研究者業績

北山 丈二

キタヤマ ジョウジ  (JOJI KITAYAMA)

基本情報

所属
自治医科大学 消化器外科 教授
学位
医学博士(東京大学)

J-GLOBAL ID
201801007452437948
researchmap会員ID
B000314953

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

 2

論文

 570
  • 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2月  査読有り
    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1月19日  査読有り
    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
    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
    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
    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
    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
    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
    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
    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
    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9月  
  • 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9月  査読有り
    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9月  査読有り
    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9月  査読有り
    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9月  査読有り
  • 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8月  査読有り
    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8月  査読有り
    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8月  査読有り
    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8月  査読有り
    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7月  査読有り
    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7月  査読有り
    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7月  査読有り
    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6月  査読有り
    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6月1日  査読有り
    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6月  査読有り
  • 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5月  査読有り
    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5月  査読有り
    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5月  査読有り
    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5月  査読有り
    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.
  • 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 115回 OP-6 2015年4月  
  • K. Kawai, S. Ishihara, H. Yamaguchi, E. Sunami, J. Kitayama, H. Miyata, K. Sugihara, T. Watanabe
    EJSO 41(4) 457-465 2015年4月  査読有り
    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4月  査読有り
    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4月  査読有り
    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3月  査読有り
    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3月  査読有り
    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3月  査読有り
    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2月7日  査読有り
    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2月  
  • 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2月  査読有り
    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2月  査読有り
    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1月  査読有り
  • Tsuyoshi Ozawa, Hironori Yamaguchi, Tomomichi Kiyomatsu, Shinsuke Saito, Soichiro Ishihara, Eiji Sunami, Joji Kitayama, Toshiaki Watanabe
    INTERNATIONAL SURGERY 100(1) 58-62 2015年1月  査読有り
    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1月  査読有り
    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
    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
    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
    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
    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
    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  

MISC

 330

講演・口頭発表等

 1196

共同研究・競争的資金等の研究課題

 51