Neoadjuvant transarterial radiation lobectomy for colorectal hepatic metastases: a small cohort analysis on safety, efficacy, and radiopathologic correlation.

Colorectal cancer patients have a high incidence of liver metastasis (ml-CRC). Surgical resection is the gold standard for treatment of hepatic metastasis but only a small percent of patients are traditional candidates based on disease extent and adequate size of the future liver remnant (FLR). Interventions such as portal vein embolization (PVE) and associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) are performed to increase FLR for operative conversion. Limitations to PVE include intrahepatic disease progression, portal vascular invasion, and utilization with concurrent chemotherapy. ALPPS is associated with a high morbidly and mortality. Radiation lobectomy (RL) with yttrium-90 (Y-90) delivers transarterial ablative brachytherapy to the future hepatectomy site which generates FLR hypertrophy similar or greater than PVE. Early results indicate that RL is safe, effective, and may offer unique benefits by providing cytoreduction of hepatic metastases which extends FLR hypertrophy time and allows FLR surveillance to gauge disease biology. A retrospective analysis of four patients with ml-CRC treated with RL prior to hepatectomy was performed to evaluate initial safety, efficacy, FLR hypertrophy, and radiopathologic correlation. Adverse events after RL and hepatectomy were evaluated. Imaging findings were analyzed for efficacy defined as FLR hypertrophy and disease control. Radiopathologic correlation was performed after histologic analysis. RL was well tolerated without major adverse events or hepatic decompensation. FLR hypertrophy ranged from 24.9% to 119% at mean follow-up of three months. The majority of complications were related to surgical instrumentation of the FLR due to upstaging at time of surgery. Hepatectomy specimen histology demonstrated complete pathologic response in 50% of patients, 50% radiopathologic concordance rate, and no significant hepatic fibrosis. Initial experience with neoadjuvant RL for ml-CRC is safe and provides both durable disease control and FLR hypertrophy with concurrent chemotherapy. A 50% complete pathologic response rate raises the possibility of definitive chemoradiation in poor surgical candidates. Prospective investigation is required.

Biotin supplementation reduces plasma triacylglycerol and VLDL in type 2 diabetic patients and in nondiabetic subjects with hypertriglyceridemia.

Biotin is a water-soluble vitamin that acts as a prosthetic group of carboxylases. Besides its role as carboxylase prosthetic group, biotin regulates gene expression and has a wide repertoire of effects on systemic processes. The vitamin regulates genes that are critical in the regulation of intermediary metabolism. Several studies have reported a relationship between biotin and blood lipids. In the present work we investigated the effect of biotin administration on the concentration of plasma lipids, as well as glucose and insulin in type 2 diabetic and nondiabetic subjects. Eighteen diabetic and 15 nondiabetic subjects aged 30-65 were randomized into two groups and received either 61.4 micromol/day of biotin or placebo for 28 days. Plasma samples obtained at baseline and after treatment were analyzed for total triglyceride, cholesterol, very low density lipoprotein (VLDL), glucose and insulin. We found that the vitamin significantly reduced (P=0.005) plasma triacylglycerol and VLDL concentrations. Biotin produced the following changes (mean of absolute differences between 0 and 28 day treatment+/-S.E.M.): a) triacylglycerol -0.55+/-0.2 in the diabetic group and -0.92+/-0.36 in the nondiabetic group; b) VLDL: -0.11+/-0.04 in the diabetic group and -0.18+/-0.07 in the nondiabetic group. Biotin treatment had no significant effects on cholesterol, glucose and insulin in either the diabetic or nondiabetic subjects. We conclude that pharmacological doses of biotin decrease hypertriglyceridemia. The triglyceride-lowering effect of biotin suggests that biotin could be used in the treatment of hypertriglyceridemia.

Effects of biotin on pyruvate carboxylase, acetyl-CoA carboxylase, propionyl-CoA carboxylase, and markers for glucose and lipid homeostasis in type 2 diabetic patients and nondiabetic subjects.

BACKGROUND: Several studies have shown that biotin affects glucose homeostasis. Serum biotin concentrations are lower in subjects with type 2 diabetes than in control subjects. Lymphocyte propionyl-CoA carboxylase (PCC; EC 6.4.1.3) activity has proved to be a sensitive indicator of biotin status that is more accurate than is serum biotin concentration. OBJECTIVE: We studied the activity of PCC, pyruvate carboxylase (PC; EC 6.4.1.1), and acetyl-CoA carboxylase (ACC; EC 6.4.1.2) in type 2 diabetic and nondiabetic subjects. The effect of biotin administration (6.14 micro mol/d) on the activity of these enzymes and on several plasma metabolites was also studied. DESIGN: We compared the activities of carboxylases in circulating lymphocytes from patients with type 2 diabetes (n = 24) with those in circulating lymphocytes from nondiabetic subjects (n = 30). We also assessed the effect of biotin administration for 14 and 28 d on the activity of these enzymes and on the concentrations of several metabolites (type 2 diabetic patients, n = 10; nondiabetic subjects, n = 7). RESULTS: No significant differences in lymphocyte carboxylase activities were found between the type 2 diabetic patients and the nondiabetic subjects. Biotin administration increased the activity of PCC, PC, and ACC in all the subjects. No significant change in glucose, insulin, triacylglycerol, cholesterol, or lactate concentration was observed with the treatment in either the diabetic or the nondiabetic subjects. CONCLUSIONS: The activity of carboxylases does not differ significantly between type 2 diabetic and nondiabetic subjects. Pharmacologic doses of biotin increase lymphocyte PCC, PC, and ACC activities.

Recurrent hepatocellular carcinoma in liver transplant recipients with hepatitis C.

PURPOSE: Hepatitis C (HCV) is the most common liver disease in patients transplanted with hepatocellular carcinoma (HCC) in the West. We examined predictors of HCC recurrence in liver transplant recipients with HCV. METHODS: From 1997 to 2006, 53 patients with HCC and HCV underwent liver transplantation. Pre-and post-operative data (including liver biopsies 4 months post-transplant) were collected. Differences between HCC recurrence and non-recurrence groups were detected by Student's t test or chi-square test. Data were analyzed as predictors of HCC recurrence by logistic regression multivariate analysis. Cumulative survival was analyzed by Kaplan-Meier curves and compared by the log-rank test. RESULTS: Eleven of 53 patients (20.8%) developed HCC recurrence at a median interval of 15 months (2 to 55 months). Median Histology Activity Index (HAI) of liver biopsies, AST, and ALT at 4 months were significantly greater in patients with HCC recurrence. Independent predictors of HCC recurrence were HAI ≥ 4 at 4 months, ALT ≥ 100 at 4 months, and vascular invasion. Patients with HCC recurrence had significantly decreased survival. CONCLUSIONS: In this preliminary study, Histology Activity Index and ALT at 4 months, as well as vascular invasion, predicted HCC recurrence in liver transplant recipients with HCV.