Michael A. Silva

Hepatic artery thrombosis following orthotopic liver transplantation: a 10-year experience from a single centre in the United Kingdom.

Hepatic artery thrombosis (HAT) occurs in 3–9% of all liver transplants and acute graft loss is a possible sequelae. We present our experience in the management of HAT over a 10‐year period. Prospectively collected data from April 1994 to April 2004 were analyzed. There were 1,257 liver transplants, 669 males, median age 51 (16–73) years. There were 61 (4.9%) cases of HAT. Early HAT occurred in 21 (1.8%). Thirty six had graft dysfunction, 11 required a regraft, and 14 died. Positive CMV serology in the donor, cold ischemia time, duration of operation, transfusions of more than 6 units of blood, and 15 units of plasma, an aortic conduit for arterial reconstruction, Roux‐en‐Y biliary reconstructions, regrafts and relaparotomy were associated with HAT. At multivariate analysis, type of biliary anastomosis was the only significant factor associated with HAT. Split or reduced liver graft were not risk factors for HAT. Number of hepatic arteries requiring multiple arterial anastomosis was not a risk for HAT. HAT resulted in a reduction in overall survival post liver transplantation. The incidence of HAT was 4.9%; with 1.8% early HAT and HAT impacted on survival. Surgical technique was not an aetiological factor for HAT. In conclusion, while a Roux‐en‐Y biliary reconstruction was an independent risk factor for HAT, cold ischemia and operative times, the use of blood and plasma and the use of aortic conduits in arterial reconstruction were associated with HAT. Regrafts and reoperation were also identified risk factors. Liver Transpl 12:146–151, 2006.

Biliary Tract Complications after Liver Transplantation: A Review

Biliary complications continue to be a major cause of morbidity in liver transplant recipients with an incidence of 10–30% following whole-organ transplantation and a mortality rate of up to 10%. Biliary leaks and strictures are most common but sphincter of Oddi dysfunction, hemobilia, and biliary obstruction are also observed. Biliary complications may be related to various factors such as hepatic artery patency, preservation injury, cytomegalovirus infection, chronic ductopenic rejection, ABO incompatibility, and technical reasons. The latter include imperfect anastomosis, T-tube-related complications and the use of partial liver grafts when cut surface biliary leaks or inadvertent bile duct injuries may occur during parenchymal division. The usage of a T-tube for duct-to-duct anastomosis in whole-organ liver transplantation remains controversial, mainly because of the high rates of T-tube-related complications observed in many series. In this article we review the etiology, as well as the main types of biliary complications according to the technique of biliary reconstruction and liver transplant procedure performed. Their management is also discussed with interventional radiology and endoscopic techniques emerging as the preferred treatment option, obviating the need for surgery in a selected majority of patients.

The marginal liver donor – an update

The number of patients awaiting liver transplantation keeps steadily rising with no corresponding rise in suitable grafts for transplantation. There also is an increasing trend of patients dying or being taken off waiting lists because of deterioration while waiting for a transplant. Over the preceding years the use of marginal grafts in liver transplantation has been driven by the critical shortage of donor organs and by emerging data that their use has resulted in a favourable outcome. This review revisits the factors defining marginality of a graft, and the issues faced by transplant units in making the decision to use such a graft. It also looks at the innovations in transplantation geared towards increasing the donor pool and the resulting issues of matching marginal grafts to suitable recipients.

Biliary complications following adult right lobe ex vivo split liver transplantation

Biliary complications are common following split liver transplantation (SLT). We analyzed the incidence, treatment, and outcome of biliary complications following adult right lobe ex vivo SLT performed between November 1992 and January 2005. There were 72 patients, of which 70 were analyzed. Early postoperative deaths resulted in 2 being excluded from the analysis. There were 44 males (median age, 48 yr; range, 19–70 yr). Biliary reconstruction was by duct‐to‐duct (DD) anastomosis in 52 (74%) and Roux‐en‐Y hepaticojejunostomy (RYHJ) in 18 (26%) patients. Until mid‐2001, no T‐tube was used for DD anastomosis (DD/non‐T‐tube) in 26 (37%) patients; subsequent to this, DD over a T‐tube (DD/T‐tube) was performed in 26 (37%) patients. Eighteen (26%) biliary complications occurred in 16 patients. Two anastomotic leaks of RYHJ were associated with hepatic artery thrombosis. The most frequent biliary complication was parenchymal radical leak from the transected liver surface (11%; 8/70), with anastomotic leaks in 6% (4/70) and strictures in 4% (3/70). There were also 2 cases of biliary leaks from T‐tube exit site following T‐tube removal, and 1 leak from the donor cystic duct stump. DD anastomosis without a T‐tube was associated with a higher rate of cut surface and anastomotic biliary leaks (7/26), compared to the DD/T‐tube group (1/26; P = 0.05). Six patients (9%) died following biliary complications, including 3 due to cut surface leaks in the DD/non‐T‐tube group and 2 cases with fatal biliary peritonitis following T‐tube removal. A patient in the RYHJ group died due to biliary sepsis associated with hepatic artery thrombosis. In conclusion, biliary complications following right lobe ex vivo SLT are associated with significant morbidity and mortality. Our results suggest that T‐tube biliary drainage of DD anastomosis may reduce parenchymal cut surface and biliary anastomotic leaks. However, bile leak following T‐tube removal could lead to potentially fatal biliary peritonitis, which should always be anticipated and treated promptly. Liver Transpl 12:839–844, 2006.

Specialist Early and Immediate Repair of Post-laparoscopic Cholecystectomy Bile Duct Injuries Is Associated With an Improved Long-term Outcome

Introduction:A majority of bile duct injuries (BDI) sustained during laparoscopic cholecystectomy require formal surgical reconstruction, and traditionally this repair is performed late. We aimed to assess long-term outcomes after repair, focusing on our preferred early approach. Methods:A total of 200 BDI patients [age 54(20–83); 64 male], followed up for median 60 (5–212) months were assessed for morbidity. Factors contributing to this were analyzed with a univariate and multivariate analysis. Results:A total of 112 (56%) patients were repaired by specialist hepatobiliary surgeons [timing of repair: immediate, n = 28; early (<21 days), n = 43; and late (>21 days) n = 41], whereas 45 (22%) underwent repair by nonspecialist surgeons before specialist referral [immediate, n = 16; early, n = 26 and late, n = 03]. Outcomes after immediate and early repairs were comparable to late repairs when performed by specialists [recurrent cholangitis:11%, 12%, and 10%; P = 0.96, NS; re-stricture:18%,5%, and 29%; P = 0.01; nonsurgical intervention: 14%, 5%, and 24%; P<0.03; redo surgery: 4%, 2%, and 5%; P = 0.81, NS; overall morbidity: 21%, 14%, and 39%; P<0.02]. On multivariate analysis, immediate and early repairs done by nonspecialist surgeons were independent risk factors (P < 0.05) for recurrent cholangitis [50% and 27%], re-stricturing (75% and 61%), redo reconstructions (31% and 61%), and overall morbidity (75% and 84%). Conclusion:Immediate and early repair after BDI results in comparable, if not better long-term outcomes compared to late repair when performed by specialists.

Treatment of Hydatid Disease of the Liver

Background: Hydatid disease of the liver though endemic in many countries, is rare in the UK. We evaluated a 16-year experience of treating hydatidosis using a management protocol combining surgery with anti-scolicidals. Patients and Methods: There were 30 patients. 14 (47%) males, median age 41 (range 25–72) years, of whom 21 (70%) were symptomatic. Diagnosis was by serological tests and imaging. All had disease confined to the liver and received peri-operative anti-scolicidal drug therapy. Results: The initial 4 (13%) patients received praziquantel combined with albendazole for 2 weeks and the following 26 (87%) patients received two cycles of albendazole 400 mg twice daily for 28 days, with a 14-day break in between. However, 2 (7%) patients could not tolerate albendazole, one due to GI side effects and the other developed deranged liver functions. These 2 patients subsequently received praziquantel for 2 weeks. All patients underwent surgery. Subtotal cystectomy was carried out on 29 (96%) patients and 1 patient required a segmentectomy. Cystobiliary communications were identified in 15 (50%) of patients which were oversewn using fine absorbable sutures. Of these, 7 had the bile ducts decompressed using a T tube, with only 1 developing a post-operative bile leak. In comparison, 8 were not drained of which 6 leaked (p = 0.03). The median post-operative hospital stay was 8 days (range 5–24). Patients who developed post-operative bile leaks, however, needed prolonged abdominal drainage for a median of 21 days (range 18–24). Two (7%) patients developed histologically proven recurrent disease. The median follow-up was 56 months (range 3–87). Conclusion: Surgery combined with anti-scolicidal therapy proved effective. Cystobiliary communications are common and, when identified, should result in the biliary system being drained, to avoid post-operative bile leaks.

Conventional versus piggyback technique of caval implantation; without extra-corporeal veno-venous bypass. A comparative study.

Conventional orthotopic liver transplantation (CON‐LT) involves resection of recipient cava, usually with extra‐corporeal circulation (veno‐venous bypass, VVB), while in the piggyback technique (PC‐LT) the cava is preserved. Along with a temporary portacaval shunt (TPCS), better haemodynamic maintenance is purported with PC‐LT. A prospective, consecutive series of 384 primary transplants (2000–2003) were analysed, 138 CON‐LT (with VVB) and 246 PC‐LT (54 without TPCS). Patient/donor characteristics were similar in the two groups. PC‐LT required less usage of fresh‐frozen plasma and platelets, intensive care stay, number of patients requiring ventilation after day 1 and total days spent on ventilator. The results were not different when comparing, total operating and warm ischaemia time (WIT), red cell usage, requirement for renal support, day 3 serum creatinine and total hospital stay. TPCS had no impact on outcome other than WIT (P = 0.02). Three patients in PC‐LT group (three of 246;1.2%) developed caval outflow obstruction (P = 0.02). There was no difference in short‐ or long‐term graft or patient survival. PC‐LT has an advantage over CON‐LT unsing VVB with respect to intraoperative blood product usage, postoperative ventilation requirement and ITU stay. VVB is no longer required and TPCS may be used selectively in adult transplantation.

Carcinosarcoma of the biliary tract : two case reports and a review of the literature

Carcinosarcoma of the biliary tract is extremely rare. Little is known about the natural course of these tumours, or the best available treatment. We present two cases of carcinosarcoma of the biliary tract, one of the gall bladder and one of the common bile duct, followed by a review of the literature.

Intrahepatic complement activation, sinusoidal endothelial injury, and lactic acidosis are associated with initial poor function of the liver after transplantation.

Background. Changes in glucose metabolism in the liver during transplantation have been recently described using microdialysis. Here, these findings are correlated with histopathologic, immunohistochemical, and ultrastructural changes in liver. Methods. Microdialysis catheters were inserted into 15 human livers, which were perfused with isotonic solution, and samples of perfusate were analyzed before harvest, after storage, and after reperfusion. At each stage Menghini needle biopsy samples were taken and each studied using light and electron microscopy. Results. Six livers showed serum biochemical evidence of initial poor function. These livers had significantly more staining for complement fragment 4d (C4d) of both lobular and periportal hepatocytes. C4d-positive hepatocytes were also found in the liver during cold storage (3 of 15). These periportal hepatocytes also showed evidence of necrosis and were found to have intracellular neutrophils. Hepatocyte rounding in zone III, necrosis, and C4d staining in recipient were also significantly correlated with the degree of lactic acidosis during this phase. Intrahepatic lactic acidosis at all time points was significantly associated with sinusoidal endothelial cell injury after reperfusion. There were no correlations between glucose, pyruvate, and glycerol levels and histopathologic changes in the liver. Discussion. In the patients studied, the degree of C4d staining correlated with initial poor function and was associated with intrahepatic lactic acidosis in the donor during cold storage and after reperfusion. Complement activity in the liver during cold storage may be after in situ activation. Intrahepatic lactic acidosis is associated with sinusoidal endothelial cell and hepatocyte injury. The role of intrahepatic neutrophils is uncertain and could possibly be in response to cell necrosis.

Prognostic value, localization and correlation of PD-1/PD-L1, CD8 and FOXP3 with the desmoplastic stroma in pancreatic ductal adenocarcinoma

We examined the prognostic value of programmed cell death-1 (PD-1) and its ligand (PD-L1) together with CD8+ tumor-infiltrating lymphocytes (TILs) and FOXP3+ Tregs in resectable pancreatic ductal adenocarcinoma (PDAC) samples treated with adjuvant chemotherapy. Whole-mount FFPE tissue sections from 145 pancreatectomies were immunohistochemically stained for PD-1, PD-L1, CD8 and FOXP3. Their expression was correlated with clinicopathological characteristics, and overall survival (OS), progression-free survival (PFS), local progression-free survival (LPFS) and distant metastases free-survival (DMFS), in the context of stroma density (haematoxylin-eosin) and activity (alpha-smooth muscle actin) and in regard to intratumoral lymphoid aggregates. The median OS was 21 months after a mean follow-up of 20 months (range, 2-69 months). In multivariate analysis, high PD-1+ TILs expression was associated with better OS (p = 0.049), LPFS (p = 0.017) and DMFS (p = 0.021). Similar findings were observed for CD8+ TILs, whereas FOXP3 and PD-L1 lacked prognostic significance. Although TIL distribution was heterogeneous, tumors of high stroma density had higher infiltration of CD8+ TILs than loose density stroma and vice versa (p < 0.001), whereas no correlation was found with stromal activity. Sixty (41.4%) tumors contained lymphoid aggregates and the presence of PD-1+ TILs was associated with better OS (p = 0.030), LPFS (p = 0.025) and DMFS (p = 0.033), whereas CD8+ TILs only correlated with superior LPFS (p = 0.039). PD-1+ and CD8+ TILs constitute independent prognostic markers in patients with PDAC treated with adjuvant chemotherapy. Our study provides important insight on the role of PD-1/PD-L1 in the context of desmoplastic stroma and could help guide future immunotherapies in PDAC.