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).
Department of Surgical Oncology
Research field is Tumor Biology and main clinical work is the treatment of peritoneal metastasis of gastric cancer (intraperitoneal chemotherapy).
研究分野
1論文
570-
World Journal of Surgery 2024年6月24日Abstract Background Osteopenia reflects frailty and has been shown to be associated with outcomes in cancer patients. This study was undertaken to examine whether osteopenia is an independent prognostic factor in patients with esophageal cancer after resection. Methods A total of 214 patients who underwent surgery for esophageal cancer were analyzed retrospectively. Bone mineral density (BMD) of the 11th thoracic vertebra was measured by computed tomography scan, and patients classified into osteopenia and normal BMD groups with BMD <160 Hounsfield units as the cutoff. Clinicopathological data and prognosis were analyzed. Results The 5‐year survival rate was 55.4% for the osteopenia group and 74.7% for the normal BMD group with a significantly worse prognosis in the osteopenia group (p = 0.0080). In multivariable analysis, osteopenia was a significant independent risk factor associated with overall survival (hazard ratio [HR] 1.90, 95% confidence interval [CI] 1.27–3.34, and p = 0.0151) along with R1/2 resection (HR 3.02, 95% CI 1.71–5.18, and p = 0.0002). Conclusion In patients with esophageal cancer undergoing resection, osteopenia may be a surrogate marker for frailty and an independent predictor of prognosis.
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Cancers 16(11) 2087-2087 2024年5月30日Background: Osteopenia is a well-known risk factor for survival in patients with hepatocellular carcinoma; however, it is unclear whether osteopenia can apply to both genders and how osteopenia is associated with cancer progression. The aim of this study was to elucidate whether osteopenia predicts reduced survival in regression models in both genders and whether osteopenia is associated with the pathological factors associated with reduced survival. Methods: This study included 188 consecutive patients who underwent hepatectomy. Bone mineral density was assessed using computed tomography (CT) scan images taken within 3 months before surgery. Non-contrast CT scan images at the level of the 11th thoracic vertebra were used. The cutoff value of osteopenia was calculated using a threshold value of 160 Hounsfield units. Overall survival (OS) curves and recurrence-free survival (RFS) were constructed using the Kaplan–Meier method, as was a log-rank test for survival. The hazard ratio and 95% confidence interval for overall survival were calculated using Cox’s proportional hazard model. Results: In the regression analysis, age predicted bone mineral density. The association in females was greater than that in males. The OS and RFS of osteopenia patients were shorter than those for non-osteopenia patients. According to univariate and multivariate analyses, osteopenia was an independent risk factor for OS and RFS. The sole pathological factor associated with osteopenia was microvascular portal vein invasion. Conclusion: Models suggest that osteopenia may predict decreased OS and RFS in patients undergoing resection of hepatocellular carcinoma due to the mechanisms mediated via microvascular portal vein invasion.
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Scientific Reports 14(1) 2024年2月26日Abstract Intestinal adaptation does not necessarily recover absorptive capacity in short bowel syndrome (SBS), sometimes resulting in intestinal failure-associated liver disease (IFALD). Additionally, its therapeutic options remain limited. Polyamines (spermidine and spermine) are known as one of the autophagy inducers and play important roles in promoting the weaning process; however, their impact on intestinal adaptation is unknown. The aim of this study was to investigate the impact of polyamines ingestion on adaptation and hepatic lipid metabolism in SBS. We performed resection of two-thirds of the small intestine in male Lewis rats as an SBS model. They were allocated into three groups and fed different polyamine content diets (0%, 0.01%, 0.1%) for 30 days. Polyamines were confirmed to distribute to remnant intestine, whole blood, and liver. Villous height and number of Ki-67-positive cells in the crypt area increased with the high polyamine diet. Polyamines increased secretory IgA and mucin content in feces, and enhanced tissue Claudin-3 expression. In contrast, polyamines augmented albumin synthesis, mitochondrial DNA copy number, and ATP storage in the liver. Moreover, polyamines promoted autophagy flux and activated AMP-activated protein kinase with suppression of lipogenic gene expression. Polyamines ingestion may provide a new therapeutic option for SBS with IFALD.
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Annals of surgical oncology 31(2) 735-743 2024年2月BACKGROUND: Intraperitoneal chemotherapy is promising for gastric cancer with peritoneal metastasis. Although a phase III study failed to show a statistically significant superiority of intraperitoneal paclitaxel combined with S-1 and intravenous paclitaxel, the sensitivity analysis suggested clinical efficacy. Thus, attempts to combine intraperitoneal paclitaxel with other systemic therapies with higher efficacy have been warranted. We sought to explore the efficacy of intraperitoneal paclitaxel with S-1 and cisplatin. PATIENTS AND METHODS: Gastric cancer patients with peritoneal metastasis were enrolled in the phase II trial. In addition to the established S-1 and cisplatin regimen every 5 weeks, intraperitoneal paclitaxel was administered on days 1, 8, and 22 at a dose of 20 mg/m2. The primary endpoint was overall survival rate at 1 year after treatment initiation. Secondary endpoints were progression-free survival and toxicity. RESULTS: Fifty-three patients were enrolled and fully evaluated for efficacy and toxicity. The 1-year overall survival rate was 73.6% (95% confidence interval 59.5-83.4%), and the primary endpoint was met. The median survival time was 19.4 months (95% confidence interval, 16.1-24.6 months). The 1-year progression-free survival rate was 49.6% (95% confidence interval, 34.6-62.9%). The incidences of grade 3/4 hematological and non-hematological toxicities were 43% and 47%, respectively. The frequent grade 3/4 toxicities included neutropenia (25%), anemia (30%), diarrhea (13%), and anorexia (17%). Intraperitoneal catheter and implanted port-related complications were observed in four patients. There was one treatment-related death. CONCLUSIONS: Intraperitoneal paclitaxel combined with S-1 and cisplatin is well tolerated and active in gastric cancer patients with peritoneal metastasis.
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Journal of thoracic disease 16(1) 391-400 2024年1月30日BACKGROUND: Adjuvant nivolumab therapy has become the standard therapy for patients with localized advanced esophageal cancer with non-pathological complete response after neoadjuvant chemoradiotherapy followed by curative surgery. However, the necessity of this therapy for patients after neoadjuvant chemotherapy (NAC) with docetaxel, cisplatin, and 5-fluorouracil (DCF) regimen followed by surgery is unclear, and the prognosis of grouping based on the presence or absence of pathological tumor and lymph node findings has not been analyzed. Therefore, our study aimed to address these questions. METHODS: This retrospective cohort study included patients with cT1N1-3M0 and cT2-3N0-3M0 esophageal cancer according to the Japanese Classification of Esophageal Cancer, 11th edition, who received NAC with DCF followed by curative surgery between 2008 and 2020 at Jichi Medical University Hospital. We divided patients with ypT0-3N0-3M0 into four histological groups, namely ypT0N0, ypT+N0, ypT0N+, and ypT+N+, and we evaluated overall survival as the primary outcome and the prognostic relationship of lymph node metastasis as the secondary outcome. RESULTS: A total of 101 patients were included in this study. Kaplan-Meier analysis showed that the curves of the ypT0N0 and ypT+N0 groups were almost identical, while they differed from the other two groups. The hazard ratio of ypN+ was 4.44 (95% confidence interval: 2.03-9.71; P<0.001). CONCLUSIONS: The prognosis of the ypT+N0 group after NAC with DCF followed by surgery was similar to that of pathological complete remission. Grouping patients according to pathological lymph node status is a reasonable predictor of prognosis.
MISC
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日本消化器外科学会雑誌 35(7) 1034-1034 2002年7月1日
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皮膚科の臨床 44(7) 769-772 2002年7月66歳女.顔面・体幹・四肢に掻痒を伴う紅斑が出現し受診した.初診時現症としてGottron徴候,爪上皮の延長,爪郭部点状出血などを認め,臨床検査でCKとLDHの上昇を認めた.皮膚生検で基底層の液状変性と真皮上層のムチン沈着を,筋生検で筋線維の大小不同や硝子様変性を認めたため皮膚筋炎と診断した.全身精査で発見されたBorrmann 3型胃癌の全摘出術後,皮膚・筋症状は速やかに消失し,CKとLDHも正常化した
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手術 56(1) 115-121 2002年1月59歳女.3年ほど前から左乳房腫瘤が徐々に増大してきたため来院し,乳房X線像,超音波検査および吸引細胞診で乳癌と診断された.便潜血反応が陽性で,注腸検査・大腸内視鏡検査にてS状結腸に3/4周性で5cm長のpolypoid lesionを認め,C型肝炎による著明な腹水を伴う肝硬変も認められた.2ヵ月後に左乳癌に対して単純乳房切除術を施行し,病理検査所見ではT4bN1M0,stage IIIb,papillotubular carcinomaと診断された.術後7ヵ月,肝機能コントロール後に再入院し,S状結腸病変の精査では病変は全周性・15cm大に増大しており,傍大動脈に著明なリンパ節腫大を認めたため開腹手術を施行した.開腹時の腫瘍の進展度から根治性は望めず,消化管穿孔や出血の危険性があること,全身状態が不良であることなどを考慮し,Hartmann術を施行した.摘出標本の病理検査所見から乳癌のS状結腸転移と考えられた.本症例は開腹術後8ヵ月に癌性胸腹膜炎で死亡した
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外科 63(7) 792-796 2001年7月通常の病理組織学的診断において診断されなかったリンパ節転移が,免疫組織学的染色や分子生物学的手法により検出されるようになり,微小転移として臨床的に注目を浴びるようになってきた.大腸癌のリンパ節転移についてみると,免疫染色,MASA法,RT-PCR法による微小転移の検出報告がなされているが,免疫染色は予後との相関が論議中であり,他の二つは意義を問うには十分な情報が得られていないのが現状である.微小転移の臨床的意義については今後さらなる検討が必要である
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外科と代謝・栄養 35(3) 130-130 2001年6月15日
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JAPANESE JOURNAL OF CANCER RESEARCH 91(8) 825-832 2000年8月Resistance to 5-fluorouracil (5-FU) has been frequently found in the treatment of digestive tract cancer patients. Our previous study suggested that high expression of endogenous Bcl-X-L, might be associated with resistance to 5-FU in colorectal cancer. The aim of this study is to analyze the role of Bcl-X-L in 5-FU resistance and to explore a new therapeutic strategy using Bcl-X-L antisense, First, western blot analysis shows that Bcl-X-L rather than Bcl-2 is overexpressed in primary adenocarcinoma of colon. Second, when Colo320 cells, with undetectable endogenous Bcl-X-L expression, were transfected with Bcl-X-L gene, they acquired high resistance to 5-FU, Finally, antisense oligodeoxynucleotides (ODNs) that targeted the start codon of Bcl-X-L mRNA (AS1) prove to be the most effective in DLD1 cells with high endogenous Bcl-X-L expression, Bcl-X-L protein expression was decreased in a dose-dependent manner when the cells mere treated with AS1 ODNs, while non sense and sense controls and 5-FU had no effect on Bcl-X-L protein. 5-FU treatment induced a level of apoptosis 10-fold higher in DLD1 cells than in untreated control cells, while the same dose of 5-FU induced a 55-fold higher level of apoptosis in DLD1 cells treated with Bcl-X-L antisense oligodeoxynucleotides (P=0.0003). Moreover, AS1 ODNs coupled with 5-FU decreased viable colon cancer cells 40% more than did 5-FU alone (P<0.05). These results suggest that Bcl-X-L is an important factor for 5-FU resistance and the suppression of Bcl-X-L expression by the specific antisense ODNs can increase the sensitivity of colon canter cells to 5-FU.
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日本消化器外科学会雑誌 33(7) 927-927 2000年7月1日
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外科と代謝・栄養 34(3) 77-77 2000年6月15日
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Jpn J Clin Oncol 30 89-94 2000年 査読有り
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BRITISH JOURNAL OF CANCER 81(8) 1274-1279 1999年12月 査読有りIt is proposed that non-steroidal anti-inflammatory drugs (NSAIDs) reduce colorectal tumorigenesis by inhibition of cyclooxygenase (COX). COX is a key enzyme in the conversion of arachidonic acid to prostaglandins and two isoforms of COX have been characterized, COX-1 and COX-2, Multiple studies have shown that COX-2 is expressed at high levels in colorectal tumours and play a role in colorectal tumorigenesis. Recently it has been reported that selective inhibition of COX-2 inhibits colon cancer cell growth. In this study we investigated the effect of a selective COX-2 inhibitor (JTE-522) on haematogenous metastasis of colon cancer. For this purpose, we selected a murine colon cancer cell line, colon-26, that constitutively expresses the COX-2 protein. The subclone P expressed a high level of COX-2 and the subclone 5 expressed a low level. The colon-26 subclones were injected into the tail vein of BALB/c mice. JTE-522 was given intraperitoneally every day from the day prior to cancer cell injection, and the mice were sacrificed 16 days after cell injection. Lung metastases were compared between groups with and without JTE-522. In the mice injected with subclone P, the number of lung metastatic nodules was significantly reduced in the treated group. However, in the mice injected with subclone 5, there was little difference between the control and the treated groups. These results indicate that there may be a direct link between inhibition of haematogenous metastasis of colon cancer and selective inhibition of COX-2, and that selective COX-2 inhibitors may be a novel class of therapeutic agents not only for colorectal tumorigenesis but also for haematogenous metastasis of colon cancer. (C) 1999 Cancer Research Campaign.
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日本外科学会雑誌 100 474-474 1999年2月10日
講演・口頭発表等
1196-
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