tacrolimus and Bile-Duct-Neoplasms

Cholangiocarcinoma has historically represented a major contraindication to liver transplantation at many centers because of its high recurrence rate and low disease-free survival rate, even after radical surgery. Novel neoadjuvant therapy protocols combined with demolitive surgery and liver transplantation seem to achieve successful results in terms of overall and disease-free survivals. Surgery frequently seems to be unsatisfactory only for patients also suffering from chronic cirrhosis or end-stage liver disease. We have reported a case of hilar cholangiocarcinoma occurring in a case of primary sclerosing cholangitis treated with neoadjuvant radiochemotherapy and endoscopic brachytherapy, followed by liver transplantation combined with pancreatoduodenectomy, who has survived free of disease for >8 years.

Topics: Antimetabolites, Antineoplastic; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Brachytherapy; Chemotherapy, Adjuvant; Cholangiocarcinoma; Cholangitis, Sclerosing; Disease-Free Survival; Female; Fluorouracil; Hepatectomy; Humans; Immunosuppressive Agents; Liver Transplantation; Middle Aged; Neoadjuvant Therapy; Pancreaticoduodenectomy; Radiotherapy, Adjuvant; Tacrolimus; Time Factors; Treatment Outcome

An enzyme multiplied immunoassay technique (EMIT) provides convenient and accurate measurements of mycophenolic acid (MPA) concentrations for determination of immunosuppression during treatment with mycophenolate mofetil (MMF). No abbreviated model for estimating the full 12-hour MPA AUC using an EMIT assay in liver transplant recipients has been described previously.. This study was conducted to determine the best model for predicting the MPA AUC using the EMIT method and a limited-sampling strategy in Chinese patients undergoing liver transplantation.. The study enrolled consecutive liver transplant patients who were receiving MMF 1 g BID along with tacrolimus. A complete MPA pharmacokinetic profile was obtained for each patient on a single day, 7 to 14 days after transplantation. The EMIT method was used to determine MPA concentrations before dosing and at 0.5, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours after dosing on the sampling day. Multiple linear regression analysis was used to evaluate potential models for estimating the full 12-hour MPA AUC. The accuracy and robustness of the models were evaluated using bootstrap analysis. Prediction error and prediction bias were calculated. Agreement between the estimated MPA AUC(0-12) and the full 12-hour MPA AUC was investigated using Bland-Altman analysis.. The study enrolled 48 Chinese liver transplant recipients (45 male, 3 female) with a mean (SD) age of 50 (12) years, mean weight of 64 (12) kg, and mean height of 169 (6) cm. Twenty-four models that included blood sampling at 1 through 4 time points were developed (r(2) = 0.015-0.950). Four models with the highest r(2) values were selected; the lack of significant differences from the original dataset on bootstrap analysis indicated acceptable accuracy and robustness. The best model for predicting the MPA AUC(0-12) employed concentrations at 1, 2, 4, and 8 hours; 40 of 48 (83.3%) MPA AUC(0-12) values estimated using this model were within 15% of the full 12-hour MPA AUC. This model had a minimal mean prediction error (mean [SD], 0.27% [1.79%]) and mean absolute prediction error (8.83% [1.24%]). On Bland-Altman analysis, this model also had the best agreement between the estimated MAP AUC(0-12) and the full 12-hour MPA AUC, with a mean error of 9.02 mg . h/L.. In this small group of Chinese liver transplant patients receiving MMF and concomitant tacrolimus, models for estimating the MPA AUC(0-12) were developed using the EMIT method and a limited-sampling strategy. The best model for prediction of the full 12-hour MPA AUC was 4.46 + 0.81 . C1 + 1.78 . C(2)+2.51.C(4)+4.94.C8.

Topics: Adult; Antibiotics, Antineoplastic; Area Under Curve; Asian People; Bile Duct Neoplasms; Carcinoma, Hepatocellular; China; Enzyme Multiplied Immunoassay Technique; Female; Glucocorticoids; Graft Rejection; Humans; Immunosuppressive Agents; Injections, Intravenous; Liver Neoplasms; Liver Transplantation; Male; Methylprednisolone; Middle Aged; Models, Biological; Mycophenolic Acid; Prednisone; Tacrolimus; Time Factors