IntAct: Intraoperative Fluorescence Angiography to Prevent Colorectal Anastomotic Leak

Scientific abstract: Colorectal cancer is the third most common cancer in the UK, with 30% of cases involving the rectum. Surgery offers the only hope of cure, but comes at a cost in terms of morbidity and mortality. The most feared complication of rectal cancer surgery is anastomotic leak, which is reported in 10% to 15% of patients. Approximately 30,000 – 40,000 colorectal anastomoses are constructed each year in the NHS, most usually for colorectal cancer. Anastomotic leak is therefore a significant healthcare burden. It has a negative impact on patient recovery and consumes NHS resources for remedial interventions. It increases morbidity from ~20% to ~60%, mortality from <5% to ~20%, and extends in-patient stay from an average of 7 to 19 days. The mean cost of care for patients undergoing uncomplicated colorectal surgery is ~£17,000, increasing to ~£45,000 in those who suffer complications. Patients who survive anastomotic leak suffer long-term consequences with reduced quality of life, high rates of wound complications and permanent stoma, and increased risk of cancer recurrence. Intraoperative fluorescence angiography (IFA) has recently been introduced into clinical practice and promises to bring about a step change in the way that anastomoses are constructed and so reduce the anastomotic leak rate. A proof of concept study (PILLAR II), using surgery with IFA in 147 patients with rectal cancer, has documented an anastomotic leak rate of 1.4%; a massive 8-9 fold reduction as compared to standard care. If proof of efficacy can be confirmed in a large, multi-centre study, the implications for patients, in terms of safer recovery from surgery and improved quality of life, and healthcare providers, in terms of cost-savings, will be substantial. It is hypothesized that the use of IFA in rectal cancer surgery will reduce the anastomotic leak rate from 12.0% to 6.0%, based on the best available literature. To confirm this, it is proposed to undertake a multi-centre, UK and European, randomized controlled trial comparing surgery with IFA against standard care (surgery with no IFA). 880 patients will be recruited from 25 centres over a period of 36 months, allowing for a 10% drop-out rate. An interim analysis will be performed when primary endpoint data is available for 554 patients; if there is significant evidence of efficacy for the primary endpoint then the trial will conclude. To facilitate recruitment, we will build on the recent success of a multicentre international randomized trial in rectal cancer surgery, involving collaborators from high volume centres recruiting 12 patients per year. The primary outcome will be clinical anastomotic leak rate. Secondary outcomes will include change in planned anastomosis, rate of defunctioning stoma, postoperative complications, rate of interventions, quality of life, and health resource utilisation. Patients will be followed for 90-days postoperative, at which point they will exit the study. A sub-study will be undertaken and will analyse the rectal microbiome to determine the changes that occur with surgery and its potential role in anastomotic leak.