Predictive Factors for Anastomotic Leakage After Colorectal Surgery (REVEAL)

September 23, 2021 updated by: Maastricht University Medical Center

Predictive Factors for Anastomotic Leakage After Colorectal Surgery: The REVEAL Study

Rationale: Colorectal cancer is the fourth most common cause of cancer death worldwide, estimated to be responsible for almost 610,000 deaths in 2008. Surgery remains the predominant curative treatment type for colorectal cancer, but has a major impact on the patient's wellbeing by demanding large amounts of metabolic reserves. This can lead to the development of frequently observed and severe postoperative complications. The most important complication after colorectal surgery is anastomotic leakage (AL), which has an incidence of 8-15% in the Netherlands. AL is associated with high short-term mortality rates of up to 40%. Even though many attempts have been made to reduce the incidence of this dreaded complication, none of these interventions have been successful so far. Despite proper patient selection and improvement in surgical techniques, the percentage of AL has been stable for years.

Objectives: To investigate whether recently identified patient-specific factors can predict the occurrence of anastomotic leakage in patients undergoing elective surgery for colorectal cancer.

Study design: Prospective observational study Study population: Adult colorectal cancer patients undergoing elective surgery. Main study parameters/endpoints: Primary endpoint: AL within 30 days postoperatively Secondary endpoints: Intestinal microbiome in fecal sample, I-FABP, SM22, Calprotectin, C-reactive protein(CRP), Citrullin, complement factors in blood, VOCs in exhaled air, COX-2 & MBL polymorphisms in buccal smear, L3-index & atherosclerosis measurements on CT-scans, SNAQ & MUST scores

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Colorectal cancer (CRC) is the fourth most common cause of cancer death worldwide, estimated to be responsible for 610,000 deaths in 20081. The number of CRC patients is concomitantly increasing due to a higher incidence, population growth, aging of the population and the recently established nationwide screening. Surgery remains the predominant curative treatment type for CRC, but has a major impact on the patient's wellbeing by demanding large amounts of metabolic reserves. This can lead to the development of frequently observed and severe postoperative complications. Anastomotic leakage (AL) is the most important complication after colorectal surgery and has an incidence of 8-15% in the Netherlands. AL is associated with high short-term mortality rates of up to 40%. Even though many attempts have been made to prevent this dreaded complication, none of these interventions have been successful so far. Despite proper patient selection, reduction of known preoperative risk factors and improved surgical techniques as well as introduction of 'fast track' protocol, AL incidence has not decreased in the past decade(s). AL is associated with a decreased disease-specific survival and an increased recurrence rate of CRC. The aim of this study is to investigate potential strategies to prevent AL, to be able to diagnose AL in time and therefore start treatment as early as possible in the process.

The etiology of anastomotic healing in the human gastrointestinal tract is not fully elucidated. Risk factors that are associated with anastomotic leakage have been identified, such as patient characteristics (age, malnutrition, tumor distally localized) and surgical factors (insufficient perfusion of the anastomosis, tension on the anastomosis).

Previous studies performed at our surgical research department of the School for Nutrition, Toxicology and Metabolism (NUTRIM) were focused on these risk factors individually. We revealed the consequences of intestinal ischemia both in small and large human intestines in a unique experimental model and described the recovery mechanism of the intestine after ischemic injury. The crucial role of Mannose Binding Lectin (MBL), an important complement factor of the immune system was shown as well as the fact that small proteins present in mature enterocytes (Intestinal-Fatty Acid Binding Proteins, I-FABP) can act as adequate markers in plasma for intestinal damage13-14. Furthermore, with the use of cyclooxygenase-2 (COX-2) knockout mice, it was shown that COX-2 is essential in the healing process of colonic anastomoses (manuscript submitted).

Another previous study showed that frailty (defined with the Groningen Frailty Index, sarcopenia (determined by measuring the skeletal muscle mass at L3 level at the CT-scan) and malnutrition (assessed with Short Nutritional Assessment Questionnaire (SNAQ) en Malnutrition Universal Screening Tool (MUST)) is associated with the occurrence of sepsis and mortality in 273 patients. In a pilot study with 90 patients, preoperative I-FABP plasma levels and postoperative inflammatory plasma concentration (C-reactive protein & calprotectin) were identified as predictive markers for anastomotic leakage after elective colorectal surgery. In addition, composition of volatile organic compounds (VOCs) in exhaled breath varies depending on health status. Various metabolic processes within the body produce volatile products that are released into the blood and will be passed on to the airway once the blood reaches the lungs. Moreover, the occurrence of chronic inflammation and/or oxidative stress can result in the excretion of volatile compounds that generate unique VOC patterns. In this study, we will measure the total amount of VOCs in exhaled air, to see if this is an eligible tool for early clinical diagnosis of anastomotic leakage.

Based on all these results, we aim to combine and translate observational results from individual studies into one multicentre prospective study in which several aspects of anastomotic leakage will be investigated. With the results of this study, we expect to be able to provide patients an adequate risk estimation regarding anastomotic leakage. This will help surgeons to make the decision to create a stoma instead of performing a primary anastomosis and to detect anastomotic leakage at an earlier stage. Furthermore, this study may provide new insights that can lead to potential new treatment.

Study Type

Observational

Enrollment (Actual)

774

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Heerlen, Netherlands
        • Zuyderland Medical Centre
      • Maastricht, Netherlands
        • Maastricht University Medical Centre
      • Sittard, Netherlands
        • Zuyderland Medical Centre
      • Venlo, Netherlands
        • Viecuri Medical Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Patients diagnosed with colorectal cancer

Description

Inclusion Criteria:

  • in need of laparoscopic or open large bowel resection with primary anastomosis as standard treatment for colorectal carcinoma

Exclusion Criteria:

  • not requiring an anastomosis
  • abdominal surgery in the past 4 weeks (with exception from temporary defunctioning ostomies for patients with obstructive colorectal tumours)
  • pregnancy
  • cognitively impaired

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Anastomotic leakage
Of the entire cohort, data collected from patients suffering from anastomotic leakage will be evaluated and compared to patients that did not develop anastomotic leakage. No interventions, only data collection.
Other: No interventions, only data collection
Only data is collected from the subjects in both groups.
No anastomotic leakage
Of the entire cohort, data collected from patients suffering from anastomotic leakage will be evaluated and compared to patients that did not develop anastomotic leakage. No interventions, only data collection.
Other: No interventions, only data collection
Only data is collected from the subjects in both groups.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Anastomotic leakage
Time Frame: within 30 days
within 30 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Maastricht University Medical Center

Collaborators

VieCuri Medical Centre
Zuyderland Medical Centre

Investigators

  • Principal Investigator: Nicole Bouvy, MD, PhD, Maastricht University Medical Centre

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2015

Primary Completion (Actual)

July 1, 2021

Study Completion (Actual)

July 1, 2021

Study Registration Dates

First Submitted

January 21, 2015

First Submitted That Met QC Criteria

January 21, 2015

First Posted (Estimate)

January 27, 2015

Study Record Updates

Last Update Posted (Actual)

September 29, 2021

Last Update Submitted That Met QC Criteria

September 23, 2021

Last Verified

March 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • METC142073

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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