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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 disease.Portal vein tumor thrombus(PVTT)is among the most ominous signs of advanced stage disease and has been associated with poor survival if untreated.Data 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 review.Results:Centers of surgical excellence have reported promising results related to the individualized surgical management of portal thrombus versus arterial chemoembolization or systemic chemotherapy.Critical 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 technique.This 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 PVTT.Conclusions: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

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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 preservation.Robust 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 preservation.This 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

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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 survival.Ablation can be utilized with surgery to achieve complete resection.Although several studies report long-term out-comes for patients undergoing ablation,none have explored perioperative effects of ablation in patients with metastatic NETs.AIM To determine if intra-operative ablation during hepatectomy increases risk of ad-verse outcomes such as surgical site infections(SSIs),bleeding,and bile leak.METHODS 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 alone.RESULTS Of the 966 patients included in the study,298(30.9%)underwent ablation during hepatectomy.There 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 group.Bile 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%),respectively.After 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 analysis.CONCLUSION Intraoperative ablation with hepatic resection for NETs is safe in the perioperative period without significant increased risk of infection,bleeding,or bile leak.Surgeons 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

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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 supplies.PDAC aggressiveness largely relies on its extraordinary capability to thrive and progress in a challenging tumor microenvironment.Dysregulation of the onco-suppressor miR-15a has been extensively documented in PDAC.Here,we identified the transcription factor Fos-related antigen-2(Fra-2)as a miR-15a target mediating the adaptive mechanism of PDAC to nutrient deprivation.We 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 patients.Mechanistically,we discovered that miR-15a repressed IGF1R expression via Fra-2 targeting.In miR-15a-low context,IGF1R hyperactivated mTOR,modulated the autophagic flux and sustained PDAC growth in nutrient deprivation.In a genetic mouse model,Mir15aKO PDAC showed Fra-2 and Igf1r upregulation and mTOR activation in response to diet restriction.Consistently,nutrient restriction improved the efficacy of IGF1R inhibition in a Fra-2 dependent manner.Overall,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

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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 first.However,due to the high failure rate of portoenterostomy,liver transplantation has been advocated as the primary procedure for patients with BA.It is still unclear if a previous portoenterostomy has a negative impact on liver transplantation outcomes.AIM To investigate the effect of prior portoenterostomy in infants un-dergoing liver transplantation for BA.METHODS 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 Brazil.Patients with BA were divided into two groups:Those undergoing primary liver transplantation without portoenterostomy and those undergoing liver transplantation with prior portoenterostomy.Continuous 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 appropriate.Multivariable Cox regression analysis was performed to determine risk factors for portal vein thrombosis.Patient and graft survival analyses were conducted with the Kaplan–Meier product-limit estimator,and patient subgroups were compared using the two-sided log-rank test.RESULTS 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 portoenterostomy.Patients 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 transplantation.The 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 significance.Prior portoenterostomy was not a protective factor against portal vein

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

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Current interventional options for palliative care for patients with advanced-stage cholangiocarcinoma

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World Journal of Clinical Oncology 2024年第3期15卷 381-390页

作者： Maryam Makki Malak Bentaleb Mohammed Abdulrahman Amal Abdulla Suhool Salem Al Harthi Marcelo AF Ribeiro Jr Department of surgery Division of TraumaCritical Care and Acute Care SurgerySheikh Shakhbout Medical CityAbu Dhabi 11001United Arab Emirates Department of surgery College of Medicine and Health SciencesKhalifa UniversityAbu Dhabi 11001United Arab Emirates Department of surgery Division of Hepato-Pancreato-Biliary(HPB)SurgerySheikh Shakhbout Medical CityAbu Dhabi 91888United Arab Emirates

Primary biliary tract tumors are malignancies that originate in the liver,bile ducts,or gallbladder.These tumors often present with jaundice of unknown etiology,leading to delayed diagnosis and advanced disease.Currently,several palliative treatment options are available for primary biliary tract tumors.They include percutaneous transhepatic biliary drainage(PTBD),biliary stenting,and surgical interventions such as biliary diversion.Systemic therapy is also commonly used for the palliative treatment of primary biliary tract tumors.It involves the administration of chemotherapy drugs,such as gemcitabine and cisplatin,which have shown promising results in improving overall survival in patients with advanced biliary tract tumors.PTBD is another palliative treatment option for patients with unresectable or inoperable malignant biliary obstruction.biliary stenting can also be used as a palliative treatment option to alleviate symptoms in patients with unresectable or inoperable malignant biliary obstruction.Surgical interventions,such as biliary diversion,have traditionally been used as palliative options for primary biliary tract tumors.However,biliary diversion only provides temporary relief and does not remove the tumor.Primary biliary tract tumors often present in advanced stages,making palliative treatment the primary option for improving the quality of life of patients.

关键词： Cholangiocarcinoma Palliative care Endoscopic treatment surgery Complications Interventional radiology

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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 experts.The Pakistan Society for the Study of liver Diseases(PSSLD)and PKLI&RC jointly organised this meeting.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 patients.This coordinated effort can minimise delays and give patients a chance for curative treatment and effective palliation.The diagnostic and staging workup includes high-quality computed tomography,magnetic resonance imaging,and magnetic resonance cholangiopancreato-graphy.Brush cytology or biopsy utilizing endoscopic retrograde cholangiopancreatography is a mainstay for diagnosis.However,histopathologic confirmation is not always required before resection.Endoscopic ultrasound with fine needle aspiration of regional lymph nodes and positron emission tomography scan are valuable adjuncts for staging.The only curative treatment is the surgical resection of the biliary tree based on the Bismuth-Corlette classification.Selected patients with unresectable hCCA can be considered for liver transplantation.Adjuvant chemotherapy should be offered to patients with a high risk of recurrence.The use of preoperative biliary drainage and the need for portal vein embolisation should be based on local multidisciplinary discussions.Patients with acute cholangitis can be drained with endoscopic or percutaneous biliary drainage.Palliative 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

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Current status of liver transplantation for human immunodeficiency virus-infected patients in China's Mainland

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World Journal of Gastroenterology 2024年第14期30卷 1958-1962页

作者： Jian-Xin Tang Dong Zhao Department of liver surgery and Organ transplantation Center Shenzhen Third People’s HospitalThe Second Affiliated Hospital of Southern University of Science and TechnologyNational Clinical Research Center for Infectious DiseaseShenzhen 518000Guangdong ProvinceChina

According to the report from the Chinese Center for Disease Control and Prevention,the prevalence of human immunodeficiency virus(HIV)infection exceeded 1.2 million individuals by the year 2022,with an annual increase of about 80000 cases.The overall prevalence of hepatitis B surface antigen among individuals co-infected with HIV reached 13.7%,almost twice the rate of the general population in China.In addition to the well-documented susceptibility to opportunistic infections and new malignancies,HIV infected patients frequently experience liver-related organ damage,with the liver and kidneys being the most commonly affected.This often leads to the development of end-stage liver and kidney diseases.Therefore,organ transplantation has emerged as an important part of active treatment for HIV infected patients.However,the curative effect is not satisfactory.HIV infection has been considered a contraindication for organ transplantation.Until the emergence of highly active anti-retroviral therapy in 1996,the once intractable replication of retrovirus was effectively inhibited.With prolonged survival,the failure of important organs has become the main cause of death among HIV patients.Therefore,transplant centers worldwide have resu-med exploration of organ transplantation for HIV-infected individuals and reached a positive conclusion.This study provides an overview of the current landscape of HIV-positive patients receiving liver transplantation(LT)in main-land China.To date,our transplant center has conducted LT for eight end-stage liver disease patients co-infected with HIV,and all but one,who died two months postoperatively due to sepsis and progressive multi-organ failure,have survived.Comparative analysis with hepatitis B virus-infected patients during the same period revealed no statistically significant differences in acute rejection reactions,cytomegalovirus infection,bacteremia,pulmonary infections,acute kidney injury,new-onset cancers,or vascular and biliary complications.

关键词： liver transplantation Human immunodeficiency virus Infection Hepatitis B virus End-stage liver disease China'Mainland

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Perihilar-cholangiocarcinoma: what really matters?

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hepatobiliary surgery and Nutrition 2022年第4期11卷 616-619页

作者： Fabrizio Di Benedetto Paolo Magistri Stefano Di Sandro hepato-pancreato-biliary surgery and liver transplantation unit University Hospital of Modena“Policlinico”University of Modena and Reggio EmiliaModenaItaly

Treatment of peri-hilar cholangiocarcinoma(PHC)is one of the most critical challenges in the modern era of liver surgery(1).In addition to the highly demanding technique and insidious diagnostic work-up,the procedure ... 详细信息

关键词： operative carcinoma liver

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Modern surgical approach to hepatocellular carcinoma

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hepatobiliary surgery and Nutrition 2023年第6期12卷 953-955页

作者： Paolo Magistri Gian Piero Guerrini Stefano Di Sandro Fabrizio Di Benedetto hepato-pancreato-biliary surgery and liver transplantation unit University Hospital of Modena“Policlinico”University of Modena and Reggio EmiliaModenaItaly

We are glad to contribute with an editorial on the important topic of therapeutic opportunities for hepatocellular carcinoma(HCC).The increasing diffusion of minimally invasive approaches to the liver and the growing experience worldwide have progressively changed our curative strategies for patients affected by primary and metastatic liver tumors(1).

关键词： Robotic surgery minimally invasive liver surgery(MILS) surgical oncology liver transplant living donor liver transplantation(LDLT)

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