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AIM: Knowledge of female urinary and sexual dysfunction after rectal cancer treatment is limited. This study addresses this in relation to the use of preoperative radiotherapy, type of surgery and presence of bowel dysfunction.METHOD: All living female patients who underwent abdominoperineal resection (APR) or low anterior resection (LAR) for rectal cancer in Denmark in 2001-2007 were identified. Validated questionnaires (the ICIQ-FLUTS and the SVQ) on urinary and sexual function were completed by 516 (75%) and 482 (72%) recurrence-free patients in 2009.RESULTS: Urgency and incontinence were reported by 77% and 63%. Vaginal dryness, dyspareunia and reduced vaginal dimensions occurred in 72%, 53% and 29%, and 69% reported that they had little/no sexual desire. Preoperative radiotherapy was associated with voiding difficulties (OR=1.63, 95% CI 1.09-2.44), reduced vaginal dimensions (OR=4.77, 95% CI 1.97-11.55), dyspareunia (OR=2.76, 95% CI 1.12-6.79), lack of desire (OR=2.22, 95% CI 1.09-4.53) and reduced sexual activity (OR=0.55, 95% CI 0.30-0.98). Patients undergoing APR had a higher risk of dyspareunia (OR=2.61, 95% CI 1.00-6.85). Bowel dysfunction after LAR was associated with bladder storage difficulties (OR=1.64, 95% CI 1.01-2.65), incontinence symptoms (OR=2.17, 95% CI 1.35-3.50), lack of sexual desire (OR=2.69, 95% CI 1.21-5.98), sexual inactivity (OR=0.48, 95% CI 0.24-0.96) and sexual dissatisfaction (OR=0.40, 95% CI 0.20-0.82).CONCLUSION: Female urinary and sexual problems are common after rectal cancer treatment. Preoperative radiotherapy interferes with several aspects of urinary and sexual functioning. Bowel dysfunction after LAR is associated with urinary dysfunction and a reduction in sexual desire, activity and satisfaction. This article is protected by copyright. All rights reserved.

Gene silencing by DNA hypermethylation of CpG islands is a well-characterized phenomenon in cancer. The effect of hypomethylation in particular of non-CpG island genes is much less well described. By genome-wide screening, we identified 105 genes in microsatellite stable (MSS) colorectal adenocarcinomas with an inverse correlation (Spearman's ? = -0.40) between methylation and expression. Of these, 35 (33%) were hypomethylated non-CpG island genes and two of them, APOLD1 (Spearman's ? = -0.82) and SRPX2 (Spearman's ? = -0.80) were selected for further analyses. Hypomethylation of both genes were localized events not shared by adjacent genes. A set of 662 FFPE DNA samples not only confirmed that APOLD1 and SRPX2 are hypomethylated in CRC but also revealed hypomethylation to be significantly (p < 0.01) associated with tumors being localized in the left side, CpG island methylator phenotype negative, MSS, BRAF wt, undifferentiated and of adenocarcinoma histosubtype. Demethylation experiments supported SRPX2 being epigenetically regulated via DNA methylation, whereas other mechanisms in addition to DNA methylation seem to be involved in the regulation of APOLD1. We further identified miR-149 as a potential novel post-transcriptional regulator of SRPX2. In carcinoma tissue, miR-149 was downregulated and inversely correlated to SRPX2 (? = -0.77). Furthermore, ectopic expression of miR-149 significantly reduced SRPX2 transcript levels. Our study highlights that in colorectal tumors, hypomethylation of non-CpG island-associated promoters deregulate gene expression nearly as frequent as do CpG-island hypermethylation. The hypomethylation of SRPX2 is focal and not part of a large block. Furthermore, it often translates to an increased expression level, which may be modulated by miR-149.

Sacral nerve stimulation (SNS) reduces symptoms in up to 80% of patients with faecal incontinence (FI). Its effects are not limited to the distal colon and the pelvic floor. Accordingly, spinal or supraspinal neuromodulation have been suggested as part of the mode of action. The effect of SNS on gastric and small-intestinal motility was studied.

Fynne L, Worsøe J, Gregersen T, Schlageter V, Laurberg S, Krogh K. Gastric and small intestinal dysfunction in spinal cord injury patients. Acta Neurol Scand: DOI: 10.1111/j.1600-0404.2011.01508.x. © 2011 John Wiley & Sons A/S. Background - Many patients with spinal cord injury (SCI) suffer from constipation, abdominal pain, nausea, or bloating, and colonic transit times are prolonged in most. Gastric and small intestinal dysfunction could contribute to symptoms but remain to be described in detail. Also, it is obscure whether the level of SCI affects gastric and small intestinal function. Aim - To study orocecal transit time and gastric emptying (GE) in patients with SCI. Methods - Nineteen patients with SCI (7 ♀, median age 54 years) and 15 healthy volunteers (9 ♀, median age 32 years) were included. All were referred because of neurogenic bowel problems. Eleven patients had low SCI (located at conus medullaris or cauda equina) affecting only the parasympathetic nerves to the left colon and eight had high SCI (above Th6) affecting parasympathetic and sympathetic innervation. Subjects ingested a small magnetic pill that subsequently was tracked by the Motility Tracking System - MTS-1 (Motilis, Lausanne, Switzerland). Results - Orocecal transit time was longer than normal both in individuals with high lesions (P

Udgivelsesdato: 2010-Jan Sacral nerve stimulation (SNS) is effective against faecal incontinence, but the mode of action is obscure. The aim of this study was to describe the effects of SNS on fasting and postprandial rectal motility. Sixteen patients, 14 women age 33-73 (mean 58), with faecal incontinence of various aetiologies were examined. Before and during SNS, rectal cross-sectional area (CSA) and ano-rectal pressures were determined with impedance planimetry and manometry for 1 h during fast and 1 h postprandially. Neither in the fasting state nor postprandially did SNS affect the number of single rectal contractions, total time with cyclic rectal contractions, the number of aborally and orally propagating contractions, the number of anal sampling reflexes or rectal wall tension during contractions. Postprandial changes in rectal tone were significantly reduced during SNS (P < 0.02). Before SNS, median rectal CSA was 2999 mm(2) (range: 1481-3822) during fast and 2697 mm(2) (range: 1227-3310) postprandially (P < 0.01). During SNS, median rectal CSA was 2990 mm(2) (1823-3678) during fast and 2547 mm(2) (1831-3468) postprandially (P = 0.22). SNS for faecal incontinence does not affect phasic rectal motility but it impairs postprandial changes in rectal tone.

Contains fulltext : 88652.pdf (Publisher’s version ) (Closed access) For international communication in cancer, staging systems such as TNM are essential; however, the principles and processes used to decide about changes in every new edition of TNM need to be subject to debate. Changes with major impact for patient treatment are introduced without evidence. We think that TNM should be a continual reactive process, rather than a proactive process. Changes should only occur after extensive discussion within the community, and before the introduction of any changes these should be tested for reproducibility and compared to the currently used gold standard. TNM should not be used to test hypotheses. It should introduce established facts that are beneficial to predicting patient prognosis. TNM should thus be restructured on a basis equivalent to evidence-based guidelines. The strength of the evidence should be explicitly stated and the evidence base given. It is time for the principles of staging to be widely debated and new principles and processes to be introduced to ensure that we are not in the same situation in the future. The disparity between therapeutic decision making and TNM staging is marked and we would appeal for the radical overhaul of TNM staging to make it fit for the twenty-first century. TNM is central to the management of cancer patients and we must protect and enhance its reputation. 01 augustus 2010

International audience; BACKGROUND AND PURPOSE: During the first decade of the 21st century a number of important European randomized studies were published. In order to help shape clinical practice based on best scientific evidence from the literature, the International Conference on 'Multidisciplinary Rectal Cancer Treatment: Looking for an European Consensus' (EURECA-CC2) was organized in Italy under the endorsement of European Society of Medical Oncology (ESMO), European Society of Surgical Oncology (ESSO), and European Society of Therapeutic Radiation Oncology (ESTRO). METHODS: Consensus was achieved using the Delphi method. The document was available to all Committee members as a web-based document customized for the consensus process. Eight chapters were identified: epidemiology, diagnostics, pathology, surgery, radiotherapy and chemotherapy, treatment toxicity and quality of life, follow-up, and research questions. Each chapter was subdivided by a topic, and a series of statements were developed. Each member commented and voted, sentence by sentence thrice. Sentences upon which an agreement was not reached after voting round # 2 were openly debated during a Consensus Conference in Perugia (Italy) from 11 December to 13 December 2008. A hand-held televoting system collected the opinions of both the Committee members and the audience after each debate. The Executive Committee scored percentage consensus based on three categories: "large consensus", "moderate consensus", and "minimum consensus". RESULTS: The total number of the voted sentences was 207. Of the 207, 86% achieved large consensus, 13% achieved moderate consensus, and only 3 (1%) resulted in minimum consensus. No statement was disagreed by more than 50% of the members. All chapters were voted on by at least 75% of the members, and the majority was voted on by >85%. CONCLUSIONS: This Consensus Conference represents an expertise opinion process that may help shape future programs, investigational protocols, and guidelines for staging and treatment of rectal cancer throughout Europe.