Sanjay Govil

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.

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.

Preserving double equipoise in living donor liver-kidney transplantation for primary hyperoxaluria type 1

Primary hyperoxaluria type 1 (PH1) is a rare, autosomal recessive metabolic disorder caused by deficiency of pyridoxal phosphate–dependent peroxisomal alanine: glyoxalate aminotransferase (AGT) in the liver resulting in increased levels of serum oxalate. The kidneys excrete oxalate where it crystallizes within renal tubules causing nephrocalcinosis and renal failure. As the glomerular filtration rate (GFR) decreases because of progressive renal involvement, oxalate saturates the plasma and accumulates in bone and other body tissues causing systemic oxalosis. When diagnosed early, patients are managed medically (pyridoxine, citrates, hydration), but once the GFR falls below a critical level of 30 to 60 mL/ minute/1.73 m, preemptive liver transplantation (LT) may be considered. LT alone may be performed for selected patients with GFR between 15 and 30 mL/ minute/1.73 m, but the likelihood of having to undergo a subsequent kidney transplant is high. Once GFR drops below approximately 15 mL/minute/ 1.73 m, renal function is not salvageable after LT, and combined liver-kidney transplantation (CLKT) is the ideal treatment. CLKT is well accepted as the treatment of choice for patients with PH1 and end-stage renal disease. In the deceased donor liver transplantation (DDLT) setting, simultaneous CLKT from the same cadaver donor is ideal when the size and general condition of the recipient permit, with the remaining patients undergoing sequential CLKT. The infantile form of PH1 manifests as acute renal failure in the first few months of life. In this situation, where the abdominal cavity of the infant is unable to accommodate simultaneous CKLT, split LT is performed first, followed by a sequential kidney transplant if renal function remains inadequate. Compagnon et al., presenting the French national experience with such patients, reported better kidney graft survival (88% versus 10% at 10 years), less rejection, and a 78% 10-year survival rate without increased short-term mortality risk with CKLT compared to kidney transplantation alone. Others report similar results, mostly from countries where cadaveric organ donation is well established. In such a scenario, CKLT from the same deceased donor is feasible and offers immunological advantages with the liver graft providing renal immunoprotection because of immunogenetic identity. Sequential liverkidney transplantation (LKT) is only performed in small children in whom the abdominal cavity would be unable to accommodate both grafts simultaneously or in patients deemed clinically unfit to undergo combined grafts. In South Asia and the Far East where deceased donor organs are in very short supply, and living donor liver transplantation (LDLT) predominates, the familial nature of PH1, the need for 2 donor organs, and the variable severity of the disease in the recipient present special challenges (Table 1). In this scenario, the decision regarding whether to perform simultaneous or sequential LKT on PH1 patients with established renal failure is largely influenced by the availability of living donors for both organs—most commonly parents or siblings of the patient. Parents are most likely to be heterozygous carriers of the disease. We, along with other centers, assume that if they have reached adulthood without developing renal stones or nephrocalcinosis, they are unlikely to be homozygous for any of the AGT mutations. Data from the Japanese Multicenter Registry determined that heterozygous carriers of autosomal recessive diseases can safely donate their organs for transplantation without risk to either themselves or the recipient. Although these data did not include patients with PH1, Sasaki et al. recently found low to intermediate levels of liver AGT (30%-70% of normal) in living related donors for PH1 patients, suggesting they might be heterozygous carriers, without any adverse effects on either the donor or recipient. Sibling donors, however, tend to be younger, may not yet have manifested disease, and have a 25% chance of being homozygous for AGT mutations. We therefore

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.

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.

Portosystemic Shunts for “Small for Size Syndrome” Following Liver Transplantation: A Philosopher’s Stone?

Dear Editor, We read with interest the systematic review on portosystemic shunts for small grafts following liver transplantation by Kinaci et al. [1]. It is an interesting area, attracting intense deliberations in recent times. The authors have done a commendable job drawing information from the available literature on this subject. However, a lack of a uniform definition of small for size syndrome (SFSS) and the fact that all but 3 of the 16 studies used in this review are case reports are not the only deficiencies in the data available to the reviewers. Additional drawbacks include the following:

Does timing of rearterialization of liver grafts affect biliary complications in living and deceased donor liver transplantation

Although the first liver transplantation was revascularized arterially before portal reperfusion, revascularization of the transplanted liver graft is most commonly achieved with initial reperfusion via the portal vein followed by reconstruction of the hepatic artery. This is done primarily because the portal vein contributes approximately 75% of the blood supply to the liver and is easily and quickly anastomosed, shortening the warm ischemia time and the anhepatic phase. The waiting period between the portal and arterial anastomosis enables the graft to settle following reperfusion and allows for the arterial anastomosis to be performed in a more leisurely and conducive manner. This time interval between portal and arterial revascularization (time to rearterialization [TR]) may have certain adverse implications especially on the biliary tract. Studies in the deceased donor liver transplantation (DDLT) setting have shown that a delay in TR may contribute to ischemic injury of the biliary tract, increasing the risk of complications. Data on this topic are sparse, with no literature being available on the relation between TR and biliary complications in living donor liver transplantation (LDLT). We present our series of 500 liver transplant recipients and analyze the impact of the TR of grafts on biliary complications following liver transplantation in both the deceased and living donor settings.

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.

Well-Differentiated Neuroendocrine Tumour of the Extrahepatic Bile Duct: a Case Report with Review of Literature.

Neuroendocrine tumours (NETs) are defined as epithelial neoplasms with predominant neuroendocrine differentiation. They arise from the neuroendocrine cell system that consists of organoid cell aggregations disseminated across various organs of the body. They are found in greatest amounts in the small intestine, with decreasing frequency in the appendix, rectum, lung and pancreas and rarely in the ovaries, testes, liver and bile ducts. About 60 % of NETs arise within the gastrointestinal system [1]. NETs of the biliary system are rare, accounting for only 0.2–2 % of all gastrointestinal NETs [2], and are difficult to distinguish from cholangiocarcinoma preoperatively. Preoperative brush cytology is known to have low sensitivity in detecting tumours of the biliary tract [3] and is inconclusive in most cases of NETs considering the sub-mucosal nature of the lesion. We report a case of a nonfunctioning well-differentiated NET of the extrahepatic bile duct diagnosed by endoscopic ultrasonography (EUS)-guided fine-needle aspiration cytology (FNAC) and treated with surgical resection.

Associated Liver Partition with Portal Vein Ligation for Staged Hepatectomy

Complete resection of primary liver tumours and selected liver metastases offers patients the best chance of cure or long-term survival although it puts them at risk of postoperative liver failure (PLF), which remains the commonest cause of death after major hepatectomy [1]. An insufficient future liver remnant (FLR) either in terms of volume or quality is the main determinant of PLF. Most surgeons would accept a FLR of 25–30 % in patients with a normal liver, and 40 % or more in patients with steatosis, fibrosis or cirrhosis [1].