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BackgroundWe previously showed microRNAs (miRNAs) in plasma are potential biomarkers for colorectal cancer detection. Here, we aimed to develop specific blood-based miRNA assay for breast cancer detection.Methodology/Principal FindingsTaqMan-based miRNA profiling was performed in tumor, adjacent non-tumor, corresponding plasma from breast cancer patients, and plasma from matched healthy controls. All putative markers identified were verified in a training set of breast cancer patients. Selected markers were validated in a case-control cohort of 170 breast cancer patients, 100 controls, and 95 other types of cancers and then blindly validated in an independent set of 70 breast cancer patients and 50 healthy controls. Profiling results showed 8 miRNAs were concordantly up-regulated and 1 miRNA was concordantly down-regulated in both plasma and tumor tissue of breast cancer patients. Of the 8 up-regulated miRNAs, only 3 were significantly elevated (p<0.0001) before surgery and reduced after surgery in the training set. Results from the validation cohort showed that a combination of miR-145 and miR-451 was the best biomarker (p<0.0001) in discriminating breast cancer from healthy controls and all other types of cancers. In the blind validation, these plasma markers yielded Receiver Operating Characteristic (ROC) curve area of 0.931. The positive predictive value was 88% and the negative predictive value was 92%. Altered levels of these miRNAs in plasma have been detected not only in advanced stages but also early stages of tumors. The positive predictive value for ductal carcinoma in situ (DCIS) cases was 96%.ConclusionsThese results suggested that these circulating miRNAs could be a potential specific biomarker for breast cancer screening.

Low anterior resection with total mesorectal excision for rectal carcinoma is associated with a high anastomotic leakage rate, and the effectiveness of a defunctioning stoma in preventing anastomotic leakage remains controversial. In this study a policy of selective defunctioning stoma for stapled colorectal anastomosis after low anterior resection with total mesorectal excision in 148 consecutive patients was evaluated prospectively. A defunctioning stoma was performed in 61 patients (41%) considered at high risk of anastomotic leakage. Clinical leakage occurred in 2 patients (3.3%) with a stoma and 11 patients (12.6%) without a stoma (p = 0.047). Among those without a stoma, the leakage rate among male patients (20.9%) was significantly higher than that for female patients (4. 5%) (p = 0.022). Leakage subsided with conservative treatment in the two patients with a stoma, but seven patients without a stoma developed peritonitis requiring laparotomy. No deaths resulted from leakage, and there was one hospital death (0.6%) in the whole group. Median hospital stay was similar with and without a stoma (13.0 vs. 12.0 days) (p = 0.290). Closure of the stoma was associated with no mortality, a morbidity rate of 8.7%, and a median hospital stay of 6. 0 days. In conclusion, a defunctioning stoma is effective in preventing clinical anastomotic leakage after low anterior resection with total mesorectal excision. The relatively high incidence of leakage in the low risk group indicates the difficulty of predicting anastomotic leakage and hence the need for more liberal use of a defunctioning stoma especially in male patients.