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

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.

Ruptured hepatocellular carcinoma following chemoembolization:a western experience

BACKGROUND: Transcatheter arterial chemoembolization (TACE) is a recommended first line therapy for unresectable hepatocellular carcinoma (HCC). Serious complications such as neutropenic sepsis and hepatic decompensation are well known, but rupture of HCC following TACE is a rare and potentially fatal complication. The aim of this study was to identify the incidence of ruptured HCC following TACE and the associated risk factors. METHODS: A retrospective analysis was performed using our liver database with "chemoembolization", "ruptured HCC" covering the patients who received chemoembolization from January 1995 to December 2005. There were no exclusions. RESULTS: A total of 294 patients received chemoemboliza- tion in 530 sessions during the 10-year period. Of these, 2 ruptured following treatment (incidence 0.68%). The mean age was 65 years and the interval between the treatment and rupture was 2 and 24 days. The common factors were male sex, large tumor size (range 11-13 cm), and exophytic tumor growth. One patient died 2 days after rupture with hepatic decompensation while the second is alive after a 6-month follow up without tumor recurrence. CONCLUSIONS: Ruptured HCC following TACE is a rare but serious complication. Large tumor size, male sex, and exophytic growth of tumor may be predisposing factors for rupture.

Selective embolization for bleeding visceral artery pseudoaneurysms in patients with pancreatitis

BACKGROUND:Pancreatitis is associated with arterial complications in 4%-10%of patients,with untreated mortality approaching 90%.Timely intervention at a specialist center can reduce the mortality to 15%.We present a single institution experience of selective embolization as first line management of bleeding pseudoaneurysms in pancreatitis. METHODS:Sixteen patients with pancreatitis and visceral artery pseudoaneurysms were identified from searches of the records of interventional angiography from January 2000 to June 2007.True visceral artery aneurysms and pseudoaneurysms arising as a result of post-operative pancreatic or biliary leak were excluded from the study. RESULTS:In 50%of the patients,bleeding complicated the initial presentation of pancreatitis.Alcohol was the offending agent in 10 patients,gallstones in 3,trauma,drug-induced and idiopathic pancreatitis in one each.All 16 patients had a contrast CT scan and 15 underwent coeliac axis angiography. The pseudoaneurysms ranging from 0.9 to 9.0 cm affected the splenic artery in 7 patients:hepatic in 3,gastroduodenal and right gastric in 2 each,and left gastric and pancreatico-duodenal in 1 each.One patient developed spontaneous thrombosis of the pseudoaneurysm.Fourteen patients had effective coil embolization of the pseudoaneurysm.One patient needed surgical exclusion of the pseudoaneurysm following difficulty in accessing the coeliac axis radiologically.There were no episodes of re-bleeding and no in-hospital mortality. CONCLUSIONS:Pseudoaneurysms are unrelated to the severity of pancreatitis and major hemorrhage can occur irrespective of their size.Co-existent portal hypertension and sepsis increase the risk of surgery.Angiography and selective coil embolization is a safe and effective way to arrest the hemorrhage.

Pseudoaneurysm following laparoscopic cholecystectomy

BACKGROUND:Laparoscopic cholecystectomy(LC)is the operation of choice for removal of the gallbladder. Unrecognized bile duct injuries present with biliary peritonitis and systemic sepsis.Bile has been shown to cause damage to the vascular wall and therefore delay the healing of injured arteries leading to pseudoaneurysm formation.Failure to deal with bile leak and secondary infection may result in pseudoaneurysm formation. This study was to report the incidence and outcomes of pseudoaneurysm in patients with bile leak following LC referred to our hospital. METHODS:A retrospective analysis of our prospectively maintained liver database using pseudoaneurysm, bile leak and bile duct injury following laparoscopic cholecystectomy from January 2000 to December 2005 was performed. RESULTS:A total of 86 cases were referred with bile duct injury and bile leak following LC and of these,4 patients (4.5%)developed hepatic artery pseudoaneurysm(HAP) presenting with haemobilia in 3 and massive intra- abdominal bleed in 1.Selective visceral angiography confirmed pseudoaneurysm of the right hepatic artery in 2 cases,cystic artery stump in one and an intact but ectatic hepatic artery with surgical clips closely applied to the right hepatic artery at the origin of the cystic artery in the fourth case.Effective hemostasis was achieved in 3 patients with coil embolization and the fourth patient required emergency laparotomy for severe bleeding and hemodynamic instability due to a ruptured right hepatic artery.Of the 3 patients treated with coil embolization, 2 developed late strictures of the common hepatic duct. . (CHD)requiring hepatico-jejunostomy and one developed a stricture of left hepatic duct.All the 4 patients are alive at a median follow up of 17 months(range 1 to 65)with normal liver function tests. CONCLUSIONS:HAP is a rare and potentially life- threatening complication of LC.Biloma and subsequent infection are reported to be associated with pseudoaneurysm formation.Late duct stricture is common either due to unrecognized injury at LC or secondary to ischemia after embolization.

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

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.

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

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).

Clinical features and treatment of sump syndrome following hepaticojejunostomy

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.

Novel en-bloc resection of locally advanced hilar cholangiocarcinoma: the Rex recess approach

Loco-regional recurrence after potentially curative resection remains a problem in hilar cholangiocarcinoma. Hilar dissection risks local spillage of tumor cells leading to suboptimal disease free survival. We have developed a new technique of radical resection for hilar cholangiocarcinoma based on the distinctive anatomy of the Rex recess of the liver, which has been assessed in two patients with locally advanced hilar cholangiocarcinoma. This technique included a right hepatectomy with en-bloc resection of the hepatoduodenal ligament and portal venous reconstruction to the left portal vein at the Rex recess. Both patients had R0 resection and have been disease-free for 26 and 38 months, respectively.

Liver transplantation for acute intermittent porphyria:a viable treatment?

BACKGROUND:Acute intermittent porphyria (AIP) is the most common hepatic porphyria.Its clinical presentation includes severe disabling and life-threatening neurovisceral symptoms and acute psychiatric symptoms.These symptoms result from the overproduction and accumulation of porphyrin precursors,5-aminoleuvulinic acid (ALA) and porphobilinogen (PBG).The effect of medical treatment is transient and is not effective once irreversible neurological damage has occurred.Liver transplantation (LT) replaces hepatic enzymes and can restore normal excretion of ALA and PBG and prevent acute attacks.METHOD:Two cases of LT for AIP were identified retrospectively from a prospectively maintained LT database.RESULT:LT was successful with resolution of AIP in two patients who suffered from repeated acute attacks.CONCLUSION:LT can correct the underlying metabolic abnormality in AIP and improves quality of life significantly.

Developing a donation after cardiac death risk index for adult and pediatric liver transplantation

AIM To identify objective predictive factors for donor after cardiac death(DCD) graft loss and using those factors, develop a donor recipient stratification risk predictive model that could be used to calculate a DCD risk index(DCD-RI) to help in prospective decision making on organ use.METHODS The model included objective data from a single institute DCD database(2005-2013, n = 261). Univariate survival analysis was followed by adjusted Cox-regressional hazard model. Covariates selected via univariate regression were added to the model via forward selection, significance level P = 0.3. The warm ischemic threshold was clinically set at 30 min. Points were given to each predictor in proportion to their hazard ratio. Using this model, the DCD-RI was calculated. The cohort was stratified to predict graft loss risk and respective graft survival calculated.RESULTS DCD graft survival predictors were primary indication for transplant(P = 0.066), retransplantation(P = 0.176), MELD > 25(P = 0.05), cold ischemia > 10 h(P = 0.292) and donor hepatectomy time > 60 min(P = 0.028).According to the calculated DCD-RI score three risk classes could be defined of low(DCD-RI < 1), standard(DCD-RI 2-4) and high risk(DCD-RI > 5) with a 5 years graft survival of 86%, 78% and 34%, respectively.CONCLUSION The DCD-RI score independently predicted graft loss(P < 0.001) and the DCD-RI class predicted graft survival(P < 0.001).

Robotic donor hepatectomy:Are we there yet?

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.

Chylous ascites after pancreatico-duodenectomy

BACKGROUND:Chylous ascites(CA) following pancreatico-duodenectomy(PD) is a rare complication secondary to disruption of the lymphatics during extended retroperitoneal lymph node dissection. The majority of cases do not develop CA,possibly due to patency of the proximal thoracic duct and good collaterals. CA may be due to a consequence of occult obstruction of the proximal thoracic duct by malignant infiltration or tumor embolus. This study was to report the incidence of CA and its outcomes of management. METHODS:A retrospective search of our liver database was performed using the "pancreatico-duodenectomy","chylous ascites" from January 2000 to December 2005. The medical records of CA patients and their management and outcome were reviewed. RESULTS:In 138 patients who had undergone PD in our centre for pancreatic malignancy,3 were identified with CA and managed by abdominal paracentesis. CA resolved in 2 patients with low fat medium chain triglyceride diet alone and 1 patient had total parenteral nutrition(TPN) for persistent CA. Resolution of CA occurred in these 3 patients at a median follow-up of 4 weeks(range 4-12 weeks). Histologically,resected specimen confirmed pancreatic adenocarcinoma in all the patients. Two patients developed loco-regional recurrences at a median follow up of 8 months(range 6-10 months). And the other was currently disease free at a 10-month follow up. CONCLUSIONS:CA as an uncommon postoperative complication requires frequent paracentesis,prolonged hospital stay,and delayed adjuvant chemotherapy. CA istreated with low fat medium chain triglyceride diet or occasionally TPN is required.

Cystic dystrophy in heterotopic pancreas:a rare indication for pancreaticoduodenectomy

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.

匹配的施主到在肝移植的接受者: 在临床的实践的关联

Achieving optimum outcomes after liver transplantation requires an understanding of the interaction between donor,graft and recipient factors.Within the cohort of patients waiting for a transplant,better matching of the donor organ to the recipient will improve transplant outcomes and benefit the overall waiting list by minimizing graft failure and need for re-transplantation.A PubMed search was conducted to identify published literature investigating the effects of donor factors such as age,gender,ethnicity,viral serology;graft factors such as size and quality,recipient factors such as age,size,gender and transplant factors such as major or minor blood group incompatibility and immunological factors.We also report technical and therapeutic modifications that can be used to manage donor-recipient mismatch identified from literature and the authors’clinical experience.Multiple donor and recipient factors impact graft survival after liver transplantation.Appropriate matching based on donor-organ-recipient variables,modification of surgical technique and innovative peri-transplant strategies can increase the donor pool by utilizing grafts from marginal donors that are traditionally turned down.

Non-invasive real-time assessment of hepatic macrovesicular steatosis in liver donors:Hypothesis,design and proof-of-concept study

Macrovesicular Steatosis(MS)is an independent risk factor for adverse post-liver transplant(LT)outcomes.The degree of MS is intimately related to the viability of the liver graft,which in turn is crucial to the success of the operation.An ideal liver graft should have no MS and most centres would find it unacceptable to use a donor liver with severe MS for LT.While a formal liver biopsy is the goldstandard diagnostic test for MS,given the logistical and time constraints it is not universally feasible.Other tests like a frozen section biopsy are plagued by issues of fallibility with reporting and sampling bias making them inferior to a liver biopsy.Hence,the development of an accurate,non-invasive,easy-to-use,handheld,real-time device for quantification of MS would fill this lacuna in the deceased donor selection process.We present the hypothesis,design and proof-ofconcept of a study,which aims to standardise and determine the feasibility and accuracy of a novel handheld device applying the principle of diffuse reflectance spectroscopy for real-time quantification of MS.

Pediatric metabolic liver diseases:Evolving role of liver transplantation

Metabolic liver diseases(MLD)are the second most common indication for liver transplantation(LT)in children.This is based on the fact that the majority of enzymes involved in various metabolic pathways are present within the liver and LT can cure or at least control the disease manifestation.LT is also performed in metabolic disorders for end-stage liver disease,its sequelae including hepatocellular cancer.It is also performed for preventing metabolic crisis’,arresting progression of neurological dysfunction with a potential to reverse symptoms in some cases and for preventing damage to end organs like kidneys as in the case of primary hyperoxalosis and methyl malonic acidemia.Pathological findings in explant liver with patients with metabolic disease include unremarkable liver to steatosis,cholestasis,inflammation,variable amount of fibrosis,and cirrhosis.The outcome of LT in metabolic disorders is excellent except for patients with mitochondrial disorders where significant extrahepatic involvement leads to poor outcomes and hence considered a contraindication for LT.A major advantage of LT is that in the post-operative period most patients can discontinue the special formula which they were having prior to the transplant and this increases their well-being and improves growth parameters.Auxiliary partial orthotopic LT has been described for patients with noncirrhotic MLD where a segmental graft is implanted in an orthotopic position after partial resection of the native liver.The retained native liver can be the potential target for future gene therapy when it becomes a clinical reality.

Pancreaticoduodenectomy with radical lymphadenectomy is not contraindicated for patients with established chronic liver disease and portal hypertension

BACKGROUND: hronic liver disease has been considered a contraindication to radical surgery for intra-abdominal tumors because of the risk of decompensation. METHODS: In a retrospective analysis of all patients undergoing pancreaticoduodenectomy for cancer treated from January 2000 to December 2006 at our center, 4 patients were identified with operable pancreatic tumors and well-compensated chronic liver disease. The preoperative staging, decompression of the biliary tree, liver biopsy, Child-Turcot-Pugh and MELD scores were described.RESULTS: All patients underwent pancreaticoduodenectomy successfully with minimal blood loss, and no peri-operative blood transfusions or liver decompensation. There was no postoperative mortality. Two patients received adjuvant chemotherapy. One patient died with recurrent disease at 18 months, one is alive with disease recurrence, and two are alive and disease free.CONCLUSION: Patients with pancreatic cancer and well-compensated chronic liver disease should routinely be considered for radical surgery at specialist hepatobiliary centres with expertise available to manage complex liver disease.

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

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.

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

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.

Liver resection in liver transplant recipients

BACKGROUND:Liver resection after liver transplantation is a relatively uncommon procedure.Indications for liver resection include hepatic artery thrombosis(HAT),non- anastomotic biliary stricture(ischemic biliary lesions), liver abscess,liver trauma and recurrence of hepatocellular carcinoma(HCC).Organ shortage and lower survival after re-transplantation have encouraged us to make attempts at graft salvage. METHODS:Eleven resections at a mean of 59 months after liver transplantation were made over 18 years.Indications for liver resection included HCC recurrence in 4 patients, ischemic cholangiopathy,segmental HAT,sepsis and infected hematoma in 2 each,and ischemic segmentⅣafter split liver transplantation in 1. RESULTS:There was no perioperative mortality.Morbidity included one re-laparotomy for small bowel perforation, one bile leak treated conservatively,one right subphrenic collection,one wound infection and 5 episodes of Gram- negative sepsis.One patient underwent re-transplantation 4 months after resection for chronic rejection.There were 3 deaths,two from HCC recurrence and one from post- transplant lymphoproliferative disorder.The overall mean follow-up after resection was 48 months. CONCLUSIONS:Liver resection in liver transplant recipients is safe,and has good outcome in selected patients and avoids re-transplantation in the majority of patients. Recipients with recurrent HCC in graft may benefit from resection,but cure is uncommon.