T-tube or no T-tube in cadaveric orthotopic liver transplantation: the eternal dilemma: results of a prospective and randomized clinical trial.

OBJECTIVE: To compare the incidence and severity of biliary complications due to liver transplantation after choledochocholedochostomy with or without a T-tube in a single-center, prospective, randomized trial. SUMMARY BACKGROUND DATA: The usefulness of the T-tube for end-to-end biliary anastomosis to reduce the incidence of biliary complications in patients undergoing liver transplantation has been controversial. METHODS: A per-protocol analysis was designed for liver recipients, who were randomly assigned to choledochocholedochostomy with (n = 95) or without (n = 92) a T-tube. RESULTS: The overall biliary complication rate was 22.5% (n = 42), with no difference between groups (P = 0.35). The majority (66.7%) of complications in the T-tube group were types I and II, whereas 50% were type IIIa and 44% were type IIIb in the non-T-tube group (P < 0.0001). Fewer anastomotic strictures were found in the T-tube group (n = 2, 2.1%) than in the non-T-tube group (n = 13, 14.1%; P = 0.002). No difference in anastomotic biliary leakage was observed between groups. Biliary complication-free survival rates showed that complications appeared earlier in the T-tube group. Graft and patient survival rates were similar in both groups. CONCLUSIONS: Complications in the T-tube group were less severe and required less aggressive treatment. The incidence of anastomotic strictures was higher in patients with no T-tube. We recommend conducting choledochocholedochostomy with a rubber T-tube during liver transplantation in risky anastomosis and when the bile duct diameter is less than 7 mm. This study is registered at http://www.clinicaltrials.gov: Clinical trial ID# NCT01546064.

Clinical outcome of hepatocyte transplantation in four pediatric patients with inherited metabolic diseases.

Hepatocyte transplantation (HT) has become an effective therapy for patients with metabolic inborn errors. We report the clinical outcome of four children with metabolic inborn errors that underwent HT, describing the cell infusion protocol and the metabolic outcome of transplanted patients. Cryopreserved hepatocytes were used as this allows scheduling of treatments. Functional competence (viability, cell attachment, major cytochrome P450 and UDP-glucuronosyltransferase 1A1 activities, and urea synthesis) and microbiological safety of cell batches were assessed prior to clinical use. Four pediatric patients with liver metabolic diseases [ornithine transcarbamylase (OTC) deficiency, Crigler-Najjar (CNI) syndrome, glycogen storage disease Ia (GSD-Ia), and tyrosinemia type I (TYR-I)] underwent HT. Indication for HT was based on severity of disease, deterioration of quality of life, and benefits for the patients, with the ultimate goal to improve their clinical status whenever liver transplantation (LT) was not indicated or to bridge LT. Cells were infused into the portal vein while monitoring portal flow. The protocol included antibiotic prophylaxis and immunosuppressant therapy. After HT, analytical data on the disease were obtained. The OTC-deficient patient showed a sustained decrease in plasma ammonia levels and increased urea production after HT. Further cell infusions could not be administered given a fatal nosocomial fungus sepsis 2 weeks after the last HT. The CNI and GSD-Ia patients improved their clinical status after HT. They displayed reduced serum bilirubin levels (by ca. 50%) and absence of hypoglycaemic episodes, respectively. In both cases, the HT contributed to stabilize their clinical status as LT was not indicated. In the infant with TYR-I, HT stabilized temporarily the biochemical parameters, resulting in the amelioration of his clinical status while diagnosis of the disease was unequivocally confirmed by full gene sequencing. In this patient, HT served as a bridge therapy to LT.

[Reflections on 250 interventions for colorectal carcinoma metastases to the liver]. / Reflexiones sobre 250 intervenciones de metástasis hepáticas de carcinoma colorrectal.

INTRODUCTION: The best results in the treatment of colorectal cancer metastases to the liver are currently achieved with surgical resection performed under high quality standards. OBJECTIVES. To analyze the results and quality standards of the surgical treatment of colorectal cancer liver metastases in a referral liver unit over an 11-year period. PATIENTS AND METHOD: From January 1995 to December 2005, 250 surgical interventions were performed in 221 patients diagnosed with colorectal cancer liver metastases, resulting in 201 hepatic resections. RESULTS: Nineteen percent of patients were >/= 70 years old and comorbidity was present in 54%. Of the 201 hepatic resections, 8.5% were second resections. Major hepatectomy was performed in 39% of the patients. R0 resection was achieved in 85% of the patients. Blood transfusions were not required in 80% of the patients. The median length of postoperative stay was 6 days. Postoperative mortality was nil and morbidity was 19%. Morbidity was associated with the number of resected segments and the need for blood transfusion. The estimated 1-, 3- and 5-year cumulative survival rates were 96%, 69% and 52%, respectively, while estimated disease-free survival rates were 58%, 32% and 24%, respectively. CONCLUSIONS: Resection of colorectal cancer liver metastases is an effective therapeutic alternative if high current quality standards are achieved.

An open, randomized, multicenter clinical trial of oral tacrolimus in liver allograft transplantation: a comparison of dual vs. triple drug therapy.

Triple therapy combining an anticalcineurin agent, corticosteroids, and azathioprine (AZA) in liver transplantation has been frequently applied, particularly in Europe. Debates have arisen concerning the use of a third drug (AZA), mainly in patients receiving tacrolimus (TAC). An open-label, multicenter, prospective, and randomized trial was performed to assess the efficacy and safety of TAC and corticosteroids (dual therapy [D]) vs. TAC, corticosteroids, and AZA (triple therapy [T]) in liver transplantation. A total of 180 patients were randomized, 92 in D and 88 in T group. Patients were followed during 3 months for efficacy and safety and up to 24 months for patient and graft survival assessments. The rate of biopsy-proven acute rejection was higher in D than in T group (40.7% vs. 24.4%; P = 0.021). A higher incidence of positive HCV status in D group (55.6% vs. 40.7%; P = 0.049) may explain this difference, since significantly more patients of this HCV subpopulation experienced acute rejection when treated with D therapy (48% vs. 20%; P = 0.008). No treatment differences were apparent for HCV-negative patients. The 24-month graft survival tended to be inferior in T group, 69.8% vs. 75.8% (P = 0.283). Similar results were observed regarding patient survival at the same time point, with values of 72.9% vs. 76.9% (P = 0.573), favoring D group. Both regimens showed comparable safety profiles with the exception of hematological abnormalities, which were more frequently observed in T group. In conclusion, both regimens were shown to be effective although increased toxicity and a trend towards a lower graft and patient survival were observed in T group.

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.