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liver transplantation and resection in patients with hepatocellular cancer and portal vein tumor thrombosis: Feasible and effective?

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Hepatobiliary & Pancreatic Diseases International 2024年第2期23卷 123-128页

作者： Prashant Bhangui institute of liver Transplantation and Regenerative Medicine Medanta–The MedicitySector 38GurgaonDelhi NCR 122001India

Patients with locally advanced hepatocellular cancer(HCC)and portal vein tumor thrombosis(PVTT)have a dismal prognosis since limited treatment options are available for *** recent years,effective systemic therapy,and advances in the understanding of technicalities and effectiveness of ablative therapies especially radiotherapy,have given some hope to prolong survival in *** review summarized recent evidence in literature regarding the possible role of liver resection(LR)and liver transplantation(LT)in patients with locally advanced HCC and PVTT with no extrahepatic *** therapies have helped make curative resection or LT a reality in selected *** review emphasizes on the key points to focus on when considering surgery in these patients,who are usually relegated to palliative systemic therapy *** patient selection based on tumor biology,documented downstaging based on imaging and decrease in tumor marker levels,and an adequate waiting period to demonstrate stable disease,may help obtain satisfactory long-term outcomes post LR or LT in an intention to treat strategy in patients with HCC and PVTT.

关键词： Hepatocellular carcinoma Portal vein tumour thrombosis Downstaging therapies Living donor liver transplantation and resection Outcomes

Machine learning in liver surgery:Benefits and pitfalls

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World Journal of Clinical Cases 2024年第12期12卷 2134-2137页

作者： Rafael Calleja Manuel Durán María Dolores Ayllón Ruben Ciria Javier Briceño Hepatobiliary Surgery and liver Transplantation unit Hospital Universitario Reina SofíaMaimonides Biomedical Research Institute of CordobaCórdoba 14004Spain

The application of machine learning(ML)algorithms in various fields of hepatology is an issue of ***,we must be cautious with the *** this letter,based on a published ML prediction model for acute kidney injury after liver surgery,we discuss some limitations of ML models and how they may be addressed in the *** the future faces significant challenges,it also holds a great potential.

关键词： Machine learning liver surgery Artificial intelligence Random forest Prediction model

Multiomics analysis reveals metabolic subtypes and identifies diacylglycerol kinase α (DGKA) as a potential therapeutic target for intrahepatic cholangiocarcinoma

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Cancer Communications 2024年第2期44卷 226-250页

作者： Weiren Liu Huqiang Wang Qianfu Zhao Chenyang Tao Weifeng Qu Yushan Hou Run Huang Zimei Sun Guiqi Zhu Xifei Jiang Yuan Fang Jun Gao Xiaoling Wu Zhixiang Yang Rongyu Ping Jiafeng Chen Rui Yang Tianhao Chu Jian Zhou Jia Fan Zheng Tang Dong Yang Yinghong Shi Department of liver Surgery and Transplantation Liver Cancer InstituteZhongshan HospitalFudan UniversityKey Laboratory of Carcinogenesis and Cancer Invasion of Ministry of EducationShanghaiP.R.China Research unit of liver cancer Recurrence and Metastasis Chinese Academy of Medical SciencesBeijingP.R.China State Key Laboratory of Medical Proteomics Beijing Proteome Research CenterNational Center for Protein Sciences(Beijing)Beijing Institute of LifeomicsBeijingP.R.China

Background:Intrahepatic cholangiocarcinoma(iCCA)is a highly heteroge-neous and lethal hepatobiliary tumor with few therapeutic *** metabolic reprogramming of tumor cells plays an essential role in the develop-ment of tumors,while the metabolic molecular classification of iCCA is largely ***,we performed an integrated multiomics analysis and metabolic classification to depict differences in metabolic characteristics of iCCA patients,hoping to provide a novel perspective to understand and treat ***:We performed integrated multiomics analysis in 116 iCCA samples,including whole-exome sequencing,bulk RNA-sequencing and proteome *** on the non-negative matrix factorization method and the protein abundance of metabolic genes in human genome-scale metabolic models,the metabolic subtype of iCCA was *** and prognostic gene analy-ses were used to compare overall survival(OS)differences between metabolic *** proliferation analysis,5-ethynyl-2’-deoxyuridine(EdU)assay,colony formation assay,RNA-sequencing and Western blotting were performed to investigate the molecular mechanisms of diacylglycerol kinaseα(DGKA)in iCCA ***:Three metabolic subtypes(S1-S3)with subtype-specific biomarkers of iCCA were *** metabolic subtypes presented with distinct prog-noses,metabolic features,immune microenvironments,and genetic *** S2 subtype with the worst survival showed the activation of some special metabolic processes,immune-suppressed microenvironment and Kirsten ratsar-coma viral oncogene homolog(KRAS)/AT-rich interactive domain 1A(ARID1A)*** the S2 subtype-specific upregulated proteins,DGKA was further identified as a potential drug target for iCCA,which promoted cell proliferation by enhancing phosphatidic acid(PA)metabolism and activating mitogen-activated protein kinase(MAPK)***:Viamultiomics analyses,we identified three metabolic subtypes of iCCA,revealing

关键词： diacylglycerol kinaseα intrahepatic cholangiocarcinoma MAPK signaling metabolic classifi-cation multiomics analysis phosphatidic acid metabolism

Ex vivo liver resection and auto-transplantation as an alternative for the treatment of liver malignancies: Progress and challenges

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Hepatobiliary & Pancreatic Diseases International 2024年第2期23卷 117-122页

作者： Xin Yang Lu Lu Wen-Wei Zhu Yi-Feng Tao Cong-Huan Shen Jin-Hong Chen Zheng-Xin Wang Lun-Xiu Qin Hepatobiliary Surgery and liver Transplantation Centers Department of General SurgeryHuashan Hospital&Cancer Metastasis InstituteFudan UniversityShanghai 200040China

Hepatectomy is still the major curative treatment for patients with liver ***,it is still a big challenge to remove the tumors in the central posterior area,especially if their location involves the retrohepatic inferior vena cava and hepatic *** vivo liver resection and auto-transplantation(ELRA),a hybrid technique of the traditional liver resection and transplantation,has brought new hope to these patients and therefore becomes a valid alternative to liver *** to its technical difficulty,ELRA is still concentrated in a few hepatobiliary centers that have experienced surgeons in both liver resection and liver *** efficacy and safety of this technique has already been demonstrated in the treatment of benign liver diseases,especially in the advanced alveolar ***,the application of ELRA for liver malignances has gained more ***,standardization of clinical practice norms and international consensus are still *** prognostic impact in these oncologic patients also needs further *** this review,we summarized the principles and recent progresses on ELRA.

关键词： Ex vivo liver resection liver auto-transplantation Oncology liver malignancies

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

Cellular strategies to induce immune tolerance after liver transplantation:Clinical perspectives

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World Journal of Gastroenterology 2024年第13期30卷 1791-1800页

作者： Ai-Wei Zhou Jing Jin Yuan Liu Department of liver Surgery Renji Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200127China Department of Nursing Renji Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200127China Department of liver Transplantation Shanghai Immune Therapy InstituteShanghai 200127China

liver transplantation(LT)has become the most efficient treatment for pediatric and adult end-stage liver disease and the survival time after transplantation is becoming longer due to the development of surgical techniques and perioperative ***,long-term side-effects of immunosuppressants,like infection,metabolic disorders and malignant tumor are gaining more *** tolerance is the status in which LT recipients no longer need to take any immunosuppressants,but the liver function and intrahepatic histology maintain *** approaches to achieve immune tolerance after transplantation include spontaneous,operational and induced *** first two means require no specific intervention but withdrawing immunosuppressant gradually during *** clinical factors or biomarkers so far could accurately predict who are suitable for immunosuppressant withdraw after *** the understanding to the underlying mechanisms of immune tolerance,many strategies have been developed to induce tolerance in LT *** strategy is one of the most promising methods for immune tolerance induction,including chimerism induced by hematopoietic stem cells and adoptive transfer of regulatory immune *** safety and efficacy of various cell products have been evaluated by prospective preclinical and clinical trials,while obstacles still exist before translating into clinical ***,we will summarize the latest perspectives and concerns on the clinical application of cellular strategies in LT recipients.

关键词： Cellular therapy Induced tolerance liver transplantation Regulatory T cells Regulatory dendritic cells

Hepatic vein reconstruction during hepatectomy:A feasible and underused technique

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 421-427页

作者： Manish Ahuja Kunal Joshi Chris Coldham Paulo Muiesan Bobby Dasari Manuel Abradelo Ravi Marudanayagam Darius Mirza John Isaac David Bartlett Nikolaos A Chatzizacharias Robert P Sutcliffe Keith J Roberts Department of HPB and liver Transplant Surgery University Hospitals Birmingham NHS Foundation TrustBirminghamUK institute of Immunology and Immunotherapy University of BirminghamBirminghamUK

Complete surgical resection(R0)of liver tumors,primary or metastatic,remains the main objective in management of primary and metastatic liver tumors[1].Tumors invading to the proximity of the hepatic venous outflow pose a peculiar challenge to achieve R0 resections,because this location may render a tumor *** median survival of patients with liver tumor without surgery is less than 12 months[2].Even with surgery,post-hepatectomy liver failure and subsequently increased mortality are the main problems associated with complex resection[3].Moreover,when the vein is affected,vein resection and subsequent reconstruction are *** resection is a standard practice in liver resection and transplantation[4],for example,hepatic vein reconstruction during a living-donor liver transplant,porto-mesenteric axis reconstruction during resection of advanced pancreatic cancer and caval reconstruction during resection of retroperitoneal ***,novel techniques like total hepatic vascular exclusion(HVE)[5],veno-venous bypass[6]and ex vivo hepatic resection[7,8]have facilitated curative resections of tumors close to one or more major hepatic veins.

关键词： hepatectomy surgery mortality

Diverse functions of sox9 in liver development and homeostasis and hepatobiliary diseases

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Genes & Diseases 2024年第4期11卷 170-187页

作者： Taiyu Shang Tianyi Jiang Xiaowen Cui Yufei Pan Xiaofan Feng Liwei Dong Hongyang Wang School of Life Sciences Institute of Metabolism and Integrative BiologyFudan UniversityShanghai 200438China National Center for liver Cancer The Naval Medical UniversityShanghai 201805China International Cooperation Laboratory on Signal Transduction Eastern Hepatobiliary Surgery InstituteThe Second Military Medical UniversityShanghai 200438China Laboratory of Signaling Regulation and Targeting Therapy of liver Cancer Second Military Medical University&Ministryof EducationShanghai 200438China

The liver is the central organ for digestion and detoxification and has unique metabolic and regenerative *** hepatobiliary system originates from the foregut endoderm,in which cells undergo multiple events of cell proliferation,migration,and differentiation to form the liver parenchyma and ductal system under the hierarchical regulation of transcription *** on liver development and diseases have revealed that SRY-related high-mobility group box 9(SOx9)plays an important role in liver embryogenesis and the progression of hepatobiliary ***9 is not only a master regulator of cell fate determination and tissue morphogenesis,but also regulates various biological features of cancer,including cancer stemness,invasion,and drug resistance,making Sox9 a potential biomarker for tumor prognosis and *** review systematically summarizes the latest findings of sox9 in hepatobiliary development,homeostasis,and *** also highlight the value of sox9 as a novel biomarker and potential target for the clinical treatment of major liverdiseases.

关键词： Biliary system Cancer Homeostasis liver diseases SOX9

From prediction to prevention:Machine learning revolutionizes hepatocellular carcinoma recurrence monitoring

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World Journal of Gastroenterology 2024年第7期30卷 631-635页

作者： Mariana Michelle Ramírez-Mejía Nahum Méndez-Sánchez Plan of Combined studies in Medicine Faculty of MedicineNational Autonomous University of MexicoDistrito Federal 04510Mexico liver Research unit Medica Sur Clinic&FoundationDistrito Federal 14050Mexico Faculty of Medicine National Autonomous University of MexicoDistrito Federal 04510Mexico

In this editorial,we comment on the article by Zhang et al entitled Development of a machine learning-based model for predicting the risk of early postoperative recurrence of hepatocellular *** carcinoma(HCC),which is characterized by high incidence and mortality rates,remains a major global health challenge primarily due to the critical issue of postoperative *** recurrence,defined as recurrence that occurs within 2 years posttreatment,is linked to the hidden spread of the primary tumor and significantly impacts patient *** predictive factors,including both patient-and treatment-related factors,have limited predictive ability with respect to HCC *** integration of machine learning algorithms is fueled by the exponential growth of computational power and has revolutionized HCC *** study by Zhang et al demonstrated the use of a groundbreaking preoperative prediction model for early postoperative HCC *** persist,including sample size constraints,issues with handling data,and the need for further validation and *** study emphasizes the need for collaborative efforts,multicenter studies and comparative analyses to validate and refine the *** these challenges and exploring innovative approaches,such as multi-omics integration,will enhance personalized oncology *** study marks a significant stride toward precise,efficient,and personalized oncology practices,thus offering hope for improved patient outcomes in the field of HCC treatment.

关键词： Hepatocellular carcinoma Early recurrence Machine learning XGBoost model Predictive precision medicine Clinical utility Personalized interventions