Karim Boudjema

Surgical resection of colorectal carcinoma metastases to the liver: A prognostic scoring system to improve case selection, based on 1568 patients

Five‐year survival rates after resection of liver metastases from colorectal carcinoma are close to 25%. Recurrences occur in two‐thirds of the patients after surgery. Selection of patients likely to benefit from surgery remains controversial and subjective.

Randomized Trial of Choledochocholedochostomy With or Without a T Tube in Orthotopic Liver Transplantation

ObjectiveTo compare the incidence of biliary complications after liver transplantation in patients undergoing choledochocholedochostomy reconstruction with or without T tube in a multicenter, prospective, randomized trial. Summary Background DataSeveral reports have suggested that biliary anastomosis without a T tube is a safe method of biliary reconstruction that could avoid complications related to the use of T tubes. No large prospective randomized trial has so far been published to compare the two techniques. MethodsOne hundred eighty recipients of orthotopic liver transplantation were randomly assigned to choledochocholedochostomy with (n = 90) or without (n = 90) a T tube in six French liver transplantation centers. All types of biliary complications were taken into account. ResultsThe overall biliary complication rate was increased in the T-tube group, even though these complications did not lead to an increase in surgical or radiologic therapeutic procedures. The major significant complication was cholangitis in the T-tube group; this did not occur in the other group. The incidence of biliary fistula was 10% in the T-tube group and 2.2% in the group without a T tube. Other biliary complications were similar. The complication rate of cholangiography performed with the T tube was greater than with other types of biliary exploration. The graft and patient survival rates were similar in the two groups. ConclusionThis study is the first large prospective, randomized trial of biliary complications with or without a T tube. The authors found an increase in the biliary complication rate in the T-tube group, which was linked to minor complications. The T tube did not provide a safer access to the biliary tree compared with the others types of biliary explorations. The authors recommend the performance of choledochocholedochostomy without a T tube in liver transplantation.

Impact of pretransplantation transarterial chemoembolization on survival and recurrence after liver transplantation for hepatocellular carcinoma.

The actual impact of transarterial chemoembolization before liver transplantation (LT) for hepatocellular carcinoma (HCC) on patient survival and HCC recurrence is not known. Between 1985 and 1998, 479 patients with HCC in 14 French centers were evaluated for LT. Among these 479 patients, this case‐control study included 100 patients who received transarterial chemoembolization before LT (TACE group) and 100 control patients who did not receive chemoembolization (no‐TACE group). Patients and controls were matched for the pre‐LT tumor characteristics, the period of transplantation, the time spent on the waiting list, and pre‐ and posttransplantation treatments. Kaplan‐Meier estimates were calculated 5 years after LT and were compared with the log‐rank test. The mean waiting time before LT was 4.2 ± 3.2 months in the TACE group and 4.3 ± 4.4 months in the no‐TACE group. The median number of TACE procedures was 1 (range: 1‐12). Demographic data, median alpha‐fetoprotein level (21.6 ng/mL and 22.0 ng/mL, respectively), and pre‐ and post‐LT morphologic characteristics of the tumors did not differ in the TACE and no‐TACE groups. Overall 5‐year survival was 59.4% with TACE and 59.3% without TACE (ns). Survival rates did not differ significantly between the two groups with respect to the time on the waiting list, the tumor diameter, or the type of TACE (selective or nonselective). In the TACE group, 30 patients had tumor necrosis ≥80% on the liver explant with a 5‐year survival rate of 63.2%, compared with 54.2% among their matched controls (P = 0.9). In conclusion, with a mean waiting period of 4.2 months and 1 TACE procedure, pre‐LT TACE does not influence post‐LT overall survival and disease‐free survival. (Liver Transpl 2005;11:767–775.)

Transcatheter oily chemoembolization for hepatocellular carcinoma. A 4-year Study of 127 French Patients

Background. In Western countries, only a small proportion of patients with hepatocellular carcinoma (HCC) can be treated with surgical resection. For other patients, locoregional management by transcatheter oily chemoembolization seems to be useful and warrants evaluation.

Is pancreaticoduodenectomy with mesentericoportal venous resection safe and worthwhile

BACKGROUND Whether or not superior mesentericoportal venous resection (SM-PVR) associated with pancreaticoduodenectomy (PD) is safe and worthwhile has not been fully confirmed. The aim of the present study was to investigate results of this surgical procedure performed for pancreatic head and periampullary neoplasms. METHODS As a first analysis, postoperative morbidity and mortality after PD with (n = 31) or without SM-PVR (n = 119) were investigated in 150 patients with pancreatic head and periampullary neoplasms. As a second analysis, rates of margin-negative resection and survival after SM-PVR (n = 21) and without SM-PVR (n = 66) were compared in 87 patients with pancreatic ductal adenocarcinoma of the pancreatic head. In these patients undergoing SM-PVR (n = 21), survival rate was investigated in patients who did (n = 13) and did not (n = 8) undergo a margin-negative resection. RESULTS In the first analysis, duration of surgery and volume of blood transfused perioperatively were higher in patients undergoing SM-PVR. However, mortality, morbidity rates, and mean hospital stay did not differ between patients who did undergo SM-PVR (31 patients, 3.2%, 48.4%, and 22.2 days, respectively) and who did not (119 patients, 2.5%, 47.1%, 25.9 days, respectively). No postoperative death occurred in the recent part of the present study, since 1994, in patients undergoing SM-PVR. In the second analysis of pancreatic ductal adenocarcinoma, rates of margin-negative resection and 2-year survival did not significantly differ between patients who did and did not undergo SM-PVR (62% and 22%, respectively, versus 73% and 24%). In patients undergoing SM-PVR, survival rate was significantly higher for patients undergoing a margin-negative resection (n = 13) than for patients undergoing a macroscopic or microscopic margin-positive resection (n = 8, 2-year survival = 57.1% versus 0%, P <0.05). CONCLUSION PD combined with SM-PVR can be performed safely. This surgical procedure is followed by a promising survival rate and can be recommended in order to obtain a margin-negative resection; however, candidates for SM-PVR should be carefully selected.

Auxiliary versus orthotopic liver transplantation for acute liver failure

BACKGROUND/AIMS/METHODS We report 1-year results after auxiliary liver transplantation for acute liver failure in a cohort of 47 patients transplanted in 12 European centers as compared with those of 384 consecutive patients undergoing orthotopic liver transplantation for acute liver failure in the Eurotransplant area. RESULTS One-year patient survival resp. retransplant-free patient survival did not differ between orthotopic (61%, 232/384 resp. 52%, 200/384) and auxiliary liver transplantation (62%, 29/47 resp. 53%, 25/47). One-year patient survival resp. retransplant-free patient survival after auxiliary partial orthotopic liver transplantation was 71% (25/35) resp. 60% (21/35), not significantly different from orthotopic liver transplantation (61%, 232/384 resp. 52%, 200/384), while both transplantation techniques had better 1-year patient survival resp. retransplant-free patient survival than after heterotopic auxiliary liver transplantation (33%, 4/12) (p < 0.05). Primary nonfunction was more frequent after heterotopic auxiliary liver transplantation (3/12, 25%) than after orthotopic liver transplantation (21/384, 5.5%), while the incidence did not differ between orthotopic liver transplantation and auxiliary partial orthotopic liver transplantation (3/35, 8.5%). Portal vein thrombosis was more frequent after both heterotopic auxiliary liver transplantation (5/12, 42%) and auxiliary partial orthotopic liver transplantation (5/35, 14%) than after orthotopic liver transplantation (2/384, 0.5%) (p < 0.001). Of the patients, 65% (17/26) surviving auxiliary liver transplantation for 1 year without retransplantation by orthotopic liver transplantation were free of immunosuppression within 1 year, compared with none of the patients transplanted by orthotopic liver transplantation (p < 0.01). CONCLUSIONS Auxiliary liver transplantation, especially auxiliary partial orthotopic liver transplantation, offers an advantage over orthotopic liver transplantation in acute liver failure in terms of a chance of a life free of immunosuppression, apparently without jeopardizing chances of survival. Reduction of the incidence of primary nonfunction and vascular complications should be a focus of research in auxiliary liver transplantation. These findings need to be confirmed in a prospective study.

Indication of liver transplantation in severe alcoholic liver cirrhosis: quantitative evaluation and optimal timing

BACKGROUND/AIMS The aim of our study was to evaluate the proportion of patients with severe alcoholic cirrhosis who would need orthotopic liver transplantation (OLT) and to determine the optimal delay to evaluate an abstinent patient for transplantation. METHODS Survival without OLT, improvement in liver function and need for OLT were studied in all patients admitted in 1997 for a first episode of Child-Pugh C alcoholic cirrhosis. RESULTS Twenty-six percent (19/74) of patients died during the initial hospitalization. The cumulative survival rates after 6 months and 1, 2 and 3 years were 56, 36, 35 and 24%, respectively. One liver transplantation (1.3%, 95% confidence interval 0.0-3.9) was performed for persisting liver failure despite abstinence. Improvement of the Child-Pugh score was observed within 3 months in 66% of the abstinent patients. OLT was indicated in four patients without liver improvement despite abstinence, but was contraindicated in three. CONCLUSIONS Only a few patients with severe alcoholic cirrhosis undergo OLT, since most of them do not stop drinking and/or die soon, and those becoming abstinent often improve their liver function. OLT should be considered when improvement in liver function is lacking after 3 months of abstinence.

Corticosteroid‐free immunosuppression with tacrolimus following induction with daclizumab: A large randomized clinical study

This open, randomized (1 : 1), multicenter, 3‐month study compared a dual tacrolimus plus steroids (Tac / steroids) regimen with a steroid‐free immunosuppressive regimen of tacrolimus following daclizumab induction therapy (Tac / Dac) in adult liver transplant recipients. The full analysis set comprised 347 patients in the Tac / steroids group and 351 in the Tac / Dac group. Mean tacrolimus dose during month 3 was 0.11 mg/kg/day in both groups; mean whole‐blood trough levels during month 3 were 10.9 ng/mL (Tac / steroids) and 10.6 ng/mL (Tac / Dac). The incidence of biopsy‐confirmed acute rejection that required treatment was similar in both groups: 26.5% in the Tac / steroids group and 25.4% in the Tac / Dac group (P = .727). However, the incidence of biopsy‐confirmed corticosteroid‐resistant acute rejection was higher in the Tac / steroids group than in the Tac / Dac group (6.3 vs. 2.8%; P = .027). Kaplan‐Meier estimates of graft survival (92.2 vs. 90.5%) and patient survival (94.5 vs. 93.7%) were similar in both groups. While also the overall adverse event profiles were similar, the incidences of diabetes mellitus (15.3 vs. 5.7%, respectively; P < .001) and cytomegalovirus infection (11.5 vs. 5.1%, respectively; P = .002) were higher in the Tac / steroids group compared with the Tac / Dac group. Mean cholesterol levels increased by 16% in the Tac / steroids group, but were unchanged in the Tac / Dac group during the study. In conclusion, tacrolimus monotherapy following daclizumab induction is an effective and safe regimen, with an advantage over concomitant steroid‐maintenance therapy in terms of a lower incidence of diabetes and viral infection, and a lower incidence of steroid‐resistant acute rejection. (Liver Transpl 2005;11:61–67.)

Auxiliary liver transplantation for fulminant and subfulminant hepatic failure.

We report the first series of 9 auxiliary liver transplantations performed as a bridge to recovery in 8 patients with fulminant and subfulminant hepatic failure. Hepatic failure was due to hepatitis A virus (n = 3), hepatitis B virus (n = 1), hepatotoxic drugs (n = 2), autoimmune disease (n = 1), or it was of unknown origin (n = 1). The donor liver was reduced to a left lobe (n = 2), a left liver (n = 4), or a right liver (n = 3), and was implanted in an orthotopic position beside the native liver after it was resected by a left or a right hepatectomy. Conventional immunosuppression was used to prevent rejection. Six patients regained normal consciousness within 2 weeks, without any sequelae. Two patients had persisting encephalopathy due to graft initial dysfunction, one of whom showed portal vein thrombosis, which was successfully cleared. The other one showed hepatic vein stenosis and was retransplanted at day 15. Five of eight patients had to be reoperated because of a surgical complication. Five patients showed rapid regeneration of their native liver, but one died at day 45 from severe herpes virus broncholitis. The auxiliary grafts were removed (n = 3) or left to atrophy by tapering immunosuppression (n = 1). One patient developed cirrhosis of the native liver and died of infectious complications at day 42. The native livers of the two remaining patients are still atrophic, one at 4 months and one at 1 month posttransplant. Finally, 6 of 8 patients are alive with a follow-up of 1 to 17 months. Four of them have permanently stopped their immunosuppressive therapy. Our experience demonstrates that auxiliary orthotopic liver transplantation (1) is feasible in children and adults, using either a left or a right liver graft, (2) is efficient in providing adequate liver function, and (3) gives a real chance to the native liver to regenerate, offering these patients a future free of immunosuppression.

Protective effects of N-acetylcysteine on hypothermic ischemia-reperfusion injury of rat liver.

We investigated whether intraportal injection of 150 mg/kg N‐acetylcysteine (NAC) into rats reduced hepatic ischemia‐reperfusion injury after 48 hours of cold storage and 2 hours of reperfusion. The organ was isolated and perfused to evaluate liver function. The control group received an intraportal injection of 5% dextrose. NAC increased L‐cysteine concentrations 15 minutes after injection (1.29 ± 0.11 μmol/g vs. 2.68 ± 0.4 μmol/g,P < .05). However, neither treatment modified glutathione liver concentrations relative to preinjection values. After 48 hours of cold storage and 2 hours of reperfusion, livers from NAC‐treated rats produced larger amounts of bile than those in the control group (5.04 ± 1.92 vs. 0.72 ± 0.37 μL/g liver; P < .05), and showed a significant reduction in liver injury, as indicated by reduced release of lactate dehydrogenase (679.4 ± 174.4 vs. 1891.3 ± 268.3 IU/L/g; P < .01), aspartate transaminase (AST) (13.94 ± 3.5 vs. 38.75 IU/L/g; P < .01), alanine transaminase (ALT) (14.92 ± 4.09 vs. 45.91 ± 10.58 IU/L/g; P < .05), and acid phosphatase, a marker of Kupffer cell injury (344.4 ± 89.6 vs. 927.3 ± 150.8 IU/L/g; P < .01) in the perfusate. Reduced glutathione concentrations in the perfusate were similar in the two groups (805 ± 69 vs. 798 ± 252 nmol/L/g), whereas oxidized glutathione (GSSG) concentrations were higher in the control group (967 ± 137 vs. 525 ± 126 nmol/L/g; P < .05). Reduced glutathione (GSH) concentrations in liver tissue collected at the end of perfusion were significantly higher in the NAC group (7.3 ± 0.9 vs. 4.1 ± 1.0 μmol/g; P < .05). The protective effect of NAC on cold ischemia‐reperfusion liver injury persisted when animals were pretreated with buthionine sulfoximine (BSO), a specific inhibitor of glutathione synthesis. Our results suggest that NAC enhances the concentrations of cysteine within hepatocytes, providing a substrate for glutathione synthesis during reperfusion. They also indicate that NAC has a direct protective effect on Kupffer cells, which are the first source of reactive oxygen intermediates during reperfusion. (HEPATOLOGY 1995; 22:539–545.)