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Trypsin in pancreatitis:The culprit,a mediator,or epiphenomenon?

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World Journal of gastroenterology 2024年第41期30卷 4417-4438页

作者： Anna S Gukovskaya Markus M Lerch Julia Mayerle Matthias Sendler Baoan Ji Ashok K Saluja Fred S Gorelick Ilya Gukovsky Department of Medicine David Geffen School of MedicineUniversity of California at Los AngelesLos AngelesCA 90073United States Department of MedicineVA Greater Los Angeles Healthcare System Los AngelesCA 90073United States Department of Medicine Ludwig Maximilian University HospitalMunich 81377Germany Department of Medicine II Ludwig Maximilian University of MunichMunich 81377Germany Department of Medicine A University of GreifswaldGreifswald 17475Germany Department of Cancer Biology Mayo ClinicJacksonvilleFL 32224United States Department of Surgery University of Miami Miller School of MedicineMiamiFL 33136United States Departments of Cell Biology and Internal Medicine Yale University School of Medicine and VA West HavenNew HavenCT 06519United States

Pancreatitis is a common,life-threatening inflammatory disease of the exocrine *** pathogenesis remains obscure,and no specific or effective treatment is *** and alcohol excess are major etiologies of pancreatitis;in a small portion of patients the disease is *** is believed to be initiated by injured acinar cells(the main exocrine pancreas cell type),leading to parenchymal necrosis and local and systemic *** primary function of these cells is to produce,store,and secrete a variety of enzymes that break down all categories of *** digestive enzymes,including all proteases,are secreted by acinar cells as inactive proforms(zymogens)and in physiological conditions are only activated when reaching the *** generation of trypsin from inactive trypsinogen in the intestine plays a critical role in physiological activation of other *** was proposed that pancreatitis results from proteolytic autodigestion of the gland,mediated by premature/inappropriate trypsinogen activation within acinar *** intra-acinar trypsinogen activation is observed in experimental models of acute and chronic pancreatitis,and in human *** the basis of these observations,it has been considered the central pathogenic mechanism of pancreatitis-a concept with a century-old *** review summarizes the data on trypsinogen activation in experimental and genetic rodent models of pancreatitis,particularly the more recent genetically engineered mouse models that mimic mutations associated with hereditary pancreatitis;analyzes the mechanisms mediating trypsinogen activation and protecting the pancreas against its’damaging effects;discusses the gaps in our knowledge,potential therapeutic approaches,and directions for future *** conclude that trypsin is not the culprit in the disease pathogenesis but,at most,a mediator of some pancreatitis ***,the search for effective therapies should

关键词： Pancreatic acinar cell Hereditary pancreatitis Autophagy Endolysosomal system Cholecystokinin Cerulein Cathepsin

Risk of hepatitis B virus reactivation in cancer patients undergoing treatment with tyrosine kinase-inhibitors

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World Journal of gastroenterology 2024年第24期30卷 3052-3058页

作者： Bansi P Savaliya Ramin Shekouhi Fatima Mubarak Harsheen K Manaise Paola Berrios Jimenez Gabrielle Kowkabany Reed A Popp Kyle Popp Emmanuel Gabriel Department of Surgery Medical Academy Named after SI Georgievsky of Vernadsky Crimean Federal UniversitySimferopol 295015CrimeaRussia Division of Plastic and Reconstructive Surgery Department of SurgeryUniversity of FloridaGainesvilleFL 32608United States Department of Surgery Aga Khan UniversityKarachi 74800SindhPakistan Department of Surgery Government Medical College and HospitalChandigarh 160030PunjabIndia Department of Surgery University of Puerto Rico School of MedicineSan Juan 00921Puerto Rico Department of Chemical and Biological Engineering University of AlabamaTuscaloosaAL 35487United States Department of Surgery University of Florida College of MedicineGainesvilleFL 32610United States Department of Surgery Florida State UniversityTallahasseeFL 32306United States Department of Surgery Mayo ClinicJacksonvilleFL 32224United States

This editorial commented on an article in the World Journal of gastroenterology titled“Risks of Reactivation of Hepatitis B Virus in Oncological Patients Using Tyrosine Kinase-Inhibitors:Case Report and Literature Analysis”by Colapietro et *** this editorial,we focused on providing a more comprehensive exploration of hepatitis B virus reactivation(HBVr)associated with the usage of tyrosine kinase inhibitors(TKIs).It includes insights into the mechanisms underlying HBV reactivation,the temporal relationship between TKIs and HBV reactivation,and preventive *** aim is to understand the need for nucleos(t)ide analogs(NAT)and serial blood tests for early recognition of reactivation and acute liver injury,along with management *** are considered to be an intermediate(1%-10%)of *** guidelines stipulate that patients receiving therapy with high or moderate risks of reactivation or recent cancer diagnosis must have at least tested hepatitis B surface antigen,anti-hepatitis B core antigen(HBc),and anti-hepatitis B surface ***-HBc screening in highly endemic areas means people with negative tests should be vaccinated against *** or nucleotide analogs(NAs)like entecavir(ETV),tenofovir disoproxil fumarate(TDF),and tenofovir alafenamide(TAF)form the basis of HBV reactivation prophylaxis and treatment during ***,lamivudine,telbivudine,and adefovir are generally discouraged due to their reduced antiviral efficacy and higher risk of fostering drug-resistant viral ***,these less effective NAs may still be utilized in cases where ETV,TDF,and TAF are not feasible treatment options.

关键词： Hepatitis B virus Reactivation Chronic hepatitis B Tyrosine-kinase inhibitor Immunomodulators Immunosuppressant Nucleoside analogue Hemato-oncology

Tumor burden score and alpha-fetoprotein level predict prognosis of patients with unresectable hepatocellular carcinoma treated with tyrosine kinase inhibitor and anti-PD-1 antibody

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iLIVER 2024年第3期3卷 22-31页

作者： Shichuan Tang Tingfeng Huang Cong Luo Jun Fu Kailing Zhang Qingjing Chen Jie Kong Jianxi Zhang Zhenghong Sun Yongkang Diao Kongying Lin Yongyi Zeng Department of Hepatobiliary Surgery Mengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhou 350025China Department of Hepatopancreatobiliary Surgery Wanyuan Central HospitalWanyuan 636350China Department of Hepatopancreatobiliary Surgery Zizhong County People's HospitalZizhong 641200China Department of gastroenterology Wenjiang District People's HospitalChengdu 611100China Department of Hepatobiliary Heze Municipal HospitalHeze 274000China Department of Hepatobiliary Surgery Xiamen Hospital of Traditional Chinese MedicineXiamen 361000China Department of General Surgery Guizhou Maotai HospitalZunyi 564500China Department of Hepatobiliary Surgery Eastern Hepatobiliary Surgery HospitalNavy Medical University(Second Military Medical University)Shanghai 200082China The Liver Disease Research Center of Fujian Province Fuzhou 350025China

Background:Tyrosine kinase inhibitors(TKIs)and anti-PD-1 antibodies in combination provide survival benefits for patients with unresectable hepatocellular carcinoma(uHCC).However,the tool used to determine which patients likely benefit most from this treatment strategy has not been *** sought to develop a prognostic scoring system based on tumor burden score(TBS)and alpha-fetoprotein(AFP)to predict the long-term prognosis of uHCC treated with TKIs and anti-PD-1 ***:Data on patients with uHCC treated with TKIs and anti-PD-1 antibodies from multiple centers were *** prognostic accuracy of TBS,AFP,Barcelona clinic Liver Cancer(BCLC),and CTA(Combined TBS and AFP)for 2-year progression-free survival(PFS)and overall survival(OS)was ***:Overall,278 patients with uHCC treated with TKIs and anti-PD-1 antibodies were enrolled,including 48 BCLC-B and 230 BCLC-C HCC ***(AUC?0.721 and 0.683)outperformed TBS(AUC?0.680 and 0.621),AFP(AUC?0.606 and 0.594),and BCLC staging(AUC?0.551 and 0.555)in predicting PFS and *** 2-year PFS and OS for low CTA(low TBS/low AFP)were 65.7%and 94.4%,respectively,which were significantly higher than 21.6%and 44.9%(p<0.001 and p?0.002),respectively,for intermediate CTA(low TBS/high AFP or high TBS/low AFP)and 8.7%and 12.1%(both p<0.001),respectively,for high CTA(high TBS/high AFP).Multivariable Cox regression analysis indicated that CTA grading was an independent prognostic factor for PFS and OS(referent:low CTA;intermediate CTA,HR 2.87 and 7.17;high CTA,HR 5.52 and 10.31,respectively).Conclusions:CTA grading is an accurate tool for stratifying the prognosis of uHCC treated with TKIs and anti-PD-1 antibodies and may help determine which patients may benefit more from this treatment strategy.

关键词： Hepatocellular carcinoma Tyrosine kinase inhibitor Anti-PD-1 antibody Tumor burden score Alpha-fetoprotein

与肠功能失调相关的肛门失禁亚型:临床、生理及社会心理方面的特征

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世界核心医学期刊文摘（胃肠病学分册） 2005年第4期1卷 19-20页

作者： Crowell M.D. Lacy B.E. Schettler V.A. 樊菁 Gastrointest. Physiol. and Motility Div. of Gastroenterol. and Hepatol. Mayo Clinic Scottsdale 13400 E. Shea Blvd. Scottsdale AZ 85259 United StatesDr.

BACKGROUND: We hypothesized that functional anal incontinence with no structur al explanation comprises distinct pathophysiologic subgroups that could be ident ified on the basis of the predominant presenting bowel pattern. METHODS: Consecu tive patients (n = 80) were prospectively grouped by bowel symptoms as 1) incont inence only, 2) incontinence +constipation, 3) incontinence +diarrhea, and 4) incontinence +alternating bowel symptoms. The Hopkins Bowel Symptom Questionnai re, the Symptom Checklist 90-R, and anorectal manometry were completed. RESULTS : Significant group differences were found between subcategories of incontinent patients on the basis of symptoms. Abdominal pain was more frequent in patients with altered bowel patterns. Patients with alternating symptoms reported the hig hest prevalence of abdominal pain, rectal pain, and bloating. Basal anal pressur es were significantly higher in alternating patients (P = 0.03). Contractile pre ssures in the distal anal canal were diminished in the incontinent only and dia rrhea groups (P = 0.004). Constipated patients with incontinence exhibited eleva ted thresholds for the urge to defecate (P = 0.027). Dyssynergia was significant ly more frequent in patients with incontinence and constipation or alternating b owel patterns. CONCLUSIONS: Distinct patterns of pelvic floor dysfunction were i dentified in patient subgroups with anal incontinence, based on the presence or absence of altered bowel patterns. Physiologic assessments suggested different p athophysiologic mechanisms among the subgroups. The evaluation of patients with fecal incontinence should consider altered bowel function.

关键词：肛门失禁功能失调肠道症状社会心理肛门直肠测压交替性便时盆底功能直肠痛腹胀症状

Prevalence and Factors Associated with Hepatic Steatosis in Patients with Metabolic Syndrome in Cameroon: Cases of 4 Reference Hospitals

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Open Journal of gastroenterology 2023年第3期13卷 99-110页

作者： Winnie Tatiana Bekolo Nga Martine Claude Etoa Bidjogo Gwet Marina Servais A. F. Eloumou Bagnaka Antonin Wilson Ndjitoyap Ndam Agnès Malongue Mathurin Kowo Christian Tzeuton Dominique Noah Noah Oudou Njoya Firmin Ankouane Andoulo Luma H. Namme Department of Internal Medicine General Hospital of Douala Douala Cameroon Faculty of Medicine and Pharmaceutical Sciences University of Douala Douala Cameroon National Obesity Centre Central Hospital of Yaoundé Yaoundé Cameroon Faculty of Medicine and Biomedical Sciences University of Yaoundé I Yaoundé Cameroon Department of Internal Medicine Gynecologic and Pediatric Hospital of Douala Douala Cameroon Department of Internal Medicine Teaching Hospital of Yaoundé Yaoundé Cameroon clinic of Capucines Douala Cameroon

Introduction: Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease worldwide and its prevalence increases with that of metabolic syndrome and its components. NAFLD is associated with complications such as cirrhosis and hepatocellular carcinoma. Diagnosis is mainly based on liver biopsy, but there are validated non-invasive methods. The purpose of the study was to assess the impact of metabolic steatopathy in patients with metabolic syndrome in Cameroon. Methods: This was a cross-sectional and analytical study conducted over a 6-month period from January 1st, 2019, to August 31st, 2022. Included were patients with metabolic syndrome who had consulted in endocrinology or gastroenterology at Yaoundé Central Hospital, Douala General Hospital and Douala Gyneco-obstetric and Pediatric Hospital. The diagnosis of NAFLD was made on abdominal ultrasound in front of a homogeneous or heterogeneous hyperechogenic aspect of the hepatic parenchyma compared to that of the right renal cortex called “brilliant liver” and fibrosis evaluated through non-invasive scores (Fib4 and NALFD Fibrosis score). Logistic regression by a uni- and multivariate analysis made it possible to search for the associated factors. Results. We included 133 patients. The female sex represented 64.7%. The mean age was 55 ± 9 years. The prevalence of NAFLD was 48.9%. At the evaluation of fibrosis was significant according to FIB-4 and NAFLD fibrosis score respectively in 6.2% and 4.6% of cases. The independently associated factors were Triglyceridemia ≤ 1.5 g/l (OR = 0.33;95% CI [0.11 - 0.95];p = 0.04) and LDL hypercholesterolemia (OR = 2.94;95% CI [1.07 - 8.11];p = 0.036). Conclusion: NAFLD was present in almost half of patients with metabolic syndrome. We had very few patients with significant fibrosis, but it needs to be further evaluated. The associated factors are hypertriglyceridemia and LDL hypercholesterolemia.

关键词： Hepatic Steatosis Metabolic Syndrome Prevalence Cameroon

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脂肪性肝病的肝移植

胃肠病学 2011年第3期16卷 149-149页

作者： John FUNG 王园园钱本余 Cleveland clinic ClevelandOhioUSA

随着肥胖症发病率在美国乃至全球的持续上升，非酒精性脂肪性肝病（NAFLD）和非酒精性脂肪性肝炎（NASH）的诊断日益增多，并被认为是终末期肝病（ESLD）的病因之一。

关键词：非酒精性脂肪性肝病肝移植非酒精性脂肪性肝炎终末期肝病发病率肥胖症

Comparison of patients with hepatitis B virus-associated hepatocellular carcinoma:Data from two hospitals from Turkey and China

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Portal Hypertension & Cirrhosis 2023年第4期2卷 165-170页

作者： Brian I.Carr Fajuan Rui Volkan Ince Sezai Yilmaz Xinya Zhao Yuemin Feng Jie Li Liver Transplantation Institute Inonu UniversityMalatyaTurkey Department of Infectious Diseases Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese MedicineNanjingJiangsuChina Department of Radiology Shandong Provincial Hospital Affiliated to Shandong UniversityJinanShandongChina Department of gastroenterology Shandong Provincial Hospital Affiliated to Shandong UniversityJinanShandongChina Department of Infectious Diseases Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjingJiangsuChina

Aims:There are many studies on the incidence of hepatitis B virus(HBV)-associated hepatocellular carcinoma(HCC),but very little is known about the HCC features in different *** study aimed to compare characteristics in two cohorts of patients with HBV-associated hepatocellular carcinoma from Turkey and ***:Data on patients with HBV-associated HCC diagnosed by imaging or liver biopsy were retrospectively collected from Shandong Provincial Hospital(n=578)and Inonu University Hospital(n=359)between January 2002 and December 2020,and the liver function and HCC characteristics were *** variables were compared using Student's t-test or Mann-Whitney U test and categorical variables were compared using the χ^(2) test or Fisher's exact ***:The patients in the Turkish cohort had significantly worse Child-Pugh scores(Child-Pugh A:38.3%vs.87.9%;Child-Pugh B:40.3%vs.11.1%;Child-Pugh C:21.4%vs.1.0%;pclinic Liver Cancer(BCLC)score(BCLC 1:5.1%vs.71.8%;BCLC 2:48.7%vs.24.4%;BCLC 3:24.4%vs.3.8%;BCLC 4:21.8%vs.0;all pclinical characteristics than patients from the Chinese cohort.

关键词： China Hepatocellular Carcinoma Turkey

Splenic-vasculature involvement is associated with poor prognosis in resected distal pancreatic cancer

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gastroenterology Report 2021年第2期9卷 139-145,I0002页

作者： Feng Yin Mohammed Saad Jingmei Lin Christopher R.Jackson Bing Ren Cynthia Lawson Dipti M.Karamchandani Belen Quereda Bernabeu Wei Jiang Teena Dhir Richard Zheng Christopher W.Schultz Dongwei Zhang Courtney L.Thomas Xuchen Zhang Jinping Lai Michael Schild Xuefeng Zhang Hao Xie Xiuli Liu Department of Pathology and Anatomical Sciences University of MissouriColumbiaMOUSA Department of Pathology Indiana UniversityIndianapolisINUSA Department of Pathology Dartmouth-Hitchcock Medical CenterLebanonNHUSA Department of Pathology Pennsylvania State Health Milton S.Hershey Medical CenterHersheyPAUSA Department of Pathology Thomas Jefferson University HospitalPhiladelphiaPAUSA Department of Pathology and Laboratory Medicine University of Rochester Medical CenterRochesterNYUSA Department of Pathology Yale UniversityNew HavenCTUSA Department of Pathology and Laboratory Medicine Kaiser Permanente Sacramento Medical CenterSacramentoCAUSA Department of Pathology Duke UniversityDurhamNCUSA Department of Pathology Cleveland ClinicClevelandOHUSA Department of Gastrointestinal Oncology Moffitt Cancer CenterTampaFLUSA Department of Pathology Immunology and Lab MedicineUniversity of FloridaGainesvilleFLUSA

Background Distal pancreatic carcinoma is one of the most lethal cancers largely due to its high incidence of distant *** study aims to assess the prognostic value of splenic-vasculature involvement in resected distal pancreatic *** In this retrospective study,we collected the clinicopathologic information of 454 patients with pancreatic cancer and performed univariate and multivariate analyses to identify factors associated with progression-free survival(PFS)and overall survival(OS),with an emphasis on the prognostic value of splenic-artery and-vein *** Univariate analysis revealed that larger tumor size,non-intraductal papillary mucinous neoplasm(non-IPMN)-associated adenocarcinoma,poor differentiation,stage pT3,nodal metastasis,lymphovascular invasion,perineural invasion,and pathologic and radiographic evidence of splenic-vein invasion were significantly associated with shorter PFS and OS(all P<0.05).Multivariate analysis confirmed non-IPMN-associated adenocarcinoma,stage pT3,stage pN1-2,and postoperative adjuvant chemotherapy as independent risk factors for both PFS and OS,and larger tumor size and radiographic evidence of splenic-artery invasion as predictors of PFS *** Guidelines should be developed for a uniform approach with regard to the examination and reporting of the status of the splenic vasculature when dealing with distal-pancreatic-cancer specimens.

关键词： pancreatic cancer splenic artery splenic vein prognosis intraductal papillary mucinous neoplasm

Apolipoprotein E polymorphism influences orthotopic liver transplantation outcomes in patients with hepatitis C virus-induced liver cirrhosis

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World Journal of gastroenterology 2021年第11期27卷 1064-1075页

作者： José Carlos Rodrigues Nascimento Lianna C Pereira Juliana Magalhães C Rêgo Ronaldo P Dias Paulo Goberlânio B Silva Silvio Alencar C Sobrinho Gustavo R Coelho Ivelise Regina C Brasil Edmilson F Oliveira-Filho James S Owen Pierluigi Toniutto Reinaldo B Oriá Department of Anesthesia and Surgery Liver Transplantation Fortaleza General HospitalFortaleza 60150-160CEBrazil Laboratory of the Biology of Tissue Healing Ontogeny and NutritionDepartment of Morphology and Institute of BiomedicineSchool of MedicineFederal University of CearáFortaleza 60430-270CEBrazil Department of Dental clinic Federal University of CearáFortaleza 60430-270CEBrazil Department of Surgery Liver Transplant Unit of Federal University of CearáFortaleza 60430-270CEBrazil Transplantation Division Hospital Geral de FortalezaFortaleza 60175-742CEBrazil Institute of Virology CharitéUniversitätsmedizin BerlinBerlin 10117Germany UCL Medical School Royal Free CampusLondon NW32PFUnited Kingdom Department of Specialized Medicine Hepatology Liver Transplantation UnitAzienda Sanitaria Universitaria Integrata of UdineUdine I-33100Italy

BACKGROUND Hepatitis C virus(HCV)infection is responsible for a chronic liver inflammation,which may cause end-stage liver disease and hepatocellular *** E(protein:ApoE,gene:APOE),a key player in cholesterol metabolism,is mainly synthesized in the liver and APOE polymorphisms may influence HCV-induced liver *** To determine whether APOE alleles affect outcomes in HCV-infected patients with liver cirrhosis following orthotopic liver transplantation(OLT).METHODS This was a cohort study in which 179 patients,both genders and aged 34-70 years,were included before or after(up to 10 years follow-up)*** injury severity was assessed using different criteria,including METAVIR and models for endstage liver *** polymorphisms were analyzed by quantitative real-time polymerase chain *** The APOE3 allele was the most common(67.3%).In inflammation severity of biopsies from 89 OLT explants and 2 patients in pre-transplant,the degree of severe inflammation(A3F4,0.0%)was significantly less frequent than in patients with minimal and moderate degree of inflammation(≤A2F4,16.2%)P=0.048,in patients carrying the APOE4 allele when compared to *** addition,a significant difference was also found(≤A2F4,64.4%vs A3F4,0.0%;P=0.043)and(A1F4,57.4%vs A3F4,0.0%;P=0.024)in APOE4 patients when compared to APOE3 *** fibrosis degree of the liver graft in 8 of 91 patients and the lack of the E4 allele was associated with more moderate fibrosis(F2)(P=0.006).CONCLUSION Our results suggest that the E4 allele protects against progression of liver fibrosis and degree of inflammation in HCV-infected patients.

关键词： Apolipoprotein E Polymorphism Liver cirrhosis Hepatitis C virus Hepatocellular carcinoma Liver transplantation