Role of the interval from completion of neoadjuvant therapy to surgery in postoperative morbidity in patients with locally advanced rectal cancer

Increasing the interval from completion of neoadjuvant therapy to surgery beyond 8 weeks is associated with increased response of rectal cancer to neoadjuvant therapy. However, reports are conflicting on whether extending the time to surgery is associated with increased perioperative morbidity. Patients who presented with a tumor within 15 cm of the anal verge in 2009-2015 were grouped according to the interval between completion of neoadjuvant therapy and surgery: < 8 weeks, 8-12 weeks, and 12-16 weeks. Among 607 patients, the surgery was performed at < 8 weeks in 317 patients, 8-12 weeks in 229 patients, and 12-16 weeks in 61 patients. Patients who underwent surgery at 8-12 weeks and patients who underwent surgery at < 8 weeks had comparable rates of complications (37% and 44%, respectively). Univariable analysis identified male sex, earlier date of diagnosis, tumor location within 5 cm of the anal verge, open operative approach, abdominoperineal resection, and use of neoadjuvant chemoradiotherapy alone to be associated with higher rates of complications. In multivariable analysis, male sex, tumor location within 5 cm of the anal verge, open operative approach, and neoadjuvant chemoradiotherapy administered alone were independently associated with the presence of a complication. The interval between neoadjuvant therapy and surgery was not an independent predictor of postoperative complications. Delaying surgery beyond 8 weeks from completion of neoadjuvant therapy does not appear to increase surgical morbidity in rectal cancer patients

Quality of life and function after rectal cancer surgery with and without sphincter preservation

Despite improvements in surgical techniques, functional outcomes and quality of life after therapy for rectal cancer remain suboptimal. We sought to prospectively evaluate the effect of bowel, bladder, and sexual functional outcomes on health-related quality of life (QOL) in patients with restorative versus non-restorative resections after rectal cancer surgery. A cohort of 211 patients with clinical stage I-III rectal cancer who underwent open surgery between 2006 and 2009 at Memorial Sloan Kettering were included. Subjects were asked to complete surveys preoperatively and at 6, 12, and 24 months after surgery. Validated instruments were used to measure QOL, bowel, bladder, and sexual function. Univariable and multivariable regression analyses evaluated predictors of 24- month QOL. In addition, longitudinal trends over the study period were evaluated using repeated measures models. In total, 180 patients (85%) completed at least 1 survey, and response rates at each time point were high (>70%). QOL was most impaired at 6 and 12 months and returned to baseline levels at 24 months. Among patients who underwent sphincter-preserving surgery (SPS; n=153 [85%]), overall bowel function at 24 months was significantly impaired and never returned to baseline. There were no differences in QOL at 24 months between patients who underwent SPS and those who did not (p=.29). Bowel function was correlated with QOL at 24 months (Pearson correlation,.41; p<.001). QOL among patients who have undergone SPS for rectal cancer is good despite poor function. Patients with ostomies are able to adjust to the functional changes and, overall, have good global QOL. Patients with low anastomoses had lower global QOL at 24 months than patients with permanent stomas. Our findings can help patients set expectations about function and quality of life after surgery for rectal cancer with and without a permanent stoma

Comparative analysis of the Memorial Sloan Kettering Bowel Function Instrument and the Low Anterior Resection Syndrome Questionnaire for assessment of bowel dysfunction in rectal cancer patients after low anterior resection

Aim Neoadjuvant therapy and total mesorectal excision (TME) for rectal cancer are associated with bowel dysfunction symptoms known as low anterior resection syndrome (LARS). Our study compared the only two validated instruments—the LARS Questionnaire (LARS-Q) and the Memorial Sloan Kettering Bowel Function Instrument (MSK-BFI)—in rectal cancer patients undergoing sphincter-preserving TME. Methods One hundred and ninety patients undergoing sphincter-preserving TME for Stage I–III rectal cancer completed the MSK-BFI and LARS-Q simultaneously at a median time of 12 (range 1–43) months after restoration of bowel continuity. Associations between the MSK-BFI total/subscale scores and the LARS-Q score were investigated using Spearman rank correlation (r s). Discriminant validity for the two questionnaires was assessed, and the questionnaires were compared with the European Quality of Life Instrument. Results Major LARS was identified in 62% of patients. The median MSK-BFI scores for no LARS, minor LARS and major LARS were 76.5, 70 and 57, respectively. We found a strong association between MSK-BFI and LARS-Q (r s −0.79). The urgency/soilage subscale (r s −0.7) and the frequency subscale (rs −0.68) of MSK-BFI strongly correlated with LARS-Q. Low correlation was observed between the MSK-BFI diet subscale and LARS-Q (r s −0.39). On multivariate analysis, both questionnaires showed worse bowel function in patients with distal tumours. A low to moderate correlation with the European Quality of Life Instrument was observed for both questionnaires. Conclusions The MSK-BFI and LARS-Q showed good correlation and similar discriminant validity. As the LARS-Q is easier to complete, it may be considered the preferred tool to screen for bowel dysfunction

CpG island methylator phenotype-positive tumors in the absence of MLH1 methylation constitute a distinct subset of duodenal adenocarcinomas and are associated with poor prognosis.

Little information is available on genetic and epigenetic changes in duodenal adenocarcinomas. The purpose was to identify possible subsets of duodenal adenocarcinomas based on microsatellite instability (MSI), DNA methylation, mutations in the KRAS and BRAF genes, clinicopathologic features, and prognosis.info:eu-repo/semantics/publishe

Epigenetic silencing of neurofilament genes promotes an aggressive phenotype in breast cancer

Neurofilament heavy polypeptide (NEFH) has recently been identified as a candidate DNA hypermethylated gene within the functional breast cancer hypermethylome. NEFH exists in a complex with neurofilament medium polypeptide (NEFM) and neurofilament light polypeptide (NEFL) to form neurofilaments, which are structural components of the cytoskeleton in mature neurons. Recent studies reported the deregulation of these proteins in several malignancies, suggesting that neurofilaments may have a role in other cell types as well. Using a comprehensive approach, we studied the epigenetic inactivation of neurofilament genes in breast cancer and the functional significance of this event. We report that DNA methylation-associated silencing of NEFH, NEFL, and NEFM in breast cancer is frequent, cancer-specific, and correlates with clinical features of disease progression. DNA methylation-mediated inactivation of these genes occurs also in multiple other cancer histologies including pancreas, gastric, and colon. Restoration of NEFH function, the major subunit of the neurofilament complex, reduces proliferation and growth of breast cancer cells and arrests them in Go/G1 phase of the cell cycle along with a reduction in migration and invasion. These findings suggest that DNA methylation-mediated silencing of the neurofilament genes NEFH, NEFM, and NEFL are frequent events that may contribute to the progression of breast cancer and possibly other malignancies.SCOPUS: ar.jinfo:eu-repo/semantics/publishe