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World Journal of Gastroenterology 2014年第10期20卷 2606-2612页

作者： satoshi yamagiwa Hiroteru Kamimura Masaaki Takamura Yutaka Aoyagi Division of Gastroenterology and Hepatology Niigata University Graduate School of Medical and Dental Sciences Niigata 951-8510 Japan

Primary biliary cirrhosis(PBC)is a chronic progressive cholestatic liver disease characterized by immunemediated destruction of the small-and medium-sized intrahepatic bile ducts and the presence of antimitochondrial antibodies(AMA)in the *** are detected in over 90%of patients with PBC,whereas their prevalence in the general population is extremely low,varying from 0.16%to 1%.Previous studies have shown that the unique characteristics of biliary epithelial cells undergoing apoptosis may result in a highly direct and very specific immune response to mitochondrial ***,recent studies have demonstrated that serum from AMA-positive PBC patients is reactive with a number of xenobiotic modified E2 subunits of the pyruvate dehydrogenase complex,which is not observed in the serum of normal *** findings indicate that chemicals originating from the environment may be associated with a breakdown in the tolerance to mitochondrial *** it is currently generally accepted that AMA are the most specific serological markers of PBC,more than 60 au-toantibodies have been investigated in patients with PBC,and some have previously been considered specific to other autoimmune *** review covers the recent progress in research on the pathogenetic and clinical significance of important autoantibodies in *** the pathogenic role of those autoantibodies in PBC remains a priority of basic and clinical research.

关键词： Primary biliary cirrhosis Autoantibodies Anti-mitochondrial antibodies Anticentromere antibodies Anti-gp210 antibodies

Spontaneous regression of hepatocellular carcinoma: A mini-review

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World Journal of Gastroenterology 2017年第21期23卷 3797-3804页

作者： Akira Sakamaki Kenya Kamimura satoshi Abe Atsunori Tsuchiya Masaaki Takamura Hirokazu Kawai satoshi yamagiwa Shuji Terai Division of Gastroenterology and Hepatology Graduate School of Medical and Dental Sciences Niigata University

Spontaneous tumor regression is an extremely rare phenomenon in the oncology field. However, there are several case reports resulted in the regression of hepatocellular carcinoma(HCC) and the accumulation of clinical information and analyses of the mechanism can contribute to the development of a novel therapy. For this purpose, we have carefully reviewed 23 cases of spontaneously regressed HCC published in recent 5 years and our case. The information regarding the tumor size, tumor marker, treatments, etc., have been summarized. The mechanism of spontaneous regression has been discussed to date and presumed to be due to many factors, including hypoxia and immunological reactions. In this careful review of the 24 cases based on the clinical information, hypoxia, systemic inflammation, and both upon spontaneous regression were seen in 3, 8, and 4 cases, respectively amo ng t he 15 c as e s f or w hic h t he inf o r mat io n regarding the proposed mechanisms are available. Recent development of immunotherapeutic approaches in oncology shows promising results, therefore, accumulation of additional cases and analysis of mechanisms underlying the spontaneous regression of HCC are essential and could lead to the development of a new generation of immunotherapies including antibodies directed against immune reactions.

关键词： Spontaneous regression Hepatocellular carcinoma Immunological reaction Immunotherapy Hypoxia

Diversion colitis and pouchitis: A mini-review

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World Journal of Gastroenterology 2018年第16期24卷 1734-1747页

作者： Kentaro Tominaga Kenya Kamimura Kazuya Takahashi Junji Yokoyama satoshi yamagiwa Shuji Terai Division of Gastroenterology and Hepatology Graduate School of Medical and Dental Sciences Niigata University

Diversion colitis is characterized by inflammation of the mucosa in the defunctioned segment of the colon after colostomy or ileostomy. Similar to diversion colitis, diversion pouchitis is an inflammatory disorder occurring in the ileal pouch, resulting from the exclusion of the fecal stream and a subsequent lack of nutrients from luminal bacteria. Although the vast majority of patients with surgically-diverted gastrointestinal tracts remain asymptomatic, it has been reported that diversion colitis and pouchitis might occur in almost all patients with diversion. Surgical closure of the stoma, with reestablishment of gut continuity, is the only curative intervention available for patients with diversion disease. Pharmacologic treatments using short-chain fatty acids, mesalamine, or corticosteroids are reportedly effective for those who are not candidates for surgical reestablishment; however, there are no established assessment criteria for determining the severity of diversion colitis, and no management strategies to date. Therefore, in this mini-review, we summarize and review various recently-reported treatments for diversion disease. We are hopeful that the information summarized here will assist physicians who treat patients with diversion colitis and pouchitis, leading to better case management.

关键词： Diversion colitis Diversion pouchitis Ileitis Inflammatory bowel disease

Effect of double platinum agents, combination of miriplatintransarterial oily chemoembolization and cisplatinhepatic arterial infusion chemotherapy, in patients with hepatocellular carcinoma: Report of two cases

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World Journal of Clinical Cases 2017年第6期5卷 238-246页

作者： Kohei Ogawa Kenya Kamimura Yukari Watanabe Yosuke Motai Daisuke Kumaki Ryoya Seki Akira Sakamaki satoshi Abe Hirokazu Kawai Takeshi Suda satoshi yamagiwa Shuji Terai Division of Gastroenterology and Hepatology Graduate School of Medical and Dental Sciences Niigata University Department of Gastroenterology and Hepatology Uonuma Institute of Community Medicine Niigata Medical and Dental Hospital

Hepatocellular carcinoma(HCC) is one of the most common cancers and the third highest cause of cancerassociated mortality worldwide. The treatment of HCC is complicated by its variable biological behavior and the frequent coexistence of chronic liver disease, particularly cirrhosis. To date, multiple treatment modalities have been developed according to the stage of the tumor and the hepatic functional reserve, including transarterial treatments such as transarterial chemoembolization, transarterial oily chemoembolization(TOCE), and hepatic arterial infusion chemotherapy(HAIC). We conducted a phase I and II study of the combination therapy with double platinum agents, miriplatin and cisplatin, and confirmed its safety and efficacy. Here, we describe two cases of unresectable HCC who were successfully treated by miriplatin-TOCE/cisplatin-HAIC combination therapy, resulting in complete responses with no significant adverse events. This report will provide that the combination therapy can be the therapeutic option for HCC patients in the advanced stage.

关键词： Hepatocellular carcinoma Double platinum Transarterial oily chemoembolization Hepatic arterial infusion chemotherapy Combination

Shear wave velocity is a useful marker for managing nonalcoholic steatohepatitis

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World Journal of Gastroenterology 2010年第23期16卷 2918-2925页

作者： Akihiko Osaki Tomoyuki Kubota Takeshi Suda Masato Igarashi Keisuke Nagasaki Atsunori Tsuchiya Masahiko Yano Yasushi Tamura Masaaki Takamura Hirokazu Kawai satoshi yamagiwa Toru Kikuchi Minoru Nomoto Yutaka Aoyagi Department of Gastroenterology and Hepatology Graduate School of Medical and Dental SciencesNiigata University Department of Homeostatic Regulation and Development Graduate School of Medical and Dental SciencesNiigata University Department of Laboratory Medicine Niigata University Medical and Dental Hospital

AIM:To investigate whether a noninvasive measurement of tissue strain has a potential usefulness for management of nonalcoholic steatohepatitis(NASH).METHODS:In total 26 patients,23 NASHs and 3 normal controls were enrolled in this *** was staged based on Brunt *** a region of interest(ROI),a shear wave was evoked by implementing an acoustic radiation force impulse(ARFI),and the propagation velocity was quantif ***:Shear wave velocity(SWV) could be reproducibly quantified at all ROIs in all subjects except for 4 NASH cases,in which a reliable SWV value was not calculated at several *** average SWV of 1.34 ± 0.26 m/s in fibrous stage 0-1 was significantly slower than 2.20 ± 0.74 m/s and 2.90 ± 1.01 m/s in stages 3 and 4,respectively,but was not significantly different from 1.79 ± 0.78 m/s in stage *** a cutoff value was set at 1.47 m/s,receiver operating characteristic analysis showed significance to dissociate stages 3 and 4 from stage 0-1(P=0.0092) with sensitivity,specificity and area under curve of 100%,75% and 94.2%,*** addition,the correlation between SWV and hyaluronic acid was significant(P<0.0001),while a tendency toward negative correlation was observed with serum albumin(P=0.053).CONCLUSION:The clinical implementation of ARFI provides noninvasive repeated evaluations of liver stiffness at an arbitrary position,which has the potential to shed new light on NASH management.

关键词： Nonalcoholic steatohepatitis Ultrasound Liver stiffness measurement Shear wave velocity Acoustic radiation force impulse

Efficacy and safety of telaprevir- and simeprevir-based triple therapies for older patients with chronic hepatitis C

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World Journal of Hepatology 2017年第5期9卷 252-262页

作者： satoshi yamagiwa Toru Ishikawa Nobuo Waguri Soichi Sugitani Hiroto Wakabayashi Shogo Ohkoshi Takashi Tsukishiro Toru Takahashi Toshiaki Watanabe Shuji Terai Division of Gastroenterology and Hepatology Niigata University Graduate School of Medical and Dental Sciences Department of Gastroenterology and Hepatology Saiseikai Niigata Daini Hospital Department of Gastroenterology and Hepatology Niigata City General Hospital Department of Gastroenterology and Hepatology Tachikawa General Hospital Department of Gastroenterology and Hepatology Takeda General Hospital Department of Internal Medicine Nippon Dental University Medical Hospital Department of Internal Medicine Itoigawa General Hospital Department of Internal Medicine Uonuma Hospital Watanabe Clinic

AIMTo evaluate and compare the efficacy and safety of telaprevir (TVR)-and simeprevir (SMV)-based triple therapies in elderly patients, specifically patients aged 66 years or older. METHODSThe present study enrolled 112 and 76 Japanese patients with chronic hepatitis C virus genotype 1b infection who were treated with a 12-wk TVR-based or SMV-based triple therapy, respectively, followed by a dual therapy that included pegylated interferon α and ribavirin (RBV) for 12 wk. The patients were categorized into two groups according to age as follows: A younger group of patients aged ≤ 65 years old and an older group of patients aged > 65 years old. Among the patients treated with TVR-based triple therapy, 34 patients were included in the older group. The median ages were 56 years (range: 28-65 years) in the younger group and 69 years (range: 66-81 years) in the older group. Among the patients treated with SMV-based triple therapy, 39 patients were included in the older group. The median ages were 59 years (range: 36-65 years) in the younger group and 71 years (range: 66-86 years) in the older group. The clinical, biochemical and virological data were analyzed before and during treatment. RESULTSAmong the patients treated with the TVR-based triple therapy, no significant difference in the sustained virological response (SVR) was found between the younger (80.8%) and older (88.2%) groups. The SVR rates for patients with the interleukin 28B (IL28B) (rs8099917) TG/GG-genotypes (73.9% and 60.0% in the younger and older groups, respectively) were significantly lower than for patients with the IL28B TT-genotype (86.3% and 92.9%, respectively). The cumulative exposure to RBV for the entire 24-wk treatment period (as a percentage of the target dose) was significantly higher in the younger group than in the older group (91.7% vs 66.7%, respectively, P vs 81.9%, respectively). A multivariate analysis identified the TT-genotype of IL28B (OR = 8.160; 95%CI: 1.593-41.804, P = 0.012) an

关键词： Telaprevir Aged patients Hepatitis C virus genotype 1b Interleukin 28B Simeprevir

Factors predicting aggressiveness of non-hypervascular hepatic nodules detected on hepatobiliary phase of gadolinium ethoxybenzyl diethylene-triamine-pentaacetic-acid magnetic resonance imaging

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World Journal of Gastroenterology 2015年第15期21卷 4583-4591页

作者： Tsutomu Kanefuji Toru Takano Takeshi Suda Kouhei Akazawa Takeshi Yokoo Hiroteru Kamimura Kenya Kamimura Atsunori Tsuchiya Masaaki Takamura Hirokazu Kawai satoshi yamagiwa Hidefumi Aoyama Minoru Nomoto Shuji Terai Deparatment of Gastro-enterology and Hepatology Uonuma Institute of Community Medicine Niigata University Medical and Dental Hospital 4132 Urasa Minami--Uonuma Department of Radiation Oncology Graduate School of Medical and Dental Sciences Niigata University Niigata Department of Medical Informatics Graduate School of Medical and Dental Sciences Niigata University Niigata Department of Gastroenterology and Hepatology Graduate School of Medical and Dental Sciences Niigata University Niigata

AIM: To establish a prognostic formula that distinguishes non-hypervascular hepatic nodules(NHNs) with higher aggressiveness from less hazardous one. METHODS: Seventy-three NHNs were detected in gadolinium ethoxybenzyl diethylene-triamine-pentaaceticacid magnetic resonance imaging(Gd-EOB-DTPA-MRI) study and confirmed to change 2 mm or more in size and/or to gain hypervascularity. All images were interpreted independently by an experienced, board-certified abdominal radiologist and hepatologist; both knew thatthe patients were at risk for hepatocellular carcinoma development but were blinded to the clinical information. A formula predicting NHN destiny was developed using a generalized estimating equation model with thirteen explanatory variables: age, gender, background liver diseases, Child-Pugh class, NHN diameter, T1-weighted imaging/T2-weighted imaging detectability, fat deposition, lower signal intensity in arterial phase, lower signal intensity in equilibrium phase, α-fetoprotein, des-γ-carboxy prothrombin, α-fetoprotein-L3, and coexistence of classical hepatocellular carcinoma. The accuracy of the formula was validated in bootstrap samples that were created by resampling of 1000 iterations. RESULTS: During a median follow-up period of 504 d, 73 NHNs with a median diameter of 9 mm(interquartile range: 8-12 mm) grew or shrank by 68.5%(fifty nodules) or 20.5%(fifteen nodules), respectively, whereas hypervascularity developed in 38.4%(twenty eight nodules). In the fifteen shrank nodules, twelve nodules disappeared, while 11.0%(eight nodules) were stable in size but acquired vascularity. A generalized estimating equation analysis selected five explanatories from the thirteen variables as significant factors to predict NHN progression. The estimated regression coefficients were 0.36 for age, 6.51 for lower signal intensity in arterial phase, 8.70 or 6.03 for positivity of hepatitis B virus or hepatitis C virus, 9.37 for des-γ-carboxy prothrombin, and-4.05 for fat d

关键词： Hepatocellular carcinoma Magnetic resonanceimaging Ethoxybenzyl moiety Non-hypervascular hepaticnodule Fate prediction

Multicentric occurrence of hepatocellular carcinoma with nonalcoholic steatohepatitis

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World Journal of Hepatology 2011年第1期3卷 15-23页

作者： Hirokazu Kawai Minoru Nomoto Takeshi Suda Kenya Kamimura Atsunori Tsuchiya Yasushi Tamura Masahiko Yano Masaaki Takamura Masato Igarashi Toshifumi Wakai satoshi yamagiwa Yasunobu Matsuda Shogo Ohkoshi Isao Kurosaki Yoshio Shirai Masahiko Okada Yutaka Aoyagi Department of Clinical Laboratory Niigata University Medical and Dental Hospital Division of Gastroenterology and Hepatology Niigata University Graduate School of Medical and Dental Sciences Division of Digestive and General Surgery Niigata University Graduate School of Medical and Dental Sciences Department of Medical Technology Niigata University Graduate School of Health Sciences Division of Preventive Medicine Niigata University Graduate School of Medical and Dental Sciences

AIM:To reveal the manner of hepatocellular carcinoma (HCC) development in patients with nonalcoholic steatohepatitis(NASH) focusing on multicentric occurrence (MO) of ***:We compared clinicopathological characteristics between patients with and without MO of HCC arising from NASH *** clinical features were implicated with reference to the literature ***:MO of HCC was identified with histological proof in 4 out of 12 patients with NASH-related HCC(2 males and 2 females).One patient had synchronous MO;an advanced HCC,two well-differentiated HCCs and a dysplastic nodule,followed by the development of metachronous MO of *** other three patients had multiple advanced HCCs accompanied by a well-differentiated HCC or a dysplastic *** these three patients,one had synchronous MO,one had metachronous MO and the other had both synchronous and metachronous *** were no obvious differences between the patients with or without MO in terms of liver function tests,tumor markers and anatomical extent of *** the other hand,all four patients with MO of HCC were older than 70 years old and had the comorbidities of obesity,type 2 diabetes mellitus(T2DM),hypertension and *** these conditions were not limited to MO of HCC,all the conditions were met in only one of eight patients without MO of ***,concurrence of these conditions may be a predisposing situation to synchronous MO of *** particular,old age,T2DM and cirrhosis were suggested to be prerequisite for MO because these factors were depicted in common among two other cases with MO of HCC under NASH in the ***:The putative predisposing factors and necessary preconditions for synchronous MO of HCC in NASH were suggested in this *** investigations are required to clarify the accurate prevalence and predictors of MO to establish better strategies for treatment and prevention leading to the prognostic improvement in NASH.

关键词： Nonalcoholic steatohepatitis Hepatocellular carcinoma Multicentric occurrence

Endoscopic ultrasound-guided fine-needle aspiration for diagnosing a rare extraluminal duodenal gastrointestinal tumor

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World Journal of Gastrointestinal Endoscopy 2017年第12期9卷 583-589页

作者： Kazunao Hayashi Kenya Kamimura Kazunori Hosaka satoshi Ikarashi Junji Kohisa Kazuya Takahashi Kentaro Tominaga Kenichi Mizuno Satoru Hashimoto Junji Yokoyama satoshi yamagiwa Kazuyasu Takizawa Toshifumi Wakai Hajime Umezu Shuji Terai Division of Gastroenterology and Hepatology Graduate School of Medical and Dental Sciences Niigata University Division of Digestive and General Surgery Graduate School of Medical and Dental Sciences Niigata University Department of Pathology Niigata University Medical and Dental Hospital

Duodenal gastrointestinal stromal tumors(GISTs) are extremely rare disease entities, and the extraluminal type is difficult to diagnose. These tumors have been misdiagnosed as pancreatic tumors; hence, pancreaticoduodenectomy has been performed, although partial duodenectomy can be performed if accurately diagnosed. Developing a diagnostic methodology including endoscopic ultrasonography(EUS) and fine-needle aspiration(FNA) has allowed us to diagnose the tumor directly through the duodenum. Here, we present a case of a 50-year-old woman with a 27-mm diameter tumor in the pancreatic uncus on computed tomography scan. EUS showed a well-defined hypoechoic mass in the pancreatic uncus that connected to the duodenal proper muscular layer and was followed by endoscopic ultrasoundguided fine-needle aspiration(EUS-FNA). Histological examination showed spindle-shaped tumor cells positively stained for c-kit. Based on these findings, the tumor was finally diagnosed as a duodenal GIST of the extraluminal type, and the patient underwent successful mass resection with partial resection of the duodenum. This case suggests that EUS and EUS-FNA are effective for diagnosing the extraluminal type of duodenal GISTs, which is difficult to differentiate from pancreatic head tumor, and for performing the correct surgical procedure.

关键词： Gastrointestinal stromal tumor Duodenum Extraluminal type Pancreatic head tumor Endoscopic ultrasonography Endoscopic ultrasound-guided fineneedle aspiration Partial resection

Active treatments are a rational approach for hepatocellular carcinoma in elderly patients

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World Journal of Gastroenterology 2013年第24期19卷 3831-3840页

作者： Takeshi Suda Aiko Nagashima Shyunsaku Takahash Tsutomu Kanefuji Kenya Kamimura Yasushi Tamura Ma-saaki Takamura Masato Igarashi Hirokazu Kawai satoshi yamagiwa Minoru Nomoto Yutaka Aoyagi Division of Gastroenterology and Hepatology Graduate School of Medical and Dental Sciences Niigata University

AIM: To determine whether an active intervention is beneficial for the survival of elderly patients with hepa-tocellular carcinoma (HCC). METHODS: The survival of 740 patients who received various treatments for HCC between 1983 and 2011 was compared among different age groups using Cox regression analysis. Therapeutic options were principal-ly selected according to the clinical practice guidelines for HCC from the Japanese Society of Hepatology. The treatment most likely to achieve regional control capa-bility was chosen, as far as possible, in the following order: resection, radiofrequency ablation, percutaneous ethanol injection, transcatheter arterial chemoembo-lization, transarterial oily chemoembolization, hepatic arterial infusion chemotherapy, systemic chemotherapy including molecular targeting, or best supportive *** treatment was used alone, or in combination, with a clinical goal of striking the best balance be-tween functional hepatic reserve and the volume of the targeted area, irrespective of their age. The percent survival to life expectancy was calculated based on a Japanese national population survey. RESULTS: The median ages of the subjects during each 5-year period from 1986 were 61, 64, 67, 68 and 71 years and increased significantly with time (P<0.0001). The Child-Pugh score was comparable among younger (59 years of age or younger), middle-aged (60-79 years of age), and older (80 years of age or older) groups (P=0.34), whereas the tumor-node-metastasis stage tended to be more advanced in the younger group (P=0.060). Advanced disease was significantly more frequent in the younger group compared with the middle-aged group (P=0.010), whereas there was no difference between the middle-aged and elderly groups (P=0.75). The median sur-vival times were 2593, 2011, 1643, 1278 and 1195 d for 49 years of age or younger, 50-59 years of age, 60-69 years of age, 70-79 years of age, or 80 years of age or older age groups, respectively, whereas the me-di

关键词： Hepatocellular carcinoma Population ag-ing Survival Life expectancy Active intervention