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.

Temporal blastemal cell gene expression analysis in the kidney reveals new Wnt and related signaling pathway genes to be essential for Wilms' tumor onset.

Wilms' tumors (WTs) originate from metanephric blastema cells that are unable to complete differentiation, resulting in triphasic tumors composed of epithelial, stromal and blastemal cells, with the latter harboring molecular characteristics similar to those of the earliest kidney development stages. Precise regulation of Wnt and related signaling pathways has been shown to be crucial for correct kidney differentiation. In this study, the gene expression profile of Wnt and related pathways was assessed in laser-microdissected blastemal cells in WTs and differentiated kidneys, in human and in four temporal kidney differentiation stages (i.e. E15.5, E17.5, P1.5 and P7.5) in mice, using an orthologous cDNA microarray platform. A signaling pathway-based gene signature was shared between cells of WT and of earliest kidney differentiation stages, revealing genes involved in the interruption of blastemal cell differentiation in WT. Reverse transcription-quantitative PCR showed high robustness of the microarray data demonstrating 75 and 56% agreement in the initial and independent sample sets, respectively. The protein expression of CRABP2, IGF2, GRK7, TESK1, HDGF, WNT5B, FZD2 and TIMP3 was characterized in WTs and in a panel of human fetal kidneys displaying remarkable aspects of differentiation, which was recapitulated in the tumor. Taken together, this study reveals new genes candidate for triggering WT onset and for therapeutic treatment targets.

FISH analysis of 107 prostate cancers shows that PTEN genomic deletion is associated with poor clinical outcome.

This study examines the clinical impact of PTEN genomic deletions using fluorescence in situ hybridisation (FISH) analysis of 107 prostate cancers, with follow-up information covering a period of up to 10 years. Tissue microarray analysis using interphase FISH indicated that hemizygous PTEN losses were present in 42/107 (39%) of prostatic adenocarcinomas, with a homozygous PTEN deletion observed in 5/107 (5%) tumours. FISH analysis using closely linked probes centromeric and telomeric to the PTEN indicated that subband microdeletions accounted for approximately 70% genomic losses. Kaplan-Meier survival analysis of PTEN genomic losses (hemizygous and homozygous deletion vs not deleted) identified subgroups with different prognosis based on their time to biochemical relapse after surgery, and demonstrated significant association between PTEN deletion and an earlier onset of disease recurrence (as determined by prostate-specific antigen levels). Homozygous PTEN deletion was associated with a much earlier onset of biochemical recurrence (P=0.002). Furthermore, PTEN loss at the time of prostatectomy correlated with clinical parameters of more advanced disease, such as extraprostatic extension and seminal vesicle invasion. Collectively, our data indicates that haploinsufficiency or PTEN genomic loss is an indicator of more advanced disease at surgery, and is predictive of a shorter time to biochemical recurrence of disease.