Introduction: Anastomotic leakage (AL) is the most severe complication following colorectal surgery and is associated with significant morbidity and mortality. VacStent therapy is a promising therapeutic approach, combining endoscopic vacuum therapy with mechanical stability of a stent and thereby allowing continued fecal passage. It may enhance anastomotic healing and reduce the need for a diverting ostomy or additional surgical procedures. VACStent Use for the treatment of anastomotic leakage following coloREctal surgery (VACURE) study aims to assess the efficacy and safety of VacStent therapy for colorectal AL.

Methods and analysis: VACURE is a prospective, multicenter efficacy study conducted at ten Dutch hospitals. Forty patients will be included over 18 months. All patients (≥18 years) with AL of the distal sigmoid, upper or mid rectum following colorectal resection will be considered for treatment with the VacStent GI Colon device. Trained endoscopists will perform stent placement, exchanges, and removal. Patients will remain hospitalized and those without diverting ostomy will receive osmotic laxatives and a fiber-free diet during treatment. Anastomotic healing will be confirmed endoscopically and radiologically posttreatment. The primary endpoint is the primary endpoint is the rate of participants that achieve complete anastomotic healing without the need for further interventions (confirmed by radiologic and endoscopic assessment). Secondary endpoints include safety, percentage of functioning anastomoses at 1 year post-treatment, 1-year stoma-free survival, diverting ostomy omission, healing time, number of stents, complications, reinterventions, length of hospitalization, pain scores, functional and quality of life outcomes up to 1 year posttreatment, patient experiences, and cost-effectiveness.

Detailed description of device and study procedures:

The first step in the treatment of AL will focus on source control of intraperitoneal or extraperitoneal sepsis if needed. This can either be performed by surgical reintervention (relaparoscopy with or without diverting ostomy) and/or drainage procedures (radiological or endoscopic). The second step of the treatment will be the placement the CE-marked VacStent GI Colon (VacStent GI, VACStent GmbH, Fulda, Germany) to facilitate anastomotic healing. This device consists of a self-expanding nitinol stent surrounded by a polyurethane sponge.

Before VacStent placement, the anastomotic defect will be visualized and evaluated endoscopically. A submucosal saline solution ('marking') will be injected in the colon mucosa at least 2 cm distal to the defect. This marking will resolve within 30 minutes and serves as visual guide during placement of the stent. The endoscope will then be further introduced into the colon and a stiff guide wire will be inserted over the scope, approximately 15 cm proximal to the defect. The delivery system of the VacStent will subsequently be guided over the stiff guide wire under direct vision, allowing precise positioning over the anastomotic defect. The VacStent is stabilized by two catheters: an external catheter which keeps the stent compressed until positioned correctly, and an internal catheter which enables precise deployment. During employment, the distal flare of the VacStent will be positioned at the marking to ensure complete coverage of the defect by the cylindrical polyurethane sponge.

After correct placement, the delivery system and guide wire will be removed. The suction catheter will be guided out of the body transanally and connected to the VAC-pump. Continuous negative pressure of -125 mmHg will be applied. During the implementation phase at each participating center, a member of the coordinating team (Amsterdam UMC) and manufacturer will provide hands-on training for VacStent placement and removal. Prior to the study a meeting with procedural instruction will be organized.

The VacStent can stay in situ for approximately seven days. Thereafter it should be replaced or removed, depending on the endoscopic findings (Figure 3). To facilitate removal, the VAC-pump should be discontinued for at least six hours before the procedure. Also, the device should be flushed with 40 ml 0.9% NaCl prior to removal to minimize tissue adherence. The VacStent is removed by using a distal attachment cap applied to the endoscope. This ensures careful separation as it allows the endoscope to be maneuvered between the VacStent and the mucosa. The VacStent is then removed endoscopically by grasping the retrieval loops at the distal end of the VacStent with a grasping forceps. If the anastomosis has healed sufficiently, no new stent will be placed and VacStent therapy will be finished.

If no diverting ostomy was created before VacStent therapy, patients will receive osmotic laxatives three times per day (e.g., Movicol) and a fiber-free diet to maintain soft stool consistency. Routinely an endoscopy will be performed two weeks after removal of the VacStent, as well as a CT scan with rectal contrast enema six weeks after stent removal. This is the routine protocol after treatment of leaks to confirm healing of the AL at Amsterdam UMC. Functional outcomes following VacStent therapy will be assessed with the Low Anterior Resection Syndrome score (LARS score) and Health-related quality of life with the EQ-5D-5L questionnaire at 3, 6, and 12 months posttreatment. In case the patient was diagnosed with colorectal cancer, patients will receive two additional questionnaires (EORTC QLQ - CR29 and EORTC QLQ - CR30).

Inclusion Criteria:

• AL in the distal sigmoid, upper or mid rectum following a colorectal resection
• ≥ 18 years old.
• Signed a written informed consent

Exclusion Criteria:

• Anastomosis that is not endoscopically accessible.
• Contra-indications for VacStent GI therapy: (a) Significant tissue ischemia in the area of the wound cavity, larger than the length of the VacStent GI Colon; (b) Anastomotic defect located <4 cm from the dentate line. This is considered a relative contraindication, as very distal placement may cause patient discomfort although not necessarily; (c) Severe coagulopathy; (d) Ileus that does not allow for endoscopic examination.
• Anastomotic fistula to surrounding organs (vagina, bladder, small bowel)

IPD data (deidentified) underlying the results reported in publications may be made available to qualified researchers upon reasonable request.