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High yield reproducible rat model recapitulating human Barrett's carcinogenesis

World Journal of Gastroenterology 2017年第33期23卷 6077-6087页

作者： Daisuke Matsui Ashten N Omstead Juliann E Kosovec Yoshihiro Komatsu Emily J Lloyd Hailey Raphael Ronan J Kelly Ali H Zaidi Blair A Jobe esophageal and Lung Institute Allegheny Health Network department of gastroenterological surgery Kanazawa University Hospital department of Oncology Sidney Kimmel Comprehensive Cancer CenterJohns Hopkins Hospital

AIM To efficiently replicate the biology and pathogenesis of human esophageal adenocarcinoma(EAC) using the modified Levrat model of end-to-side esophagojejunostomy. METHODS End-to-side esophagojejunostomy was performed on rats to induce gastroduodenoesophageal reflux to develop EAC. Animals were randomly selected and serially euthanized at 10(n = 6),17(n = 8),24(n = 9),31(n = 6),38(n = 6),and 40(n = 6) wk postoperatively. The esophagi were harvested for downstream histopathology and gene expression. Histological evaluation wascompleted to determine respective rates of carcinogenic development. Quantitative reverse transcriptionpolymerase chain reaction was performed to determine gene expression levels of MUC2,CK19,and CK20,and results were compared to determine significant differences throughout disease progression *** The overall study mortality was 15%. Causes of mortality included anastomotic leak,gastrointestinal hemorrhage,stomach ulcer perforation,respiratory infection secondary to aspiration,and obstruction due to tumor or late anastomotic stricture. 10 wk following surgery,100% of animals presented with esophagitis. Barrett's esophagus(BE) was first observed at 10 wk,and was present in 100% of animals by 17 wk. Dysplasia was confirmed in 87.5% of animals at 17 wk,and increased to 100% by 31 wk. EAC was first observed in 44.4% of animals at 24 wk and increased to 100% by 40 wk. In addition,two animals at 38-40 wk post-surgery had confirmed macro-metastases in the lung/liver and small intestine,respectively. MUC2 gene expression was progressively down-regulated from BE to dysplasia to EAC. Both CK19 and CK20 gene expression significantly increased in a stepwise manner from esophagitis to EAC. CONCLUSION Esophagojejunostomy was successfully replicated in rats with low mortality and a high tumor burden,which may facilitate broader adoption to study EAC development,progression,and therapeutics.

关键词： esophageal adenocarcinoma gastroeso phageal reflux disease Levrat Esophagojejunostomy Experimental rat model Mucin genes Cytokeratins

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Optimizing management of pancreaticopleural fistulas

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World Journal of Gastroenterology 2011年第42期17卷 4696-4703页

作者： Marek Wronski Maciej Slodkowski Wlodzimierz Cebulski Daniel Moronczyk Ireneusz W Krasnodebski department of General Gastroenterological and Oncological SurgeryMedical University of Warsaw

AIM:To evaluate the management of pancreaticopleural fistulas involving early endoscopic instrumentation of the pancreatic ***:Eight patients with a spontaneous pancre-aticopleural fistula underwent endoscopic retrograde cholang iopancreatography(ERCP) with an intentionto stent the site of a ductal disruption as the primarytreatment. Imaging features and management were evaluated retrospectively and compared with ***:In one case,the stent bridged the site of aductal disruption. The fistula in this patient closed with in3 wk. The main pancreatic duct in this case appearednormal,except for a leak located in the body of the pancreas. In another patient,the papilla of Vater couldnot be found and cannulation of the pancreatic ductfailed. This patient underwent surgical treatment. In the remaining 6 cases,it was impossible to insert a stentinto the main pancreatic duct properly so as to coverthe site of leakage or traverse a stenosis situated down-stream to the fistula. The placement of the stent failed because intraductal stones(n = 2) and ductal strictures(n = 2) precluded its passage or the stent was too short to reach the fistula located in the distal part of the pancreas(n = 2) . In 3 out of these 6 patients,the pancre-aticopleural fistula closed on further medical *** these cases,the main pancreatic duct was normalor only mildly dilated,and there was a leakage at the body/tail of the pancreas. In one of these 3 patients,additional percutaneous drainage of the peripancre atic fluid collections allowed better control of the leakageand facilitated resolution of the fistula. The remaining3 patients had a tight stenosis of the main pancreatic duct resistible to dilatation and the stent could not beinserted across the stenosis. Subsequent conservative treatment proved unsuccessful in these patients. Aftera failed the rapeutic ERCP,3 patients in our series developed superinfection of the pleural or peripancreatic fluid collections. Four out of

关键词： Pancreaticopleural fistula Pancreatitis surgery Endoscopic retrograde cholangiopancreatography Magnetic resonance cholangiopancreatography

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Long-lasting discussion: Adverse effects of intraoperative blood loss and allogeneic transfusion on prognosis of patients with gastric cancer

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World Journal of Gastroenterology 2019年第22期25卷 2743-2751页

作者： Koki Nakanishi Mitsuro Kanda Yasuhiro Kodera department of gastroenterological surgery(surgery Ⅱ) Nagoya University Graduate School of Medicine

Gastrectomy with radical lymph node dissection is the most promising treatment avenue for patients with gastric cancer. However, this procedure sometimes induces excessive intraoperative blood loss and requires perioperative allogeneic blood transfusion. There are lasting discussions and controversies about whether intraoperative blood loss or perioperative blood transfusion has adverse effects on the prognosis in patients with gastric cancer. We reviewed laboratory and clinical evidence of these associations in patients with gastric cancer. A large amount of clinical evidence supports the correlation between excessive intraoperative blood loss and adverse effects on the prognosis. The laboratory evidence revealed three possible causes of such adverse effects: anti-tumor immunosuppression, unfavorable postoperative conditions, and peritoneal recurrence by spillage of cancer cells into the pelvis. Several systematic reviews and meta-analyses have suggested the adverse effects of perioperative blood transfusions on prognostic parameters such as all-cause mortality, recurrence, and postoperative complications. There are two possible causes of adverse effects of blood transfusions on the prognosis: Anti-tumor immunosuppression and patient-related confounding factors (e.g., preoperative anemia). These factors are associated with a worse prognosis and higher requirement for perioperative blood transfusions. Surgeons should make efforts to minimize intraoperative blood loss and transfusions during gastric cancer surgery to improve patients’ prognosis.

关键词： Gastric cancer Blood loss Prognosis Transfusion Adverse effect Immunosuppression Mortality Recurrence Complication

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Hemosuccus pancreaticus: Problems and pitfalls in diagnosis and treatment

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World Journal of Gastroenterology 2008年第17期14卷 2776-2779页

作者： Yoshikazu Toyoki Kenichi Hakamada Shunji Narumi Masaki Nara Keinosuke Ishido Mutsuo Sasaki department of gastroenterological surgery Hirosaki University School of Medicine

Hemosuccus pancreaticus is a rare cause of intermittent upper gastrointestinal bleeding. We report two cases of hemosuccus pancreaticus with multiple episodes of upper gastrointestinal bleeding. The causes of hemorrhage were rupture of pseudoaneurysm of the splenic artery and bleeding from the wall of pancreatic pseudocyst. Interventional radiology is the first modality for early diagnosis and possible treatment of hemosuccus pancreaticus. When angiography shows no abnormal findings or interventional radiological therapy can not be successful, surgery should be considered without delay. Our patients herein underwent surgery without recurrence or sequelae. Intraoperative ultrasonography and pancreatoscopy were helpful modalities for confirming the source of hemorrhage and determining the cutting line of the pancreas. When we encounter intermittent upper gastrointestinal bleeding with an obscure source, hemosuccus pancreaticus should be included in differential diagnoses especially in patients with chronic pancreatitis, which would lead to a prompt and proper treatment.

关键词： Hernosuccus pancreaticus Gastrointestinalbleeding Interventional radiology Intraoperativesonography Intraoperative pancreatoscopy

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Genetic and epigenetic aspects of initiation and progression of hepatocellular carcinoma

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World Journal of Gastroenterology 2015年第37期21卷 10584-10597页

作者： Mitsuro Kanda Hiroyuki Sugimoto Yasuhiro Kodera department of gastroenterological surgery (surgery Ⅱ) Nagoya University Graduate School of Medicine

Hepatocellular carcinoma(HCC) is a primary cancer of the liver that is predominant in developing countries and is responsible for nearly 600000 deaths each year worldwide. Similar to many other tumors, the development of HCC must be understood as a multistep process involving the accumulation of genetic and epigenetic alterations in regulatory genes, leading to the activation of oncogenes and the inactivation or loss of tumor suppressor genes. Extensive research over the past decade has identified a number of molecular biomarkers, including aberrant expression of HCCrelated genes and microRNAs. The challenge facing HCC research and clinical care at this time is to address the heterogeneity and complexity of these genetic and epigenetic alterations and to use this information to direct rational diagnosis and treatment strategies. The multikinase inhibitor sorafenib was the first molecularly targeted drug for HCC to show some extent of survival benefits in patients with advanced tumors. Although the results obtained using sorafenib support the importance of molecular therapies in the treatment of HCC, there is still room for improvement. In addition,no molecular markers for drug sensitivity, recurrence and prognosis are currently clinically available. In this review, we provide an overview of recently published articles addressing HCC-related genes and microRNAs to update what is currently known regarding genetic and epigenetic aspects of the pathogenesis of HCC and propose novel promising candidates for use as diagnostic and therapeutic targets in HCC.

关键词： Hepatocellular carcinoma Oncogene Tumor suppressor

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Clinicopathological features of alpha-fetoprotein producing early gastric cancer with enteroblastic differentiation

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World Journal of Gastroenterology 2016年第36期22卷 8203-8210页

作者： Kohei Matsumoto Hiroya Ueyama Kenshi Matsumoto Yoichi Akazawa Hiroyuki Komori Tsutomu Takeda Takashi Murakami Daisuke Asaoka Mariko Hojo Natsumi Tomita Akihito Nagahara Yoshiaki Kajiyama Takashi Yao Sumio Watanabe department of Gastroenterology Juntendo University School of Medicine department of esophageal and gastroenterological surgery Juntendo University School of Medicine department of Gastroenterology Juntendo University Shizuoka Hospital department of Pathology Juntendo University School of Medicine

AIM To investigate clinicopathological features of early stage gastric cancer with enteroblastic differentiation(GCED).METHODS We retrospectively investigated data on 6 cases of early stage GCED and 186 cases of early stage conventional gastric cancer(CGC: well or moderately differentiated adenocarcinoma) who underwent endoscopic submucosal dissection or endoscopic mucosal resection from September 2011 to February 2015 in our *** was defined as a tumor having a primitive intestine-like structure composed of cuboidal or columnar cells with clear cytoplasm and immunohistochemical positivity for either alpha-fetoprotein, Glypican 3 or SALL4. The following were compared between GCED and CGC: age, gender, location and size of tumor, macroscopic type, ulceration, depth of invasion, lymphatic and venous invasion, positive horizontal and vertical margin, curative resection *** Six cases(5 males, 1 female; mean age 75.7 years; 6 lesions) of early gastric cancer with a GCED component and 186 cases(139 males, 47 females; mean age 72.7 years; 209 lesions) of early stage CGC were investigated. Mean tumor diameters were similar but rates of submucosal invasion, lymphatic invasion, venous invasion, and non-curative resection were higher in GCED than CGC(66.6% vs 11.4%, 33.3% vs 2.3%, 66.6% vs 0.4%, 83.3% vs 11% respectively, P < 0.01). Deep submucosal invasion was not revealed endoscopically or by preoperative biopsy. Histologically, in GCED the superficial mucosal layer was covered with a CGC component. The GCED component tended to exist in the deeper part of the mucosa to the submucosa by lymphatic and/or venous invasion, without severe stromal reaction. In addition, Glypican 3 was the most sensitive marker for GCED(positivity, 83.3%), *** Even in the early stage GCED has high malignant potential, and preoperative diagnosis is considered difficult. Endoscopists and pathologists should know the clinicopathological features of this h

关键词： Alpha-fetoprotein-producing gastric cancer Gastric cancer with enteroblastic differentiation Early gastric cancer Glypican 3 SALL4

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Conservative reconstruction using stents as salvage therapy for disruption of esophago-gastric anastomosis

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World Journal of Gastroenterology 2015年第28期21卷 8723-8729页

作者： Taro Oshikiri Yoshinobu Yamamoto Ikuya Miki Masahiro Tsuda Tetsu Nakamura Yasuhiro Fujino Masahiro Tominaga Yoshihiro Kakeji department of gastroenterological surgery Hyogo Cancer Center department of gastroenterological Oncology Hyogo Cancer Center Division of Gastrointestinal surgery Department of Surgery Graduate School of MedicineKobe University

Esophagectomy with extended lymphadenectomy and gastric conduit reconstruction is a radical procedure for the treatment of esophageal cancer that is associated with a high morbidity *** conduit necrosis is a fatal complication that occurs in 2%of ***,two-stage salvage surgery consisting of removal of the necrotic gastric conduit followed by reconstruction has been performed;however,this procedure has a high morbidity *** describe a61-year-old man who underwent minimally invasive esophagectomy complicated by slowly progressive gastric conduit necrosis associated with complete neck drainage and a stable overall *** was a 2 cm gap in the *** there was no evidence of residual gastric conduit necrosis,a removable,covered self-expanding metal stent(SEMS)was inserted to bridge the *** stent was fixed to the patient's ear with silk thread through the lasso on its proximal end to prevent *** weeks after insertion,the stent was removed easily without any associated *** anastomotic defect was completely bridged with granulation tissue,showing progressive epithelialization without leakage or *** patient was discharged home in good general *** is the first report of the successful conservative management of esophago-gastric conduit anastomosis disruption with SEMS placement.

关键词： Esophagectomy Gastric conduit necrosis Disruption of anastomosis Self-expanding metal stent Hanarostent Conservative management

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Gastric cancer arising from the remnant stomach after distal gastrectomy:A review

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World Journal of Gastroenterology 2014年第38期20卷 13734-13740页

作者： Shinsuke Takeno Tatsuya Hashimoto Kenji Maki Ryosuke Shibata Hironari Shiwaku Ippei Yamana Risako Yamashita Yuichi Yamashita department of gastroenterological surgery Fukuoka University Faculty of Medicine

Gastric stump carcinoma was initially reported by Balfore in 1922,and many reports of this disease have since been published. We herein review previous reports of gastric stump carcinoma with respect to epidemiology,carcinogenesis,Helicobacter pylori(H. pylori) infection,Epstein-Barr virus infection,clinicopathologic characteristics and endoscopic treatment. In particular,it is noteworthy that no prognostic differences are observed between gastric stump carcinoma and primary upper third gastric cancer. In addition,endoscopic submucosal dissection has recently been used to treat gastric stump carcinoma in the early stage. In contrast,many issues concerning gastric stump carcinoma remain to be clarified,including molecular biological characteristics and the carcinogenesis of *** *** herein review the previous pertinent literature and summarize the characteristics of gastric stump carcinoma reported to date.

关键词： Remnant gastric cancer Distal gastrectomy Carcinogenesis Helicobacter pylori Endoscopic submucosal dissection

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Novel diagnostics for aggravating pancreatic fistulas at the acute phase after pancreatectomy

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World Journal of Gastroenterology 2014年第26期20卷 8535-8544页

作者： Mitsuro Ka Tsutomu Fujii Hideki Takami Masaya Suenaga Yoshikuni Inokawa Suguru Yamada Daisuke Kobayashi Chie Tanaka Hiroyuki Sugimoto Masahiko Koike Shuji Nomoto Michitaka Fujiwara Yasuhiro Kodera department of gastroenterological surgery (surgery Ⅱ) Nagoya University Graduate School of Medicine

AIM: To identify sensitive predictors of clinically relevant postoperative pancreatic fistula (POPF) at the acute phase after pancreatectomy.

关键词： Pancreatectomy Pancreatic fistula Prediction Inflammatory marker C-reactive protein

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Des-gamma-carboxy prothrombin as an important prognostic indicator in patients with small hepatocellular carcinoma

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World Journal of Gastroenterology 2008年第9期14卷 1370-1377页

作者： Kenichi Hakamada Norihisa Kimura Takuya Miura Hajime Morohashi Keinosuke Ishido Masaki Nara Yoshikazu Toyoki Shunji Narumi Mutsuo Sasaki department of gastroenterological surgery Hirosaki University Graduate School of MedicineJapan

AIM:To clarify the effect of a high des-gamma-carboxy prothrombin (DCP) level on the invasiveness and prognosis of small hepatocellular carcinoma. METHODS: Among 142 consecutive patients with known DCP levels, who underwent hepatectomy because of hepatocellular carcinoma, 85 patients met the criteria for small hepatocellular carcinoma, i.e. one ≤ 5 cm sized single tumor or no more than three ≤ 3 cm sized tumors. RESULTS: The overall survival rate of the 142 patients was 92.1% for 1 year, 69.6% for 3 years, and 56.9% for 5 years. Multivariate analysis showed that microscopic vascular invasion (P = 0.03) and serum DCP ≥ 400 mAU/mL (P = 0.02) were independent prognostic factors. In the group of patients who met the criteria for small hepatocellular carcinoma, DCP ≥ 400 mAU/mL was found to be an independent prognostic factor for recurrence-free (P = 0.02) and overall survival (P = 0.0005). In patients who did not meet the criteria, the presence of vascular invasion was an independent factor for recurrence-free (P = 0.02) and overall survivals (P = 0.01). In 75% of patients with small hepatocellular carcinoma and high DCP levels, recurrence occurred extrahepatically. CONCLUSION: For small hepatocellular carcinoma, a high preoperative DCP level appears indicative fortumor recurrence. Because many patients with a high preoperative DCP level develop extrahepatic recurrence, it is necessary to screen the whole body.

关键词： Small hepatocellular carcinoma Hepatic resection Des-gamma-carboxy prothrombin Vascular invasion Prognostic factor

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