Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02347735 |
| Other study ID # |
METC142073 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
August 2015 |
| Est. completion date |
July 1, 2021 |
Study information
| Verified date |
March 2016 |
| Source |
Maastricht University Medical Center |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
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
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.
