Comparative profiling of primary colorectal carcinomas and liver metastases identifies LEF1 as a prognostic biomarker.

PURPOSE: We sought to identify genes of clinical significance to predict survival and the risk for colorectal liver metastasis (CLM), the most common site of metastasis from colorectal cancer (CRC). PATIENTS AND METHODS: We profiled gene expression in 31 specimens from primary CRC and 32 unmatched specimens of CLM, and performed Significance Analysis of Microarrays (SAM) to identify genes differentially expressed between these two groups. To characterize the clinical relevance of two highly-ranked differentially-expressed genes, we analyzed the expression of secreted phosphoprotein 1 (SPP1 or osteopontin) and lymphoid enhancer factor-1 (LEF1) by immunohistochemistry using a tissue microarray (TMA) representing an independent set of 154 patients with primary CRC. RESULTS: Supervised analysis using SAM identified 963 genes with significantly higher expression in CLM compared to primary CRC, with a false discovery rate of <0.5%. TMA analysis showed SPP1 and LEF1 protein overexpression in 60% and 44% of CRC cases, respectively. Subsequent occurrence of CLM was significantly correlated with the overexpression of LEF1 (chi-square p = 0.042), but not SPP1 (p = 0.14). Kaplan Meier analysis revealed significantly worse survival in patients with overexpression of LEF1 (p<0.01), but not SPP1 (p = 0.11). Both univariate and multivariate analyses identified stage (p<0.0001) and LEF1 overexpression (p<0.05) as important prognostic markers, but not tumor grade or SPP1. CONCLUSION: Among genes differentially expressed between CLM and primary CRC, we demonstrate overexpression of LEF1 in primary CRC to be a prognostic factor for poor survival and increased risk for liver metastasis.

A new operation with inadequate Brescia fistulae for preservation of more proximal veins.

PURPOSE: The purpose of this study was to test the hypothesis that venous outflow of a Brescia fistula that is patent but unusable for one of a variety of reasons can provide adequate drainage to sustain a prosthetic arteriovenous graft based on the brachial artery, thus sparing more proximal veins for future access procedures. METHODS: The operation consists of placement of a prosthetic graft between the brachial artery in the antecubital space and the cephalic vein at the wrist. RESULTS: Between December 1998 and November 1999, 14 patients (eight male and six female; age range, 34 to 73 years; mean age, 51 years) underwent the operation. The original fistulae had been in place for 5 to 27 months (mean, 13 months). Thirteen grafts were patent at 30 days; the one early failure (24 days) was caused by infection. As of May 31, 2001, four grafts were being used (18 (1/2), 20, 23, and 28 months after placement) and four had been withdrawn in a functional state because of death (n = 3) or transplantation (n = 1). Primary functional patency rate with life-table analysis was 71%, 57%, 41%, and 41% at 3, 6, 9, and 12 months; secondary functional patency rate was 86%, 78%, 52%, and 52% at these same intervals. Three grafts had primary functional patencies greater than 18 months. CONCLUSION: Patent but unusable Brescia fistulae can provide adequate outflow to sustain arteriovenous grafts, thus sparing more proximal veins for future access procedures. The operation can extend by months or years the time during which satisfactory vascular access can be maintained in these patients, potentially increasing survival in some cases. We hope that the availability of this salvage option will encourage vascular surgeons to attempt arteriovenous fistulae at the wrist even in patients with suboptimal venous anatomy.