Treatment of Anastomotic Leakage After Rectal Cancer Resection (TENTACLE:R)

Treatment of AnastomotiC Leakage After Rectal Cancer Resection. TENTACLE Rectum Study

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.

Study Overview

• Status: Unknown
• Conditions: Rectal Cancer; Anastomotic Leak Rectum
• Intervention / Treatment: Procedure: The efficacy of various interventions for anastomotic leakage after rectal cancer resection are investigated

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.

• Study Type: Observational
• Enrollment (Anticipated): 1246

Contacts and Locations

• Study Contact: Name: Frans van Workum, MD; Phone Number: 0031621282881; Email: frans.vanworkum@radboudumc.nl
• Study Contact Backup: Name: Pieter Tanis, MD, PhD; Phone Number: 0031629068275; Email: p.j.tanis@amsterdamumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

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;

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-year stomafree survival	Survival of the patient and absence of a stoma	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ICU length of stay	Length of stay in the intensive care unit	1 year
1 year mortality		1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comprehensive complications index	According to Clavien	1 year
Readmission rate	Readmission to the hospital after discharge	1 year
Reintervention rate	Total number of reinterventions (radiological, surgical, endoscopic)	1 year
Hospital length of stay	Total days in the hospital	1 year
Stoma time	Total time of having a stoma	1 year
Type of stoma present at 1 year		1 year
Secondary leak related complication rate	extrapelvic abscess, cutaneous fistula, vaginal fistula, bladder fistula, small bowel fistula, ureteric fibrosis with hydronefrosis	1 year
Hospital related costs	Costs of hospital/ICU stay and interventions/diagnostics	1 year

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Collaborators: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Investigators: Principal Investigator: Hans de Wilt, MD, PhD, Radboud University Medical Center

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2020
• Primary Completion (Anticipated): December 31, 2020
• Study Completion (Anticipated): September 30, 2021

Study Registration Dates

• First Submitted: October 14, 2019
• First Submitted That Met QC Criteria: October 14, 2019
• First Posted (Actual): October 16, 2019

Study Record Updates

• Last Update Posted (Actual): October 21, 2019
• Last Update Submitted That Met QC Criteria: October 17, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Postoperative Complications; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms; Anastomotic Leak
• Other Study ID Numbers: 2019-5849

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

IPD Plan Description

Planning to share IPD with collaborators if interesting research questions are submitted to the study steering committee.

Specifics will be determined in study meetings in the nearby future.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No