Title: A multicentre, randomised controlled trial of Laparoscopic versus Open Colorectal Surgery in the Acute Setting
Funder: Department of Health and Social Care

Abstract: Background_x000D_ Approximately 30,000 patients undergo an emergency laparotomy within the NHS yearly. An emergency laparotomy is an open operation which is undertaken for a variety of diseases, a third of those are for diseases affecting the large bowel, including colorectal cancer, diverticular disease and inflammatory bowel disease. There is emerging evidence in the emergency setting that a keyhole (laparoscopic) operation can be undertaken. However, the evidence is limited to reports based on small numbers of patients who have been highly selected; this prevents the evidence from being applicable to all patients requiring an emergency colorectal operation. In the planned (elective) setting, keyhole surgery is routinely used for operations involving the large bowel, with good results, including less pain, better recovery and improved quality of life, however in the emergency setting an open operation is carried out more frequently. Surgeons speculate that a keyhole operation for these patients is beneficial, however we are not sure, this is why more research is needed to give us better quality data before this technique is recommended in the emergency setting. _x000D_ _x000D_ Aim and Objectives_x000D_ The aim of LACES2 is to determine whether keyhole surgery for large bowel diseases in the emergency setting has better outcomes for patients than open surgery, assessed primarily by examining complications. The trial will also look at patients’ quality of life, severity of complications, length of hospital stay, survival rates, rates of re-operation and re-admission, and health economic outcomes. _x000D_ _x000D_ Study Design_x000D_ The trial will recruit 512 patients from UK hospitals. Patients will receive either keyhole or open surgery decided randomly. The trial has been designed to reflect standard practice where possible. The follow-up schedule reflects the current clinical pathway for patients with colorectal cancer. Patients with other diseases may have one additional trial-related visit. Patients will be asked to fill out a number of questionnaires over 12-months to record quality of life and health care resource use. This will involve 3 questionnaires at the start of the trial and 4 questionnaires at 30 days and 3 months, and then 3 monthly up to 12 months after their operation; following surgery questionnaires will be posted to the participants. Patients who decline to take part will be asked to participate in an interview to discuss their reasons for not taking part. _x000D_ _x000D_ Patient and Public Involvement _x000D_ We have carried out a lot of work with patients in parallel to LaCeS. The results from this work have informed the design of LACES2. We have a PPI co-applicant, who is a member of the TMG and provides feedback from a LACES PPI group who will inform key aspects of the trial relevant to patients, for example information sheets, consent forms, questionnaire completion and the possible additional burden on trial participants, as well as advising on the format and content of the dissemination of the trial findings._x000D_ _x000D_ Dissemination _x000D_ Findings of the trial will be presented at national and international conferences and published in peer reviewed journals. Results from this trial will be disseminated to participating patients by participating sites via a newsletter on request. We will also develop a plan for the wider adoption of keyhole surgery in the emergency setting if the trial results support this.

Lay abstract: Research Question_x000D_ Does laparoscopic surgery in the emergency colorectal setting improve post-operative outcomes compared to open surgery?_x000D_ _x000D_ Background_x000D_ The National Emergency Laparotomy Audit (NELA) reports approximately 30,000 people/year undergo major, abdominal, gastrointestinal surgery, of which 36% are carried out for emergency colorectal pathology. The majority of patients undergo open surgery (laparotomy), which is associated with significant post-operative morbidity and mortality, and has an adverse effect on patients’ well-being and quality of life. There are emerging reports that the use of laparoscopic surgery in the emergency setting may be associated with improved clinical and patient-reported outcomes. However, the current evidence base is not robust enough to inform clinical practice due to the methodological weaknesses of cohort studies and case series, coupled with the lack of randomised controlled trials (RCT)._x000D_ _x000D_ Aims and Objectives_x000D_ Aim: To test the hypothesis that laparoscopic surgery in the emergency colorectal setting improves post-op outcomes compared to open surgery._x000D_ _x000D_ Objective: To conduct a definitive randomised controlled trial comparing laparoscopic with open colorectal resection in the emergency setting, reporting clinical, patient-reported and health economic outcome data for 12 months post-operatively. _x000D_ _x000D_ Methods_x000D_ A pragmatic, multicentre, randomised controlled superiority trial, with internal pilot and embedded qualitative and cost-effectiveness studies. 512 patients are required to detect a 15% absolute reduction in the 30-day complication rate with 90% power and 5% 2-sided significance level. Patients will be randomised on a 1:1 basis to laparoscopic or open resection, stratified by intended consultant surgeon, age, BMI, ASA, nature of underlying colorectal pathology & intended procedure. Data will be collected at baseline, 30 days (patient-reported outcomes), 6 weeks (clinical data), 90 days, 6 months, 9 months (patient-reported outcomes only) & 12 months. The primary outcome will be 30-day post-op complication rate defined as the number of patients with a complication (any grade) occurring within 30 days of surgery as a proportion of all randomised patients. Patient-reported QoL is included as a secondary outcome measure_x000D_ _x000D_ Timelines for Delivery_x000D_ 9 months is required for protocol development, ethical /HRA approval and trial/site set-up. Recruitment will take 36 months (12 month pilot phase), with a 12 month minimum follow up period during which short term outcomes will be analysed followed by an additional 3 month analysis phase. _x000D_ _x000D_ Anticipated impact and dissemination_x000D_ The anticipated impact to patients is improved post-operative recovery and quality of life benefitting current health services and the NHS overall. This will be the first RCT to provide evidence for the use of laparoscopic colorectal resection in the emergency setting, providing the evidence required for adoption into clinical practice with the potential of reducing the high economical burden of emergency surgery. The results of the trial will be disseminated through international conference presentations, publications in high impact peer reviewed journals and to patients and the wider public under the guidance of the LaCeS2 PPI group.

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