Title: UK Cohort study to Investigate the prevention of Parastomal Hernia (CIPHER)
Funder: Department of Health and Social Care

Abstract: DESIGN: Our proposed research project has two components: Phase A: Phase A will comprise preliminary work to establish the key surgical steps that may influence parastomal hernia (PSH) formation and test patient reported outcome measures (PROs) for symptomatic PSH to use in Phase B. Phase B: Phase B will be the main multicentre pragmatic cohort study. It will identify key technical surgical factors, defined during Phase A, that are associated with PSH. Participants will be recruited at the time of surgery. SETTING: 50 acute hospital Trusts in the UK. POPULATION: Adults (18+ yrs) undergoing planned surgery with the intention to form a stoma. Inclusion: Surgery requiring formation of ileostomy or colostomy. Exclusion: Emergency surgery; intention to form loop ileostomy; double-barrelled stoma; urostomy formation; previous abdominal wall stoma; life expectancy <12 months. SURGICAL TECHNIQUES OF INTEREST: Surgical techniques [estimated use] of stoma formation; a) creation of stoma trephine in abdominal wall (location within or without the rectus sheath); b) use of mesh/type (none [80%] vs biologic [10%] vs synthetic [10%]); c) mesh position (intra-abdominal [15%] vs sublay/ retrorectus [80%] vs onlay [<5%]); d) trephine shape in the mesh (circle [30%] vs cross [60%] vs slit AND none [10%](Sugarbaker)). These techniques will be defined in Phase A. COSTS: Cost-utility of different surgical methods of stoma formation with respect to the risk of PSH will be estimated using data collected from participants and from routine sources. It will consider the costs of in-theatre, in-hospital, community care and social service resources, time off work, and personal out-of-pocket expenditure. Cost-utility will be estimated from NHS and societal perspectives. HES data will describe hospital resource use and the NHS Central Register will provide vital status. OUTCOME MEASURES: The primary outcome will be PSH incidence in the 2-years following surgery, defined as symptomatic PSH (participant-reported quarterly) with radiological (CT) confirmation. Symptoms of PSH include difficulties with stoma appliances or discomfort/pain. A defined pre-agreed threshold will be used (see above and Research Plan). Clinical and radiological protocols will be used to confirm PSH. Secondary outcomes will include hospital stay, surgical site infection and other complications, PSH repair and generic (EQ-5D-5L, SF12) and disease specific patient-reported outcomes. Follow up will be optimised using post/web/social media/SMS. RECRUITMENT: About 13,000 stoma-related procedures were recorded in HES in 2012-13, excluding loop ileostomies. We estimate that 50 Trusts will carry out about stoma forming procedures eligible for CIPHER on about 4,000 patients/year and that 50% will consent; this gives a sample of 4,000 in 2 years, each centre recruiting about 4 patients/month. SAMPLE SIZE: The incidence of PSH is unknown; we assume that it is 30-40% by 2 years. Surgical techniques of interest are used with varying frequencies. Considering extremes, i.e. ratios of 1:2 and 1:20, the study will have 90% power to detect adjusted hazard ratios between 1.2 and 1.9 at the 5% significance level (2-sided). ANALYSES: Survival multilevel model of time to PSH, estimating hazards of key predictors (see Surgical techniques) after adjusting for important procedure, patient and surgeon confounding factors. Follow-up will be censored if bowel function is restored or participants die.

Lay abstract: Parastomal hernia (PSH) is a complication of surgery to remove some bowel with the creation of a stoma (with the end of the bowel passing through the side of the body and emptying bowel contents into a bag worn around the waist). PSH develops when the muscle in the body wall splits, causing a bulging of the skin next to a stoma. PSH develops quite often, affecting about 40% of patients within 2 years of their bowel surgery. Having a PSH makes it difficult to attach stoma bags which, in turn, causes bowel contents to leak, irritation of the skin and anxiety. PSH may also cause pain and, sometimes, unexpected hospital admissions to treat serious problems related to the hernia and bowel obstruction. Treatment is difficult and mostly involves specialist stoma care with expensive appliances; in some cases, further surgery may be required. Surgery for PSH, however, is associated with an increased risk of developing another hernia. Therefore, it is very important to prevent a PSH forming in the first place. Surgical methods for creating a stoma vary considerably but there is almost no high quality research evaluating whether the risk of a PSH is less with some methods than others. It has been suggested that the shape and size of the hole that the surgeon cuts in the body wall, whether or not a mesh is used and, if so, the type of mesh and where it is placed may be important. The lack of research about these variations in surgical methods means that it is not sensible currently to invest a lot of money in comparing just one or two surgical methods. Therefore, we are proposing a large study to find out what methods a large number of surgeons are using and the extent to which single factors, and combinations of factors, influence the risk of developing a PSH. This study will not be able to quantify accurately how much one particular factor can reduce the risk but it will identify key factors that need to be studied in a future randomised controlled trial. Our proposal is for a study of 4000 patients in 50 UK centres, involving surgeons who carry out operations in which they create a stoma. First, we will study a selected sample of operations and surgeons in-depth, to define precisely how their surgical methods vary. This will allow us to specify clearly the information we want to obtain in the subsequent, main study. In the main study, patients requiring surgery with formation of a stoma from the large or small bowel (colostomy or ileostomy) will be invited to take part. Joining the study will not affect patients’ treatment but we will ask participants to complete questionnaires regularly over this period and seek their consent to study their outcomes a minimum of 2 years. This information will tell us how often PSH occurs. A study of this size will allow us to assess many surgical risk factors for PSH formation. We will also measure costs, health related quality of life, treatments given to reduce problems created by PSH and the rates of repeat surgery. This work will inform the design of a large trial to compare the effectiveness of different surgical methods to create a stoma, focusing on one or two specific factors identified by our study as being the most important for minimising the risk of a PSH developing. In the study an experienced team including patient representatives, specialist and academic surgeons and methodologists will work together linked to a surgical trials centre to deliver the work on time and target.

Research activity codes: 6.4 SURGERY
Health categories: ORAL AND GASTROINTESTINAL