CYP2D6 in the brain: genotype effects on resting brain perfusion.

The cytochrome P450 2D6 (CYP2D6) is a genetically polymorphic enzyme involved in the metabolism of several psychoactive drugs. Beside its expression in the liver, CYP2D6 is highly expressed in several regions of the brain, such as the hippocampus, thalamus, hypothalamus and the cortex, but its function in the brain is not well understood. The CYP2D6 enzyme may also have a physiological role due to its involvement in neurotransmitter biotransformation. In this study, CYP2D6 genotyping was performed in N=188 healthy individuals and compared with brain perfusion levels at rest, which may reflect an ongoing biological process regulating the reactivity of the individual to emotional stimuli and the detection of signals evoking fear. Relative to N=42 matched extensive metabolizers, N=14 poor metabolizers were associated with 15% higher perfusion levels in the thalamus (P=0.03 and 0.003). Effects were also present in the whole (N=188) sample divided into metabolizer groups, or finely graded into seven CYP2D6 activity levels. A weaker effect was observed in the right hippocampus (P=0.05). An exploratory analysis, extended to the whole brain, suggested the involvement of CYP2D6 in regions associated with alertness or serotonergic function. These findings support the hypothesis of a functional role of CYP2D6 in the brain.

Extended preoperative chemotherapy, extent of liver resection and blood transfusion are predictive factors of liver failure following resection of colorectal liver metastasis.

AIM: The aim of this study was to determine the incidence and prognostic factors of postoperative liver failure in patients submitted to liver resection for colorectal metastases. METHOD: Patients with CLM who underwent hepatectomy from 1998 to 2009 were included in retrospective analysis. Postoperative liver failure was defined using either the 50-50 criteria or the peak of serum bilirubin level above 7 mg/dL independently. RESULTS: Two hundred and nine (209) procedures were performed in 170 patients. 120 surgeries were preceded by chemotherapy within six months. The overall morbidity rate was 53.1% and 90-day mortality was 2.3%. Postoperative liver failure occurred in 10% of all procedures, accounting for a mortality rate of 9.5% among this group of patients. In multivariate analysis, extent of liver resection, need of blood transfusion and more than eight preoperative chemotherapy cycles were independent prognostic factors of postoperative liver insufficiency. This complication was not related with the chemotherapy regimen used. CONCLUSION: We conclude that postoperative liver failure has a relatively low incidence (10%) after CLM resection, but a remarkable impact on postoperative mortality rate. The amount of liver resected, the need of blood transfusion and extended preoperative chemotherapy are independent predictors of its occurrence and this knowledge can be used to prevent postoperative liver failure in a multidisciplinary approach.