Trial Information

Epidural or Patient-controlled Analgesia for Colorectal Cancer Surgery. Long-term Outcomes.

An application was sent to the Regional Ethics Committee at the Linköping University
Hospital and the study was approved recently. Informed consent will be obtained from 300
patients (ASA status 1-3) in the age group 40-80 years who are undergoing elective surgery
for colorectal cancer. The exact type of cancer, its staging, degree of spread to proximal
or distant sites and the pathologic type of cancer will be recorded. Patients on chronic
narcotic analgesic medication, those with known immunologic diseases, those with known
allergy to LA and those where epidural catheter placement is contraindicated will be
excluded. This study will be a multi-centre study in Central Sweden. Patients will be
randomized to one of two groups according to a computer-generated random number: Group E -
Epidural anaesthesia (EDA) or Group P - Patient-controlled analgesia (PCA).

Anaesthesia and surgery will be standardized, other than for group randomization. Surgical
management of patients in the hospitals will also be standardized. Postoperative parameters
will include pain intensity, rescue analgesic (morphine) consumption, surgical complications
(e.g., re-operation, surgical site infection, or bleeding), other perioperative
complications (e.g., deep vein thrombosis, cardiac complications, or chest infections),
cancer recurrence diagnosed by CT or MRI (done yearly over 5 years) and mortality, both
cancer-related and all-cause mortality. In addition, blood will be taken preoperatively for
analysis of the following inflammatory and immunological markers:

VEGF will be determined in peritoneal fluid and in serum during surgery. HIF-1A will be
determined by immunohistochemistry and microRNA measurements in normal and neoplastic
colonic mucosa.

In addition, the microRNA mi21 will be analyzed in by quantitative reverse transcriptase-PCR
in colon adenocarcinomas and adjacent non-cancerous tissues.

The CTC in whole blood (in 5-7.5 ml) will be measured with the CellSearch System, according
to the manufacturer´s instructions, and the Cell Tracks Analyzer II (Cristofanilli M et al.
N Engl J Med 2004:351:781-91).

Inflammatory mediator assay-ELISA Patient serum or EDTA/Heparin plasma will be assessed for
cytokine levels by a Luminex multiplex assay (Human Inflammation 12-Plex kit; GM.CSF, IFN-g,
IL-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, TNF-a and VEGF from R&D system) and PGE2
levels will be measured by an ELISA kit from Cayman Chemicals Company. In addition, markers
of systemic inflammatory response, including CRP, white blood cell count, differential count
and total platelet count, will also be measured before and after surgery.