IMARI trial

Rationale

Anastomotic leakage (AL) is one of the most feared complications after rectal cancer surgery. AL leads to a significant increase in postoperative morbidity, long-term surgical complications, negative impact on quality of life, higher permanent stoma rates and impaired oncological outcomes. Despite improvement in surgical and oncological outcomes in recent years, AL still occurs in up to 20% of all patient undergoing rectal cancer surgery in the Netherlands. Of all these leaks, half will not heal by conventional treatment and might require major salvage surgery.

Many adjustable and non-adjustable risk-factors have been identified for anastomotic leakage. Modifiable surgical factors include tension on the anastomosis and anastomotic perfusion. A more recently described pathophysiological mechanism relates to the intestinal microbiome. Given the multifactorial etiology, a multi-interventional program is required for the prevention of AL.

If AL occurs, early diagnosis and “active” treatment allows for optimal control of pelvic sepsis, anastomotic healing and stoma reversal. No international consensus exists on a diagnostic pathway for early detection of AL, even though evidence is building for the use of C-reactive protein (CRP) in the early postoperative period. Active treatment with vacuum-assisted drainage (EVAC) of the abscess cavity in combination with early transanal closure of the anastomotic defect appears to improve anastomotic healing rate.

In the IMARI-trial we want to address all the interventions mentioned above within existing institutional enhanced recovery programs and prehabilitation initiatives (i.e. correction of anemia, optimization of nutritional status, cessation of smoking).

Primary objective

To increase the one year anastomotic integrity rate in patients undergoing total mesorectal excision (TME) for rectal cancer by the routine and quality controlled implementation of a multi-interventional program.

Study design

Multicenter prospective clinical effectiveness trial, whereby current local practice (control cohort) will be subsequently compared to the results of a multi-interventional program (intervention cohort) in patients undergoing total mesorectal excision (TME) for rectal cancer. This program includes:

• Mechanical bowel preparation with oral antibiotics
• Tailored full splenic flexure mobilization
• Intraoperative fluorescence using indocyanine
• Routine CRP-measurement at day three postoperatively, CT-scan with rectal contrast on indication
• EVAC with early transanal closure of the anastomotic defect

Microbiome analysis will be conducted to investigate changes in rectal microbiome environment and correlation to AL.

Inclusion criteria

1. Patients with a diagnosis of primary rectal cancer with the lower border below the level of the sigmoid take-off on MRI, or regrowth in a watch and wait protocol, or undergoing completion/salvage surgery after local excision;
2. Age above 18;
3. Able to fill in questionnaires in Dutch and to come to out-patient-clinic visits;
4. Written informed consent

Exclusion criteria

1. Patients not undergoing resection with colo-rectal/anal anastomosis;
2.  Local recurrent rectal cancer;
3.  Locally advanced rectal cancer requiring extended or multi-visceral excision;
4.  Synchronous colonic resections;

Outcomes

The primary outcomes is the one year anastomotic integrity rate, determined by CT-scan.
The most important secondary outcomes are: the impact on the incidence of AL within 30 and 90 days and one year post-operative. Other outcomes include quality of life, protocol compliance, changes in rectal microbiome, FA details and other postoperative outcomes.

Participating Centers

Approved by central and local IRB for inclusion:

• Amsterdam UMC, location AMC, Amsterdam
• Amsterdam UMC, location VUMC, Amsterdam
• Isala Ziekenhuis
• Meander Medisch Centrum
• OLVG
• Spaarne Gasthuis

Formally approved by central IRB, local approval pending:

• Amphia Ziekenhuis
• Bernhoven
• Catharina ziekenhuis
• Flevo Ziekenhuis
• Ziekenhuis Gelderse Vallei
• Ziekenhuis Groep Twente
• Jeroen Bosch Ziekenhuis
• Maastricht UMC
• Radboud UMC
• IJsselland ziekenhuis

Voor vragen of extra informatie kunt u kijken op onze website (www.imari-trial.nl) of contact opnemen met de coördinerend onderzoeker.