AIM: The prevalence of carotid stenosis is reported to be high among patients with arteriosclerosis, but the hazards of carotid stenosis and the benefits of carotid endarterectomy (CEA) on long-term event-free survival are still unknown. The aim of this prospective study was to screen preoperative patients with arterial disease for carotid stenosis, and to determine whether CEA had any effect on stroke during the postoperative follow-up period. METHODS: From 1999 to 2003, 406 consecutive preoperative patients with arterial disease underwent routine carotid duplex scan. Patients with known carotid stenosis and those due to undergo operation in emergency were excluded from the study. CEA was performed before or simultaneously with vascular surgery if necessary. The prevalence and risk factors for carotid stenosis were studied, and the patients were followed up for stroke or death. RESULTS: Among the 406 patients examined, 19.4% had greater than 50% stenosis and 11.3% had greater than 70% stenosis. The risk factors for carotid stenosis were having occlusive arterial disease (P=0.0001), and history of stroke (P=0.0038). Long-term follow-up study revealed that patients with greater than 70% carotid stenosis without CEA had a higher tendency for stroke or death, but the stroke rate in patients with severe stenosis who underwent CEA remained low, as in patients with less than 70% stenosis. CONCLUSIONS: Patients with greater than 70% carotid stenosis, diagnosed before arterial operation who did not undergo CEA, had a higher risk for stroke during the postoperative follow-up period. However, their risk could be reduced by performing CEA before or simultaneously with scheduled vascular surgery.
Abstract Promoter methylation of the mismatch repair gene plays a key role in sporadic microsatellite instability (MSI) colorectal cancers. However, promoter methylation often occurs in proximal colon cancers, and molecular phenotypes underlying MSI cancers in distal colon have not been fully clarified. Our goal was to clarify the difference between MSI and microsatellite stability (MSS) cancers and, furthermore, to determine distinct characteristics of proximal and distal MSI cancers. By DNA microarray analysis of 84 cancers (33 MSI and 51 MSS), we identified discriminating genes (177 probe sets), which predicted MSI status with a high accuracy rate (97.6%). These genes were related to phenotypic characteristics of MSI cancers. Next, we identified 24 probe sets that were differentially expressed in proximal and distal MSI cancers. These genes included promoter methylation-mediated genes, whose expression was significantly down-regulated in proximal MSI cancers. Among discriminating genes between MSI and MSS, nine methylation-mediated genes showed down-regulation in MSI cancers. Of these, 7 (77.8%) showed down-regulation in proximal MSI cancers. Furthermore, methylation-specific PCR confirmed that frequency of hMLH1 promoter methylation was significantly higher in proximal MSI cancers (P = 0.0317). These results suggested that there is a difference between proximal and distal MSI cancers in methylation-mediated influence on gene silencing. In conclusion, using DNA microarray, we could distinguish MSI and MSS cancers. We also showed distinct characteristics of proximal and distal MSI cancers. The inactivation form of hMLH, per se, differed between proximal and distal MSI cancers. These results suggested that distal MSI cancers constitute a distinct subgroup of sporadic MSI cancers. (Cancer Res 2006; 66(20): 9804-8)
Poorly differentiated adenocarcinomas of the colon and rectum (Por) feature the worst prognosis among the various types of colorectal carcinomas. Por is highly associated with microsatellite instability (MSI), although MSI is associated with an improved prognosis in colorectal cancers.To investigate the influence of MSI on clinicopathological features and survival of patients affected by Por.53 patients affected by Por were investigated. DNA extracted from tumour sections and the corresponding normal tissue was analysed by PCR at five microsatellite loci: BAT25, BAT26, D2S123, D5S346 and D17S250. Tumours with alterations at two or more loci were classified as MSI-Por. The others were classified as microsatellite stability (MSS)-Por. The clinicopathological features and survival of patients with MSI-Por and MSS-Por were investigated.Of the 53 patients who were examined, 12 (22.6%) were MSI-Por, whereas 41 (77.4%) were MSS-Por. Significant differences were found between MSI-Por and MSS-Por regarding the following clinicopathological features: age, gender, lymph-node metastasis (MSI-Por: 4/12; MSS-Por: 33/41), TNM stage (MSI-Por: T1/T2/T3/T4 = 2/6/2/2; MSS-Por: 3/3/19/16) and lymphatic invasion (MSI-Por: 4/10; MSS-Por: 27/35). Kaplan-Meier survival curves and log-rank analysis showed that MSI-Por was associated with better prognosis than MSS-Por, although no significant difference was found.Compared with MSS-Por, MSI-Por is significantly associated with a low incidence of lymph-node metastases and a low stage. This indicates that MSI-Por is a less aggressive subtype.
