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Digestive oncologist in the gastroenterology training curriculum

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World Journal of gastroenterology 2011年第9期17卷 1109-1115页

作者： Chris Jacob Johan Mulder Marc Peeters Annemieke Cats Anna Dahele Jochim Terhaar sive Droste department of gastroenterology and hepatology VU University Medical Center department of Oncology Antwerp University Hospital Antwerp department of gastroenterology and hepatology Netherlands Cancer Institute

Until the late 1980s, gastroenterology (GE) was considered a subspecialty of internal Medicine. Today, GE also incorporates hepatology. However, Digestive Oncology training is poorly defined in the Hepatogastroenterology (HGE)-curriculum. Therefore, a Digestive Oncology curriculum should be developed and this document might be a starting point for such a curriculum. HGE-specialists are increasingly resisting the paradigm in which they play only a diagnostic and technical role in the management of digestive tumors. We suggest minimum endpoints in the standard HGE-curriculum for oncology, and recommend a focus year in the Netherlands for Digestive Oncology in the HGE-curriculum. To produce welltrained digestive oncologists, an advanced Digestive Oncology training program with specific qualifications in Digestive Oncology (2 years) has been developed. The schedule in Belgium includes a period of at least 6 mo to be spent in a medical oncology department. The goal ofthese programs remains the production of well-trained digestive oncologists. HGE specialists are part of the multidisciplinary oncological teams, and some have been administering chemotherapy in their countries for years. In this article, we provide a road map for the organization of a proper training in Digestive Oncology. We hope that the World gastroenterology Organisation and other (inter)national societies will support the necessary certifications for this specific training in the HGE-curriculum.

关键词： gastroenterology Training Digestive oncologist Curriculum Chemotherapy Immunotherapy Oncology Targeted therapy

Evaluation of Ultrasound-based Surveillance for Hepatocellular Carcinoma in Patients at Risk:Results From a German Multicenter Retrospective Cohort Study

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Journal of Clinical and Translational hepatology 2023年第3期11卷 626-637页

作者： Johannes Gillessen Philipp Reuken Peter-Marton Hunyady Matthias Christian Reichert Lucian Lothschütz Fabian Finkelmeier Matthias Nowka Gabriel Allo Fabian Kütting Martin Bürger Dirk Nierhoff Hans-Michael Steffen Christoph Schramm University Hospital Cologne Department of Gastroenterology and HepatologyCologneGermany University Hospital Jena Department of Internal Medicine IV-GastroenterologyHepatologyInfectious DiseaseJenaGermany University Hospital Frankfurt Department of Internal Medicine 1-Gastroenterology und HepatologyPulmonology und AllergologyEndocrinologyFrankfurtGermany department of Medicine II Saarland University Medical CenterHomburgGermany department of gastroenterology and hepatology University Hospital of EssenEssenGermany

Background and Aims:Hepatocellular carcinoma(HCC)surveillance in patients at risk is strongly recommended and usually performed by ultrasound(US)semiannually with or without alfa-fetoprotein(AFP)*** pa-rameters except for surveillance intervals have not been strictly *** aimed to evaluate surveillance success and risk factors for surveillance ***:Patients with≥1 US prior to HCC diagnosis performed at four tertiary referral hospitals in Germany between 2008 and 2019 were retrospectively *** success was defined as HCC detection within Milan ***:Only 47%of 156 patients,median age 63(interquartile range:57-70)years,56%male,and 96%with cirrhosis,received recom-mended surveillance modality and *** fail-ure occurred in 29%and was significantly associated with lower median model for end-stage liver disease(MELD)score odds ratio(OR)1.154,95%confidence interval(CI):1.027-1.297,p=0.025)and HCC localization within right liver lobe(OR:6.083,95%CI:1.303-28.407,p=0.022),but not with AFP≥200μg/*** with surveillance failure had sig-nificantly more intermediate/advanced tumor stages(93%vs.6%,p<0.001),fewer curative treatment options(15%vs.75%,p<0.001)and lower survival at 1 year(54%vs.75%,p=0.041),2 years(32%vs.57%,p=0.019)and 5 years(0%vs.16%,p=0.009).Alcoholic and non-alcoholic fatty liver disease(OR:6.1,95%CI:1.7-21.3,p=0.005)and ascites(OR:3.9,95%CI:1.2-12.6,p=0.021)were in-dependently associated with severe visual limitations on ***:US-based HCC surveillance in patients at risk frequently fails and its failure is associated with unfavorable patient-related *** MELD score and HCC lo-calization within right liver lobe were significantly associated with surveillance failure.

关键词： Hepatocellular carcinoma Surveillance success Screening Ultra-sound.

Efficacy of treatment with rebamipide for endoscopic submucosal dissection-induced ulcers

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World Journal of gastroenterology 2013年第34期19卷 5706-5712页

作者： Masaki Takayama Shigenaga Matsui Masanori Kawasaki Yutaka Asakuma Toshiharu Sakurai Hiroshi Kashida Masatoshi Kudo department of gastroenterology and hepatology Kinki University

AIM:To prospectively compare the healing rates of endoscopic submucosal dissection(ESD)-induced ulcers treated with either a proton-pump inhibitor(PPI)or ***:We examined 90 patients with early gastric cancer who had undergone *** patients were administered an intravenous infusion of the PPI lansoprazole(20 mg)every 12 h for 2 d,followed by oral administration of lansoprazole(30 mg/d,5 d).After7-d treatment,the patients were randomly assigned to 2 groups and received either lansoprazole(30 mg/d orally,n=45;PPI group)or rebamipide(300 mg orally,three times a day;n=45;rebamipide group).At 4and 8 wk after ESD,the ulcer outcomes in the 2 groups were ***:No significant differences were noted in patient age,underlying disease,tumor location,Helicobacter pylori infection rate,or ESD-induced ulcersize between the 2 *** both 4 and 8 wk,the healing rates of ESD-induced ulcers were similar in the PPI-treated and the rebamipide-treated patients(4 wk:PPI,27.2%;rebamipide,33.3%;P=0.5341;8 wk:PPI,90.9%;rebamipide,93.3%;P=0.6710).At 8 wk,the rates of granulation lesions following ulcer healing were significantly higher in the PPI-treated group(13.6%)than in the rebamipide-treated group(0.0%;P=0.0103).Ulcer-related symptoms were similar in the2 treatment groups at 8 *** medication cost of 8-wk treatment with the PPI was 10945 yen vs 4889 yen for *** ulcer bleeding or complications due to the drugs were observed in either treatment ***:The healing rate of ESD-induced ulcers was similar with rebamipide or PPI treatment;however,rebamipide treatment is more cost-effective and prevents granulation lesions following ulcer healing.

关键词： Early gastric cancer Rebamipide Endoscopic submucosal dissection Gastric ulcer Protonpump inhibitor

Transpapillary incision of refractory circumscript pancreatic duct stricture using wire-guided snare forceps

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World Journal of gastroenterology 2010年第12期16卷 1541-1544页

作者： Takao Itoi Atsushi Sofuni Fumihide Itokawa Toshio Kurihara Takayoshi Tsuchiya Kentaro Ishii Shujiro Tsuji Nobuhito Ikeuchi Fuminori Moriyasu department of gastroenterology and hepatology Tokyo Medical University

Endoscopic therapy of pancreatic duct(PD)strictures using balloon dilation and pancreatic duct stent(PS) placement has been reported to improve the severity of abdominal pain in selected patients with chronic pancreatitis(CP).However,some strictures are refractory and require frequent PS exchange to control *** describe two cases of successful endoscopic PD incision for difficult PD stricture using a wireguided *** snare is partially opened within the strictured pancreatic duct while applying current,thus incising the *** both cases were successful without complications we do not advocate that this method be used routinely because of the potential for severe complications,***,ductal perforation or pancreatic parenchymal *** order to prevent these complications,we developed a wire-guided technique under fluoroscopic *** think this procedure may be useful in patients with short,straight PD *** further study is required,this approach may have potential for selected patients with refractory PD strictures due to CP.

关键词： Chronic pancreatitis Pancreatic duct stricture Pancreatic duct incision

Branched-chain amino acid treatment before transcatheter arterial chemoembolization for hepatocellular carcinoma

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World Journal of gastroenterology 2012年第12期18卷 1379-1384页

作者： Hiroki Nishikawa Yukio Osaki Tadashi Inuzuka Haruhiko Takeda Jun Nakajima Fumihiro Matsuda Shinichiro Henmi Azusa Sakamoto Tetsuro Ishikawa Sumio Saito Ryuichi Kita Toru Kimura department of gastroenterology and hepatology Osaka Red Cross Hospital

AIM： To examine the significance of branched-chain amino acid （BCAA） treatment before transcatheter arterial chemoembolization （rACE） for hepatocellular carcinoma （HCC）.METHODS： This study included 99 patients who underwent TACE therapy for HCC at our hospital and were followed up without treatment for at least 6 mo between January 2004 and January 2010. They were divided into 2 groups： those receiving BCAA granules （/7 = 40） or regular diet （n = 59, control）. Data obtained were retrospectively analyzed （prior to TACE, and 1 wk, 1, 3, and 6 mo after TACE） in terms of nutritional condition and clinical laboratory parameters （serum albumin level and Child-Pugh score）, both of which are determinants of hepatic functional reserve.RESULTS： The BCAA group comprised 27 males and 13 females with a mean age of 69,9 ：E 8,8 years, The patients of the BCAA group were classified as follows： Child-Pugh A/B/C in 22/15/3 patients, and Stage Ⅱ/Ⅲ/ /IVA HCC in 12/23/5 patients, respectively. The controlgroup comprised 32 males and 27 females with a mean age of 73.2 ± 10.1 years. In the control group, 9 patients had chronic hepatitis, Child-Pugh A/B/C in 39/10/1 patients, and Stage Ⅰ/Ⅱ/Ⅲ/IVA HCC in 1/11/35/12 patients, respectively. Overall, both serum albumin level and Child-Pugh score improved significantly in the BCAA group as compared with the control 3 and 6 mo after TACE （P 〈 0.05）. Further analysis was performed by the following categorization：（1） child-Pugh classification; （2） liver cirrhosis subgroup with a serum albumin level 〉 3.5 g/dL; and （3） epirubicin dose. A similar trend indicating a significant improvement of all variables in the BCAA group was noted （P 〈 0.05）.CONCLUSION： Treatment with BCAA granules in patients who have undergone TACE for HCC is considered useful to maintain their hepatic functional reserve.

关键词： Hepatocellular carcinoma Branched-chainamino acid granules Transcatheter arterial chemoembo-lization Liver function Improvement Cirrhosis Protein-energy malnutrition

Drugs for Non-alcoholic Steatohepatitis (NASH): Quest for the Holy Grail

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Journal of Clinical and Translational hepatology 2021年第1期9卷 40-50页

作者： Mithun Sharma Madhumita Premkumar Anand V Kulkarni Pramod Kumar D Nageshwar Reddy Nagaraja Padaki Rao department of hepatology Asian Institute of GastroenterologyHyderabadIndia department of hepatology PGIMERChandigarhIndia department of gastroenterology Asian Institute of GastroenterologyHyderabadIndia

Nonalcoholic fatty liver disease (NAFLD) is a global epidemic that is likely to become the most common cause of chronic liver disease in the next decade, worldwide. Though numerous drugs have been evaluated in clinical trials, most of them have returned inconclusive results and shown poorly-tolerated adverse effects. None of the drugs have been approved by the Food and Drug Administration for treating biopsy-proven non-alcoholic steatohepatitis (NASH). Vitamin E and pioglitazone have been extensively used in treatment of biopsy-proven nondiabetic NASH patients. Although some amelioration of inflammation has been seen, these drugs did not improve the fibrosis component of NASH. Therefore, dietary modification and weight reduction have remained the cornerstone of treatment of NASH;moreover, they have shown to improve histological activity as well as fibrosis. The search for an ideal drug or ‘Holy Grail’ within this landscape of possible agents continues, as weight reduction is achieved only in less than 10% of patients. In this current review, we summarize the drugs for NASH which are under investigation, and we provide a critical analysis of their up-to-date results and outcomes.

关键词： Fatty liver NAFLD NASH Obeticholic acid Saroglitazar

Transcriptional silencing of Dickkopf gene family by CpG island hypermethylation in human gastrointestinal cancer

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World Journal of gastroenterology 2008年第17期14卷 2702-2714页

作者： Tadateru Maehata Hiroaki Taniguchi Hiroyuki Yamamoto Katsuhiko Nosho Yasushi Adachi Nobuki Miyamoto Chie Miyamoto Noriyuki Akutsu Satoshi Yamaoka Fumio Itoh department of gastroenterology and hepatology St. Marianna University School of Medicine First department of internal Medicine Sapporo Medical University

AIM： To clarify alterations of Dickkopfs （Dkks） and Kremen2 （Krm2） in gastrointestinal cancer. METHODS： We investigated the expression profiles and epigenetic alterations of Dkks and Krm2 genes in gastrointestinal cancer using RT-PCR, tissue microarray analysis, and methylation specific PCR （MSP）. Cancer cells were treated with the demethylating agent and/or histone deacetylase inhibitor. WST-8 assays and/n y/tro invasion assays after treatment with specific siRNA for those genes were performed. RESULTS： Dkks and Krm2 expression levels were reduced in a certain subset of the gastrointestinal cancer cell lines and cancer tissues. This was correlated with promoter hypermethylation. There were significant correlations between Dkks over-expression levels and beta-catenin over-expression in colorectal cancer. In colorectal cancers with beta-catenin over-expression, Dkk-1 expression levels were significantly lower in those with lymph node metastases than in those without. Down-regulation of Dkks expression by siRNA resulted in a significant increase in cancer cell growth and invasiveness in vitro.CONCLUSION： Down-regulation of the Dkks associated to promoter hypermethylation appears to be frequently involved in gastrointestinal tumorigenesis.

关键词： Dickkopf genes Kremen2 gene Methylation Wnt signaling Gastrointestinal cancer

Immunoregulatory Role of B7-H1 in Chronicity of Inflammatory Responses

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Cellular & Molecular Immunology 2006年第3期3卷 179-187页

作者： Haidong Dong Xianming Chen department of Immunology Division of gastroenterology and hepatology Department of Internal Medicine Mayo Clinic College of Medicine Rochester MN 55905 USA

Pathogenesis of most chronic human diseases, including chronic infections, autoimmune diseases and cancers, often involves a persistent, unresolved inflammatory response. The molecular mechanisms that determine the conversion of an acute inflammatory response into a chronic process had puzzled researchers for many years. Recent studies reveal that B7-H1 （CD274, PD-L1）, a newly identified co-stimulatory molecule, possesses dual functions of co-stimulation of naive T cells and inhibition of activated effector T cells. The aberrant cellular expression and deregulated function of B7-H1 have been reported during chronic viral and intracellular bacterial infection, as well as in many autoimmune diseases and cancers. Importantly, the deregulation of B7-H1＇s dual functions appears to be associated with a prolonged and incomplete immune response by luring naive T cells for activation and dampening activated effector T cells. Moreover, development of strategies targeting B7-H1 signals provides a new and promising approach to manipulate the devastating diseases associated with chronic inflammation. Thus, B7-H1 may play a critical immunoregulatory role in the chronicity of inflammatory responses. Cellular ＆ Molecular Immunology. 2006;3（3）：179-187.

关键词： B7-HI immune response inflammation chronization infection tumor

Nonalcoholic fatty liver disease: An overview of current insights in pathogenesis, diagnosis and treatment

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World Journal of gastroenterology 2008年第16期14卷 2474-2486页

作者： Tim CMA Schreuder Bart J Verwer Carin MJ van Nieuwkerk Chris JJ Mulder department of gastroenterology and hepatology VU University Medical Center

Estimates of people suffering from overweight (one billion) and obesity (300 million) are increasing. The accumulation of triglycerides in the liver, in the absence of excess alcohol intake, has been described in the early sixties. It was not until 1980, however, that Ludwig et al named this condition nonalcoholic steatohepatitis (NASH). Subsequently, nonalcoholic fatty liver disease (NAFLD) has been used as a general name for conditions ranging from simple steatosis through steatohepatitis to end-stage liver disease (cirrhosis). Many studies have demonstrated the significant correlation with obesity and insulin resistance. Other studies have revealed a signifi- cant correlation between hepatic steatosis, cardiovascu- lar disease and increased intima-media thickness. WHO estimated that at least two million patients will develop cirrhosis due to hepatic steatosis in the years to come. Longitudinal cohort studies have demonstrated that those patients with cirrhosis have a similar risk to devel- op hepatocellular carcinoma as those with other causes of cirrhosis. Taken all together, NAFLD has become the third most important indication for liver transplantation. There- fore, training programmes in internal medicine, gastroen- terology and hepatology should stress the importance of diagnosing this entity and treat properly those at risk for developing complications of portal hypertension and con- comittant cardiovascular disease. This review will focus on the clinical characteristics, pathophysiology, imaging tech- niques and the readily available therapeutic options.

关键词： Non-alcoholic fatty liver disease Non-alcoholicsteatohepatitis Insulin resistance Liver Obesity Steatosis