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Hyperbaric oxygenation promotes regeneration of biliary cells and improves cholestasis in rats

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World Journal of Gastroenterology 2011年第17期17卷 2229-2235页

作者： Akihito Idetsu Taketoshi Suehiro Kohji Okada Tatsuo shimura hiroyuki kuwano Department of General Surgical Science Gunma University Graduate School of Medicine 3-39-22 Showamachi Maebashi Gunma 371-8511 Japan

AIM:To investigate the effects of hyperbaric oxygenation(HBO) on regeneration of the biliary ductal system and postoperative cholestasis in hepatectomized ***:HBO was performed in Wistar rats daily starting 12 h after a 70% partial *** liver weight,serum parameters and the proliferating cell nuclear antigen labeling index of hepatocytes and biliary ductal cells were *** growth factor(HGF),c-Met and transforming growth factor(TGF) β-1 mRNA expression levels were analyzed by quantitative reverse transcription polymerase chain ***:HBO improved the postoperative serum levels of total bile acid but not transaminase *** promoted hepatocyte and biliary ductal cell *** hematoxylin and eosin-stained specimens revealed fewer ballooned hepatocytes and higher cell densities in the HBO group compared to the control *** suppressed c-Met mRNA levels at 15 h but did not modulate HGF or TGF β-1 mRNA expression levels.

关键词： Hyperbaric oxygenation Liver regeneration Partial hepatectomy Cholestasis Ballooning

Cancer-associated fibroblasts in hepatocellular carcinoma

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World Journal of Gastroenterology 2016年第30期22卷 6841-6850页

作者： Norio Kubo Kenichiro Araki hiroyuki kuwano Ken Shirabe Department of Hepatobiliary and Pancreatic Surgery Gunma University Graduate School of Medicine Department of General Surgical Science Gunma University Graduate School of Medicine

The hepatic stellate cells in the liver are stimulated sustainably by chronic injury of the hepatocytes, activating myofibroblasts, which produce abundant collagen. Myofibroblasts are the major source of extracellular proteins during fibrogenesis, and may directly, or secreted products, contribute to carcinogenesis and tumor progression. Cancer-associated fibroblasts(CAFs) are one of the components of the tumor microenvironment that promote the proliferation and invasion of cancer cells by secreting various growth factors and cytokines. CAFs crosstalk with cancer cells stimulates tumor progression by creating a favorable microenvironment for progression, invasion, and metastasis through the epithelial-mesenchymal transition. Basic studies on CAFs have advanced, and the role of CAFs in tumors has been elucidated. In particular, for hepatocellular carcinoma, carcinogenesis from cirrhosis is a known fact, and participation of CAFs in carcinogenesis is supported. In this review, we discuss the current literature on the role of CAFs and CAF-related signaling in carcinogenesis, crosstalk with cancer cells, immunosuppressive effects, angiogenesis, therapeutic targets, and resistance to chemotherapy. The role of CAFs is important in cancer initiation and progression. CAF-targeted therapy may be effective for suppression not only of fibrosis but also cancer progression.

关键词： Cancer associated fibroblast Hepatic stellate cell Hepatocellular carcinoma Immunosuppression Therapeutic target

Relationship between clinicopathological features and mucin phenotypes of advanced gastric adenocarcinoma

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World Journal of Gastroenterology 2010年第22期16卷 2764-2770页

作者： Fumiaki Toki Atsushi Takahashi Ryusuke Aihara Kyoichi Ogata hiroyuki Ando Tetsuro Ohno Erito Mochiki hiroyuki kuwano Department of General Surgical Science (Surgery I) Gunma University Graduate School of Medicine

AIM: To investigate a relationship between the clinicopathological features and mucin phenotypes in advanced gastric adenocarcinoma (AGA). METHODS: Immunohistochemical staining was performed to determine the mucin phenotypes in 38 patients with differentiated adenocarcinomas (DACs), 9 with signet-ring cell carcinomas (SIGs), and 48 with other diffuse-type adenocarcinomas (non-SIGs) of AGA. The mucin phenotypes were classified into 4 types: gastric (G), gastrointestinal (GI), intestinal, and unclassified. RESULTS: The G-related mucin phenotypes were highly expressed in all the histological subtypes of AGA. The expression of the GI phenotype in SIG patients was lower than that in DAC patients (P = 0.02), and this phenotype was observed in 56% of the non-SIG patients in the intramucosal layer. Among non-SIG cases, the expression of the GI phenotype was significantly higherin patients with extended adenocarcinomas and those with positive rates of lymph node metastasis. There was no difference between the expressions of the G and other GI phenotypes factors. Among DAC and non-SIG patients, there were no differences between the survival rates of the corresponding patient groups. CONCLUSION: The GI phenotype might possess more invasive characteristics than the G phenotype in nonSIG. Neither of the phenotypes indicated a poor prognosis of DAC and non-SIG.

关键词： Mucins Phenotype Diffuse type Undifferentiated type Gastric neoplasms Adenocarcinoma Prognosis

Extracapsular invasion as a risk factor for disease recurrence in colorectal cancer

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World Journal of Gastroenterology 2011年第15期17卷 2003-2006页

作者： Takaaki Fujii Yuichi Tabe Reina Yajima Satoru Yamaguchi Soichi Tsutsumi Takayuki Asao hiroyuki kuwano Depart ment of General Surgical Science Graduate School of Medicine Gunma University Gunma 371-8511 Japan

AIM: To evaluate the presence of extracapsular invasion (ECI) in positive nodes as a predictor of disease recurrence disease in colorectal cancer. METHODS: Two hundred and twenty-eight consecutive patients who underwent colorectal resection were identified for inclusion in this study, of which 46 had positive lymph nodes. Among 46 cases with stage Ⅲcolorectal cancer, 16 had ECI at positive nodes and 8 had disease recurrence. The clinical and pathological features of these cases were reviewed. RESULTS: In the univariate analysis, the number of positive lymph nodes and depth of tumor invasion were significantly associated with the presence of ECI at positive nodes. Multivariate analysis demonstrated that only ECI was a predictor of recurrence. The recurrence-free interval differed significantly among patients with ECI at positive ***: Our results suggest that ECI at metastatic nodes can identify which cases are at high risk of short-term disease recurrence in colorectal cancer.

关键词： Extracapsular invasion Lymph node Metastasis Colorectal cancer Risk factor Adjuvant therapy

Mechanism of gastrointestinal abnormal motor activity induced by cisplatin in conscious dogs

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World Journal of Gastroenterology 2014年第42期20卷 15691-15702页

作者： hiroyuki Ando Erito Mochiki Tetsuro Ohno Mitsuhiro Yanai Yoshitaka Toyomasu Kyoichi Ogata Yuichi Tabe Ryuusuke Aihara Toshihiro Nakabayashi Takayuki Asao hiroyuki kuwano Department of General Surgical Science Gunma University Graduate School of Medicine

AIM: To investigate whether 5-hydroxytryptamine (serotonin; 5-HT) is involved in mediating abnormal motor activity in dogs after cisplatin administration.

关键词： Cisplatin Emesis 5-hydroxytryptamine Abnormal motor activity Dog

Nuclear heat shock protein 110 expression is associated with poor prognosis and hyperthermo-chemotherapy resistance in gastric cancer patients with peritoneal metastasis

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World Journal of Gastroenterology 2017年第42期23卷 7541-7550页

作者： Akiharu Kimura Kyoichi Ogata Bolag Altan Takehiko Yokobori Erito Mochiki Mitsuhiro Yanai Norimichi Kogure Toru Yanoma Masaki Suzuki Tuya Bai hiroyuki kuwano Department of General Surgical Science Gunma University Graduate School of Medicine Department of Oncology Clinical Development Gunma University Graduate School of Medicine Department of Molecular Pharmacology and Oncology Gunma University Graduate School of Medicine Department of Digestive Tract and General Surgery Saitama Medical CenterSaitama Medical University

AIM To investigate the significance of heat shock protein 110(HSP110) in gastric cancer(GC) patients with peritoneal metastasis undergoing *** Primary GC patients(n = 14) with peritoneal metastasis or positive peritoneal lavage cytology who underwent distal or total gastrectomy between April 2000 and December 2011 were enrolled in this study. The patients underwent postoperative intraperitoneal hyperthermo-chemotherapy using a Thermotron RF-8 heating device two weeks after surgery. We analyzed nuclear HSP110 expression in surgically resected tumors using immunohistochemistry. Additionally, the effect of HSP110 suppression on hyptherthermochemosensitivity was assessed in vitro in the MKN45 GC cell line using the HSP inhibitor KNK437. RESULTS HSP110 immnohistochemical staining in 14 GC patients showed that five(35.7%) samples belonged to the low expression group, and nine(64.3%) samples belonged to the high expression group. Progression-free survival was significantly shorter in the HSP110 high-expression group than in the low-expression group(P = 0.0313). However, no significant relationships were identified between HSP110 expression and the clinicopathological characteristics of patients. Furthermore, high HSP110 expression was not an independent prognostic factor in GC patients with peritoneal metastasis(P = 0.0625). HSP110 expression in MKN45 cells was suppressed by KNK437 at the hyperthermic temperature of 43 ℃ in vitro. Comparison of MKN45 cell proliferation in the presence and absence of KNK437 at 43 ℃, revealed that proliferation was significantly decreased when HSP110 was inhibited by KNK437. Additionally, HSP110 suppression via HSP inhibitor treatment increased cellular sensitivity to hyperthermo-chemotherapy in *** The expression of nuclear HSP110 in GC patients might be a new marker of chemosensitivity and a therapeutic target for patients who are tolerant to existing hyperthermo-chemotherapies.

关键词： Peritoneal metastasis Hyperthermia Hyperthermo-chemotherapy Heat shock protein 110 Gastric cancer Drug resistance

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World Journal of Gastroenterology 2006年第11期12卷 1805-1809页

作者： Yoshimi Nakajima Hitoshi Takagi Naondo Sohara Ken Sato Satoru Kakizaki Kenichi Nomoto Hideki Suzuki Taketoshi Suehiro Tatsuo Shimura Takayuki Asao hiroyuki kuwano Masatomo Mori Ken Nishikura Department of Medicine and Molecular Science Gunma University Graduate School of Medicine MaebashiGunma 371-8511Japan Department of Surgery Gunma University Graduate School of Medicine MaebashiGunma 371-8511Japan Division of Molecular and Functional Pathology Department of Cellular Function Niigata University Graduate School of Medicine and Dental SciencesNiigataNiigata 951-8510Japan

A 42-year-old woman was admitted to our hospital because of multiple liver tumors detected by ultrasonography. Colonoscopy revealed submucosal tumor in the rectum, which was considered the primary lesion. Endoscopic mucosal resection followed by histopathological examination revealed that the tumor was carcinoid. The resected margin of the tumor was positive for malignant cells. Two courses to transcatheter arterial chemotherapy for liver metastasis were ineffective. Accordingly, the rectal tumor and metastatic lymph nodes were surgically resected. One month after the operation, she received liver transplantation （left lateral segment and caudate lobe） from her son. No recurrent lesion has been observed at two years after the liver transplantation. Liver transplantation should be considered as a treatment option even in advanced case of carcinoid metastasis to the liver. We also discuss the literature on liver transplantation for metastatic carcinoid tumor.

关键词： Carcinoid Liver metastasis Living related liver transplantation

Xanthogranulomatous cholecystitis:Difficulty in differentiating from gallbladder cancer

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World Journal of Gastroenterology 2015年第35期21卷 10166-10173页

作者： Hideki Suzuki Satoshi Wada Kenichiro Araki Norio Kubo Akira Watanabe Mariko Tsukagoshi hiroyuki kuwano Department of General Surgical Science (Surgery I) Gunma University Graduate School of Medicine Gunma University

AIM: To compare cases of xanthogranulomatous cholecystitis(XGC) and advanced gallbladder cancer and discuss the differential diagnoses and surgical ***: From April 2000 to December 2013, 6 XGC patients received extended surgical resections. During the same period, 16 patients were proven to have gallbladder(GB) cancer, according to extended surgical resection. Subjects chosen for analysis in this study were restricted to cases of XGC with indistinct borders with the liver as it is often difficult to distinguish these patients from those with advanced GB cancer. We compared the clinical features and computed tomography findings between XGC and advanced GB cancer. The following clinical features were retrospectively assessed: age, gender, symptoms, and tumor markers. As albumin and the neutrophil/lymphocyte ratio(NLR) are prognostic in several cancers, we compared serum albumin levels and the NLR between the two groups. The computerized tomography findings were used to compare the two diseases, determine the coexistence of gallstones, the pattern of GB thickening(focal or diffuse), the presence of a hypoattenuated intramural nodule, and continuity of the mucosal ***: Based on the preoperative image findings, we suspected GB carcinoma in all cases includingXGC in this series. In addition, by pathological examination, we found that the group of patients with XGC developed inflammatory disease after surgery. Patients with XGC tended to have abdominal pain(4/6, 67%). However, there was no significant difference in clinical symptoms, including fever, between the two groups. Serum albumin and NLR were also similar in the two groups. Serum tumor markers, such as carcinoembryonic antigen(CEA) and carbohydrate antigen 19-9(CA19-9), tended to increase in patients with GB cancer. However, no significant differences in tumor markers were identified. On the other hand, gallstones were more frequently observed in patients with XGC(5/6, 83%) than in patients wit

关键词： Xanthogranulomatous cholecystitis Advanced gallbla

Gastrojejunostomy for pyloric stenosis after acute gastric dilatation due to overeating

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World Journal of Gastroenterology 2015年第5期21卷 1670-1674页

作者： Akiharu Kimura Norihiro Masuda Norihiro Haga Tomokazu Ito Kichirou Otsuka Jyunko Takita Hitoshi Satomura Yuji Kumakura hiroyuki Kato hiroyuki kuwano Department of Surgery Utsunomiya National HospitalTochigi 329-1193Japan Department of General Surgical Science Gunma UniversityGraduate School of MedicineMaebashiGunma 371-8511Japan Department of Surgery I Dokkyo Medical UniversityTochigi 321-0293Japan

A 34-year-old woman presented at our hospital withabdominal distention due to *** gastric dilatation was *** patient was hospitalized,and nasogastric decompression was *** hospitalization day 3,she developed shock,and her respiratory state deteriorated,requiring intubation and mechanical *** decompression contributed to the improvement in her clinical *** was discharged 3 mo after *** outpatient follow-up,her dietary intake decreased,and her body weight gradually decreased by 14 *** upper gastrointestinal series and endoscopy revealed pyloric stenosis; therefore,we performed gastrojejunostomy 18 mo after her initial *** patient was discharged from the hospital with no postoperative *** necrosis and perforation due to overeating-induced gastric dilatation are life-threatening *** intervention may be required if delayed pyloric stenosis occurs after conservative *** report a case of pyloric stenosis due to overeating-induced gastric dilatation treated by gastrojejunostomy 18 mo after the initial presentation.

关键词： Acute gastric dilatation Bulimia Pyloric stenosis