This study investigates the efficacy of the C-seal in the prevention of clinical AL in stapled colorectal anastomoses. The concept of the protection of a colorectal anastomosis by means of an intraluminal device has already been described [13
]. Based on the idea that intraluminal devices in colorectal anastomoses protect the fecal stream from anastomotic contact, there will be no leakage if anastomotic dehiscence develops. Under the device a perforation can still arise, but because there is no fecal spill this probably will not lead to a fecal peritonitis. Local inflammation may cause adhesions and cover the defect and symptoms of a possible leak are probably less severe [13
It is also hypothesized that AL in colorectal anastomoses is frequently caused by poor vascularization through intraoperative mechanical manipulation [17
], often from the distal rectal stump [19
]. Since the C-seal is attached to the proximal bowel loop, the C-seal remains in situ if the rectal stump is poorly vascularized and leads the fecal stream in the first postoperative weeks outside the body without contact with the rectal wall. After about two weeks the biodegradable drain degrades and is excreted through the anus.
In this study the required sample size is determined based on the current AL rate in the Netherlands. To give a good reflection of the colorectal surgery in the Netherlands and in order to approach this AL incidence, 35 different hospitals, ranging from small referral hospitals to academic centers, are participating in the trial. The participation of this large number of clinics creates possible challenges in protocol adherence. To standardize procedures all operating surgeons are trained by the C-seal research team from the UMCG and during the surgery a student from the C-seal team attends the procedure. To overcome a possible bias regarding the participation of many clinics the randomization is stratified for center.
In addition to the stratification for center, there is also stratified for the intention to create a deviating ostomy and for anastomotic height. The stratification for the intention to create a deviating ostomy is performed to prevent selection bias. The outcome of randomization (C-seal or not) may influence operating surgeons in their decision to create a deviating ostomy. Therefore, the intention to create a deviating ostomy must be documented before the patient is randomized at the OR.
A limitation of the study may be that we have chosen not to stratify for neoadjuvant therapy. Most patients with rectal cancer in the Netherlands are treated with neoadjuvant radiotherapy. From the literature it is concluded that short scheme radiotherapy is not a significant risk factor for the occurrence of AL [20
]. Results of studies with long scheme chemo radiation however are inconsistent in the influence on the incidence of AL. Some studies describe a significant increase in the occurrence of AL [22
], while results from other studies did not found this increase in the incidence of AL [24
Because a large study population will be included in this trial, the patients will be proportionally allocated to both groups.
With the results of this randomized controlled trial we compare the incidence of AL leading to re-intervention in patients treated with a C-seal to patients treated without a C-seal.
Secondary to this prospective trial a few side studies will be performed. With the use of intraoperative collected data of anaesthesiological parameters as oxygenation, blood tension, temperature and the use of vasoconstrictive medication eg, we attempt to identify potential contributing factors for the occurrence of AL. Also intraoperative data of the technical aspects of the stapling process are noted in the CRF to evaluate the surgical technique used to create an anastomosis in the Netherlands and the possible relation this could have in causing AL. Adjacent to the clinical trial translational research will be conducted with blood draws and bowel samples of the proximal and distal donuts of the included patients, collected during the surgery. With these patient materials we aim to correlate molecular tissue characteristics as pro-inflammatory proteins, Matrix Metallo Proteinases and C-reactive protein with clinical outcome. In blood plasma, indicators of inflammation, bacterial translocation and intestinal damage will be determined and will be correlated with the molecular profile of the patients.