The APPEAL-study
Analysis of Parameters Predictive for Evident Anastomotic Leakage

The main complication after colorectal surgery is anastomotic leakage, with an
incidence varying between 5% and 15%. In an insufficient anastomosis wall
defects can develop, through which non-sterile contents of the colon can leak
into the abdominal cavity. This can cause peritonitis that leads to sepsis,
multiple organ failure and, finally, death in approximately 10 % to 20 %.
Current diagnostic methods include observation of clinical symptoms and
imaging, both with several disadvantages. Observation of clinical symptoms is
not specific; the symptoms can mimic several common, less severe, postoperative
infections, which delays the actual diagnosis. On top of that, when anastomotic
leakage has already progressed to a state of clinical manifestation, the
patient is already ill and treatment should be initiated. Imaging is used to
confirm a clinical diagnosis of anastomotic leakage. This means that when
imaging is done the patient is already ill and treatment should be initiated.
An accepted method for prevention of this complication is prophylactic
drainage. This enables postoperative evacuation of blood and wound fluid
collections that could lead to infection. In this study these collections,
retrieved from the drain*s reservoir, will be analysed for parameters with
potentially diagnostic value for anastomotic leakage.

Primary objective
To define a parameter, or parameters, in peritoneal drain fluid that have
diagnostic value for clinically manifest anastomotic leakage of a colorectal
anastomosis in the early postoperative period.

Secondary objectives
To compare the evaluated parameters for their accuracy, cost-effectiveness and
speed.
To investigate if, with these parameters, a distinction can be made between
sub-clinical and clinical anastomotic leakage

The APPEAL-study will be a multicentre cohort study.
The participating hospitals will be asked to include 30 patients every year.
This is possible since each centre will operate approximately 50 to 80 patients
a year suitable for the APPEAL-study.
For now 8 centres have agreed to participate and two more will be asked to do
so as well, so that the total number of centres will come to ten. This results
in 300 patients in approximately a year.
The patients who undergo a colorectal operation, mentioned in the inclusion
criteria, will be included at the moment of hospitalisation by a physician.
They will receive an explanation of the contents of the APPEAL-study, a patient
brochure and they will be asked to give their informed consent. If the patient
decides to participate a drain will be left in the abdomen during the operation
and will remain in place for five days. After the procedure, each postoperative
day, the overnight drain fluid collection will be send to the laboratory of
clinical chemistry and microbiology for further processing (table 1). With each
20 included patients (100 samples) analysis of the parameters mentioned in
table 1 will be done.

The patients will receive a drain which remains in place during 5 days unless
the treating physician decides otherwise. The burden and risk that go along
with placement of the drain are minimal.
Withdrawl of drainfluids from the reservoir will take place each day and is
considered not to be a burden.