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Liver transplantation as an alternative for the treatment of intrahepatic cholangiocarcinoma: Past, present, and future directions

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Hepatobiliary & Pancreatic Diseases International 2024年第2期23卷 129-138页

作者： Sudha Kodali Ashton A Connor Souhail Thabet Elizabeth W Brombosz R Mark Ghobrial Sherrie and Alan Conover Center for Liver Disease and transplantation Houston Methodist HospitalHoustonTX 77030USA JC Walter Jr transplant Center Houston Methodist HospitalHoustonTX 77030USA Department of Medicine Weill Cornell Medical CollegeNew YorkNYUSA Department of Surgery Houston Methodist HospitalHoustonTX 77030USA Department of Surgery Weill Cornell Medical CollegeNew YorkNYUSA School of Medicine New Giza UniversityGizaEgypt

Intrahepatic cholangiocarcinoma(iCCA)is a rare biliary tract cancer with high mortality rate.Complete resection of the iCCA lesion is the first choice of treatment,with good prognosis after margin-negative resection.Unfortunately,only 12%-40% of patients are eligible for resection at presentation due to cirrhosis,portal hypertension,or large tumor size.Liver transplantation(LT)offers margin-negative iCCA extirpation for patients with unresectable tumors.Initially,iCCA was a contraindication for LT until size-based selection criteria were introduced to identify patients with satisfied post-LT outcomes.Recent studies have shown that tumor biology-based selection can yield high post-LT survival in patients with locally advanced iCCA.Another selection criterion is the tumor response to neoadjuvant therapy.Patients with response to neoadjuvant therapy have better outcomes after LT compared with those without tumor response to neoadjuvant therapy.Another index that helps predict the treatment outcome is the biomarker.Improved survival outcomes have also opened the door for living donor LT for iCCA.Patients undergoing LT for iCCA now have statistically similar survival rates as patients undergoing resection.The combination of surgery and locoregional and systemic therapies improves the prognosis of iCCA patients.

关键词： Liver transplantation Cholangiocarcinoma Hepatectomy transplant oncology Liver neoplasm

Expanding indications for liver transplantation in the era of liver transplant oncology

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World Journal of Gastrointestinal Surgery 2021年第5期13卷 392-405页

作者： Guergana Panayotova Keri E Lunsford Nyan L Latt Flavio Paterno James V Guarrera Nikolaos Pyrsopoulos Division of transplant and Hepatobiliary Surgery Department of SurgeryRutgers New Jersey Medical SchoolNewarkNJ 07103United States Center for Immunity and Inflammation Institute for Infectious and Inflammatory DiseasesRutgers New Jersey Medical SchoolNewarkNJ 07103United States Division of Gastroenterology and Hepatology Department of MedicineRutgers New Jersey Medical SchoolNewarkNJ 07103United States

Despite numerous advances and emerging data,liver transplantation in the setting of gastrointestinal malignancies remains controversial outside of certain accepted indications.In an era of persistent organ shortage and increasing organ demand,allocation of liver grafts must be considered carefully.While hepatocellular carcinoma and hilar cholangiocarcinoma have become accepted indications for transplantation,tumor size and standardized multi-disciplinary treatment protocols are necessary to ensure optimal patient outcomes.As more studies seeking to expand the oncologic indications for liver transplantation are emerging,it is becoming increasingly clear that tumor biology and response to therapy are key factors for optimal oncologic outcomes.In addition,time from diagnosis to transplantation appears to correlate with survival,as stable disease over time portends better outcomes post-operatively.Identifying aggressive disease pre-transplant remains difficult with current imaging and tissue sampling techniques.While tumor size and stage are important prognostic predictors for most malignancies,patient and tumor selection protocols are necessary.As the fields of medical and surgical oncology continue to evolve,it is clear that a protocolized interdisciplinary treatment approach is necessary for combatting any cancer effectively.Disease stability over time and response to neoadjuvant therapy may be the best predictors for successful patient outcomes and can be easily incorporated in our treatment paradigms.Current data evaluating liver transplantation for expanded oncologic indications such as:expanded criteria hepatocellular carcinoma,intrahepatic cholangiocarcinoma,mixed tumors,and liver limited metastatic colorectal carcinomas,incorporate multi-modal therapies and evaluation of tumor treatment response.While further investigation is necessary,initial results suggest there is an expanded role for transplant surgery in malignancy in a new era of liver transplant oncology.

关键词： Liver transplantation transplant oncology Intrahepatic cholangiocarcinoma Hepatocellular carcinoma Colorectal metastases Mixed hepatocholangiocarcinoma

Role of surgical treatments in high-grade or advanced gastroenteropancreatic neuroendocrine neoplasms

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World Journal of Gastrointestinal Surgery 2022年第5期14卷 397-408页

作者： Qing-Yang Que Lin-Cheng Zhang Jia-Qi Bao Sun-Bin Ling Xiao Xu Key Laboratory of Integrated oncology and Intelligent Medicine of Zhejiang Province Hangzhou 310006Zhejiang ProvinceChina Zhejiang University Cancer Center Hangzhou 310006Zhejiang ProvinceChina NHC Key Laboratory of Combined Multi-organ transplantation Hangzhou 310006Zhejiang ProvinceChina Department of Hepatobiliary and Pancreatic Surgery Affiliated Hangzhou First People’s HospitalZhejiang University School of MedicineHangzhou 310006Zhejiang ProvinceChina Institute of Organ transplantation Zhejiang UniversityHangzhou 310003Zhejiang ProvinceChina

Over the last 40 years,the incidence and prevalence of gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs)have continued to increase.Compared to other epithelial neoplasms in the same organ,GEP-NENs exhibit indolent biological behavior,resulting in more chances to undergo surgery.However,the role of surgery in high-grade or advanced GEP-NENs is still controversial.Surgery is associated with survival improvement of well-differentiated highgrade GEP-NENs,whereas poorly differentiated GEP-NENs that may benefit from resection require careful selection based on Ki67 and other tissue biomarkers.Additionally,surgery also plays an important role in locally advanced and metastatic disease.For locally advanced GEP-NENs,isolated major vascular involvement is no longer an absolute contraindication.In the setting of metastatic GEP-NENs,radical intended surgery is recommended for patients with low-grade and resectable metastases.For unresectable metastatic disease,a variety of surgical approaches,including cytoreduction of liver metastasis,liver transplantation,and surgery after neoadjuvant treatment,show survival benefits.Primary tumor resection in GEP-NENs with unresectable metastatic disease is associated with symptom control,prolonged survival,and improved sensitivity toward systemic therapies.Although there is no established neoadjuvant or adjuvant strategy,increasing attention has been given to this emerging research area.Some studies have reported that neoadjuvant therapy effectively reduces tumor burden,improves the effectiveness of subsequent surgery,and decreases surgical complications.

关键词： Gastroenteropancreatic neuroendocrine neoplasms Neuroendocrine carcinomas Surgery Hepatic debulking Liver transplant transplant oncology

Liver transplantation for non-resectable colorectal liver metastases

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Hepatobiliary Surgery and Nutrition 2023年第4期12卷 595-597页

作者： Hassan Aziz Saima Sharif Irena Gribovskaja-Rupp Alan W.Hemming University of Iowa Hospitals and Clinics Iowa CityIAUSA

At present,there are no absolute practice guidelines for liver transplants in colorectal liver metastases(CRLM),and treatment protocols for unresectable CRLM are institution-specific(1).One of the first prospective studies evaluating the safety of liver transplants for CRLM was the SECA-I trial(1,2).A 5-year overall survival rate of 60% was observed in this trial,which far outperformed survival with chemotherapy alone(3).In the SECA-Ⅱ trial,enrollment was increased,and patients with better prognostic factors,including at least a 10% response to chemotherapy before the transplant,were selected.

关键词： Colorectal liver metastases(CRLM) liver transplant International Hepato-Pancreato-Biliary Association transplant oncology

Translational research and innovation in modern transplant practice:Paradigms from Greece and around the world

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World Journal of transplantation 2023年第2期13卷 25-27页

作者： Georgios Tsoulfas Ioannis Boletis Vassilios Papalois Department of transplantation Surgery Aristotle University School of MedicineThessaloniki 54124Greece Department of Nephrology EKPA UniversityAthens 11527Greece Department of transplant Surgery Imperial College Renal and Transplant CentreLondon W120HSUnited Kingdom

The continuous clinical and technological advances,together with the social,health and economic challenges that the global population faces,have created an environment where the evolution of the field of transplantation is essentially necessary.The goal of this special issue is to provide a picture of the current status of transplantation in Greece as well as in many other countries in Europe and around the world.Authors from Greece and several other countries provide us with valuable insight into their respective areas of transplant expertise,with a main focus on the field of translational research and innovation.The papers that are part of this Special Issue“Translational Research and Innovation and the current status of transplantation in Greece”have presented innovative and meaningful approaches in modern transplant research and practice.They provide us with a clear overview of the current landscape in transplantation,including liver transplantation in the context of a major pandemic,the evolution of living donor kidney transplantation or the evolution of the effect of hepatitis C virus infection in transplantation,while at the same time explore more recent challenges,such as the issue of frailty in the transplant candidate and the changes brought by newer treatments,such as immunotherapy,in transplant oncology.Additionally,they offer us a glimpse of the effect that technological innovations,such as virtual reality,can have on transplantation,both in terms of clinical and educational aspects.Just as critical is the fact that this Special Issue emphasizes the multidisciplinary,collaborative efforts currently taking place that link transplant research and innovation with other cutting-edge disciplines such as bioengineering,advanced information technology and artificial intelligence.In this Special Issue,in addition to the clinical and research evolution of the field of transplantation,we are witnessing the importance of interdisciplinary collaboration in medicine.

关键词： Translational research Non-alcoholic fatty liver disease Immunotherapy Pandemic Liver transplantation Bioengineering Artificial intelligence Immunosuppression transplant oncology Living donor kidney transplantation

Advances in liver transplantation for unresectable colon cancer liver metastasis

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World Journal of Gastrointestinal Surgery 2021年第12期13卷 1615-1627页

作者： Xiao Cui Xiao-Ping Geng Da-Chen Zhou Ming-Hao Yang Hui Hou Department of General Surgery The Second Hospital of Anhui Medical UniversityHefei 230601Anhui ProvinceChina

It is estimated that 50%of patients with colorectal cancer will develop liver metastasis.Surgical resection significantly improves survival and provides a chance of cure for patients with colorectal cancer liver metastasis(CRLM).Increasing the resectability of primary unresectable liver metastasis provides more survival benefit for those patients.Considerable surgical innovations have been made to increase the resection rate and decrease the potential risk of hepatic failure postoperation.Liver transplantation(LT)has been explored as a potential curative treatment for unresectable CRLM.However,candidate selection criteria,chemotherapy strategies,refined immunity regimens and resolution for the shortage of grafts are lacking.This manuscript discusses views on surgical indication,peritransplantation anti-tumor and anti-immunity therapy and updated advances in LT for unresectable CRLM.A literature review of published articles and registered clinical trials in PubMed,Google Scholar,and Clinicaltrials.gov was performed to identify studies related to LT for CRLM.Some research topics were identified,including indications for LT for CRLM,oncological risk,antitumor regimens,graft loss,administration of anti-immunity drugs and solutions for graft deficiency.The main candidate selection criteria are good patient performance,good tumor biological behavior and chemosensitivity.Chemotherapy should be administered before transplantation but is not commonly administered posttransplantation for preventive purposes.Mammalian target of rapamycin regimens are recommended for their potential oncological benefit,although there are limited cases.In addition to extended criterion grafts,living donor grafts and small grafts combined with two-stage hepatectomy are efficient means to resolve organ deficiency.LT has been proven to be an effective treatment for selected patients with liver-only CRLM.Due to limited donor grafts,high cost and poorly clarified oncological risks,LT for unresectable CRLM should be strictly performed under a well-

关键词： Liver transplantation Colon cancer Colorectal cancer liver metastasis transplant oncology

Living donor liver transplantation for patients with advanced hepatocellular carcinoma

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Hepatoma Research 2020年第11期6卷 18-31页

作者： J.Michael Cullen Paola Vargas Nicolas Goldaracena Department of Surgery University of VirginiaCharlottesvilleVA 22908USA Division of transplantation Department of SurgeryUniversity of VirginiaCharlottesvilleVA 22908USA

Liver transplantation(LT)is the treatment of choice for patients with hepatocellular carcinoma(HCC)and underlying liver disease.Given the organ scarcity,LT for patients with HCC have been restricted to those patients associated with the highest survivals.However,many patients with extended criteria HCC can still benefit from LT,but due to deceased organ shortage,they are not offered that opportunity.Living donor liver transplantation(LDLT)emerged as a successful strategy to overcome organ shortage around the world and as LDLT experience grows,this technique might offer the opportunity to expand the indications of LT to patients with advanced HCC.Therefore,since LDLT is not competing for deceased donor organs,many patients with extended criteria HCC who could still benefit from transplantation may have access to this treatment option.In this review,we will discuss the role of LDLT for patients with advanced-stage HCC and how LDLT allows for safe expansion of HCC transplant criteria.

关键词： Living donor liver transplantation hepatocellular carcinoma liver transplantation transplant oncology clinical outcomes

Role of liver transplantation in the management of colorectal liver metastases:Challenges and opportunities

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World Journal of Clinical oncology 2021年第12期12卷 1193-1201页

作者： Panagiotis T Tasoudis Ioannis A Ziogas Sophoclis P Alexopoulos John J Fung Georgios Tsoulfas School of Health Sciences University of ThessalyLarissa 41500Greece Department of Surgery Division of Hepatobiliary Surgery and Liver TransplantationVanderbilt University Medical CenterNashvilleTN 37232United States Department of Surgery University of Chicago Medicine Transplant InstituteChicagoIL 60637United States Department of transplant Surgery Aristotle University School of MedicineThessaloniki 54622Greece

The liver is the most common site of colorectal cancer metastasis.Complete resection of the metastatic tumor is currently the only treatment modality available with a potential for cure.However,only 20%of colorectal liver metastases(CRLM)are considered resectable at the time of presentation.Liver transplantation(LT)has been proposed as an alternative oncologic treatment for patients with unresectable CRLM.This review summarizes the published experiences of LT in the setting of unresectable CRLM from the previous decades and discusses the challenges and future horizons in the field.Contemporary experiences that come mostly from countries with broader access to liver grafts are also explored and their promising findings in terms of overall survival(OS)and disease-free survival(DFS)are outlined along with their study design and methods.The rationale of establishing specific patient selection criteria and the dilemmas around immunosuppressive regimens in patients undergoing LT for CRLM are also highlighted.Additionally,this review describes the findings of studies comparing LT vs chemotherapy alone and LT vs portal vein embolization plus resection for CRLM in terms of OS and DFS.Last but not least,we present current perspectives and ongoing prospective trials that try to elucidate the role of LT for CRLM.

关键词： Colorectal cancer Colorectal liver metastases Liver transplantation transplant oncology Liver cancer Oslo score