Clinical trial NCT04127734: Treatment of Anastomotic Leakage After Rectal Cancer Resection
Official title: Treatment of AnastomotiC Leakage After Rectal Cancer Resection. TENTACLE Rectum Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Anastomotic Leak Rectum
Rectal Cancer
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
First posted: 2019-10-16
Enrollment: 1246
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All consecutive adult rectal cancer patients who have been operated between January 2014-December 2018 will be retrospectively analyzed and evaluated for an anastomotic leakage. All patients with an anastomotic leakage diagnosed within one year from primary surgery are suitable for inclusion.

Brief summary: The TENTACLE: Rectum study is a multinational retrospective cohort study that includes patients with anastomotic leakage after rectal cancer resection.

The study aims to develop an anastomotic leakage severity score and to evaluate the efficacy of different treatments of anastomotic leakage.

Detailed description: Rationale:

Anastomotic leakage occurs in up to 20% after low anterior resection for rectal cancer. It is a severe complication with high associated morbidity, ICU admission, prolonged hospital stay and need for reinterventions and readmissions. Anastomotic leakage is independently associated with the risk of local recurrence and reduced long term survival. Most literature focusses on incidence and predictive factors. Remarkably, there is almost no data on the efficiency of different treatments of anastomotic leakage after low anterior resection.

Anastomotic leakage after rectal cancer resection is generally underreported, mainly due to subclinical leaks below a diverting stoma. However, up to 50% of the leaks do not heal with fecal diversion alone, especially not in an irradiated field, related to a competent sphincter which hampers adequate drainage of the presacral abscess. Late diagnosis of 'reactivated' leaks after stoma reversal is not an infrequent phenomenon. Chronic sinus, gluteal abscess, and fistula formation have been reported in up to 10%, and permanent stoma rates around 20%, both having significant impact on quality of life.

Examples of factors that may influence the severity and chance of healing of the anastomotic leakage are: timing of diagnosis, degree of systemic inflammatory response, etiology (e.g. ischemia of the afferent loop), degree of dehiscence and retraction, location of the leak (e.g. circular staple line, blind loop), whether or not a diverting stoma is in place, and extent of abdominal contamination. However, little is known about to what extent these and other factors contribute to anastomotic leakage severity and chance of healing. In addition, it is not known which anastomoses are likely to be preserved by which type of treatment, and which anastomotic failures require redo surgery at a certain time frame.

Primary study objectives

1. To investigate which factors contribute to anastomotic leakage severity and to compose an evidence based anastomotic leakage severity score, in which clinically relevant subgroups will be explored (e.g. diversion or not), as well as different clinical settings (e.g. leak diagnosis within or beyond 90 days postoperatively).
2. To evaluate the effects of different treatment approaches on all different pre-specified outcome parameters, stratified for severity score, anatomical characteristics of leakages and timing of diagnosis of leakage.

Study design:

International multicenter retrospective cohort study.

Study population:

Adult patients with anastomotic leakage after low anterior resection for rectal cancer.

Primary outcome parameter:

1-year stoma-free survival.

Secondary outcome parameters:

ICU length of stay, mortality, comprehensive complications index, total number of reinterventions (surgical, radiological, endoscopic) within one year, total number of unplanned readmissions within one year, total hospital stay during one year, total time of having a stoma until one year, stoma present at one year, type of stoma present at one year (diverting, permanent), secondary leakage related complications (extrapelvic abscess, cutaneous fistula, vaginal fistula, bladder fistula, small bowel, ureteric fibrosis with hydronephrosis), hospital related costs.

Sample size calculation:

Inclusion of 980 patients will be sufficient to analyze primary study objective 1 and this is 1246 patients for primary study objective 2. Therefore, the aim is to include at least 1246 patients.

Eligibility criteria: Inclusion Criteria:

* Aged 18 years or older;
* Cancer located in the rectum, defined according to the international definition of the rectum consensus \[D'Souza 2019\];
* Rectal cancer resection with primary anastomosis (with or without diverting loop ileostomy) for either primary cancer, completion after local excision or salvage resection for regrowth after watch \& wait or local excision;
* Postoperative anastomotic leakage according to the following definition: "a breach in a surgical join between two hollow viscera, with or without active leak of luminal contents" \[Peel 1991\].

Exclusion Criteria:

* Rectal resection for benign disease;
* Rectal resection for recurrent rectal cancer after previous low anterior resection or other primary malignancies;
* Multivisceral resection (lateral lymph node dissection can be included)
* Emergency resection;

Primary outcomes:
measure: 1-year stomafree survival
timeFrame: 1 year
Secondary outcomes:
measure: ICU length of stay
timeFrame: 1 year
measure: 1 year mortality
timeFrame: 1 year
Other outcomes:
measure: Comprehensive complications index
timeFrame: 1 year
measure: Readmission rate
timeFrame: 1 year
measure: Reintervention rate
timeFrame: 1 year
measure: Hospital length of stay
timeFrame: 1 year
measure: Stoma time
timeFrame: 1 year
measure: Type of stoma present at 1 year
timeFrame: 1 year
measure: Secondary leak related complication rate
timeFrame: 1 year
measure: Hospital related costs
timeFrame: 1 year
Locations:
Study officials:
affiliation: Radboud University Medical Center
name: Hans de Wilt, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: