Gonzalo Sapisochin

Indications and management of everolimus after liver transplantation.

OBJECTIVE Our aim was to assess our experience with the use and management of everolimus after orthotopic liver transplantation (OLT). MATERIALS AND METHODS Among the 759 patients who underwent transplantation from 1988 to 2008, 25 (3.2%) received immunosuppression with everolimus. Their mean age was 55.6 years. We analyzed indications for use, time between transplantation and introduction of everolimus, as well as its efficacy, side effects, and patient survival. RESULTS The indications for everolimus treatment were: extended hepatocellular carcinoma (HCC) in the explanted liver (n = 6; 24%); HCC recurrence during follow-up (n = 4; 16%); de novo tumor (n = 6; 24%); refractory rejection (n = 3; 12%); side effects of calcineurin inhibitors (CNI; n = 3; 12%); and other causes (n = 3; 12%). Mean time between OLT and everolimus treatment was 40 +/- 33 months (range, 10 days-178 months). Mean follow-up after conversion was 10 +/- 9 months (range, 1.5-25 months). More than half of the patients resolved the event for which the drug was indicated: 75% of patients with refractory rejection; 60% of those with renal insufficiency; and 100% of those converted for neurotoxicity or hepatotoxicity. Two patients with recurrent HCC and 1 with extended HCC died at a mean time of 10.5 months. The 6 cases of de novo tumors were operated and are healthy. Side effects were dyslipidemia in 8 and infection in 2. Five patients (20%) discontinued the drug. CONCLUSIONS In the early posttransplantation period, everolimus is indicated for refractory rejection or as prophylaxis for recurrence of extended tumors. In any time but especially in the late period, everolimus is indicated for patients with serious side effects due to a CNI or to a de novo tumor.

Outcome of patients following hepatic resection for metastatic cutaneous and ocular melanoma

Background/purposeThe aim of this study was to analyze the outcome of patients undergoing hepatic resection for melanoma liver metastases.MethodsPatients undergoing liver resection for melanoma metastases at the Hospital Vall d’Hebron and Hospital Clinic, Barcelona, were reviewed. Selection criteria were: good performance status, feasibly complete and safe resection, and absence of visceral extrahepatic metastases.ResultsBetween 1994 and 2007, 14 liver resections were performed for melanoma liver metastases. The primary tumor was cutaneous in 8 patients and ocular in 6. Two patients underwent urgent liver surgery due to tumor bleeding. In these patients, complete melanoma staging was not performed and extrahepatic metastases were found during surgery or during the postoperative course. Six of 13 patients (46.2%) developed liver recurrence during follow-up. One- and 3-year actuarial patient survivals were 77 and 49%, respectively. Excluding the patients who underwent urgent liver surgery, the 1- and 3-year actuarial patient survivals in those with primary ocular and cutaneous melanoma were 83 and 56% and 80 and 60%, respectively.ConclusionsLiver resection may be considered as part of oncosurgical treatment in patients with melanoma liver metastases, since prolonged survival was observed, albeit with a high recurrence rate. Nevertheless, it should be taken into account that our study included only a small number of patients.

Severe Rhabdomyolysis and Acute Renal Failure Secondary to Concomitant Use of Simvastatin With Rapamycin Plus Tacrolimus in Liver Transplant Patient

OBJECTIVE To report a severe interaction between simvastatin and rapamycin resulting in rhabdomyolysis and acute renal failure in a liver transplant patient. BACKGROUND A 56-year-old man with hepatitis C virus cirrhosis (Child B) was diagnosed with hepatocellular carcinoma and underwent liver transplantation in April 2007. He was immunosuppressed with tacrolimus (FK) and mycophenolate mofetil (MMF). Postoperative complications were arterial hypertension and renal insufficiency. In June 2007, liver dysfunction was detected and acute rejection was diagnosed by biopsy. He received three 500-mg boluses of methylprednisolone and FK levels were maintained between 10 and 12 ng/mL. Laboratory values revealed persistent rejection and MMF was stopped with initiation of rapamicin. One month later, hyperlipidemia appeared as a consequence of rapamicin therapy; simvastatin was administered. In August 2007, the patient was readmitted due to severe muscule pain and the inability to ambulate. Laboratory values were: total bilirubin 16 mg/dL, serum creatinine 4.3 mg/dL, and total creatine kinase (CK) 42,124 U/L. With the suspicion of rhabdomyolysis, leading to worsening of his basal renal insufficiency, rapamycin and tacrolimus were stopped. Hemodialysis was initiated owing to renal failure and hyperkalemia. Some hours later, the patient developed ventricular fibrillation and respiratory failure and succumbed. DISCUSSION Calcineurin inhibitors (CNI), corticosteroids, and mammalian target of rapamycin (m-TOR) inhibitors are associated with adverse dyslipidemic effects. To reduce the overall cardiovascular risk in these patients, lipid-lowering drugs, especially 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, have been widely used. CNI and m-TOR inhibitors, as well as most statins, are metabolized by cytochrome P450 (CYP)3A4; thus, pharmacokinetic interactions between these drugs are possible. Previous reports have indicated an increased risk of rhabdomyolysis in the presence of concomitant drugs that inhibit simvastatin metabolism. CONCLUSIONS Concomitant administration of statin therapy and drugs that inhibit cytochrome P450 (CYP)3A4 increased the risk of rhabdomyolysis in a patient suffering liver and renal dysfunction.

Evolution of Biliary Complications After Liver Transplantation: A Single European Series

BACKGROUND The aim of this study was to analyze the evolution of biliary complications over 20 years among adult patients undergoing liver transplantation (OLT) at our institution. PATIENTS AND METHODS Between 1985 and 2007, we performed 1000 OLT in 789 adults and 211 children. To ascertain the evolution of biliary complications among adult OLT from October 1988 to September 2007, we compared the first 100 to with the last 200 adult OLT. RESULTS Duct-to-duct was the most common biliary anastomosis performed in both periods (1st; 89% and 2nd; 94%; P = NS). However, a T-tube was used more frequently in the first period (1st; 46% vs 2nd; 6.6%; P < .001). The remaining cases underwent a hepaticojejunostomy (1st; 11% vs 2nd; 7.6%). Biliary complications were more frequent in the first period (1st; 20% vs 2nd; 9%; P < .01). In the first period, the use of a T-tube caused 32% of complications, all of them being bile leaks; but there were none in the second period. Arterial thrombosis or strictures were related to biliary complications in 10% and 33.3% among the first and second periods, respectively. The severity of complications according to the Clavien classification was similar in both periods: IIIa, 15% versus 33.3%; IIIb, 55% versus 55.5%; and IV, 15% versus 11.1%, respectively (P = NS). CONCLUSION The biliary complication rate among adult patients post-OLT decreased over 20 years at our institution, probably owing to the abandonment of the routine use of a T-tube as well as to advances in immunosuppressive protocols, organ preservation, and preoperative patient management.

Resultados a largo plazo de la duodenopancreatectomía cefálica con resección de la vena mesentérica superior y vena porta por adenocarcinoma de la cabeza de páncreas

INTRODUCTION The benefit of pancreaticoduodenectomy (PD) with superior mesenteric-portal vein resection (PVR) for pancreatic adenocarcinoma (PA) is still controversial in terms of morbidity, mortality and survival. We conducted a retrospective study to analyze outcomes of PD with PVR in a Spanish tertiary centre. METHODS Between 2002 and 2012, 10 patients underwent PVR (PVR+ group) and 68 standard PD (PVR- group). Morbidity, mortality, overall survival (OS) and disease-free survival (DFS) were compared between PVR+ and PVR- group. Prognostic factors were identified by a Cox regression model. RESULTS Postoperative mortality was 5% (4/78), all patients in PVR- group. Morbidity was higher in the PVR- group compared to PVR+ (63 vs. 30%, P=.004). OS at 3 and 5 years was 43 and 43% in PVR+ group, 35 and 29% in PVR- group (P=.07). DFS at 3 and 5 years DFS were 28 and 15% in PVR+ group, 25 and 20% in PVR- group (P=.84). Median survival was 23.1 months in PVR- group, and 22.8 months in PVR+ group (P=.73). Factors related with OS were absence of adjuvant treatment (OR 2.9, 95%IC: 1.39-6.14, P=.003), R1 resection (OR 2.3, 95%IC: 1.2-4.43, P=.006), preoperative CA 19.9 level ≥ 170 UI/mL (OR 2.3, 95%IC: 1.22-4.32, P=.01). DFS risk factors were R1 resection (OR 2.6, 95%IC: 1.41-4.95, P=.002); moderate or poor tumor differentiation grade (OR 2.7, 95%IC: 1.23-6.17, P=.01); N1 lymph node status (OR 1.8, 95%IC: 1.02-3.19, P=.04); CA 19.9 level ≥ 170 UI/mL (OR 2.4, 95%IC: 1.30-4.54, P=.005). CONCLUSIONS PVR for PA can be performed safely. Patients with PVR have a comparable survival to patients undergoing standard PD if disease-free margins can be obtained.

Acute Antibody-Mediated Rejection as Cause of Late Liver Allograft Failure: A Case Report

BACKGROUND Despite now being an infrequent complication in liver transplantation (LT) recipients, acute liver failure is still associated with high mortality. CASE REPORT Here we report a case of acute liver failure 11 months after AB0-compatible LT in a hepatitis C-positive 50-year-old male recipient caused by late antibody-mediated rejection (AMR). De novo donor-specific antibodies appeared later in a previously negative donor-recipient crossmatch, leading to a rapid deterioration of liver function. CONCLUSIONS We highlight the importance of an accurate diagnosis and an early therapeutic intervention. The analysis of this case brings novel and generalizable insights to the differential diagnosis of acute liver failure after LT.