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How many people suffer from bowel problems following surgery for colorectal cancer, and what treatments are the best for managing these problems?

ABSTRACT: Background and study aims Colorectal cancer is the third most common cancer worldwide with 14,000 patients in the UK being diagnosed with rectal cancer per year. Over half of those patients will undergo major resectional surgery. Low anterior resection syndrome (LARS) is a consequence of this surgery and describes a constellation of bowel symptoms including urgency, faecal incontinence, stool clustering and incomplete evacuation. It has a significant adverse impact on quality of life (QoL). LARS symptoms are present in up to 75% of the patients in the first year after surgery and may persist in 25%, remaining in up to half of these patients for more than 10 years. There is poor evidence to support the various treatment options currently in use. As disease-free survival is regarded as the most important factor following curative rectal cancer surgery, QoL and potential ways to improve it may be overlooked. Patients are often not aware or not told that bowel function can change significantly following surgery and radiotherapy and may think any adverse effects will be short-term. It is not known when post-operative bowel dysfunction, which may occur after any colonic resection, can be defined as LARS and how the trajectory of LARS changes over time, especially in patients undergoing radiotherapy. An introductory cohort study aims to explore the natural history of LARS, identify predictors of major LARS and screen patients for recruitment to a randomised controlled trial (RCT) that will measure the effectiveness of the new intervention. The aims of the RCT are to evaluate the clinical and cost-effectiveness of transanal irrigation (TAI) or sacral neuromodulation (SNM) versus optimised conservative management (OCM) for people with major LARS. Who can participate? Adult participants aged over 18 years old who have undergone a high or low anterior resection for colorectal cancer in the last 10 years. Participants with major LARS symptoms, defined as a LARS score of 30+, will be eligible to be randomised to the randomised controlled trial element. What does the study involve? Participants who enter the cohort will be asked to complete questionnaires about their quality of life and bowel symptoms every 3 months for 24 months. Clinical study data will be collected at baseline and then at 12 and 24 months from registration from medical notes. Participants who enter the RCT will be randomised to receive either TAI, SNM or OCM and will then go on to receive their allocated treatment. Patients will attend the hospital at various times depending on the treatment they are receiving and will also be followed up for trial purposes at 3, 6, 9 and 12 months post-randomisation via a combination of clinic or telephone assessments. At 24 months clinical study data will be collected from medical notes.

DISEASE(S): Low Anterior Resection Syndrome

PROVIDER: 71872 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Project description:Background On-pump cardiac surgery provokes a predictable perioperative myocardial ischaemia–reperfusion injury which is associated with poor clinical outcomes. We determined the occurrence of time-of-the-day variation in perioperative myocardial injury in patients undergoing aortic valve replacement and its molecular mechanisms. Methods We studied the incidence of major adverse cardiac events in a prospective observational single-centre cohort study of patients with severe aortic stenosis and preserved left ventricular ejection fraction (>50%) who were referred to our cardiovascular surgery department at Lille University Hospital (Lille, France) for aortic valve replacement and underwent surgery in the morning or afternoon. Patients were matched into pairs by propensity score. We also did a randomised study, in which we evaluated perioperative myocardial injury and myocardial samples of patients randomly assigned (1:1) via permuted block randomisation (block size of eight) to undergo isolated aortic valve replacement surgery either in the morning or afternoon. We also evaluated human and rodent myocardium in ex-vivo hypoxia–reoxygenation models and did a transcriptomic analysis in myocardial samples from the randomised patients to identify the signalling pathway(s) involved. The primary objective of the study was to assess whether myocardial tolerance of ischaemia–reperfusion differed depending on the timing of aortic valve replacement surgery (morning vs afternoon), as measured by the occurrence of major adverse cardiovascular events (cardiovascular death, myocardial infarction, and admission to hospital for acute heart failure). The randomised study is registered with ClinicalTrials.gov, number NCT02812901. Findings In the cohort study (n=596 patients in matched pairs who underwent either morning surgery [n=298] or afternoon surgery [n=298]), during the 500 days following aortic valve replacement, the incidence of major adverse cardiac events was lower in the afternoon surgery group than in the morning group: hazard ratio 0·50 (95% CI 0·32–0·77; p=0·0021). In the randomised study, 88 patients were randomly assigned to undergo surgery in the morning (n=44) or afternoon (n=44); perioperative myocardial injury assessed with the geometric mean of perioperative cardiac troponin T release was significantly lower in the afternoon group than in the morning group (estimated ratio of geometric means for afternoon to morning of 0·79 [95% CI 0·68–0·93; p=0·0045]). Ex-vivo analysis of human myocardium revealed an intrinsic morning–afternoon variation in hypoxia–reoxygenation tolerance, concomitant with transcriptional alterations in circadian gene expression with the nuclear receptor Rev-Erbα being highest in the morning. In a mouse Langendorff model of hypoxia–reoxygenation myocardial injury, Rev-Erbα gene deletion or antagonist treatment reduced injury at the time of sleep-to-wake transition, through an increase in the expression of the ischaemia–reperfusion injury modulator CDKN1a/p21. Interpretation Perioperative myocardial injury is transcriptionally orchestrated by the circadian clock in patients undergoing aortic valve replacement, and Rev-Erbα antagonism seems to be a pharmacological strategy for cardioprotection. Afternoon surgery might provide perioperative myocardial protection and lead to improved patient outcomes compared with morning surgery.

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How many people suffer from bowel problems following surgery for colorectal cancer, and what treatments are the best for managing these problems?

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