[Analysis of Palliative Stent Placement for Acute Malignant Colorectal Obstruction].

INTRODUCTION: Recently, endoscopic placement of self-expanding-metal stents (SEMS) has been widely performed for treatment of acute malignant colorectal obstruction. This study aimed to compare the efficacy of SEMS placement as palliative treatment with that of surgical treatment in patients presenting with acute malignant colorectal obstruction. MATERIALS AND METHODS: A retrospective review was performed for 20 patients with unresectable malignant colorectal obstruction who had received insertion of SEMS (n=9) or surgical treatment (n=11) for palliation between July 2006 and M ay 2014. RESULTS: Patients who had received SEMS were in poorer clinical condition regarding age and performance status. Duration of treatment was significantly lesser and the postoperative date of initial oral intake after intervention was statistically earlier in the SEMS group. SEMS-related morbidity was found in only 2 cases of obstruction due to tumor ingrowth; these patients were successfully treated by reinsertion of SEMS. The prognosis of both groups showed no statistical difference. CONCLUSION: Palliative SEMS placement for unresectable colorectal malignant obstruction in patients with more severe clinical condition relieved obstruction without severe morbidity. Palliative SEMS placement could be an alternative to surgery for the treatment of acute unresectable colorectal obstruction.

Microsatellite instability-low colorectal cancer acquires a KRAS mutation during the progression from Dukes' A to Dukes' B.

The classification of colorectal cancer (CRC) by microsatellite instability (MSI) status is important for effective clinical management. In fact, microsatellite instability-high (MSI-H) cancer has distinctive clinicopathological and molecular features. However, microsatellite instability-low (MSI-L) cancer is not clearly defined. The objective of this study was to further clarify the characteristics of MSI-L CRC. A consecutive series of 940 primary CRCs were subdivided into three groups according to the level of MSI and analyzed the clinicopathological features and genetic changes in the KRAS, BRAF and p53 mutation and the loss of heterozygosity (LOH) of adenomatous polyposis coli (APC) gene and methylation status of the O(6)-methylguanine-DNA methyltransferase (MGMT) and MLH1 promoter. Of the 940 CRCs, 5.9% were MSI-H, 7.1% were MSI-L and 87% were microsatellite stable (MSS). KRAS and BRAF mutations were detected in 39.4 and 4.6% of the CRCs, respectively. The frequency of KRAS mutations in MSI-H, MSI-L and MSS cancer was 30, 48 and 39%, respectively. The proportion of KRAS mutations in MSI-L cancer increased from 16 to 63% accompanying the progression from Dukes' A to Dukes' B. While the LOH of D5S346, which is located near the APC gene, and p53 mutation was observed in 75 and 67% of MSI-L CRC at Dukes' A, respectively. These results indicated that the LOH of APC and p53 mutation has already occurred by the Dukes' A lake 'suppressor pathway' but not the KRAS mutation in MSI-L CRCs. The genes involving MSI-L carcinogenesis are similar to MSS but the timing and frequency of the KRAS mutation is different.

Genetic prognostic index influences patient outcome for node-positive breast cancer.

PURPOSE: To establish a novel genetic prognostic index among node-positive breast cancer patients. METHODS: Using a cDNA microarray, the gene expression profiles of 20 primary breast cancers that had metastasis to four or more axillary lymph nodes were examined. Ten patients survived disease-free for more than 5 years (5S), while ten patients died of breast cancer within 5 years of surgery (5D). RESULTS: A set of genes characterizing each group was identified. Sixteen genes were underexpressed in 5D compared to 5S, and 15 genes were underexpressed in 5S in comparison to 5D. The prognostic index (PI) was established, which could predict the postoperative outcome with five genes that were commonly underexpressed in the 5D group; these genes encoded granulin (GRN), heat shock 90 kDa protein 1 beta (HSPCB), large tumor suppressor homolog 1 (LATS1), valosin-containing protein (VCP), and LIM-and-SH3 protein1 (LASP1). CONCLUSION: These five genes might play an important role in deciding the behavior of node-positive breast cancer. The PI system could thus predict the prognosis of node-positive breast cancer, and might therefore be able to provide valuable information for the prognosis of breast cancer patients.

Up-regulation of transcriptional factor E2F1 in papillary and anaplastic thyroid cancers.

Expression of genes in the Rb-E2F signaling pathway is controlled by E2F transcriptional factors originally defined as molecules that bind to the promoter of E2 adenovirus. The E2F gene family consists of six members and is designated E2F1-6. The Rb-E2F signaling pathway is among the main regulators of the cell cycle, hence its importance in differentiation and oncogenesis. We document here up-regulation of E2F1, but not other members of the E2F gene family, in 15 of 18 primary papillary thyroid cancers examined (83%) in comparison to corresponding noncancerous thyroid tissues and in all of 11 anaplastic thyroid cancer (ATC) cell lines (100%). The E2F4 gene, however, was down-regulated in 12 of the papillary thyroid cancers (67%). Immunohistochemical analysis with antibody to E2F1 revealed prominent intracellular E2F1 protein in most of the primary papillary cancers (16 of 18; 89%) but was not detectable in normal thyroid tissues. These data indicated that increased expression of the E2F1 gene might play a significant role in human thyroid carcinogenesis through derangement of the Rb-E2F signaling pathway.