Quality of life after rectal cancer surgery is not worse than that of the general population. The major adverse impact of bowel and urogenital dysfunction is on social functioning. These adverse effects need to be discussed with the patient and preoperative function needs to be taken into account when choosing between treatment options. Permanent colostomy is not always the factor that disrupts a person's quality of life most.
Juvenile polyposis syndrome (JPS) is an inherited hamartomatous-polyposis syndrome with a risk for colon cancer. JPS is a clinical diagnosis by exclusion, and, before susceptibility genes were identified, JPS could easily be confused with other inherited hamartoma syndromes, such as Bannayan-Riley-Ruvalcaba syndrome (BRRS) and Cowden syndrome (CS). Germline mutations of MADH4 (SMAD4) have been described in a variable number of probands with JPS. A series of familial and isolated European probands without MADH4 mutations were analyzed for germline mutations in BMPR1A, a member of the transforming growth-factor beta-receptor superfamily, upstream from the SMAD pathway. Overall, 10 (38%) probands were found to have germline BMPR1A mutations, 8 of which resulted in truncated receptors and 2 of which resulted in missense alterations (C124R and C376Y). Almost all available component tumors from mutation-positive cases showed loss of heterozygosity (LOH) in the BMPR1A region, whereas those from mutation-negative cases did not. One proband with CS/CS-like phenotype was also found to have a germline BMPR1A missense mutation (A338D). Thus, germline BMPR1A mutations cause a significant proportion of cases of JPS and might define a small subset of cases of CS/BRRS with specific colonic phenotype.
Abnormal glycosylation of cellular glycoconjugates is a common phenotypic change in many human tumors. Here, we explore the possibility that an altered Golgi pH may also be responsible for these cancer-associated glycosylation abnormalities. We show that a mere dissipation of the acidic Golgi pH results both in increased expression of some cancer-associated carbohydrate antigens and in structural disorganization of the Golgi apparatus in otherwise normally glycosylating cells. pH dependence of these alterations was confirmed by showing that an acidification-defective breast cancer cell line (MCF-7) also displayed a fragmented Golgi apparatus, whereas the Golgi apparatus was structurally normal in its acidification-competent subline (MCF-7/AdrR). Acidification competence was also found to rescue normal glycosylation potential in MCF-7/AdrR cells. Finally, we show that abnormal glycosylation is also accompanied by similar structural disorganization and fragmentation of the Golgi apparatus in colorectal cancer cells in vitro and in vivo. These results suggest that an inappropriate Golgi pH may indeed be responsible for the abnormal Golgi structure and lowered glycosylation potential of the Golgi apparatus in malignant cells. ß
Background:The objective of the study was to examine the role of microsatellite instability (MSI) and BRAFV600Emutation in colorectal cancer (CRC) by categorising patients into more detailed subtypes based on tumour characteristics.Methods:Tumour samples from 762 population-based patients with sporadic CRC were analysed for MSI and BRAFV600E by immunohistochemistry. Patient survival was followed-up for a median of 5.2 years.Results:Compared with microsatellite stable (MSS) CRC, MSI was prognostic for better disease-free survival (DFS; 5 years: 85.8% vs 75.3%, 10 years: 85.8% vs 72.9%, P=0.027; HR 0.49, CI 0.30–0.80, P=0.005) and disease-specific survival (DSS; 5 years: 83.2% vs 70.5% 10 years: 83.2 vs 65.0%, P=0.004). Compared with BRAF wild type, BRAFV600E was a risk for poor survival (overall survival; 5 years: 62.3% vs 51.6%, P=0.014; HR 1.43, CI 1.07–1.90, P=0.009), especially in rectal cancer (for DSS, HR: 10.60, CI: 3.04–36.92, P<0.001). The MSS/BRAFV600E subtype was a risk for poor DSS (HR: 1.88, CI: 1.06–3.31, P=0.030), but MSI/BRAFV600E was a prognostic factor for DFS (HR: 0.42, CI: 0.18–0.96, P=0.039). Among stage I–II patients, the MSS/BRAFV600E subtype was independently associated with poor DSS (HR: 5.32, CI: 1.74–16.31, P=0.003).Conclusions:Microsatellite instable tumours were associated with better prognosis compared with MSS. BRAFV600E was associated with poor prognosis unless it occurred together with MSI. The MSI/BRAFV600E subtype was a favourable prognostic factor compared with the MSS/BRAF wild-type subtype. BRAFV600E rectal tumours showed particularly poor prognosis. The MSS/BRAFV600E subtype was associated with increased disease-specific mortality even in stage I–II CRC.
Prophylactic laparoscopic placement of intraperitoneal onlay mesh does not significantly reduce the overall risk of radiologically detected parastomal hernia after laparoscopic abdominoperineal resection. However, prophylactic mesh repair was associated with significantly lower risk of clinically detected parastomal hernia.
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