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Comprehensive review of hepatocellular carcinoma with portal vein tumor thrombus:State of art and future perspectives

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hepatobiliary & Pancreatic Diseases International 2024年第3期23卷 221-227页

作者： Paschalis Gavriilidis Timothy M Pawlik Daniel Azoulay Department of surgery Colchester General HospitalTurner RoadColchester CO45JLUK Department of surgery The Ohio State Wexner Medical CenterJames Comprehensive Cancer CenterColumbusOHUSA Department of hepato-biliary and liver transplantation surgery Paul Brousse University HospitalParis-Saclay UniversityVillejuif 94800France

Background:Despite advances in the diagnosis of patients with hepatocellular carcinoma(HCC),70%-80%of patients are diagnosed with advanced stage *** vein tumor thrombus(PVTT)is among the most ominous signs of advanced stage disease and has been associated with poor survival if *** sources:A systematic search of MEDLINE(PubMed),Embase,Cochrane Library and Database for Systematic Reviews(CDSR),Google Scholar,and National Institute for Health and Clinical Excellence(NICE)databases until December 2022 was conducted using free text and MeSH terms:hepatocellular carcinoma,portal vein tumor thrombus,portal vein thrombosis,vascular invasion,liver and/or hepatic resection,liver transplantation,and systematic ***:Centers of surgical excellence have reported promising results related to the individualized surgical management of portal thrombus versus arterial chemoembolization or systemic *** elements to the individualized surgical management of HCC and portal thrombus include precise classification of the portal vein tumor thrombus,accurate identification of the subgroups of patients who may benefit from resection,as well as meticulous surgical *** review addressed five specific areas:(a)formation of PVTT;(b)classifications of PVTT;(c)controversies related to clinical guidelines;(d)surgical treatments versus non-surgical approaches;and(e)characterization of surgical techniques correlated with classifications of ***:Current evidence from Chinese and Japanese high-volume centers demonstrated that patients with HCC and associated PVTT can be managed with surgical resection with acceptable results.

关键词： Hepatectomy liver surgery liver neoplasms Portal vein tumor thrombus

Routine utilization of machine perfusion in liver transplantation:Ready for prime time?

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World Journal of Gastroenterology 2024年第11期30卷 1488-1493页

作者： Alessandro Parente Keyue Sun Philipp Dutkowski AM James Shapiro Andrea Schlegel Department of surgery Division of TransplantationUniversity of Alberta HospitalEdmonton T6G 2B7Canada Immunity and Inflammation Lerner Research InstituteClevelandOH 44195United States Swiss hepato-pancreato-biliary Center Department of Visceral and Transplantation SurgeryUniversity Hospital ZurichZurich 8091Switzerland Immunity and Inflammation Digestive Disease and Surgery InstituteClevelandOH 44195United States

The last decade has been notable for increasing high-quality research and dramatic improvement in outcomes with dynamic liver *** evidence from numerous randomized controlled trials has been pooled by meta-analyses,providing the highest available evidence on the protective effect of machine perfusion(MP)over static cold storage in liver transplantation(LT).Based on a protective effect with less complications and improved graft survival,the field has seen a paradigm shift in organ *** editorial focuses on the role of MP in LT and how it could become the new“gold standard”.Strong collaborative efforts are needed to explore its effects on long-term outcomes.

关键词： liver transplantation Machine perfusion Viability assessment Hypothermic oxygenated perfusion Normothermic machine perfusion

Role of ablation therapy in conjunction with surgical resection for neuroendocrine tumors involving the liver

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World Journal of Gastrointestinal surgery 2024年第3期16卷 768-776页

作者： Alexander Ostapenko Stephanie Stroever Lud Eyasu Minha Kim Krist Aploks Xiang Da Dong Ramanathan Seshadri Department of General surgery Danbury HospitalDanburyCT 06810United States Department of Research and Innovation Nuvance HealthDanburyCT 06810United States Division of Surgical Oncology/hepato-pancreato-biliary surgery Danbury HospitalDanburyCT 06810United States

BACKGROUND Resection of hepatic metastasis from neuroendocrine tumors(NETs)improves quality of life and prolongs 5-year *** can be utilized with surgery to achieve complete *** several studies report long-term out-comes for patients undergoing ablation,none have explored perioperative effects of ablation in patients with metastatic *** To determine if intra-operative ablation during hepatectomy increases risk of ad-verse outcomes such as surgical site infections(SSIs),bleeding,and bile *** A retrospective analysis of the hepatectomy National Surgical Quality Impro-vement Program database from 2015-2019 was performed to determine the odds of SSIs,bile leaks,or bleeding in patients undergoing intraoperative ablation when compared to hepatectomy *** Of the 966 patients included in the study,298(30.9%)underwent ablation during *** were 78(11.7%)patients with SSIs in the hepatectomy alone group and 39(13.1%)patients with a SSIs in the hepatectomy with ablation *** leak occurred in 41(6.2%)and 14(4.8%)patients in the two groups,respec-tively;bleeding occurred in 117(17.5%)and 33(11.1%),*** con-trolling for confounding variables,ablation did not increase risk of SSI(P=0.63),bile leak(P=0.34)or bleeding(P=0.07)when compared to patients undergoing resection alone on multivariate *** Intraoperative ablation with hepatic resection for NETs is safe in the perioperative period without significant increased risk of infection,bleeding,or bile *** should utilize this modality when appropriate to a-chieve optimal disease control and outcomes.

关键词： Hepatectomy Neuroendocrine tumor Ablation Bile leaks Bleeding Surgical site infections

Nutrient restriction-activated Fra-2 promotes tumor progression via IGF1R in miR-15a downmodulated pancreatic ductal adenocarcinoma

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1132-1146页

作者： Gian Luca Rampioni Vinciguerra Marina Capece Luca Reggiani Bonetti Giovanni Nigita Federica Calore Sydney Rentsch Paolo Magistri Roberto Ballarin Fabrizio Di Benedetto Rosario Distefano Roberto Cirombella Andrea Vecchione Barbara Belletti Gustavo Baldassarre Francesca Lovat Carlo M.Croce Department of Cancer Biology and Genetics and Comprehensive Cancer Center The Ohio State UniversityColumbus 43210 OHUSA Department of Clinical and Molecular Medicine Faculty of Medicine and PsychologySant’Andrea HospitalUniversity of Rome“Sapienza”Rome 00189Italy Department of Diagnostic Clinic and Public Health MedicineUniversity of Modena and Reggio EmiliaModena 41100Italy hepato-pancreato-biliary surgery and liver transplantation unit University of Modena and Reggio EmiliaModena 41100Italy Division of Molecular Oncology Centro di Riferimento Oncologico di Aviano(CRO)Istituto di Ricovero e Cura a Carattere Scientifico(IRCCS)National Cancer InstituteAviano 33081Italy

Pancreatic ductal adenocarcinoma(PDAC)is a lethal disease,characterized by an intense desmoplastic reaction that compresses blood vessels and limits nutrient *** aggressiveness largely relies on its extraordinary capability to thrive and progress in a challenging tumor *** of the onco-suppressor miR-15a has been extensively documented in ***,we identified the transcription factor Fos-related antigen-2(Fra-2)as a miR-15a target mediating the adaptive mechanism of PDAC to nutrient *** report that the IGF1 signaling pathway was enhanced in nutrient deprived PDAC cells and that Fra-2 and IGF1R were significantly overexpressed in miR-15a downmodulated PDAC ***,we discovered that miR-15a repressed IGF1R expression via Fra-2 *** miR-15a-low context,IGF1R hyperactivated mTOR,modulated the autophagic flux and sustained PDAC growth in nutrient *** a genetic mouse model,Mir15aKO PDAC showed Fra-2 and Igf1r upregulation and mTOR activation in response to diet ***,nutrient restriction improved the efficacy of IGF1R inhibition in a Fra-2 dependent ***,our results point to a crucial role of Fra-2 in the cellular stress response due to nutrient restriction typical of pancreatic cancer and support IGF1R as a promising and vulnerable target in miR-15a downmodulated PDAC.

关键词： IGF1R Fra miR

Primary liver transplantation vs transplant after Kasai portoenterostomy in children with biliary atresia: A retrospective Brazilian single-center cohort

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World Journal of transplantation 2024年第1期14卷 112-119页

作者： Melina Utz Melere Valberto Sanha Marco Farina Carolina Soares da Silva Luiza Nader Cristine Trein Angelica Maria Lucchese Cristina Ferreira Antonio Nocchi Kalil Flavia Heinz Feier Department of hepatology and liver transplantation Santa Casa de Porto AlegrePorto Alegre 90050170Brazil Department of hepato-biliary-pancreatic surgery and liver transplantation Irmandade Santa Casa de Misericórdia de Porto AlegrePorto Alegre 90020-090Brazil Department of Surgical Oncology Santa Rita Hospital/Santa Casa de Misericórdia de Porto AlegrePorto Alegre 90050-170Rio Grande do SulBrazil

BACKGROUND biliary atresia(BA)is the most common indication for pediatric liver transplantation,although portoenterostomy is usually performed ***,due to the high failure rate of portoenterostomy,liver transplantation has been advocated as the primary procedure for patients with *** is still unclear if a previous portoenterostomy has a negative impact on liver transplantation *** To investigate the effect of prior portoenterostomy in infants un-dergoing liver transplantation for *** This was a retrospective cohort study of 42 pediatric patients with BA who underwent primary liver transplantation from 2013 to 2023 at a single tertiary center in *** with BA were divided into two groups:Those undergoing primary liver transplantation without portoenterostomy and those undergoing liver transplantation with prior *** variables were compared using the Student’s t-test or the Kruskal-Wallis test,and categorical variables were compared using theχ2 or Fisher’s exact test,as *** Cox regression analysis was performed to determine risk factors for portal vein *** and graft survival analyses were conducted with the Kaplan–Meier product-limit estimator,and patient subgroups were compared using the two-sided log-rank *** Forty-two patients were included in the study(25[60%]girls),23 undergoing liver transplantation without prior portoenterostomy,and 19 undergoing liver transplantation with prior *** with prior portoenterostomy were older(12 vs 8 months;P=0.02)at the time of liver transplantation and had lower Pediatric End-Stage liver Disease scores(13.2 vs 21.4;P=0.01).The majority of the patients(35/42,83%)underwent livingdonor liver *** group of patients without prior portoenterostomy appeared to have a higher incidence of portal vein thrombosis(39 vs 11%),but this result did not reach statistical *** portoenterostomy

关键词： Hepatic portoenterostomy biliary atresia liver transplantation Patient outcome assessment Portal vein Survival

Autophagy in hepatic progenitor cells modulates exosomal miRNAs to inhibit liver fibrosis in schistosomiasis

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Frontiers of Medicine 2024年第3期18卷 538-557页

作者： Yue Yuan Jiaxuan Li Xun Lu Min Chen Huifang Liang Xiao-ping Chen Xin Long Bixiang Zhang Song Gong Xiaowei Huang Jianping Zhao Qian Chen Division of Gastroenterology Department of Internal Medicine at Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Hepatic surgery Center Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Hubei Key Laboratory of hepato–pancreato–biliary Diseases Wuhan430030China Department of Trauma surgery Tongji Trauma CenterTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China

Schistosoma infection is one of the major causes of liver *** roles of hepatic progenitor cells(HPCs)in the pathogenesis of liver fibrosis have been ***,the precise mechanism underlying the role of HPCs in liver fibrosis in schistosomiasis remains *** study examined how autophagy in HPCs affects schistosomiasis-induced liver fibrosis by modulating exosomal *** activation of HPCs was verified by immunohistochemistry(IHC)and immunofluorescence(IF)staining in fibrotic liver from patients and mice with Schistosoma japonicum *** coculturing HPCs with hepatic stellate cells(HSCs)and assessing the autophagy level in HPCs by proteomic analysis and in vitro phenotypic assays,we found that impaired autophagy degradation in these activated HPCs was mediated by lysosomal *** autophagy by the autophagy inhibitor chloroquine(CQ)significantly diminished liver fibrosis and granuloma formation in ***-infected ***-secreted extracellular vehicles(EVs)were further isolated and studied by miRNA ***-1306-3p,miR-493-3p,and miR-34a-5p were identified,and their distribution into EVs was inhibited due to impaired autophagy in HPCs,which contributed to suppressing HSC *** conclusion,we showed that the altered autophagy process upon HPC activation may prevent liver fibrosis by modulating exosomal miRNA release and inhibiting HSC activation in *** the autophagy degradation process may be a therapeutic strategy for liver fibrosis during Schistosoma infection.

关键词： schistosomiasis hepatic progenitor cell autophagy extracellular vesicle fibrosis miRNA

Association of preoperative antiviral treatment with incidences of post-hepatectomy liver failure in hepatitis B virus-related hepatocellular carcinoma

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World Journal of Gastrointestinal surgery 2024年第7期16卷 2106-2118页

作者： Xiao Wang Zhao-Yi Lin You Zhou Qin Zhong Zong-Ren Li Xi-Xiang Lin Ming-Gen Hu Kun-Lun He Medical Big Data Research Center Chinese PLA General HospitalBeijing 100853China Medical School of Chinese PLA Chinese PLA General HospitalBeijing 100853China Department of hepatobiliary surgery Chinese PLA 970th HospitalYantai 264001Shandong ProvinceChina Faculty of hepato-pancreato-biliary surgery The First Medical Center of Chinese PLA General HospitalBeijing 100853China School of Medicine Nankai UniversityTianjin 300071China

BACKGROUND Post-hepatectomy liver failure(PHLF)is a common consequence of radical partial hepatectomy in hepatocellular carcinoma(HCC).AIMS To investigate the relationship between preoperative antiviral therapy and PHLF,as well as assess the potential efficacy of hepatitis B virus(HBV)DNA level in predicting *** A retrospective study was performed involving 1301 HCC patients with HBV who underwent radical *** operating characteristic(ROC)analysis was used to assess the capacity of HBV DNA to predict PHLF and establish the optimal cutoff value for subsequent *** regression analyses were performed to assess the independent risk factors of *** increase in the area under the ROC curve,categorical net reclassification improvement(NRI),and integrated discrimination improvement(IDI)were used to quantify the efficacy of HBV DNA level for predicting *** P<0.05 was considered statistically *** Logistic regression analyses showed that preoperative antiviral therapy was independently associated with a reduced risk of PHLF(P<0.05).HBV DNA level with an optimal cutoff value of 269 IU/mL(P<0.001)was an independent risk factor of *** the reference models by adding the variable of HBV DNA level had an improvement in area under the curve,categorical NRI,and IDI,particularly for the fibrosis-4 model,with values of 0.729(95%CI:0.705-0.754),1.382(95%CI:1.341-1.423),and 0.112(95%CI:0.110-0.114),*** the above findings were statistically *** In summary,preoperative antiviral treatment can reduce the incidence of PHLF,whereas an increased preoperative HBV DNA level has a correlative relationship with an increased susceptibility to PHLF.

关键词： hepatocellular carcinoma Hepatitis B virus Preoperative antiviral treatment liver resection Post-hepatectomy liver failure

Human leukocyte antigen compatibility and incidence of donorspecific antibodies in pediatric liver transplant recipients

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World Journal of Gastroenterology 2024年第33期30卷 3837-3845页

作者： Melina U Melere Flavia H Feier Jorge Neumann Antônio N Kalil Juliana de M Montagner Luiza S Nader Carolina S da Silva Marco Aurélio F Junior Gabriela P Coral Guilherme P Bobsin Cristina T Ferreira Department of hepatology and liver transplantation Santa Casa de Porto AlegrePorto Alegre 90050170Rio Grande do SulBrazil Department of hepato-biliary-pancreatic surgery and liver transplantation Irmandade Santa Casa de Misericórdia de Porto AlegrePorto Alegre 90020-090Rio Grande do SulBrazil Postgraduation Program in Medicine:hepatology Federal University of Health Sciences of Porto AlegrePorto Alegre 90050-170Rio Grande do SulBrazil Laboratory of transplantation Immunology Irmandade Santa Casa de Misericórdia de Porto AlegrePorto Alegre 90020-090Rio Grande do SulBrazil

BACKGROUND Antibody-mediated rejection following liver transplantation(LT)has been increasingly recognized,particularly with respect to the emergence of de novo donor-specific antibodies(DSAs)and their impact on graft *** substantial evidence for adult populations exists,research focusing on pediatric LT outcomes remains *** To investigate the prevalence of human leukocyte antigen(HLA)mismatches and DSA and evaluate their association with rejection episodes after pediatric *** A cohort of pediatric LT recipients underwent HLA testing at Santa Casa de Porto Alegre,Brazil,between December 2013 and December *** patients who survived for>30 days after LT with at least one DSA analysis were *** classes I and II and cross-matches were *** presence of de novo DSA(dnDSA)was evaluated at least 3 months after LT using the Luminex®single antigen bead method,with a positive reaction threshold set at 1000 *** episodes were confirmed by liver *** Overall,67 transplanted children were analyzed;61 received grafts from living donors,85%of whom were related to ***-transplant DSA(class I or II)was detected in 28.3%of patients,and dnDSA was detected in 48.4%.The median time to DSA detection after LT was 19.7[interquartile range(IQR):4.3-35.6]*** rejection occurred in 13 patients at follow-up,with C4d positivity observed in 5/13 liver *** median time to rejection was 7.8(IQR:5.7-12.8)*** presence of dnDSA was significantly associated with rejection(36%vs 3%,Ptransplantation protocols for pediatric LT *** implications may include immunosuppression minimization strategies based on this analysis in pediatric LT recip

关键词： Human leukocyte antigens Donor-specific antibodies liver transplantation Pediatric Rejection

National guidelines for the diagnosis and treatment of hilar cholangiocarcinoma

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World Journal of Gastroenterology 2024年第9期30卷 1018-1042页

作者： Faisal Saud Dar Zaigham Abbas Irfan Ahmed Muhammad Atique Usman Iqbal Aujla Muhammad Azeemuddin Zeba Aziz Abu Bakar Hafeez Bhatti Tariq Ali Bangash Amna Subhan Butt Osama Tariq Butt Abdul Wahab Dogar Javed Iqbal Farooqi Faisal Hanif Jahanzaib Haider Siraj Haider Syed Mujahid Hassan Adnan Abdul Jabbar Aman Nawaz Khan Muhammad Shoaib Khan Muhammad Yasir Khan Amer Latif Nasir Hassan Luck Ahmad Karim Malik Kamran Rashid Sohail Rashid Mohammad Salih Abdullah Saeed Amjad Salamat Ghias-un-Nabi Tayyab Aasim Yusuf Haseeb Haider Zia Ammara Naveed Department of hepatopancreatic biliary surgery&liver Transplant Pakistan Kidney and Liver Institute&Research CentreLahore 54000Pakistan Department of hepatogastroenterology and liver transplantation Dr.Ziauddin University HospitalKarachi 75600SindhPakistan University of Aberdeen Aberdeen B243FXUnited Kingdom Department of Pathology Pakistan Kidney and Liver Institute&Research CentreLahore 54000Pakistan Department of Gastroenterology&hepatology Pakistan Kidney and Liver Institute&Research CentreLahore 54000Pakistan Department of Radiology Aga Khan UniversityKarachi 74800Pakistan Department of Oncology Hameed Latif HospitalLahore 54000Pakistan Division of hepatopancreatic biliary surgery&liver transplantation Shifa International HospitalIslamabad 44000Pakistan Department of hepatopancreatic biliary surgery&liver Transplant Shaikh Zayed Hospital and Post Graduate Medical InstituteLahore 54000Pakistan Department of Medicine Aga Khan University HospitalKarachi 74800Pakistan Department of liver Transplant Pir Abdul Qadir Shah Jeelani Institute of Medical SciencesGambat 66020Pakistan Department of Medicine&Gastroenterology Lifecare Hospital and Research CentrePeshawar 25000Khyber PakhtunkhwaPakistan Department of hepatopancreatobiliary&liver Transplant Bahria International HospitalLahore 54000Pakistan Department of surgery Hepatopancreatobiliary&Liver TransplantDow University of Health SciencesKarachi 74800Pakistan Department of Gastroenterology Hepatology&NutritionPir Abdul Qadir Shah Jeelani Institute of Medical SciencesGambat 66020Pakistan Department of Oncology Dr.Ziauddin HospitalKarachi 74800Pakistan Department of Radiology Rehman Medical InstitutePeshawar 25000Pakistan Army liver Transplant unit Pak Emirates Military HospitalRawalpindi 46000Pakistan Department of Gastroenterology Sindh Institute of Urology and TransplantationKarachi 75500Pakistan Rashid Nursing Home and Cancer Clinic Rashid Nursing Home and Cancer ClinicRawalpindi 46000Pakistan Department of Gastroentero

A consensus meeting of national experts from all major national hepatobiliary centres in the country was held on May 26,2023,at the Pakistan Kidney and liver Institute&Research Centre(PKLI&RC)after initial consultations with the *** Pakistan Society for the Study of liver Diseases(PSSLD)and PKLI&RC jointly organised this *** effort was based on a comprehensive literature review to establish national practice guidelines for hilar cholangiocarcinoma(hCCA).The consensus was that hCCA is a complex disease and requires a multidisciplinary team approach to best manage these *** coordinated effort can minimise delays and give patients a chance for curative treatment and effective *** diagnostic and staging workup includes high-quality computed tomography,magnetic resonance imaging,and magnetic resonance *** cytology or biopsy utilizing endoscopic retrograde cholangiopancreatography is a mainstay for ***,histopathologic confirmation is not always required before *** ultrasound with fine needle aspiration of regional lymph nodes and positron emission tomography scan are valuable adjuncts for *** only curative treatment is the surgical resection of the biliary tree based on the Bismuth-Corlette *** patients with unresectable hCCA can be considered for liver *** chemotherapy should be offered to patients with a high risk of *** use of preoperative biliary drainage and the need for portal vein embolisation should be based on local multidisciplinary *** with acute cholangitis can be drained with endoscopic or percutaneous biliary *** chemotherapy with cisplatin and gemcitabine has shown improved survival in patients with irresectable and recurrent hCCA.

关键词： Hilar cholangiocarcinoma Bismuth-Corlette classification Memorial Sloan Kettering Cancer Centre Staging Preoperative biliary drainage Portal vein embolisation Surgical resection Hepatectomy