Indications and effectiveness of the mammalian target of rapamycin in liver transplantation.

BACKGROUND: The mammalian target of rapamycin (mTOR) inhibitors are new immunosuppressive drugs for organ transplantation. They are interesting for liver transplantation because of their absence of nephrotoxicity and potential antitumor effects, because calcineurin inhibitors (CNI) are associated with renal dysfunction post-CNI and tumors. We sought to analyze the indications, safety, and efficacy of mTOR among liver transplant patients at our center. METHODS: We retrospectively identified patients who were treated with mTOR for their indications for liver transplantation, type of immunosuppressive therapy, acute rejection episodes, and evolution of kidney function. RESULTS: We identified 43 (19.02%) patients treated with mTOR including 35 (81.4%) males and 8 (18.6%) females of overall average age of 56.7 (range, 44-68). In 30% of patients, the drug was introduced for kidney failure, and in 23% for actual or a high risk of hepatocellular carcinoma (HCC) recurrence. The average time to introduction of the mTOR was 6.4 months (range, 1-46). The final immunosuppressive regimen was mTOR alone (73%), or mTOR plus CNI (23%), or mTOR plus mycophenolate mofetil (4%). The average values of creatinine and urea were lower after conversion to mTOR (P < .05) with a 6.9% incidence of acute rejection episodes. CONCLUSION: The mTOR immunosuppressive drugs are safe for liver transplant patients, effectively controlling renal dysfunction. They can be used in other indications, such as neurotoxicity, de novo tumors, and high risk of HCC recurrence. More studies are needed to clarify their long-term effectiveness.

FibroScan evaluation of liver fibrosis in liver transplantation.

INTRODUCTION: Liver biopsy remains the gold standard to evaluate fibrosis. However, it is invasive and uncomfortable as well as associated with complications. Transient elastography (FibroScan) is a simple and noninvasive method to assess liver fibrosis by measuring liver stiffness in kilopascals. Body mass index (BMI) greater than 28 is associated with high rates of invalid tests. Liver transplant patients show increased rates of obesity. We do not yet have many data about the usefulness of FibroScan in liver transplantation. AIMS: To analyze the applicability of FibroScan to assess fibrosis in liver transplantation and study the association between obesity and valid tests. MATERIAL AND METHODS: We prospectively assessed the performance of transient elastography in 29 liver transplant patients from February to May 2008. We prospectively studied the success rate, the elasticity (stiffness) in kilopascals, and the BMI. RESULTS: The BMI was greater than 30 kg/m(2) in four patients; 25 to 30 kg/m(2) in eight; and 17 had BMI < 25 kg/m(2). The overall success of FibroScan was 24/29 (82.7%). However, among patients with BMI > 30 kg/m(2), it was 2/4 (50%), whereas for BMI <25 kg/m(2) it climbed to 100%. The average duration of the procedure was 211.52 seconds for BMI <25 kg/m(2); 236 seconds for BMI between 25 and 30 kg/m(2); and 361 seconds in patients with a BMI > 30 kg/m(2)-differences that were statistically significant. CONCLUSIONS: FibroScan seemed to be a promising approach to assess liver fibrosis.BMI is a limiting factor toward achieving a valid test; FibroScan had limited usefulness in obese patients.

Interleucina-18 (IL-18) y otros parámetros inmunológicos como marcadores de gravedad en la pancreatitis aguda / No disponible

Objetivo: se trata de comparar prospectivamente el comportamientodurante la primera semana del ingreso de los niveles de interleucina-18 (IL-18), y otros parámetros inmunológicos entre pacientescon pancreatitis aguda con y sin criterios de gravedad, así comoentre pacientes con y sin desarrollo ulterior de seudoquiste.Pacientes y métodos: se compararon en 36 pacientes conpancreatitis aguda los resultados de sTNF-RI, IL-1Ra, IL-6 e IL-18los días 1, 2, 3 y 7 desde el ingreso entre pancretitis leve, grave y ungrupo control (13 pacientes) con cólico biliar simple, así como entrepacientes con o sin seudoquiste.Resultados: al comparar pancreatitis leve con grave, IL-18 fuesignificativamente superior sólo el primer día en las pancreatitis gravesy los otros parámetros a partir del segundo día de forma mantenida.También en pacientes que desarrollaron seudoquiste, IL-18 estuvosignificativamente elevada el primer día.Conclusiones: IL-18 resultó el marcador más precoz de complicacionesy gravedad de la pancreatitis aguda a nivel sistémico y local(seudoquiste)

Objective: our aim was to prospectively compare the behaviorof interleukin 18 (IL-18) levels and other immunological parametersduring the first week of hospitalization between acute pancreatitispatients with and without severity criteria, as well asbetween patients with and without late pseudocyst development.Patients and methods: in 36 patients with acute pancreatitiswe compared sTNF-RI, IL-1Ra, IL-6, and IL-18 levels at days1, 2, 3 and 7 after hospitalization between mild pancreatitis, severepancreatitis, and a “control” group (13 patients) with uncomplicatedbiliary colic, as well as between patients with and withoutpseudocyst.Results: on comparing mild to severe pancreatitis, IL-18 wassignificantly higher only the first day in severe pancreatitis, whilethe other parameters were steadily higher after the second day. Inpatients developing pseudocyst, IL-18 was also noticeably higherthe first day.Conclusions: IL-18 appears to be the earliest marker of complicationsand severity in acute pancreatitis at both the systemicand local level (pseudocyst)

[Interleukin 18 (IL-18) and other immunological parameters as markers of severity in acute pancreatitis]. / Interleucina-18 (IL-18) y otros parámetros inmunológicos como marcadores de gravedad en la pancreatitis aguda.

OBJECTIVE: Our aim was to prospectively compare the behavior of interleukin 18 (IL-18) levels and other immunological parameters during the first week of hospitalization between acute pancreatitis patients with and without severity criteria, as well as between patients with and without late pseudocyst development. PATIENTS AND METHODS: In 36 patients with acute pancreatis we compared sTNF-RI, IL-1Ra, IL-6, and IL-18 levels at days 1, 2, 3 and 7 after hospitalization between mild pancreatitis, severe pancreatitis, and a "control" group (13 patients) with uncomplicated biliary colic, as well as between patients with and without pseudocyst. RESULTS: On comparing mild to severe pancreatitis, IL-18 was significantly higher only the first day in severe pancreatitis, while the other parameters were steadily higher after the second day. In patients developing pseudocyst, IL-18 was also noticeably higher the first day. CONCLUSIONS: IL-18 appears to be the earliest marker of complications and severity in acute pancreatitis at both the systemic and local level (pseudocyst).

Liver transplantation: experience with our first 100 cases.

OBJECTIVES: Our goal was to evaluate the results of the first 100 liver transplants performed in our institution. METHODS: We retrospectively analyzed the first 100 liver transplants undertaken in adults from November 2001 to August 2005. RESULTS: The mean age of the recipients was 50 years (20 to 69) and 73% were men. The mean waiting time was 35 days. The mean age of the donors was 60 years (15 to 87), and 60% were men. One-year patient and graft survival rates were 93% and 90%, respectively. Three-year patient and graft survival rates were 85% and 82%, respectively. The need for retransplantation was 3%. Surgical complications included hepatic artery stenoses, 2%; hepatic artery thromboses, 2%; biliary leaks, 6%; and biliary stenoses, 14%. CONCLUSIONS: These results are no different from the overall results for liver transplantation in Spain during the same period.

Subluxación atloidoaxoideaidiopática: una causa infrecuentede mielopatía / Idiopathic atlas-axis subluxation: a rare cause of myelopathy

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Long-term effects of ursodeoxycholic acid in primary biliary cirrhosis: results of a double-blind controlled multicentric trial. UDCA-Cooperative Group from the Spanish Association for the Study of the Liver.

BACKGROUND/AIM: The aim of this study was to assess the efficacy of ursodeoxycholic acid (UDCA) for primary biliary cirrhosis in a randomized, double-blind placebo-controlled trial. METHODS: Consecutive patients (n=192) were randomized to receive 14-16 mg UDCA/kg/day or placebo. Patients underwent a complete history, physical examination, liver chemistries, immunological determinations and liver biopsy at entry and at the end of the trial, which lasted for at least 2 years. Patients were seen every 3 months and the median follow-up was 3.4 years (range 0.3 to 6.1 years). RESULTS: Patients receiving UDCA (99) or placebo (93) were comparable with regard to age, sex, biochemical parameters and liver histology. UDCA treatment was associated with decreases in alkaline phosphatase, gammaglutamyl transferase, alanine aminotransferase, and cholesterol levels, effects which were conspicuous after 3 months of treatment and remained similar during the follow-up. During the study 31 patients (10 receiving UDCA and 21 placebo) discontinued the trial because of noncompliance (n=11), voluntary withdrawal (n=19) or adverse effects (n=1). Treatment failure (death or liver transplantation) was observed in 17 patients receiving UDCA and in 11 patients receiving placebo. Times to death or liver transplantation and to clinical complications were not significantly different in patients receiving UDCA or placebo. Histological analysis indicates that UDCA improved portal inflammation and prevented histological stage progression. By contrast, histological stage as well as ductular proliferation and ductopenia progressed in patients receiving placebo. CONCLUSIONS: Although UDCA treatment did not significantly affect time to death or liver transplantation and to clinical complications, the effects on both cholestasis and liver histology suggest that UDCA is safe and may be useful for preventing the progression of primary biliary cirrhosis.

Carcinoma of the extrahepatic biliary tree: analysis of 15 cases.

AIM: to analyze the epidemiology, prognosis and treatment of those diagnosed as having cholangiocarcinoma of the extrahepatic biliary tree. METHODS: a prospective study including all cases diagnosed over a period of 26 months. Fifteen patients with primary bile duct carcinoma were included. RESULTS: the incidence rate was 3.23 cases/10(4). The tumor locations were: 40% proximal bile duct, 33% distal bile duct, and 27% mid-duct. The treatments used were: curative resection in 1 case (7%); palliative surgery in 3 cases (20%); internal drainage through a prosthetic biliary stent by endoscopic retrograde cholangiopancreatography in 6 cases (40%) and by percutaneous transhepatic cholangiography in 2 cases (13%); external bile drainage in case (7%), and in the remaining 2 patients (13%) no treatment was possible. The 1-month, 6-month and 10-month survival rates were 67%, 40% and 33% respectively. Factors associated with a worse survival in this study were age over 70 years and female sex. The worst prognostic location was the mid-duct compared to the distal and proximal thirds. CONCLUSIONS: the incidence of the primary bile duct carcinoma is high in our population. The commonest location is the proximal bile duct. Curative surgical resection is possible in only a few cases, and thus the overall prognosis is very bad.

[Primary intestinal T lymphoma]. / Linfoma T primario intestinal.

Primary gastrointestinal lymphoma comprises a group of distinctive clinicopathological entities. They may be of B or T-cell type. Intestinal T-cell lymphomas are much less common and include the entity: lymphomas T enteropathy-associated T-cell lymphoma, the most common, and T-cell lymphoma without features of enteropathy. The morphologic and immunologic findings suggest that derived from mucosal T lymphocytes population. Clinically, the patients were usually males with constitutional symptoms and acute perforation and/or obstruction of the small bowel. Their prognosis are very poor and tumor are very aggressive.

Hepatic disease in the Spanish toxic oil syndrome. A thirty months follow-up study.

Clinical and biological evidence of liver disease was found in 99 out of 242 (40%) patients hospitalized with acute manifestations of the Spanish toxic oil syndrome. No patient was alcoholic. According to the severity of liver involvement, patients were classified in 3 groups and followed up for at least 30 months. Group I included 65 patients with a transient increase of serum aminotransferase activity as the only evidence of liver disease. This abnormality disappeared within 2 months in all these patients. Group II included 18 patients with raised aminotransferases and alkaline phosphatase. At the end of follow-up, liver tests remained slightly abnormal in 4 patients of this group (22%) and a liver biopsy revealed minor changes in 3 of them. Group III included 16 patients with raised aminotransferases, alkaline phosphatase and bilirubin. Thirty months after the acute episode, liver function tests remained abnormal in 8 patients (50%); a liver biopsy, performed in 5 cases, showed changes suggesting chronic biliary disease in 2, and fibrosteatosis, chronic hepatitis and minimal changes in each of the remaining 3. Pulmonary, cutaneous, vascular, neuromuscular and other extra-hepatic disturbances were noted in a large number of patients but no relationship was observed between the degree of hepatic disfunction and the presence and severity of systemic manifestations of the toxic oil syndrome.