佐久間 康成, 堀江 久永, 細谷 好則, 北山 丈二, アラン・レフォー, 佐田 尚宏
    日本肝胆膵外科学会・学術集会プログラム・抄録集 2016年06月
  • Meckel憩室内翻による腸重積症に対し小切開・腹腔鏡補助下手術を施行した2例  [通常講演]
    太白 健一, 堀江 久永, 田原 真紀子, 巷野 佳彦, 森本 光昭, 小泉 大, 鯉沼 広治, 佐久間 康成, 細谷 好則, 北山 丈二, 佐田 尚宏
    小切開・鏡視外科学会雑誌 2016年05月
  • 癌性腹膜炎をターゲットとしたPHOENIX-GC試験 腹腔内化学療法の一般化に向けた取り組み  [通常講演]
    山口 博紀, 北山 丈二, 石神 浩徳, 渡邉 聡明
    日本外科学会定期学術集会抄録集 2016年04月
  • 進行胃癌に対する集学的治療の現状と展望 腹膜播種陽性胃癌に対する集学的治療  [通常講演]
    石神 浩徳, 北山 丈二, 山口 博紀, 渡邉 聡明
    日本外科学会定期学術集会抄録集 2016年04月
  • 直腸癌側方リンパ節転移に対する術前化学放射線療法を併用した治療戦略とその成績  [通常講演]
    石原 聡一郎, 大谷 研介, 安田 幸嗣, 田中 敏明, 田中 潤一郎, 清松 知充, 畑 啓介, 川合 一茂, 野澤 宏彰, 風間 伸介, 山口 博紀, 須並 英二, 北山 丈二, 渡邉 聡明
    日本外科学会定期学術集会抄録集 2016年04月
  • 直腸癌におけるLGR5,CD133免疫組織学的発現と臨床病理学的因子の検討  [通常講演]
    原田 有三, 風間 伸介, 大谷 研介, 安田 幸嗣, 西川 武司, 田中 潤一郎, 田中 敏明, 清松 知充, 川合 一茂, 畑 啓介, 野澤 宏彰, 山口 博紀, 石原 聡一郎, 北山 丈二, 渡邉 聡明
    日本外科学会定期学術集会抄録集 2016年04月
  • 直腸癌に対する腹腔鏡下前方切除術は肥満患者においても低侵襲である  [通常講演]
    松崎 裕幸, 石原 聡一郎, 大谷 研介, 安田 幸嗣, 西川 武司, 田中 敏明, 田中 潤一郎, 清松 知充, 畑 啓介, 川合 一茂, 野澤 宏彰, 山口 博紀, 北山 丈二, 渡邉 聡明
    日本外科学会定期学術集会抄録集 2016年04月
  • 胃癌腹膜播種における腹腔内化学療法奏功後の胃切除(Interval devalking gastrectomy)の意義  [通常講演]
    北山 丈二, 石神 浩徳, 山口 博紀, 佐藤 優実子, 矢冨 裕, 渡邉 聡明
    日本外科学会定期学術集会抄録集 2016年04月
  • 直腸癌における中直腸動脈の走行と側方画像シミュレーション ロボット手術への応用  [通常講演]
    清松 知充, 安田 幸嗣, 大谷 研介, 西川 武司, 田中 敏明, 畑 啓介, 川合 一茂, 野澤 宏彰, 山口 博紀, 石原 聡一郎, 北山 丈二, 渡邉 聡明
    日本外科学会定期学術集会抄録集 2016年04月
  • 切除不能大腸癌に対するVEGFまたはEGF-R阻害抗体併用による全身化学療法  [通常講演]
    野澤 宏彰, 安田 幸嗣, 大谷 研介, 西川 武司, 田中 敏明, 清松 知充, 畑 啓介, 川合 一茂, 山口 博紀, 石原 聡一郎, 北山 丈二, 渡邉 聡明
    日本外科学会定期学術集会抄録集 2016年04月
  • 潰瘍性大腸炎術後慢性回腸嚢炎のリスクファクターに対するメタアナリシス  [通常講演]
    畑 啓介, 石原 聡一郎, 野澤 宏彰, 山口 博紀, 川合 一茂, 清松 知充, 田中 敏明, 田中 潤一郎, 安田 幸嗣, 西川 武司, 大谷 研介, 北山 丈二, 石井 博章, 安西 紘幸, 北山 丈二, 渡邉 聡明
    日本外科学会定期学術集会抄録集 2016年04月
  • 腹腔内遊離癌細胞白血球比(Tumor leukocyte Ratio)による胃癌腹膜再発予測  [通常講演]
    小野山 温那, 山下 裕玄, 渡邉 聡明, 北山 丈二, 瀬戸 泰之
    日本胃癌学会総会記事 2016年03月
  • 術前prognostic nutritional indexは、胃癌における血行性再発の独立予測因子である(Preoperative prognostic nutritional index robustly predicts hematogenous relapse in gastric cancer)  [通常講演]
    浦辺 雅之, 山下 裕玄, 八木 浩一, 愛甲 丞, 西田 正人, 竹中 芳治, 野村 幸世, 北山 丈二, 渡邉 聡明, 瀬戸 泰之
    日本胃癌学会総会記事 2016年03月
  • 腹膜播種に対するタキサン反復腹腔内化学療法の展望(Combination chemotherapy including repeated intraperitoneal taxane for peritoneal metastasis)  [通常講演]
    北山 丈二, 石神 浩徳, 山口 博紀
    日本胃癌学会総会記事 2016年03月
  • 直腸癌手術における縫合不全リスク因子および肥満が短期成績に与える影響の検討  [通常講演]
    松崎 裕幸, 石原 聡一郎, 大谷 研介, 安田 幸嗣, 西川 武司, 田中 敏明, 田中 潤一郎, 清松 知充, 畑 啓介, 川合 一茂, 野澤 宏彰, 山口 博紀, 北山 丈二, 渡邉 聡明
    日本成人病(生活習慣病)学会会誌 2016年01月
  • 血管疾患合併例における腹腔鏡下大腸手術の治療成績  [通常講演]
    永田 洋士, 野澤 宏彰, 安田 幸嗣, 大谷 研介, 西川 武司, 田中 敏明, 田中 潤一郎, 清松 知充, 畑 啓介, 川合 一茂, 山口 博紀, 石原 聡一郎, 須並 英二, 北山 丈二, 渡邉 聡明
    日本内視鏡外科学会雑誌 2015年12月
  • ロボット補助大腸手術の標準化 安全な導入に向けて 大腸癌に対するロボット支援手術の標準化  [通常講演]
    石原 聡一郎, 大谷 研介, 安田 幸嗣, 西川 武司, 田中 敏明, 田中 潤一郎, 清松 知充, 畑 啓介, 川合 一茂, 野澤 宏彰, 風間 伸介, 山口 博紀, 須並 英二, 北山 丈二, 渡邉 聡明
    日本内視鏡外科学会雑誌 2015年12月
  • 腹腔鏡/ロボット支援手術における骨盤内リンパ節郭清の要点 ロボット支援下直腸癌手術における側方郭清の要点 安全に施行するための工夫  [通常講演]
    須並 英二, 清松 知充, 川合 一茂, 風間 伸介, 野澤 宏彰, 畑 啓介, 田中 潤一郎, 田中 敏明, 西川 武司, 大谷 研介, 安田 幸嗣, 山口 博紀, 石原 聡一郎, 北山 丈二, 渡邉 聡明
    日本内視鏡外科学会雑誌 2015年12月
  • 化学放射線療法後の直腸癌に対する鏡視下手術の短期治療成績
    石原 聡一郎, 西川 武司, 田中 敏明, 田中 潤一郎, 清松 知充, 川合 一茂, 畑 啓介, 野澤 宏彰, 風間 伸介, 山口 博紀, 須並 英二, 北山 丈二, 渡邉 聡明
    日本消化器外科学会雑誌 2015年10月 (一社)日本消化器外科学会
  • ステロイド長期投与中のSLEにサイトメガロウイルス感染症を合併し大腸穿孔に至った1例
    舘川 裕一, 野澤 宏彰, 田中 潤一郎, 西川 武司, 田中 敏明, 清松 知充, 畑 啓介, 川合 一茂, 風間 伸介, 山口 博紀, 石原 聡一郎, 須並 英二, 北山 丈二, 渡邉 聡明
    日本消化器外科学会雑誌 2015年10月 (一社)日本消化器外科学会
  • Translational science消化器疾患における診断・治療バイオマーカー-ベンチからベッドへ- 胃癌腹膜播種症例の治療効果予測因子としての腹腔洗浄液中CEA mRNA定量
    山口 博紀, 北山 丈二, 渡邉 聡明
    日本消化器外科学会雑誌 2015年10月 (一社)日本消化器外科学会
  • 胃癌に対する集学的治療 Up-to-date<アンサーパッド> P1またはCY1胃癌に対する集学的治療
    石神 浩徳, 北山 丈二, 渡邉 聡明
    日本消化器外科学会雑誌 2015年10月 (一社)日本消化器外科学会
  • 胃癌腹膜播種に対する奏功後胃切除の適応における腹腔液中CEAmRNAの定量の意義  [通常講演]
    北山 丈二, 石神 浩徳, 山口 博紀
    日本癌学会総会記事 2015年10月
  • 当院における大腸癌腹膜播種の治療成績  [通常講演]
    永田 洋士, 石原 聡一郎, 大谷 研介, 安田 幸嗣, 西川 武司, 田中 敏明, 田中 潤一郎, 清松 知充, 畑 啓介, 川合 一茂, 野澤 宏影, 山口 博紀, 須並 英二, 北山 丈二, 渡邉 聡明
    日本臨床外科学会雑誌 2015年10月
  • 直腸癌術後局所再発の治療戦略  [通常講演]
    西川 武司, 石原 聡一郎, 安田 幸嗣, 大谷 研介, 田中 敏明, 田中 潤一郎, 清松 知充, 川合 一茂, 畑 啓介, 野澤 宏彰, 風間 伸介, 山口 博紀, 須並 英二, 北山 丈二, 渡邉 聡明
    日本臨床外科学会雑誌 2015年10月
  • 縫合・吻合不全の予防と治療(小腸、結腸、直腸) 直腸癌に対する腹腔鏡下DSTにおける縫合不全リスク因子の検討  [通常講演]
    松崎 裕幸, 安田 幸嗣, 西川 武司, 田中 敏明, 田中 潤一郎, 清松 知充, 畑 啓介, 川合 一茂, 野澤 宏彰, 風間 伸介, 山口 博紀, 石原 聡一郎, 須並 英二, 北山 丈二, 渡邉 聡明
    日本臨床外科学会雑誌 2015年10月
  • 外科医が行う臨床試験 その方法と問題点 腹膜播種に対する腹腔内化学療法に関する臨床試験 経過と問題点  [通常講演]
    北山 丈二, 石神 浩徳, 山口 博紀
    日本臨床外科学会雑誌 2015年10月
  • Stage IV胃癌・大腸癌に対する治療戦略 Stage IV大腸癌治癒切除後長期生存例の検討  [通常講演]
    野澤 宏彰, 石原 聡一郎, 安田 幸嗣, 大谷 研介, 西川 武司, 田中 敏明, 田中 潤一郎, 清松 知充, 畑 啓介, 川合 一茂, 風間 伸介, 山口 博紀, 須並 英二, 北山 丈二, 渡邉 聡明
    日本臨床外科学会雑誌 2015年10月
  • Stage IV胃癌・大腸癌に対する治療戦略 腹膜播種を伴う胃癌に対する腹腔内化学療法後の胃切除  [通常講演]
    山口 博紀, 北山 丈二, 石神 浩徳, 渡邉 聡明
    日本臨床外科学会雑誌 2015年10月
  • 更なる治療成績の向上を目指した大腸癌治療 当科における大腸ステント留置後化学療法症例の外科手術の経験  [通常講演]
    田中 敏明, 安田 幸嗣, 大谷 研介, 西川 武司, 田中 潤一郎, 清松 知充, 畑 啓介, 川合 一茂, 野澤 宏彰, 山口 博紀, 石原 聡一朗, 北山 丈二, 渡邉 聡明
    日本臨床外科学会雑誌 2015年10月
  • ロボット支援手術の有用性を知る 直腸癌に対するロボット支援手術の安全性と有用性  [通常講演]
    石原 聡一郎, 大谷 研介, 安田 幸嗣, 西川 武司, 田中 敏明, 田中 潤一郎, 清松 知充, 畑 啓介, 川合 一茂, 野澤 宏彰, 風間 伸介, 山口 博紀, 須並 英二, 北山 丈二, 渡邉 聡明
    日本臨床外科学会雑誌 2015年10月
  • 他臓器疾患を有する癌患者の外科治療 当科における併存症を有する大腸癌患者の周術期合併症の検討  [通常講演]
    阿部 真也, 川合 一茂, 大谷 研介, 西川 武司, 田中 敏明, 田中 潤一郎, 清松 知充, 畑 啓介, 野澤 宏彰, 風間 伸介, 山口 博紀, 石原 聡一郎, 須並 英二, 北山 丈二, 渡邉 聡明
    日本臨床外科学会雑誌 2015年10月
  • 手術支援ロボット手術の実際 直腸癌に対するロボット支援下手術の現状  [通常講演]
    須並 英二, 清松 知充, 川合 一茂, 風間 伸介, 野澤 宏彰, 畑 啓介, 田中 潤一郎, 田中 敏明, 西川 武司, 大谷 研介, 安田 幸嗣, 山口 博紀, 石原 聡一郎, 北山 丈二, 渡邉 聡明
    日本臨床外科学会雑誌 2015年10月
  • 合併症ゼロを目指した再建、吻合手術手技(大腸) 縫合不全防止のための直腸再建時の工夫  [通常講演]
    田中 潤一郎, 大谷 研介, 安田 幸嗣, 西川 武司, 田中 敏明, 清松 知充, 畑 啓介, 川合 一茂, 野澤 宏彰, 風間 伸介, 山口 博紀, 石原 聡一郎, 須並 英二, 北山 丈二, 渡邉 聡明
    日本臨床外科学会雑誌 2015年10月
  • 手術・処置・診断などのシミュレーションの現状と展望 ロボット支援下直腸癌手術における側方領域血管の3Dシミュレーション  [通常講演]
    清松 知充, 安田 幸嗣, 大谷 研介, 西川 武司, 田中 敏明, 田中 潤一郎, 畑 啓介, 川合 一茂, 野澤 宏彰, 山口 博紀, 石原 聡一郎, 北山 丈二, 渡邉 聡明
    日本臨床外科学会雑誌 2015年10月
  • 大腸 直腸がんに対する腹腔鏡手術 鏡視下直腸癌手術における骨盤内解剖の画像シミュレーション 中直腸動脈のvariation  [通常講演]
    清松 知充, 安田 幸嗣, 大谷 研介, 西川 武司, 田中 敏明, 田中 潤一郎, 畑 啓介, 川合 一茂, 野澤 宏彰, 風間 伸介, 山口 博紀, 石原 聡一郎, 須並 英二, 北山 丈二, 渡邉 聡明
    日本癌治療学会誌 2015年09月
  • 腹腔鏡手術導入による高齢者大腸癌手術の変遷  [通常講演]
    西川 武司, 石原 聡一郎, 安田 幸嗣, 大谷 研介, 田中 敏明, 田中 潤一郎, 清松 知充, 川合 一茂, 畑 啓介, 野澤 宏彰, 風間 伸介, 山口 博紀, 須並 英二, 北山 丈二, 渡邉 聡明
    日本癌治療学会誌 2015年09月
  • 胃 胃がん腹膜播種へのアプローチ 腹膜播種を伴う胃癌に対する腹腔内投与併用化学療法の開発  [通常講演]
    石神 浩徳, 北山 丈二, 山口 博紀, 渡邉 聡明
    日本癌治療学会誌 2015年09月
  • 胃癌に対する集学的治療 Up-to-date P1またはCY1胃癌に対する集学的治療  [通常講演]
    石神 浩徳, 北山 丈二, 渡邉 聡明
    Gastroenterological Endoscopy 2015年09月
  • 外科的治療を行った腸管ベーチェット病の2例  [通常講演]
    品川 貴秀, 畑 啓介, 風間 伸介, 安田 幸嗣, 大谷 研介, 西川 武司, 田中 敏明, 田中 潤一郎, 清松 知充, 川合 一茂, 野澤 宏彰, 山口 博紀, 石原 聡一郎, 須並 英二, 北山 丈二, 渡邉 聡明
    日本大腸肛門病学会雑誌 2015年09月
  • 術後2ヵ月で鼡径、側方リンパ節再発をきたした痔瘻癌の1例  [通常講演]
    奥野 貴之, 清松 知充, 西川 武司, 安田 幸嗣, 田中 敏明, 田中 潤一郎, 畑 啓介, 川合 一茂, 野澤 宏彰, 風間 伸介, 山口 博紀, 石原 聡一郎, 須並 英二, 北山 丈二, 渡邉 聡明
    日本大腸肛門病学会雑誌 2015年09月
  • 原発性肺高血圧症患者のS状結腸癌術後に結腸浮腫を認めた一例  [通常講演]
    荒川 敬一, 川合 一茂, 安田 幸嗣, 大谷 研介, 西川 武司, 田中 敏明, 田中 潤一郎, 清松 知充, 畑 啓介, 野澤 宏彰, 風間 伸介, 山口 博紀, 石原 聡一郎, 須並 英二, 北山 丈二, 渡邉 聡明
    日本大腸肛門病学会雑誌 2015年09月
  • 異時性多発肛門管癌の一例  [通常講演]
    瀧山 博年, 野澤 宏彰, 石原 聡一郎, 田中 潤一郎, 安田 幸嗣, 大谷 研介, 西川 武司, 田中 敏明, 清松 知充, 畑 啓介, 川合 一茂, 風間 伸介, 山口 博紀, 須並 英二, 北山 丈二, 渡邉 聡明
    日本大腸肛門病学会雑誌 2015年09月
  • 腹腔鏡補助下回盲部切除術を施行した単純性小腸潰瘍の一例  [通常講演]
    原田 有三, 清松 知充, 大谷 研介, 西川 武司, 安田 幸嗣, 田中 潤一郎, 田中 敏明, 川合 一茂, 畑 啓介, 風間 伸介, 野澤 宏彰, 山口 博紀, 石原 聡一郎, 須並 英二, 北山 丈二, 渡邉 聡明
    日本大腸肛門病学会雑誌 2015年09月
  • 大腸癌患者における抗p53抗体の術後サーベイランスに関する検討  [通常講演]
    阿部 真也, 川合 一茂, 安田 幸嗣, 大谷 研介, 西川 武司, 田中 敏明, 田中 潤一郎, 清松 知充, 畑 啓介, 野澤 宏彰, 風間 伸介, 山口 博紀, 石原 聡一郎, 須並 英二, 北山 丈二, 渡邉 聡明
    日本大腸肛門病学会雑誌 2015年09月
  • 50歳未満の若年で発症した大腸癌の臨床病理学的検討  [通常講演]
    永井 雄三, 畑 啓介, 安田 幸嗣, 西川 武司, 田中 敏明, 田中 潤一郎, 清松 知充, 川合 一茂, 野澤 宏彰, 風間 伸介, 山口 博紀, 石原 聡一郎, 須並 英二, 北山 丈二, 渡邉 聡明
    日本大腸肛門病学会雑誌 2015年09月
  • 回盲部およびS状結腸・直腸S状部同士の直接浸潤癌の2例  [通常講演]
    瀧山 亜希, 野澤 宏彰, 風間 伸介, 川合 一茂, 田中 潤一郎, 安田 幸嗣, 大谷 研介, 西川 武司, 田中 敏明, 清松 知充, 畑 啓介, 山口 博紀, 石原 聡一郎, 須並 英二, 北山 丈二, 渡邉 聡明
    日本大腸肛門病学会雑誌 2015年09月
  • 大腸癌術前検査としてのCTコロノグラフィー検査の有用性  [通常講演]
    佐藤 一仁, 田中 敏明, 安田 幸嗣, 大谷 研介, 西川 武司, 田中 潤一郎, 清松 知充, 畑 啓介, 川合 一茂, 野澤 宏彰, 風間 伸介, 山口 博紀, 石原 聡一郎, 須並 英二, 北山 丈二, 渡邉 聡明
    日本大腸肛門病学会雑誌 2015年09月
  • 当科における直腸癌局所再発の治療戦略  [通常講演]
    西川 武司, 石原 聡一郎, 安田 幸嗣, 大谷 研介, 田中 敏明, 田中 潤一郎, 清松 知充, 川合 一茂, 畑 啓介, 野澤 宏彰, 風間 伸介, 山口 博紀, 須並 英二, 北山 丈二, 渡邉 聡明
    日本大腸肛門病学会雑誌 2015年09月
  • 大腸癌に対する内視鏡的治療後追加腸切除症例の特徴 ESD症例とEMR症例の比較  [通常講演]
    野澤 宏彰, 安田 幸嗣, 大谷 研介, 西川 武司, 田中 敏明, 田中 潤一郎, 清松 知充, 川合 一茂, 畑 啓介, 風間 伸介, 山口 博紀, 石原 聡一郎, 須並 英二, 北山 丈二, 渡邉 聡明
    日本大腸肛門病学会雑誌 2015年09月
  • ISRの現状と展望 下部直腸癌に対する腹腔鏡下括約筋間切除術の治療成績  [通常講演]
    石原 聡一郎, 瀧山 亜希, 瀧山 博年, 原田 有三, 柴田 淳一, 大谷 研介, 安田 幸嗣, 西川 武司, 田中 敏明, 田中 潤一郎, 清松 知充, 畑 啓介, 川合 一茂, 野澤 宏彰, 風間 伸介, 山口 博紀, 須並 英二, 北山 丈二, 渡邉 聡明
    日本大腸肛門病学会雑誌 2015年09月
  • cT3N1下部直腸癌に対する治療戦略 cT3N1M0の下部進行直腸癌に対する術前放射線療法と術前化学放射線療法の効果に関する比較検討  [通常講演]
    安田 幸嗣, 石原 聡一郎, 大谷 研介, 西川 武司, 田中 敏明, 田中 潤一郎, 清松 知充, 畑 啓介, 川合 一茂, 野澤 宏彰, 風間 伸介, 山口 博紀, 須並 英二, 北山 丈二, 渡邉 聡明
    日本大腸肛門病学会雑誌 2015年09月
  • IBDに対する癌サーベイランスの現状と今後の展望 潰瘍性大腸炎合併大腸癌の特徴  [通常講演]
    畑 啓介, 岸川 純子, 安西 紘幸, 大谷 研介, 安田 幸嗣, 西川 武史, 田中 敏明, 田中 潤一郎, 清松 知充, 川合 一茂, 野沢 宏彰, 風間 伸介, 山口 博紀, 石原 聡一郎, 須並 英二, 北山 丈二, 渡邉 聡明
    日本大腸肛門病学会雑誌 2015年09月
  • 大腸肛門機能の諸問題 術前化学放射線療法後に切除した下部進行直腸癌患者における術後肛門機能の検討  [通常講演]
    柴田 淳一, 石原 聡一郎, 清松 知充, 安西 紘幸, 瀧山 亜希, 瀧山 博年, 原田 有三, 大谷 研介, 安田 幸嗣, 西川 武司, 田中 敏明, 田中 潤一郎, 畑 啓介, 川合 一茂, 野澤 宏彰, 風間 伸介, 山口 博紀, 須並 英二, 北山 丈二, 渡邉 聡明
    日本大腸肛門病学会雑誌 2015年09月
  • 大腸領域におけるロボット手術の現状と展望 当科における直腸癌ロボット手術の現状と課題  [通常講演]
    須並 英二, 清松 知充, 川合 一茂, 風間 伸介, 野澤 宏彰, 畑 啓介, 田中 潤一郎, 田中 敏明, 西川 武司, 大谷 研介, 安田 幸嗣, 山口 博紀, 石原 聡一郎, 北山 丈二, 渡邉 聡明
    日本大腸肛門病学会雑誌 2015年09月
  • ストーマ合併症の現状と治療 当院におけるストーマ合併症例とその治療の検討  [通常講演]
    田中 潤一郎, 安田 幸嗣, 大谷 研介, 西川 武司, 田中 敏明, 清松 知充, 畑 啓介, 川合 一茂, 野澤 宏彰, 風間 伸介, 山口 博紀, 石原 聡一郎, 須並 英二, 北山 丈二, 渡邉 聡明
    日本大腸肛門病学会雑誌 2015年09月
  • 大腸癌に対する集学的治療 直腸 局所進行直腸癌に対する術前放射線療法と腹腔鏡手術  [通常講演]
    川合 一茂, 須並 英二, 山口 博紀, 石原 聡一郎, 風間 伸介, 野澤 宏彰, 畑 啓介, 清松 知充, 田中 潤一郎, 田中 敏明, 西川 武司, 北山 丈二, 渡邉 聡明
    日本大腸肛門病学会雑誌 2015年09月
  • 上行結腸癌術後異時性回腸癌を認めたリンチ症候群の1例  [通常講演]
    舘川 裕一, 山口 博紀, 畑 啓介, 川合 一茂, 野澤 宏彰, 風間 伸介, 石原 聡一郎, 須並 英二, 北山 丈二, 渡邉 聡明
    日本消化器外科学会総会 2015年07月
  • 消化器外科における凝固線溶異常 胃がんにおいて術前の血漿フィブリノーゲン値は転移と予後に相関する(Coagulation Abnormalities in Gastroenterological Surgery Preoperative plasma fibrinogen levels correlate with metastasis and prognosis in gastric cancer)  [通常講演]
    浦辺 雅之, 山下 裕玄, 愛甲 丞, 森 和彦, 野村 幸世, 北山 丈二, 渡邉 聡明, 瀬戸 泰之
    日本消化器外科学会総会 2015年07月
  • 胃癌腹膜播種の病態と診断・治療 腹膜播種を伴う胃癌に対する腹腔内投与併用化学療法  [通常講演]
    石神 浩徳, 北山 丈二, 山口 博紀, 渡邉 聡明
    日本消化器外科学会総会 2015年07月
  • Colitis-associated cancerの診断と治療 当科における潰瘍性大腸炎サーベイランス内視鏡についての検討  [通常講演]
    安西 紘幸, 畑 啓介, 岸川 純子, 風間 伸介, 山口 博紀, 石原 聡一郎, 須並 英二, 北山 丈二, 渡邉 聡明
    日本消化器外科学会総会 2015年07月
  • 潰瘍性大腸炎手術症例における、腹腔鏡下手術の有用性の検討  [通常講演]
    風間 伸介, 畑 啓介, 石原 聡一郎, 須並 英二, 北山 丈二, 渡邉 聡明
    日本消化器外科学会総会 2015年07月
  • 進行性消化器癌の多職種連携治療 進行性消化器癌の治療の最近の動向 腹膜転移を伴う進行性の胃がんに対する集学的治療(Multidisciplinary Treatment of Progressive Gastroenterological Cancers: Update on Treatment of Progressive Gastroenterological Cancers Multidisciplinary treatment for advanced gastric cancer with pe  [通常講演]
    山口 博紀, 石神 浩徳, 北山 丈二, 渡邉 聡明
    日本消化器外科学会総会 2015年07月
  • 下部直腸癌に対する側方郭清の意義 JCOG0215の結果から得たもの 術前化学放射線療法による直腸癌側方リンパ節転移の制御  [通常講演]
    清松 知充, 川合 一茂, 山口 博紀, 石原 聡一郎, 須並 英二, 北山 丈二, 渡邉 聡明
    日本消化器外科学会総会 2015年07月
  • 腹腔内遊離細胞群の解析と臨床的意義 次世代の腹膜播種治療の確立に向けて  [通常講演]
    北山 丈二, 石神 浩徳, 山口 博紀, 小野山 温那, 山下 裕玄, 瀬戸 泰之, 松崎 圭祐, 渡邉 聡明
    日本消化器外科学会総会 2015年07月
  • 腹腔鏡下直腸切除術の工夫 当科の腹腔鏡補助下直腸切除術における吻合の工夫  [通常講演]
    西川 武司, 須並 英二, 須並 英二, 山口 博紀, 石原 聡一郎, 北山 丈二, 渡邉 聡明
    日本消化器外科学会総会 2015年07月
  • 手術手技 特殊腹腔鏡下大腸手術 ロボット支援下括約筋間直腸切除術(ISR)の短期治療成績  [通常講演]
    石原 聡一郎, 田中 敏明, 田中 潤一郎, 清松 知充, 川合 一茂, 野澤 宏彰, 風間 伸介, 山口 博紀, 北山 丈二, 渡邉 聡明
    日本消化器外科学会総会 2015年07月
  • ステント留置された閉塞性大腸癌に対する腹腔鏡下大腸切除術の成績  [通常講演]
    田中 敏明, 石原 聡一郎, 須並 英二, 北山 丈二, 渡邉 聡明
    日本消化器外科学会総会 2015年07月
  • 潰瘍性大腸炎術後の回腸嚢炎のリスクファクター  [通常講演]
    畑 啓介, 石井 博章, 風間 伸介, 川合 一茂, 野澤 宏彰, 山口 博紀, 石原 聡一郎, 須並 英二, 北山 丈二, 渡邉 聡明
    日本消化器外科学会総会 2015年07月
  • FACSを用いた腹膜播種患者における腹腔内遊離癌細胞(floating tumor cell)定量の試み  [通常講演]
    北山 丈二, 石神 浩徳, 山口 博紀
    Cytometry Research 2015年07月
  • 内視鏡を活用したあらたな診療展開 大腸 進行胃癌による悪性大腸閉塞に対するSEMS留置術の成績  [通常講演]
    成田 明子, 吉田 俊太郎, 太田 弓子, 神宝 隆行, 高原 楠昊, 平田 喜裕, 伊佐山 浩通, 山下 裕玄, 石神 浩徳, 北山 丈二, 渡邉 聡明, 瀬戸 泰之, 小池 和彦
    Progress of Digestive Endoscopy 2015年06月
  • 内視鏡を活用したあらたな診療展開 胃、食道 切除不能進行胃癌による胃排出路障害へのステント留置成績とステント長期開存に寄与する因子の検討  [通常講演]
    太田 弓子, 吉田 俊太郎, 山下 裕玄, 石神 浩徳, 成田 明子, 高原 楠昊, 神宝 隆行, 山田 篤生, 木暮 宏史, 山本 夏代, 中井 陽介, 平田 喜裕, 伊佐山 浩通, 北山 丈二, 渡邉 聡明, 瀬戸 泰之, 小池 和彦
    Progress of Digestive Endoscopy 2015年06月
  • 生活習慣病が大腸腹腔鏡術後の合併症発生に及ぼす影響  [通常講演]
    石井 博章, 石原 聡一郎, 西川 武司, 田中 敏明, 田中 潤一郎, 清松 知充, 川合 一茂, 畑 啓介, 野澤 宏彰, 風間 伸介, 山口 博紀, 須並 英二, 北山 丈二, 渡邉 聡明, 松田 圭二
    成人病と生活習慣病 2015年05月
  • 左総腸骨動脈閉塞に伴う側副血行に注意し腹腔鏡下手術を安全に施行しえた直腸癌の一例  [通常講演]
    永田 洋士, 野澤 宏彰, 田中 潤一郎, 畑 啓介, 杉浦 彩, 川合 一茂, 石原 聡一郎, 須並 英二, 北山 丈二, 渡邉 聡明
    成人病と生活習慣病 2015年05月
  • 併存疾患を有する大腸癌患者の周術期合併症の検討  [通常講演]
    阿部 真也, 川合 一茂, 西川 武司, 田中 敏明, 田中 潤一郎, 清松 知充, 畑 啓介, 野澤 宏彰, 風間 伸介, 山口 博紀, 石原 聡一郎, 須並 英二, 北山 丈二, 渡邉 聡明
    成人病と生活習慣病 2015年05月
  • stage III大腸癌患者における補助化学療法の検討 若年者と高齢者の比較  [通常講演]
    野澤 宏彰, 西川 武司, 田中 敏明, 田中 潤一郎, 清松 知充, 川合 一茂, 畑 啓介, 風間 伸介, 金沢 孝満, 山口 博紀, 石原 聡一郎, 須並 英二, 北山 丈二, 渡邉 聡明
    日本大腸肛門病学会雑誌 2015年05月
  • 下部消化管 大腸癌肝転移症例におけるCD133発現の免疫組織学的検討  [通常講演]
    岸川 純子, 風間 伸介, 長谷川 潔, 山口 博紀, 石原 聡一郎, 須並 英二, 牛久 哲男, 北山 丈二, 深山 正久, 國土 典宏, 渡邉 聡明
    日本外科学会定期学術集会抄録集 2015年04月
  • 下部消化管 オキサリプラチンによる補助化学療法後の大腸癌再発に関わる因子の検討  [通常講演]
    野澤 宏彰, 西川 武司, 田中 敏明, 田中 潤一郎, 清松 知充, 川合 一茂, 畑 啓介, 風間 伸介, 山口 博紀, 石原 聡一郎, 須並 英二, 北山 丈二, 渡邉 聡明
    日本外科学会定期学術集会抄録集 2015年04月
  • 局所進行直腸癌に対する集学的治療戦略 下部消化管 局所進行直腸癌に対する術前放射線療法と化学放射線療法の比較  [通常講演]
    川合 一茂, 石原 聡一郎, 山口 博紀, 須並 英二, 北山 丈二, 渡邉 聡明
    日本外科学会定期学術集会抄録集 2015年04月
  • 胃癌の周術期化学療法 上部消化管 根治切除可能な漿膜浸潤を伴う胃癌に対する周術期化学療法 TS-1、パクリタキセル経静脈・腹腔内投与併用療法 第II相試験  [通常講演]
    今野 元博, 石神 浩徳, 藪崎 裕, 小林 大介, 伊藤 誠二, 上之園 芳一, 上田 修吾, 木村 豊, 山口 博紀, 今本 治彦, 梨本 篤, 古河 洋, 安田 卓司, 竹吉 泉, 福島 亮治, 小寺 泰弘, 北山 丈二
    日本外科学会定期学術集会抄録集 2015年04月
  • 下部消化管 直腸癌手術における周術期感染予防のための吻合法の工夫  [通常講演]
    西川 武司, 須並 英二, 田中 敏明, 田中 潤一郎, 清松 知充, 川合 一茂, 畑 啓介, 野澤 宏彰, 風間 伸介, 山口 博紀, 石原 聡一郎, 北山 丈二, 渡邉 聡明
    日本外科学会定期学術集会抄録集 2015年04月
  • 上部消化管 腹膜転移を伴う胃癌治療のためのパクリタキセルを用いた腹腔内化学療法(Intraperitoneal chemotherapy with paclitaxel for treatment of gastric cancer with peritoneal metastasis)  [通常講演]
    山口 博紀, 石神 浩徳, 北山 丈二, 渡邉 聡明
    日本外科学会定期学術集会抄録集 2015年04月
  • 下部消化管 直腸癌に対するロボット手術(Robotic surgery for rectal cancer in our institute)  [通常講演]
    須並 英二, 川合 一茂, 清松 知充, 風間 伸介, 野澤 宏彰, 畑 啓介, 田中 潤一郎, 田中 敏明, 西川 武司, 山口 博紀, 石原 聡一郎, 北山 丈二, 渡邉 聡明
    日本外科学会定期学術集会抄録集 2015年04月
  • 下部消化管 直腸癌に対するロボット手術 CT解剖に基づく手術手技  [通常講演]
    清松 知充, 西川 武司, 田中 敏明, 田中 潤一郎, 畑 啓介, 川合 一茂, 野澤 宏彰, 風間 伸介, 山口 博紀, 石原 聡一郎, 須並 英二, 北山 丈二, 渡邉 聡明
    日本外科学会定期学術集会抄録集 2015年04月
  • 栄養・感染症・緩和 切除不能遠隔転移を伴う大腸癌に対する姑息的原発巣切除の意義 propensity score matching法による多施設データの解析  [通常講演]
    石原 聡一郎, 西川 武司, 田中 敏明, 田中 潤一郎, 清松 知充, 川合 一茂, 畑 啓介, 野澤 宏彰, 金沢 孝満, 風間 伸介, 山口 博紀, 須並 英二, 北山 丈二, 杉原 健一, 渡邉 聡明
    日本外科学会定期学術集会抄録集 2015年04月
  • 上部消化管 腹膜播種陽性または腹腔洗浄細胞診陽性胃癌に対する集学的治療  [通常講演]
    石神 浩徳, 北山 丈二, 山口 博紀, 渡邉 聡明
    日本外科学会定期学術集会抄録集 2015年04月
  • 消化器疾患における線維化の病態と診療 腹腔内間葉系細胞による線維化を標的とした胃癌腹膜播種に対する新規治療戦略  [通常講演]
    北山 丈二, 山口 博紀, 石神 浩徳
    日本消化器病学会雑誌 2015年03月
  • 胃癌腹膜播種患者における腹腔内遊離癌細胞白血球比(Tumor Leukocyte Ratio)の臨床的意義  [通常講演]
    北山 丈二, 江本 成伸, 山口 博紀, 石神 浩徳, 小野山 温菜, 山下 裕玄, 松崎 圭佑, 瀬戸 泰之, 渡邉 聡明
    日本胃癌学会総会記事 2015年03月
  • 胃癌腹膜播種症例に対する新たな治療戦略 内科、外科の立場から 腹膜播種を伴う胃癌に対するカペシタビン/シスプラチン+ドセタキセル腹腔内投与併用療法  [通常講演]
    石神 浩徳, 北山 丈二, 山口 博紀, 渡邉 聡明
    日本胃癌学会総会記事 2015年03月
  • 胃癌腹膜播種症例に対する新たな治療戦略 内科、外科の立場から 腹膜播種を伴う胃癌に対するS-1/オキサリプラチン+パクリタキセル腹腔内投与併用療法  [通常講演]
    上之園 芳一, 石神 浩徳, 藤原 義之, 富田 寿彦, 今本 治彦, 今野 元博, 梨本 篤, 藪崎 裕, 福島 亮治, 小寺 泰弘, 今村 和広, 上田 修吾, 山下 裕玄, 山口 博紀, 北山 丈二
    日本胃癌学会総会記事 2015年03月
  • 胃癌腹膜播種症例に対する新たな治療戦略 内科、外科の立場から 胃癌腹膜播種に対するS-1+PTX経静脈・腹腔内併用化学療法  [通常講演]
    山口 博紀, 石神 浩徳, 北山 丈二, 渡邉 聡明
    日本胃癌学会総会記事 2015年03月
  • 胃癌腹膜播種症例に対する新たな治療戦略 内科、外科の立場から 胃癌腹膜播種に対する腹腔内化学療法の展望 基礎的検討から  [通常講演]
    北山 丈二, 石神 浩徳, 山口 博紀, 渡邉 聡明
    日本胃癌学会総会記事 2015年03月
  • conversion therapyの現状と将来展望 定義、適応と手術の時期 腹膜播種を伴う胃癌に対する腹腔内投与併用化学療法後胃切除  [通常講演]
    石神 浩徳, 北山 丈二, 山口 博紀, 渡邉 聡明
    日本胃癌学会総会記事 2015年03月
  • 腹膜播種・癌性腹水に対する治療戦略 癌性腹水を伴う高度胃癌腹膜播種症例に対するCARTと腹腔内化学療法を併用した積極的治療  [通常講演]
    北山 丈二
    日本胃癌学会総