Title: Hughes Abdominal Repair Trial - abdominal wall closure technique to reduce incidence of incisional hernias: multi-centre pragmatic randomised trial
Funder: Health and Care Research Wales (Welsh Government)

Abstract: Design: Multi-centre pragmatic randomized controlled trial. Setting: Hospital inpatients, colorectal cancer outpatient clinics. Strategy for reviewing literature: We have searched multiple databases including Cochrane, OVID and PubMed for the terms "incisional hernia”, "laparotomy", "closure" and their synonyms. We also searched the references of relevant articles and abstracts. This search yielded 14,710 titles, of which 291 were selected for abstract review and 98 publications for full review. 66 were judged as relevant to the trial. We have performed a systematic review of the available evidence of incisional hernias (IHs) after laparotomy wounds, assessing: rates of IHs detected during clinical examination (+/-radiological imaging) at one year post op and further follow up, rates of symptomatic IHs, rates of emergency repairs required for IHs, effect(s) of IHs on Quality of Life (QoL) and other key outcome measures. Target population: All patients undergoing surgery for colorectal cancer involving a midline incision. Due to the pragmatic design of the study, it will include elective and emergency patients undergoing open or laparoscopic assisted surgery with a midline specimen extraction site. Randomisation will be stratified to these variables, and to consultant surgeon. Health technology to be assessed: The ‘Hughes Repair’ [1] is a method of abdominal wall closure first described by the emeritus Professor of Surgery at the University of Wales, School of Medicine. In addition to the frequently utilised continuous ‘mass closure’ suture method described by Jenkins [2], the Hughes Repair involves a horizontal and two vertical mattress sutures within a single suture, thus closing the fascia using a series of interrupted sutures. This double mattress suture technique theoretically distributes the load along the incision length as well as across it. It is described for closure of patients at high risk of IH or following a ‘burst abdomen’, and is also used as an alternative to the standard mesh repair in treating patients with IHs [1, 3, 4]. Measurement of cost and outcome: The primary outcome measure will be the rates of IHs one year post operatively. This is a well recognised primary outcome from allied studies examining interventions designed to alter rates of IHs [5, 6]. One year follow up allows a time interval for IHs to develop and become clinically identifiable (>50% will be evident by this time [7]) and avoids increased loss-to-follow up with a longer primary outcome. The definition used herein for an IH is as per the 2009 consensus opinion of the European Hernia Society: “Any abdominal wall gap with or without a bulge in the area of a postoperative scar perceptible or palpable by clinical examination or imaging’’ [8]. Our definition thus includes both clinically and radiologically detected hernias, as used by others in similar trials [5, 9, 10]. Radiological detection is used to identify those hernias which may be missed on clinical examination due to their small size, and/or patient obesity [9, 11], pain limiting adequate examination and scarring [12]. We felt that inclusion of this subset of patients (approximately 20% of all identified IHs [9]) is essential – those found to have hernias on imaging alone essentially have occult hernias, but are still at risk of complications such as strangulation and pain. We also hypothesise that a certain proportion of those diagnosed with IHs on CT alone will progress to clinical hernias at longer follow up. Though the Core Outcome Measures in Effectiveness Trials (COMET) initiative plan to identify key outcomes for IHs, none are currently available (www.comet-initiative.org). Secondary outcomes will include: QoL, cost, incidence of post operative ‘burst abdomen’ (full thickness abdominal wall dehiscence). Recognising that including a radiological diagnosis of IH in our primary outcome is open to debate, we shall undertake two secondary analyses; 1st a sensitivity analysis restricted to clinically detected hernias; and 2nd an analysis of the correlation between QoL and IH detected clinically or radiologically. Sample size: An opportunistic retrospective review of 98 patients receiving Hughes Repair or standard mass closure in one institution found an incidence of IHs at one year of 15% in the Hughes Repair group, and 33% in the mass closure group. As control groups generally perform better in trials, and the Hughes Repair is likely to perform worse prospectively than in this retrospective study, we seek to identify a more modest reduction of IH rates from 30% (mass closure) to 20% (Hughes Repair). This would require 640 patients at one year. Given that loss to follow up from similar trials (e.g. COGNATE [13]) is about 20% at one year, we aim to recruit 800 patients in total. This target is similar to, but slightly greater than, those of recent trials comparing different closure techniques for reducing IHs (737 [6], 600 [9] and 576 [5]). A completed sample of 640 participants will also yield 80% power of detecting with a 5% significance level a standardised difference of 0.225 in QoL (our second principal outcome). Thus HART, powered to detect an important difference of 10% in the binary clinical outcome of IH, will also detect a difference generally regarded as small in the more patient-centred quantitative outcome of QoL. Project timetables: HART will recruit centres based on the ROSSINI [14] and DREAMS models. These randomised multicentre studies have used regional and national surgical research collaboratives to recruit many sites from around the UK. ROSSINI (trial finished) recruited ahead of schedule [15] whilst DREAMS is on target to recruit ahead of schedule. HART has been recently presented at the national research collaborative, with considerable interest from around the UK. To date we have confirmation of 8 sites from within Wales that are going to run the pilot study. Project milestones: • 01/11/13- 31/12/13 - feasibility of trial procedures in lead applicants site • 01/01/14 – 31/02/14 - review feasibility study findings and refine for pilot study • 01/03/14 - 31/5/14 - pilot full trial protocol in 8 welsh sites • 01/06/13 – 31/07/14 - Trial Steering Committee to review data against ACCEPT criteria [16] (see Detailed Project Description) • 01/08/14 – if successful in funding to initiate full trial in 20 centres across UK Flow diagram: see attached file. Expertise in team: see 15.1

Lay abstract: The proposed research aims to decrease the occurrence of a common but potentially serious complication after surgery on the abdomen: incisional hernias (IHs). A hernia is where an internal part of the body pushes through a weakness in the muscle or surrounding tissue wall. When the abdominal wall is closed after an operation within the abdomen, the strong connective tissue (fascia) which has been divided to allow entry to the abdomen, is closed. The most common technique used by surgeons today, described almost 40 years ago [2], involves a relatively simple ‘running suture’ down the entire length of the fascia. However, post operative IHs are common – occurring in over 30% of individuals undergoing surgery. These hernias occur when the fascial closure fails, so that the abdominal contents (including bowel) bulge out underneath the skin. These IHs can be very problematic for patients. They can cause symptoms of pain and discomfort, they look unsightly and have a substantial detrimental impact on QoL. There is evidence that 4 out of 5 patients who have IH’s complain of symptoms and feel that the IH reduces QoL [17]. In a smaller number of patients, bowel gets stuck in the hernia – requiring an emergency operation to repair, which is typically fraught with difficulties and dangers to patient and surgeon alike. This may involve long hospital stays and if the bowel loses blood supply, patients may require a stoma (bag for excretion of bowel contents). For those fortunate enough to avoid this complication, and who are fit enough to undergo further elective operations, surgical repair is available. Approximately 10,000 patients undergo this operation in the UK every year [7] – which highlights the size of the problem. Unfortunately, despite numerous techniques being described, the outcomes for the repair of IHs are poor, with recurrence rates of up to 50% being reported. We feel good quality clinical trials are urgently needed to address this significant post operative problem. Professor Hughes [18] meticulous attention to abdominal wall closure led him to develop his now eponymously titled repair technique. This repair closes the fascia using a sequence of separate sutures, designed to transfer the tension of the closure both along and across the incision. Its value is well recognised by surgeons, who use it for closing abdomens when patients are at high risk of IHs, after the rare occurrence of a “burst abdomen” (where the closure falls apart in the early period after the operation) and during elective repair of IHs. We propose to evaluate this as a primary technique, rather than after complications have occurred. The Hughes Repair requires a few more minutes than standard mass closure, but no more materials. It does not affect any other aspect of the surgical treatment of the patient, or how their skin is closed. Our previous work on surgical learning curves, notably in laparoscopic cholecystectomy [19], suggests that learning the Hughes Repair will not be a major challenge. Nevertheless we shall monitor secular trends in our primary outcome, and characterise these trends within our analysis plan. We have selected to examine the effect of this repair on colorectal cancer patients. This has the advantage of using a population sample with routine follow up, so that data may easily be collected following surgery. Therefore we can capture the presence of an IH at one year post-operatively detected during clinical examination or CT imaging, both of which routinely occur at this time point after cancer surgery. This trial therefore does not require any expensive or dangerous surgical intervention, additional outpatient appointments, or extra abdominal imaging, but simply utilises pre-existing services to ascertain IH rates between these two groups. HART is applicable to all colorectal departments across the UK, and has the potential to improve patient QoL and surgical practice, reduce morbidity and result in financial savings to the NHS. During the trial development phase, we have built up a strong team to ensure this research is a success. In recent years, surgical registrars have realised the importance of collaborative work in order to undertake projects such as these across many hospitals. The Welsh Barbers Research Group (WBRG) has built a team of enthusiastic individuals that have been key in getting this research started. We have also had strong support from the recent National Research Collaborative (NRC) Meeting. We aim to build on the huge success of recent clinical trials run by the NRC to enable widespread recruitment. We liaised with the local clinical trials unit (West Wales Organisation for Rigorous Trials in Health - WWORTH) at the very inception of the study, with extensive methodological support during our monthly trial meetings. We have access to an award winning surgical techniques teaching centre (Welsh Institute of Minimal Access Therapy – WIMAT) to firstly teach the technique to participating surgeons, and secondly to disseminate this technique throughout the UK, should our study show the Hughes Repair to be beneficial to patients. We have two excellent patient representatives, who have attended over 6 of our trial development meetings, have reviewed study paperwork, and given us very useful feedback on their thoughts of patients being recruited into the study.

Research activity codes: 6.4 SURGERY
Health categories: CANCER AND NEOPLASMS;ORAL AND GASTROINTESTINAL