Short summary

Anastomotic leakage after low anterior resection for rectal cancer is a serious and life threatening complication with both short and long term consequences. Early intervention is mandatory for a good clinical outcome. Symptoms are insidious and often masked by postoperative analgesia and new methods for improved clinical monitoring are warranted like e.g. intraperitoneal microdialysis, poor functional outcome, an increased risk of a permanent stoma and low quality of life.

Approximately 1400 patients a year are treated for rectal cancer in Denmark. Approximately 500 undergo a low anterior resection. With a known frequency of clinical anastomotic leakage on 10-15%, a total of 50-75 patients may suffer from severe complications with prolonged hospitalization, additional surgery, poor functional outcome, an increased risk of a permanent stoma and low quality of life.

The following study presentation will be diverted into 3 subprojects (see Rationale).  

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Rationale

1. LAR 2 (Microdialysis study):

The principle in microdialysis is a continuous measurement of changes in the concentration of different metabolic and inflammatory parameters in the abdominal cavity. Intraperitoneal microdialysis has proven to be a promising tool to measure local ischemia in animal studies and a few human studies with the lactate/pyrovate (L/P) ratio as the most sensitive parameter. The results from our pilot study showed an increase in L/P ratio together with a decrease in glucose concentration in all of the four patients that developed clinical anastomotic leakage. The changes were observed several days prior to the development of significant clinical symptoms. However, it was not known whether the changes were a result of ischemia or inflammation. Other studies on small patient series have shown increase in inflammatory parameter such as interleukins (5). In conclusion, significant changes in metabolism and inflammation occurred locally prior to the development of clinical symptoms. However, none of the existing studies focused on the problem with "sub-clinical" leakages, which may be a significant confounder.

Objective: Intraperitoneal microdialysis can detect anastomotic leakage prior to the development of significant symptoms

Method: Microdialysis will be performed in 7 days postoperative, and compared with leakage score (Dulk score) and a CT-water-soluble contrast enema examination per rectum performed at day 7, to evaluate the anastomosis.

2. Early closure of temporary loop ileostomy after rectal resection for cancer:

The aim of this prospective randomized study is to compare early vs. late closer of the protecting ileostoma in patients requiring rectal resection for rectal cancer. Early closer is defined as postoperativday 8-12 and delayed as later than 3 month. Inclusion criteria is aged 18 years or older with rectal carcinoma, requiring rectal resection with a protecting ileostoma. A CT-water-soluble contrast enema examination per rectum is performed at day 7, to evaluate the anastomisis in all patients. The patients will be randomized after the "intention-to-treat" principelle, before the primary operation.  If there is no radiologic signs of contrast leakage ore other contraindications for early closer as septic episodes ore missing bowl movements the early closure will be performed. Primary end point is the rate of either postoperative death or postoperative complications occurring at 90 days after the rectal resection.

Major and minor postoperative complications (anastomotic leakage, post operative death, anastomotic fistula, postoperative peritonitis, pneumonia etc) and stoma related complications (prolapsus or peristomial eventration, erosive peristomial dermitis, dehydration with hydroelectrolytic disorders, occlusive syndrome) would be registered.

3. Anorectal evaluation with longterm followup in rectal cancer patients

In Denmark, more than 11,000 persons live with rectal cancer or with the consequences of the disease and the surgical treatments. Late side effects include incontinence for flatus or liquid stools, frequency, clustering, urgency, bleeding and pain. Likewise, urinary - and sexual dysfunctions are bothersome long-term consequences survivors may suffer.

The present study aim to evaluate prevalence, degree, and influence on quality of life and daily activities of the aforementioned symptoms in detail in a long-term follow-up setting. Via questionnaires and extensive physiological examinations of anorectal pathology we hope to get a better understanding of how different surgical treatments and adverse effects to the surgery influence outcome. 

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Description of the cohort

Inclusion criteria:
Patients operated for rectal cancer with Low Anterior Resection with or without a diverting ileostomy, and age above 18.
The patients are included at 4 surgical departments (Odense, Vejle, Esbjerg and Slagelse)

Exclusion criteria:
Unconquerable disease

Data and biological material

Intraperitoneal microdialysis samples for the analysis of lactate, pyrovate, glycerol, glucose and cytokines.
Questionaries: QLQ-C30, LARS-score.

Clinical data: d Dulk score, CT-scan.

Collaborating researchers and departments

Department of Surgery, Odense University Hospital

• Niels Qvist, MD, DMSc
• Pia Møller Faabrog, MD, PhD
• Thomas Kolbro, MD

Department of Surgery, Vejle Hospital

• Head of Department Hans B. Rahr, MD, DMSc

OPEN Odense Patient data Explorative Network, Odense University Hospital

• Head of Research Unit Torben Barington, MD, DMSc

Department of Surgery, Hospital of Southwest Denmark, Esbjerg

• Thomas Buchbjerg, MD

Department of Surgery, Slagelse Hospital

• Sharaf Karim Perdawood, MD