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Long-term liver allograft fibrosis:A review with emphasis on idiopathic post-transplant hepatitis and chronic antibody mediated rejection

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World Journal of Hepatology 2022年第8期14卷 1541-1549页

作者： Mukul Vij Ashwin Rammohan mohamed rela Department of Pathology Dr.Rela Institute and Medical CenterChennai 600044Tamil NaduIndia Institute of Liver disease and Transplantation Dr.Rela Institute and Medical CenterChennai 600044Tamil NaduIndia

Liver transplantation(LT)is a life-saving surgical procedure and the current standard of care for most patients with end stage liver disease.With improvements in organ preservation techniques,perioperative care,and immunosuppression,there is better patient and graft survival following LT,and assessment of the liver allograft in long-term survivors is becoming increasingly important.Recurrent or de novo viral or autoimmune injury remains the most common causes of chronic hepatitis and fibrosis following liver transplantation in adults.However,no obvious cause can be identified in many adults with controlled recurrent disease and the majority of pediatric LT recipients,as they have been transplanted for non-recurrent liver diseases.Serial surveillance liver biopsies post LT have been evaluated in several adult and pediatric centers to identify long-term pathological changes.Pathological findings are frequently present in liver biopsies obtained after a year post LT.The significance of these findings is uncertain as many of these are seen in protocol liver biopsies from patients with clinically good allograft function and normal liver chemistry parameters.This narrative review summaries the factors predisposing to long-term liver allograft fibrosis,highlighting the putative role of idiopathic post-LT hepatitis and chronic antibody mediated rejection in its pathogenesis.

关键词： Liver allograft fibrosis Long term Idiopathic hepatitis Chronic antibody mediated rejection

Current perspectives on the role of liver transplantation for Langerhans cell histiocytosis:A narrative review

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World Journal of Gastroenterology 2022年第30期28卷 4044-4052页

作者： Jagadeesh Menon Ashwin Rammohan Mukul Vij Naresh Shanmugam mohamed rela Institute of Liver Disease&Transplantation Dr.Rela Institute&Medical CentreBharath Institute of Higher Education&ResearchChennai 600044India

Langerhans cell histiocytosis(LCH)is a malignant disease of the histiocytes involving various organ systems.The spectrum of liver involvement in LCH ranges from mild transaminitis to end-stage liver disease.The hallmark of hepatic LCH is secondary sclerosing cholangitis,which manifests due to a progressive destruction of the biliary tree by malignant histiocytes.Chemotherapy remains the mainstay of treatment for active LCH.Early recognition,diagnosis and a systematic approach to the management of LCH can ameliorate the disease process.Nonetheless,the liver involvement in these patients may progress despite the LCH being in remission.Liver transplantation(LT)remains central in the management of such patients.Various facets of the management of LCH,especially those with liver involvement remain unclear.Furthermore,aspects of LT in LCH with regards to the indication,timing and post-LT management,including immunosuppression and adjuvant therapy,remain undefined.This review summarises the current evidence and discusses the practical aspects of the role of LT in the management of LCH.

关键词： Langerhans cell histiocytosis Liver transplantation Outcomes Management Chemotherapy Ethics

Pathological,molecular,and clinical characteristics of cholangiocarcinoma:A comprehensive review

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World Journal of Gastrointestinal Oncology 2022年第3期14卷 607-627页

作者： Mukul Vij Yogesh Puri Ashwin Rammohan Gowripriya G Rajesh Rajalingam Ilankumaran Kaliamoorthy mohamed rela Department of Pathology Dr Rela Institute and Medical centerChennai 600044Tamil NaduIndia Institute of Liver Disease and Transplantation Dr Rela Institute and Medical CenterChennai 600044Tamil NaduIndia

Cholangiocarcinomas are a heterogeneous group of highly aggressive cancers that may arise anywhere within the biliary tree.There is a wide geographical variation with regards to its incidence,and risk-factor associations which may include liver fluke infection,primary sclerosing cholangitis,and hepatolithiasis amongst others.These tumours are classified into intrahepatic,perihilar and distal based on their anatomical location.Morphologically,intrahepatic cholangiocarcinomas are further sub-classified into small and large duct variants.Perihilar and distal cholangiocarcinomas are usually mucin-producing tubular adenocarcinomas.Cholangiocarcinomas develop through a multistep carcinogenesis and are preceded by dysplastic and in situ lesions.While clinical characteristics and management of these tumours have been extensively elucidated in literature,their ultra-structure and tumour biology remain relatively unknown.This review focuses on the current knowledge of pathological characteristics,molecular alterations of cholangiocarcinoma,and its precursor lesions(including biliary intraepithelial neoplasia,intraductal papillary neoplasms of the bile duct,intraductal tubulopapillary neoplasms and mucinous cystic neoplasm).

关键词： Cholangiocarcinoma Classification Pathology Molecular features Precursors lesions Treatment

Post-COVID-19 cholangiopathy:Current understanding and management options

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World Journal of Gastrointestinal Surgery 2023年第5期15卷 788-798页

作者： Fadl H Veerankutty Kushan Sengupta Mukul Vij Ashwin Rammohan Dinesh Jothimani Ananthavadivelu Murali mohamed rela Institute of Liver Disease and Transplantation Dr.Rela Institute and Research CentreChennai 600044India Institute of Liver Disease and Transplantation Dr.Rela Institute and Medical CentreChennai 600044India Department of Pathology Institute of Liver Disease and TransplantationChennai 600044India Gastroenterology and Hepatology Clinician’s PointChennai 600014Tamil NaduIndia

Post-coronavirus disease 2019(COVID-19)cholangiopathy(PCC)is a rare but lifethreatening complication of COVID-19 infection.PCC typically presents when patients recovering from the contagion and manifests as cholestasis in patients with no history of pre-existing liver disease.The pathogenesis of PCC is little understood.Hepatic injury in PCC could be mediated by the predilection of severe acute respiratory syndrome coronavirus 2 for cholangiocytes.Though PCC shows some resemblance to secondary sclerosing cholangitis in critically ill patients,it is considered as a separate and unique entity in the literature.Various treatment options like ursodeoxycholic acid,steroids,plasmapheresis,and endoscopic retrograde cholangiopancreatography guided interventions have been tried but with limited success.We have noticed significant improvement in liver function with antiplatelet therapy in a couple of patients.PCC can progress to end-stage liver disease necessitating liver transplantation.In this article,we discuss the current knowledge of PCC focusing on its pathophysiology,clinical manifestations,and management strategies.

关键词： COVID-19 Liver Post-COVID-19 syndrome Long haulers Cholangiopathy Cholestasis

Robotic donor hepatectomy:Are we there yet?

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World Journal of Gastrointestinal Surgery 2021年第7期13卷 668-677页

作者： Ashwin Rammohan mohamed rela Institute of Liver Disease&Transplantation Dr.Rela Institute&Medical CentreBharath Institute of Higher Education&ResearchChennai 600044India

In living donor liver transplantation(LDLT)the safety of the live donor(LD)is of paramount importance.Despite all efforts,the morbidity rates approach 25%-40%with conventional open donor hepatectomy(DH)operations.However,most of these complications are related to the operative wound and despite increased selfesteem and satisfaction in various quality of life analyses on LD,the most common grievance is that of the scar.Performing safe and precise DH through a conventional laparoscopic approach is a formidable task with a precipitous learning curve for the whole team.Due to the ramifications the donor operation carries for the donor,the recipient,the transplant team and for the LDLT program in general,the development and acceptance of minimally invasive DH(MIDH)has been slow.The robotic surgical system overcomes the reduced visualization,restricted range of motion and physiological tremor associated with laparoscopic surgery and allows for a comparatively easier transition from technical feasibility to reproducibility.However,many questions especially with regards to standardization of surgical technique,comparison of outcomes,understanding of the learning curve,etc.remain unanswered.The aim of this review is to provide insights into the evolution of MIDH and highlight the current status of robotic DH,appreciating the existing challenges and its future role.

关键词： Liver transplantation Donor hepatectomy Minimal invasive surgery Robotic surgery Outcomes

Cancer of the uncinate process of the pancreas:surgical anatomy and clinicopathological features

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Hepatobiliary & Pancreatic Diseases International 2009年第6期8卷 569-574页

作者： Adrian W. O'Sullivan Nigel Heaton mohamed rela Institute of Liver Studies King's College Hospital National Health Service(NHS) Foundation Trust

BACKGROUND:The clinicopathological features of uncinate process pancreatic cancer(UPPC) are poorly described.Furthermore the anatomy of the uncinate process and its division during surgery are central to pancreaticoduodenectomy for UPPC.We set out to describe the embryology and anatomy of the uncinate process and the clinicopathological features of UPPC.DATA SOURCES:All published case series of UPPC were reviewed and included in this review.RESULTS:The true incidence of UPPC is difficult to quantify,with the reported incidence ranging from 2.5% to 10.7% of pancreatic cancer.There are 5 published series of UPPC including 117 patients,72 males and 45 females,aged from 45-53 years to 61-84 years.The median survival was 5 or 5.5 months in 3 of the series,12.1 months in another based only on potentially resectable lesions and 17 months in another based only on resected cases.CONCLUSIONS:The number of reported series of UPPC is limited,with vague symptoms as the predominant presenting features of the disease.The prognosis is poor with synchronous venous resection demonstrating a survival advantage.

关键词： pancreatic neoplasms uncinate process anatomy embryology surgery

Cystic dystrophy in heterotopic pancreas:a rare indication for pancreaticoduodenectomy

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Hepatobiliary & Pancreatic Diseases International 2009年第2期8卷 215-217页

作者： Harun Thomas Paul Marriott Bernard Portmann Nigel Heaton mohamed rela Institute of Liver Studies Kings College School of Medicine at Denmark Hill

BACKGROUND:Cystic dystrophy in heterotopic pancreas (CDHP)is a rare benign condition characterized by the presence of cysts in the wall of the digestive tract associated with inflammation and fibrosis,intermingled with heterotopic pancreatic tissue.Treatment options for CDHP are poorly defined. METHOD:We report a case of CDHP,and review the literature focusing on the diagnosis and management. RESULTS:CDHP is mainly encountered in men in the fifth decade of life in association with chronic pancreatitis secondary to alcohol ingestion.Alcohol and mechanical obstruction of heterotopic pancreatic ducts have been implicated in its pathogenesis.Clinical presentation is varied and current imaging provides the diagnosis. Treatment options include somatostatin analogue injections, endoscopic cyst fenestration and surgical resection (pancreaticoduodenectomy or gastrointestinal bypass). CONCLUSION:CDHP is rare and presents a diagnostic and therapeutic challenge.The long term efficacy and indications for different treatment options need to be refined.

关键词： pancreas diseases duodenum cysts heterotopia

Clinical features and treatment of sump syndrome following hepaticojejunostomy

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Hepatobiliary & Pancreatic Diseases International 2011年第3期10卷 261-264页

作者： Gabriele Marangoni Amir Ali Walid Faraj Nigel Heaton mohamed rela King's College London School of Medicine at King's College Hospital Institute of Liver StudiesDenmark Hill

BACKGROUND:Cholangitis after Roux-en-Y hepaticojejunostomy is usually caused by anastomotic stricture.A small number of cases present without evidence of obstruction and are ascribed to reflux of gastro-intestinal content into the biliary tree above the anastomosis (sump syndrome).Despite prophylactic rotating antibiotic therapy,the cholangitic episode may be severe and life-threatening.METHODS:From 2001 to 2006,six patients who had undergone an end-to-side hepaticojejunostomy presented to our institution with recurrent episodes of biliary sepsis.Anastomotic stricture was excluded by liver MRI/MRCP and percutaneous transhepatic cholangiogram (PTC).Barium meal showed reflux of contrast into the biliary tree in all patients.Three patients had a short jejunal Roux limb (less than 50 cm) on pre-operative imaging.RESULTS:Five patients underwent surgery and two of them had two operations.One patient had a Tsuchida antireflux valve and subsequently underwent lengthening of the Roux loop.Three patients had lengthening of the Roux loop;one underwent re-do hepaticojejunostomy and one had concomitant revision of the hepaticojejunostomy and lengthening of the Roux loop.The latter underwent further lengthening of the Roux loop.Three patients are cholangitis-free 6,36 and 60 months after surgery;two still experience mild episodes of cholangitis.CONCLUSIONS:An adequate length of the Roux loop is important to prevent reflux.However,Roux loop lengthening to 70 cm or more does not always resolve the problem and cholangitis,although generally less frequent and severe,may recur despite appropriate reconstructive or antireflux surgery.In these cases,life-long rotating antibiotics is the only available measure.

关键词： biliary tract surgical procedures biliary tract disease septicemia

Non-functioning well-differentiated neuroendocrine tumor of the extrahepatic bile duct:an unusual suspect?

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Hepatobiliary & Pancreatic Diseases International 2007年第5期6卷 549-552页

作者： Harsheet Sethi Mansoor Madanur Parthi Srinivasan Bernard Portmann Nigel Heaton mohamed rela Department of Hepatobiliary and Transplant Surgery Kings College HospitalDenmark HillLondon SE5 9RSUK Department of Histopathology Kings College HospitalDenmark HillLondon SE5 9RSUK

BACKGROUND:Neuroendocrine tumors(NETs)arising in the biliary tree are extremely rare,and 37 cases were identified in the English literature. METHODS:A well-differentiated NET was found arising from the junction of the cystic and common hepatic ducts, in a 51-year-old male presenting with pedal edema and weight loss with abnormal liver enzymes and a normal serum bilirubin level.No mass was seen on radiological imaging and biopsy of the liver was suggestive of an early cholangiopathy.A bile leak complicating the liver biopsy led to an ERCP that demonstrated a filling defect suggestive of a mass in the common bile duct(CBD). RESULTS:He underwent a successful excision of the tumor with a Roux-en-Y hepaticojejunostomy.The diagnosis of NET was made on histological and immunohistochemical analysis of the resected specimen.He remains well and disease free 22 months after surgery. CONCLUSIONS:Recognition of biliary NET continues to be a challenge and an increased awareness of these tumors in rare sites will result in optimal management of these tumors.

关键词： carcinoid neuroendocrine tumor biliary common bile duct