The potential liver donor with tuberculosis: A fresh look at international recommendations based on a survey of practice in Indian liver transplant centres.

Background The western recommendations for the use of organs from liver donors with tuberculosis (TB) come from an environment where the burden of disease is low and cadaveric organ donation rates are high-in complete contrast to the Indian scenario, where these recommendations may be too restrictive. Methods A questionnaire relating to current practice on the use of organs from liver donors with TB was sent to all liver transplant centres in India. Results Responses were obtained from 94% of centres. Two-thirds accepted organs from deceased donors with TB in the elective setting, especially for recipients with a high MELD (Model for end-stage liver disease) score. The proportion rose by 1.5 times in the setting of acute liver failure. Two-thirds advised anti-TB treatment (ATT) for corresponding recipients, and the remaining advised isonicotinic acid hydrazide (INH) prophylaxis. Untreated living donors with TB were not accepted. Half the respondents accepted living donors after completion of ATT, and did not treat recipients postoperatively. The remainder accepted them after 8 weeks of treatment and advised INH prophylaxis or ATT for recipients. Conclusions That this practice has not impacted recipient outcomes suggests that the guidelines for management of liver donors and recipients may need to be altered for populations endemic for TB.

The pathogenesis of portal hypertension differs between small for size syndrome (SFSS) and postoperative liver Failure(POLF).

The pathogenesis of portal hypertension differs in patients with small for size syndrome (SFSS) after living donor liver transplantation (LDLT) and postoperative liver failure (POLF) after liver resection. This difference has important implications in the prevention and management of POLF.

Vein resection in patients with adenocarcinoma of the head of pancreas adherent to the portomesenteric venous axis is beneficial despite a high rate of R1 resection.

BACKGROUNDS/AIMS: En-bloc vein resection (VR) for pancreatic ductal adenocarcinoma (PDAC) of the head of pancreas adherent to the portomesenteric axis benefits patients when the vein wall is not infiltrated by tumour and an R0 resection is achieved, albeit at the expense of greater morbidity and mortality. METHODS: A retrospective review of pancreaticoduodenectomy for PDAC over 6 years was conducted. Patients were divided into a standard resection group (Group SR) and simultaneous vein resection group (Group VR) and compared for outcome. RESULTS: The study group consisted of 41 patients (Group SR 15, Group VR 26). VR was performed by end-to-end reconstruction in 12 patients and with interposition grafts in 13 cases (autologous vein in 10, PTFE in 3). R1 resections occurred in 49% patients, with the superior mesenteric artery margin most commonly involved. Patients with Ishikawa grade III and IV vein involvement were more likely to carry a positive SMA margin (p=0.04). Involvement of the splenoportal junction was associated with a significantly greater risk of pancreatic transection margin involvement. No difference in morbidity was seen between the groups. Median survival in the entire group of patients was 17 months and did not vary significantly between the groups. The only significant predictor of survival was lymph node status. CONCLUSIONS: Venous involvement by proximal PDAC is indicative of tumor location rather than tumor biology. VR improves outcomes in patients with tumor adhesion to the portomesenteric venous axis despite a high incidence of R1 resections and greater operative mortality.

Combination of TACE and Sorafenib Improves Outcomes in BCLC Stages B/C of Hepatocellular Carcinoma: A Single Centre Experience

ABSTRACT Background & Aim. Transarterial chemoembolization (TACE) or sorafenib is recommended for hepatocellular carcinoma BCLC stages B and C respectively. We studied the role of combination of TACE and sorafenib in BCLC stages B/C. Material and methods. We undertook an observational study on a cohort of cirrhotics with HCC from August 2010 through October 2014. Patients in BCLC stages B/C who had received TACE and/or sorafenib were included. mRECIST criteria were used to assess tumor response. The primary end point was overall survival. Results. Out of 124 patients, 47.6% were in BCLC-B and 52.4% in BCLCC. Baseline characteristics were comparable. The predominant etiology was cryptogenic (37.2% and 38.5%, p = NS). 49.1% in BCLC-B and 56.9% in BCLC-C had received TACE+sorafenib. In BCLC-B, the overall survival improved from 9 months (95% CI 6.3-11.7) using TACE only to 16 months (95% CI 12.9-19.1) using TACE+sorafenib (p < 0.05). In BCLC-C, addition of TACE to sorafenib improved the overall survival from 4 months (95%CI 3-5) to 9 months (95%CI 6.8-11.2) (p < 0.0001). As per mRECIST criteria, patients on TACE+sorafenib had reduced progressive disease (37.8% vs. 83.3%), improved partial response (43.2% vs. 3.3%) and one had complete response compared to those on sorafenib alone (p < 0.0001) in BCLC-C but not in BCLC-B group. Hand foot syndrome was noted in 27.7% patients on sorafenib and post TACE syndrome in 80.2% patients, but both were reversible. No major adverse events were noted. Conclusion. TACE+sorafenib was more effective than TACE or sorafenib alone in HCC BCLC stages B or C with a significant survival benefit and improved tumour regression especially in BCLC-C patients.

Combination of TACE and Sorafenib Improves Outcomes in BCLC Stages B/C of Hepatocellular Carcinoma: A Single Centre Experience.

BACKGROUND AND AIM: Transarterial chemoembolization (TACE) or sorafenib is recommended for hepatocellular carcinoma BCLC stages B and C respectively. We studied the role of combination of TACE and sorafenib in BCLC stages B/C. MATERIAL AND METHODS: We undertook an observational study on a cohort of cirrhotics with HCC from August 2010 through October 2014. Patients in BCLC stages B/C who had received TACE and/or sorafenib were included. mRECIST criteria were used to assess tumor response. The primary end point was overall survival. RESULTS: Out of 124 patients, 47.6% were in BCLC-B and 52.4% in BCLCC. Baseline characteristics were comparable. The predominant etiology was cryptogenic (37.2% and 38.5%, p = NS). 49.1% in BCLC-B and 56.9% in BCLC-C had received TACE+sorafenib. In BCLC-B, the overall survival improved from 9 months (95% CI 6.3-11.7) using TACE only to 16 months (95% CI 12.9-19.1) using TACE+sorafenib (p < 0.05). In BCLC-C, addition of TACE to sorafenib improved the overall survival from 4 months (95%CI 3-5) to 9 months (95%CI 6.8-11.2) (p < 0.0001). As per mRECIST criteria, patients on TACE+sorafenib had reduced progressive disease (37.8% vs. 83.3%), improved partial response (43.2% vs. 3.3%) and one had complete response compared to those on sorafenib alone (p < 0.0001) in BCLC-C but not in BCLC-B group. Hand foot syndrome was noted in 27.7% patients on sorafenib and post TACE syndrome in 80.2% patients, but both were reversible. No major adverse events were noted. CONCLUSION: TACE+sorafenib was more effective than TACE or sorafenib alone in HCC BCLC stages B or C with a significant survival benefit and improved tumour regression especially in BCLC-C patients.

Changing pattern of biliary complications in an evolving liver transplant unit.

Biliary complications (BCs) remain a significant cause of morbidity following liver transplantation (LT). This series of 640 LT recipients with a blend of living and deceased donor transplants was analyzed to determine the incidence, risk factors, management protocol, and outcomes in these patients. Review of a prospectively collected database of transplant recipients operated between August 2009 and June 2016 was performed. Patients were divided into those with and without BCs and data analyzed. The 640 LT recipients from both living (n = 481) and deceased donors (n = 159) were evaluated for BCs. The overall incidence of BCs was 13.7%. It reduced from 23% to 5% (P = 0.003) over a 6-year period. Risk factors for BCs on multivariate analysis were living donor liver transplantation, prolonged time to rearterialization, recipient age above 16 years, prolonged cold ischemia time (CIT) after deceased donor liver transplantation, and biliary reconstruction performed by anyone but the senior author. One-fifth of bile leaks progressed to strictures, and 40% of strictures followed leaks. Endoscopic therapy resolved 60% of the strictures. Surgical repair of strictures was successful in 90% of those in whom endoscopy failed, those who could not undertake the follow-up schedules endoscopic therapy entails, and those presenting with late strictures. BCs significantly prolonged hospital stay but did not alter survival after LT. BCs affect 1 in 7 recipients, although they are not associated with increased mortality. The frequency of these complications is influenced by potentially modifiable factors like evolving surgical expertise and CIT. Liver Transplantation 23 478-486 2017 AASLD.

Hepatocarcinogenesis in multidrug-resistant P-glycoprotein 3 deficiency.

MDR3 is a hepatocyte canalicular membrane protein encoded by the ABCB4 gene located on chromosome 7. MDR3 mediates the translocation of phosphatidylcholine into bile. Severe MDR 3 deficiency typically presents during early childhood with chronic cholestasis evolving to cirrhosis and portal hypertension, requiring liver transplantation. Herein, we report a case of severe MDR3 deficiency in a male child diagnosed with negative MDR3 immunostaining in hepatic canaliculi who underwent LDLT at our centre. We also describe single incidentally detected early well-differentiated HCC in the explant liver. The patient is on regular follow-up and is doing well. Our report shows that MDR3 deficiency may be a risk factor for the development of HCC.

Pediatric hepatocellular carcinoma in a developing country: Is the etiology changing?

HCC is the second most common malignant liver tumor of childhood. It typically affects children with a median age of 10-14 yr on background hepatitis B-related liver disease and is often metastatic or locally advanced at diagnosis. Children below the age of five yr typically constitute <10% of all children with HCC. In these children, it occurs on a background of congenital or metabolic liver disease. The records of all children with HCC who presented to our department over a six-yr study period were reviewed. Twelve patients with a median age of 5.9 yr (range 1.6-15.4) were diagnosed to have HCC. All patients underwent liver transplantation, and none were resected. Eleven patients had background congenital or metabolic liver disease. All five of those with hereditary tyrosinemia type 1 who presented to us were found to have HCC. No patient had hepatitis B-related liver (HBV) disease. Eight (66.7%) patients had incidentally discovered HCC on examination of the explant. Incidentally discovered HCC were smaller, well differentiated, and did not show microvascular invasion compared to those diagnosed preoperatively. There was no recurrence with a median follow-up of five months. The patient demographic for pediatric HCC is changing probably as a consequence of successful immunization against HBV. Younger patients with congenital and metabolic liver disease in whom liver transplantation is the ideal treatment are likely to constitute an ever-increasing proportion of patients with pediatric HCC as HBV disease is controlled or eradicated.

Liver resection for perihilar cholangiocarcinoma - why left is sometimes right.

INTRODUCTION: Left-sided liver resection (LLR) for perihilar cholangiocarcinoma (PHC) may require right hepatic artery (RHA) resection and reconstruction because of its intimate relationship with the biliary confluence. Consequently right-sided resections (RLR) are preferred for Bismuth-Corlette IIIb tumours, and resections avoided in Bismuth-Corlette IV tumours with left lobar atrophy when the RHA is involved by tumour. METHODS: A retrospective analysis of patients with PHC who presented between December 2009 and June 2015. RESULTS: Thirty-six patients underwent resection for PHC (23 LLR, 13 RLR). The number of Bismuth-Corlette IV patients undergoing LLR was significantly greater than those undergoing RLR (8/23 vs 0/13, p = 0.032). The need for arterial reconstruction (AR) was significantly greater during LLR than RLR (10/23 vs 0/13, p = 0.006). Postoperative liver dysfunction was greater after RLR (5/13 vs 0/23, p = 0.003), and hospital stay was shorter after LLR (10 vs 15 days, p = 0.013). CONCLUSIONS: Safe AR increases the ability to perform potentially curative LLR for PHC. This improves the resectability rate for PHC, particularly for Bismuth-Corlette Type IV tumours. The larger liver remnant after LLR results in less postoperative liver dysfunction and shorter hospital stay without increased operating time, blood loss or morbidity.

Management of post liver transplantation recurrent hepatitis C infection with directly acting antiviral drugs: a review.

Recurrent HCV infection (rHCV) of the liver allograft following transplantation is universal and is associated with poor graft and patient survival in comparison with other indications. Treatment of rHCV infection in the previous era with pegylated interferon and ribavirin was associated with low sustained virological response (SVR) due to poor tolerability, adverse events and graft rejection. Recently, directly acting antiviral drugs (DAA) have been approved for the treatment of hepatitis C infection and a number of clinical trials have been conducted across various centers in the management of rHCV infection of the graft. In this review we discuss about recent studies that have emerged on the use of NS5b polymerase inhibitor, sofosbuvir in combination with second generation protease inhibitor, simeprevir, fixed dose ledipasvir or daclatasvir with or without ribavirin in the treatment of post transplant rHCV infection.

Safety of Live Liver Donation by Individuals With G6PD Deficiency: Initial Results and Comparative Study.

BACKGROUND: G6PD deficiency (G6PDd) is the commonest genetic enzyme defect in the world. However, baring a single case report, there is no published literature regarding the safety of donor hepatectomy in G6PDd individuals. METHODS: Potential donors with World Health Organization class III or class IV G6PDd without evidence of hemolysis were evaluated for donation, if there was no other suitable donor. Postoperatively, donors were closely monitored for hemolysis and medications, which can induce hemolysis, were avoided. Outcomes of our first 14 G6PDd donors are presented. Postoperative course of these donors was also compared with a matched cohort of 30 non-G6PDd donors. RESULTS: There were 9 left lateral segment, 2 left lobe, and 3 right lobe donors. Two G6PDd donors had biochemical evidence of postoperative hemolysis not needing any specific treatment. Postoperative liver function tests, intensive care unit stay, hospital stay, and morbidity (greater than Clavien II) were similar in the G6PDd and non-G6PDd donor cohorts. Donors in the G6PDd group had lower trough hemoglobin in postoperative period (P = 0.006), greater drop in postoperative hemoglobin (P = 0.007), and a higher need for postoperative blood transfusion (4/14 vs 2/30, P = 0.071). CONCLUSIONS: This is the first case series reporting the safety of liver resection in G6PDd individuals. Hepatectomy in G6PD-deficient donors is associated with a greater drop in postoperative hemoglobin and a marginally increased need for postoperative transfusion. Use of these donors can be considered with caution, and it should not be an absolute contraindication for live liver donation.

Central hepatic resection under hypothermic total vascular exclusion using ante-situm techniques while maintaining liver blood supply.

Ante-situm liver resection under hypothermic total vascular exclusion is used to resect large tumours that involve the hepatic veins close to the vena cava or the cava itself. This procedure traditionally requires venovenous bypass when it is necessary to clamp the cava, or portocaval shunt when caval continuity is maintained by piggyback dissection of the liver. We present a technique of ante-situm liver resection, operating on one side of the liver at a time while maintaining prograde portal flow through the opposite side of the liver, thereby avoiding venovenous bypass, portacaval shunt and portal vein reconstruction.

Surgical resection techniques for locally advanced hilar cholangiocarcinoma.

BACKGROUND: Resection of perihilar cholangiocarcinoma involves major hepatectomy including caudate lobectomy. It is technically challenging because of the complex, intimate and variable relationship between biliary and vascular structures in the liver hilum. Resectability rates vary from 30 to 80 % and about one third of patients have microscopically involved margins. However, adequately performed resections provide 5-year survival of 30-40 % and are worth pursuing. PURPOSE: Better understanding of anatomy, better imaging, improved surgical techniques and progress in perioperative care of these patients have pushed the limits of resection of these tumours. Many of the traditional indicators of inoperability such as bilateral involvement of second-order hepatic ducts, contralateral biliary and vascular involvement, and need for arterial resection have been overcome or are being challenged. This review discusses techniques that may increase margin-free resectability of Bismuth-Corlette type III and IV perihilar cholangiocarcinoma. CONCLUSION: Advanced perihilar cholangiocarcinoma requires extended liver resection and often vascular resection, despite which the margin may be compromised in about one third of patients. Right sided tumours are likely to need right trisectionectomy and portal vein resection, best served by an en bloc hilar resection or Rex-recess approach. Left-sided tumours often involve contralateral blood vessels and require left trisegmentectomy with possible right portal vein or right hepatic artery reconstruction. These tumours are best tackled by hepatobiliary surgeons with experience in microvascular techniques. Salvage procedures when arterial reconstruction is not feasible are still under evaluation.

Is superior mesenteric artery reimplantation during surgery for pancreaticoduodenal tumors an underutilized procedure?

Resection and reimplantation of the superior mesenteric artery (SMA) as part of a pancreaticoduodenal resection for cancer is rarely performed even in high-volume centers because of the risks inherent in this procedure and the perceived lack of oncological benefit associated with arterial resection during pancreaticoduodenectomy. The role of arterial resection during pancreaticoduodenectomy has recently been reevaluated, and this procedure may be of greater benefit than previously believed in selected patients. It also has a definite role when necessary to resect low-grade pancreatic and peripancreatic malignancies or to salvage intraoperative injury to the SMA. This small case series presents the authors experience with this procedure.