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Liver transplantation for hepatocellular carcinoma in India: Are we ready for 2040?

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World Journal of transplantation 2024年第1期14卷 141-153页

作者： Hirak Pahari Amruth Raj Ambreen Sawant Dipak S Ahire Raosaheb Rathod Chetan Rathi Tushar Sankalecha Sachin Palnitkar Vikram Raut Department of Liver transplant and hpb Surgery Medicover HospitalsNavi Mumbai 410210MaharashtraIndia Department of Liver transplant Anaesthesia Medicover HospitalsNavi Mumbai 410210MaharashtraIndia Department of Gastroenterology and Hepatology Medicover HospitalsNavi Mumbai 410210India Department of Gastroenterology and Hepatology Medicover HospitalsNavi Mumbai 410210MaharashtraIndia Department of Gastroenterology and Hepatology Medicover HospitalsAurangabad 431003India Department of Gastroenterology and Hepatology Medicover HospitalsNashik 422009India Department of Gastroenterology and Hepatology Medicover HospitalsPune 411026India

BACKGROUND Liver transplantation(LT)for hepatocellular carcinoma(HCC)has been widely researched and is well established worldwide.The cornerstone of this treatment lies in the various criteria formulated by expert consensus and experience.The variations among the criteria are staggering,and the short-and long-term outcomes are controversial.AIM To study the differences in the current practices of LT for HCC at different centers in India and discuss their clinical implications in the future.METHODS We conducted a survey of major centers in India that performed LT in December 2022.A total of 23 responses were received.The centers were classified as high-and low-volume,and the current trend of care for patients undergoing LT for HCC was noted.RESULTS Of the 23 centers,35%were high volume center(>500 Liver transplants)while 52%were high-volume centers that performed more than 50 transplants/year.Approximately 39%of centers had performed>50 LT for HCC while the percent distribution for HCC in LT patients was 5%–15%in approximately 73%of the patients.Barring a few,most centers were divided equally between University of California,San Francisco(UCSF)and center-specific criteria when choosing patients with HCC for LT,and most(65%)did not have separate transplant criteria for deceased donor LT and living donor LT(LDLT).Most centers(56%)preferred surgical resection over LT for a Child A cirrhosis patient with a resectable 4 cm HCC lesion.Positron-emission tomography-computed tomography(CT)was the modality of choice for metastatic workup in the majority of centers(74%).Downstaging was the preferred option for over 90%of the centers and included transarterial chemoembolization,transarterial radioembolization,stereotactic body radiotherapy and atezolizumab/bevacizumab with varied indications.The alphafetoprotein(AFP)cut-off was used by 74%of centers to decide on transplantation as well as to downstage tumors,even if they met the criteria.The criteria for successful downstaging varied,but most centers conformed to the UCSF or

关键词： Hepatocellular carcinoma Liver transplant India Downstaging Survey Milan University of California,San Francisco Portal vein tumor thrombus Expanded criteria

Hepatolithiasis:Epidemiology,presentation,classification and management of a complex disease

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World Journal of Gastroenterology 2024年第13期30卷 1836-1850页

作者： Rodrigo V.Motta Francesca Saffioti Vasileios K Mavroeidis Translational Gastroenterology and Liver unit Nuffield Department of MedicineUniversity of OxfordOxford OX39DUUnited Kingdom Department of Gastroenterology and Hepatology Oxford University Hospitals NHS Foundation TrustJohn Radcliffe HospitalOxford OX39DUUnited Kingdom UCL Institute for Liver and Digestive Health and Sheila Sherlock Liver unit Royal Free Hospital and University College LondonLondon NW32QGUnited Kingdom Department of hpb Surgery Bristol Royal InfirmaryUniversity Hospitals Bristol and Weston NHS Foundation TrustBristol BS28HWUnited Kingdom Department of transplant Surgery North Bristol NHS TrustSouthmead HospitalBristol BS105NBUnited Kingdom Department of Gastrointestinal Surgery North Bristol NHS TrustSouthmead HospitalBristol BS105NBUnited Kingdom

The term hepatolithiasis describes the presence of biliary stones within the intrahepatic bile ducts,above the hilar confluence of the hepatic ducts.The disease is more prevalent in Asia,mainly owing to socioeconomic and dietary factors,as well as the prevalence of biliary parasites.In the last century,owing to migration,its global incidence has increased.The main pathophysiological mechanisms involve cholangitis,bile infection and biliary strictures,creating a self-sustaining cycle that perpetuates the disease,frequently characterised by recurrent episodes of bacterial infection referred to as syndrome of“recurrent pyogenic cholangitis”.Furthermore,long-standing hepatolithiasis is a known risk factor for development of intrahepatic cholangiocarcinoma.Various classifications have aimed at providing useful insight of clinically relevant aspects and guidance for treatment.The management of symptomatic patients and those with complications can be complex,and relies upon a multidisciplinary team of hepatologists,endoscopists,interventional radiologists and hepatobiliary surgeons,with the main goal being to offer relief from the clinical presentations and prevent the development of more serious complications.This comprehensive review provides insight on various aspects of hepatolithiasis,with a focus on epidemiology,new evidence on pathophysiology,most important clinical aspects,different classification systems and contemporary management.

关键词： Cholelithiasis Intrahepatic stones Cholangiocarcinoma Biliary parasites Recurrent pyogenic cholangitis Oriental cholangiohepatitis Hepatectomy Cholangioscopy Liver transplant Paediatric

Clinical profile and outcomes of hepatocellular carcinoma in primary Budd-Chiari syndrome

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 699-715页

作者： Ankit Agarwal Sagnik Biswas Shekhar Swaroop Arnav Aggarwal Ayush Agarwal Gautam Jain Anshuman Elhence Arun Vaidya Amit Gupte Ravi Mohanka Ramesh Kumar Ashwani Kumar Mishra Shivanand Gamanagatti Shashi Bala Paul Subrat Kumar Acharya Akash Shukla Shalimar Department of Gastroenterology and Human Nutrition All India Institute of Medical SciencesNew Delhi 110029DelhiIndia Department of Gastroenterology Seth Gordhandas Sunderdas Medical College and KEM HospitalMumbai 400012MaharashtraIndia Department of Gastroenterology Sir HN Reliance Foundation HospitalMumbai 400004India Department of Liver transplant and hpb Sir HN Reliance Foundation HospitalMumbai 400004India Department of Gastroenterology All India Institute of Medical SciencesPatna 801507India Professor of Biostatistics National Drug Dependence Treatment Centre(NDDTC)All India Institute of Medical SciencesNew Delhi 110029India Department of Radiodiagnosis All India Institute of Medical SciencesNew Delhi 110029DelhiIndia

BACKGROUND There is scant literature on hepatocellular carcinoma(HCC)in patients with Budd-Chiari syndrome(BCS).AIM To assess the magnitude,clinical characteristics,feasibility,and outcomes of treatment in BCS-HCC.METHODS A total of 904 BCS patients from New Delhi,India and 1140 from Mumbai,India were included.The prevalence and incidence of HCC were determined,and among patients with BCS-HCC,the viability and outcomes of interventional therapy were evaluated.RESULTS In the New Delhi cohort of 35 BCS-HCC patients,18 had HCC at index presentation(prevalence 1.99%),and 17 developed HCC over a follow-up of 4601 person-years,[incidence 0.36(0.22-0.57)per 100 person-years].BCS-HCC patients were older when compared to patients with BCS alone(P=0.001)and had a higher proportion of inferior vena cava block,cirrhosis,and long-segment vascular obstruction.The median alpha-fetoprotein level was higher in patients with BCS-HCC at first presentation than those who developed HCC at follow-up(13029 ng/mL vs 500 ng/mL,P=0.01).Of the 35 BCS-HCC,26(74.3%)underwent radiological interventions for BCS,and 22(62.8%)patients underwent treatment for HCC[transarterial chemoembolization in 18(81.8%),oral tyrosine kinase inhibitor in 3(13.6%),and transarterial radioembolization in 1(4.5%)].The median survival among patients who underwent interventions for HCC compared with those who did not was 3.5 years vs 3.1 mo(P=0.0001).In contrast to the New Delhi cohort,the Mumbai cohort of BCS-HCC patients were predominantly males,presented with a more advanced HCC[Barcelona Clinic Liver Cancer C and D],and 2 patients underwent liver transplantation.CONCLUSION HCC is not uncommon in patients with BCS.Radiological interventions and liver transplantation are feasible in select primary BCS-HCC patients and may improve outcomes.

关键词： Budd chiari syndrome Cancer Cirrhosis Thrombosis Liver Varices Transarterial chemoembolization Hepatic venous outflow tract obstruction

Prophylactic drains in totally laparoscopic distal gastrectomy:are they always necessary?

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World Journal of Gastroenterology 2022年第3期28卷 399-401页

作者： Tommaso Maria Manzia Alessandro Parente Roberta Angelico hpb and transplant unit Department of Surgery ScienceUniversity of Rome Tor VergataRome 00133Italy Queen Elizabeth Hospital Liver UnitUniversity of BirminghamBirmingham UK and HPB and Transplant UnitDepartment of Surgery ScienceUniversity of Rome Tor VergataRome 00133Italy

Prophylactic drains have always been a useful tool to detect early complications and prevent postoperative fluid collections,particularly in gastrointestinal surgery.Recently,the utilization of such drains has been debated,due to mounting evidence that they could be harmful rather than beneficial.Based on recent published articles,Liu et al reported that the routine use of prophylactic drains in total laparoscopic distal gastrectomy might not be necessary for all patients.Herein,we express our opinion regarding this interesting publication.

关键词： Gastric cancer Prophylactic drainage Totally laparoscopic gastrectomy Enhanced recovery after surgery Minimally invasive surgery Early gastric cancer

Incidental gallbladder cancer diagnosis confers survival advantage irrespective of tumour stage and characteristics

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World Journal of Gastroenterology 2022年第18期28卷 1996-2007页

作者： Moath Alarabiyat Syed Soulat Raza John Isaac Darius Mirza Ravi Marudanayagam Keith Roberts Manuel Abradelo David C Bartlett Bobby V Dasari Robert P Sutcliffe Nikolaos A Chatzizacharias hpb and Liver transplant unit Queen Elizabeth HospitalBirmingham B152GWUnited Kingdom Department of hpb and Liver transplantation Queen Elizabeth HospitalUniversity Hospitals BirminghamBirmingham B152THUnited Kingdom

BACKGROUND Incidental gallbladder cancer(IGBC)represents 50%-60%of gallbladder cancer cases.Data are conflicting on the role of IGBC diagnosis in oncological outcomes.Some studies suggest that IGBC diagnosis does not affect outcomes,while others that overall survival(OS)is longer in these cases compared to non-incidental diagnosis(NIGBC).Furthermore,some studies reported early tumour stages and histopathologic characteristics as possible confounders,while others not.AIM To investigate the role of IGBC diagnosis on patients’overall survival,especially after surgical treatment with curative intent.METHODS Retrospective analysis of all patient referrals with gallbladder cancer between 2008 and 2020 in a tertiary hepatobiliary centre.Statistical comparison of patient and tumour characteristics between IGBC and NIGBC subgroups was performed.Survival analysis for the whole cohort,surgical and non-surgical subgroups was done with the Kaplan-Meier method and the use of log rank test.Risk analysis was performed with univariable and multivariable Cox regression analysis.RESULTS The cohort included 261 patients with gallbladder cancer.65%of cases had NIGBC and 35%had IGBC.A total of 90 patients received surgical treatment(66%of IGBC cases and 19%of NIGBC cases).NIGBC patients had more advanced T stage and required more extensive resections than IGBC ones.OS was longer in patients with IGBC in the whole cohort(29 vs 4 mo,P<0.001),as well as in the non-surgical(14 vs 2 mo,P<0.001)and surgical subgroups(29 vs 16.5 mo,P=0.001).Disease free survival(DFS)after surgery was longer in patients with IGBC(21.5 mo vs 8.5 mo,P=0.007).N stage and resection margin status were identified as independent predictors of OS and DFS.NIGBC diagnosis was identified as an independent predictor of OS.CONCLUSION IGBC diagnosis may confer a survival advantage independently of the pathological stage and tumour characteristics.Prospective studies are required to further investigate this,including detailed pathological analysis and molecular gene express

关键词： Gallbladder cancer Incidental gallbladder cancer Non-incidental gallbladder cancer Gallbladder cancer survival

Resection of isolated liver oligometastatic disease in pancreatic ductal adenocarcinoma:Is there a survival benefit?A systematic review

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World Journal of Gastrointestinal Surgery 2023年第7期15卷 1512-1521页

作者： James M Halle-Smith Sarah Powell-Brett Keith Roberts Nikolaos A Chatzizacharias Department of hpb and Liver transplant Queen Elizabeth HospitalUniversity of BirminghamBirmingham B152GWUnited Kingdom

BACKGROUND Presence of liver metastatic disease in pancreatic ductal adenocarcinoma(PDAC),either synchronous or metachronous after pancreatic resection,is a terminal diagnosis that warrants management with palliative intent as per all international practice guidelines.However,there is an increasing interest on any potential value of surgical treatment of isolated oligometastatic disease in selected cases.AIM To present the published evidence on surgical management of PDAC liver metastases,synchronous and metachronous,and compare the outcomes of these treatments to the current standard of care.METHODS A systematic review was performed in line with the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines to compare the outcomes of both synchronous and metachronous liver metastases resection to standard care.RESULTS 356 studies were identified,31 studies underwent full-text review and of these 10 were suitable for inclusion.When synchronous resection of liver metastases was compared to standard care,most studies did not demonstrate a survival benefit with the exception of one study that utilised neoadjuvant treatment.However,resection of metachronous disease appeared to confer a survival advantage when compared to treatment with chemotherapy alone.CONCLUSION A survival benefit may exist in resection of selected cases of metachronous liver oligometastatic PDAC disease,after disease biology has been tested with time and systemic treatment.Any survival benefit is less clear in synchronous cases;however an approach with neoadjuvant treatment and consideration of resection in some selected cases may confer some benefit.Future studies should focus on pathways for selection of cases that may benefit from an aggressive approach.

关键词： Pancreas cancer Liver metastases Surgical resection Systematic review

COVID-19 in a pregnant kidney transplant recipient-what we need to know:A case report

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World Journal of transplantation 2022年第10期12卷 325-330页

作者： Roberta Angelico Maria Luisa Framarino-dei-Malatesta Giuseppe Iaria Department of Surgical Sciences HPB and Transplant UnitUniversity of Rome Tor VergataRome 00100Italy Department of Gynecologic-Obstetrical and Urologic Sciences Policlinico Umbero ISapienza University of RomeRome 00100Italy Kidney transplant unit San Camillo ForlaniniRome 00100Italy

BACKGROUND In the era of the coronavirus disease 2019(COVID-19)pandemic,kidney transplant recipients are more susceptible to severe acute respiratory syndrome coronavirus(SARS-CoV-2)infection,developing severe morbidity and graft impairment.Pregnant women are also more likely to develop severe COVID-19 disease,causing pregnancy complications such as preterm births and acute kidney injury.CASE SUMMARY Herein,we report the case of a pregnant woman with a third kidney transplantation who developed COVID-19 disease.The reduction of immunosuppressive drugs and strict monitoring of trough blood levels were needed to avoid severe SARS-CoV-2-related complications,and permitted to continue a healthy pregnancy and maintain good graft function.In such a complex scenario,the concomitance of COVID-19-related morbidity,the risk of acute rejection in the hyperimmune recipient,graft dysfunction and pregnancy complications make the management of immunosuppression a very difficult task and clinicians must be aware.CONCLUSION Tailoring the immunosuppressive regimen is a key factor affecting both the graft outcome and pregnancy safety.

关键词： Kidney transplantation Pregnancy SARS-CoV-2 infection COVID-19 disease Immunosuppression Complications Case report

Intraoperative pancreas stump perfusion assessment during pancreaticoduodenectomy:A systematic scoping review

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世界胃肠外科杂志:英文版(电子版) 2023年第8期15卷 1799-1807页

作者： Francis P Robertson Harry V M Spiers Wei Boon Lim Benjamin Loveday Keith Roberts Sanjay Pandanaboyana Department of hpb and transplant Surgery Freeman HospitalNewcastle Upon Tyne NE77DNUnited Kingdom Department of hpb Surgery Addenbrookes HospitalCambridge CB20QQUnited Kingdom Department of General Surgery Royal Melbourne HospitalMelbourne VIC 3050Australia Department of hpb Surgery University Hospitals Birmingham NHS Foundation TrustBirmingham BG152GWUnited Kingdom

BACKGROUND Post-operative pancreatic fistula(POPF)is the primary cause of morbidity following pancreaticoduodenectomy.Rates of POPF have remained high despite well known risk factors.The theory that hypoperfusion of the pancreatic stump leads to anastomotic failure has recently gained interest.AIM To define the published literature with regards to intraoperative pancreas perfusion assessment and its correlation with POPF.METHODS A systematic search of available literature was performed in November 2022.Data extracted included study characteristics,method of assessment of pancreas stump perfusion,POPF and other post-pancreatic surgery specific complications.RESULTS Five eligible studies comprised two prospective non-randomised studies and three case reports,total 156 patients.Four studies used indocyanine green fluorescence angiography to assess the pancreatic stump,with the remaining study assessing pancreas perfusion by visual inspection of arterial bleeding of the pancreatic stump.There was significant heterogeneity in the definition of POPF.Studies had a combined POPF rate of 12%;intraoperative perfusion assessment revealed hypoperfusion was present in 39%of patients who developed POPF.The rate of POPF was 11%in patients with no evidence of hypoperfusion and 13%in those with evidence of hypoperfusion,suggesting that not all hypoperfusion gives rise to POPF and further analysis is required to analyse if there is a clinically relevant cut off.Significant variance in practice was seen in the pancreatic stump management once hypoperfusion was identified.CONCLUSION The current published evidence around pancreas perfusion during pancreaticoduodenectomy is of poor quality.It does not support a causative link between hypoperfusion and POPF.Further well-designed prospective studies are required to investigate this.

关键词： Pancreatico-duodenectomy Post-operative pancreatic fistula Perfusion Indocyanine green Post pancreatectomy pancreatitis

Chronic rejection after liver transplantation:Opening the Pandora’s box

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World Journal of Gastroenterology 2021年第45期27卷 7771-7783页

作者： Roberta Angelico Bruno Sensi Tommaso M Manzia Giuseppe Tisone Giuseppe Grassi Alessandro Signorello Martina Milana Ilaria Lenci Leonardo Baiocchi Department of Surgery Sciences HPB and Transplant UnitUniversity of Tor VergataRome 00100Italy Hepatology unit University of Tor VergataRome 00100Italy

Chronic rejection(CR)of liver allografts causes damage to intrahepatic vessels and bile ducts and may lead to graft failure after liver transplantation.Although its prevalence has declined steadily with the introduction of potent immunosuppressive therapy,CR still represents an important cause of graft injury,which might be irreversible,leading to graft loss requiring re-transplantation.To date,we still do not fully appreciate the mechanisms underlying this process.In addition to T cell-mediated CR,which was initially the only recognized type of CR,recently a new form of liver allograft CR,antibody-mediated CR,has been identified.This has indeed opened an era of thriving research and renewed interest in the field.Liver biopsy is needed for a definitive diagnosis of CR,but current research is aiming to identify new non-invasive tools for predicting patients at risk for CR after liver transplantation.Moreover,the minimization or withdrawal of immunosuppressive therapy might influence the establishment of subclinical CR-related injury,which should not be disregarded.Therapies for CR may only be effective in the“early”phases,and a tailored management of the immunosuppression regimen is essential for preventing irreversible liver damage.Herein,we provide an overview of the current knowledge and research on CR,focusing on early detection,identification of non-invasive biomarkers,immunosuppressive management,re-transplantation and future perspectives of CR.

关键词： Liver transplantation Chronic rejection Immunosuppression T cell-mediated rejection Antibody-mediated rejection Donor-specific antibody Re-transplantation Graft loss Complications Outcomes