Most patients with rectal cancer undergo surgery, which involves removal of the rectum and a new connection between the colon and anus. The most worrisome complication after this operation is leakage from the new connection, which results in stool and bacterial contamination of the abdomen. Patients who experience a leakage spend more time hospitalized and have a higher risk of other complications, compared to patients who do not have a leakage. Many risk factors contribute to the risk of leakage, including certain medications such as non-steroidal anti-inflammatory drugs (e.g., ibuprofen). In research studies using animal models, there is evidence that opioid medications (“narcotics”) also increase the risk of leakage; however, this has not previously been demonstrated in large studies including human patients. Patients who develop leakage also are exposed to more invasive procedures while in hospital, and may experience chronic abdominal-pelvic pain resulting from persistent inflammation caused by the leakage. As such, leakage may lead to more exposure to opioid-related pain medications, which may result in dependency and/or addiction to these medications. This study aims to examine whether opioid prescriptions in the year before surgery are associated with increased risk of leakage, and whether or not leakage after rectal cancer surgery is associated with increased opioid usage in the first year after surgery.
Postoperative anastomotic leak is the most dreaded complication after restorative proctectomy performed for rectal cancer. Patients with an anastomotic leak are at increased risk of morbidity and mortality, and also experience worse oncologic outcomes. Many risk factors are associated with anastomotic leak, including certain medications such as non-steroidal anti-inflammatory drugs. Opioids represent a potentially interesting exposure for anastomotic leak for which there is little existing research. Animal models have demonstrated an association between opioids and increased tissue concentrations of bacteria and enzymes known to contribute towards anastomotic leak. However, no previous large cohort study has studied the association between opioids and anastomotic leak in colorectal surgery. The primary aim of this study will be to evaluate the association between opioid prescriptions in the year prior to proctectomy and postoperative anastomotic leak. Patients who experience an anastomotic leak are also exposed to additional invasive procedures as part of their treatment, and may experience chronic abdomino-pelvic symptoms secondary to persistent/smoldering pelvic sepsis. As a secondary aim, we will evaluate the association between anastomotic leak and postoperative opioid prescriptions. The proposed study will be a large cohort study using two linked databases. Cohort inclusion criteria will be based on relevant rectal surgery procedures codes and rectal cancer diagnostic codes in the HES inpatient database, and data on opioid prescriptions will be based on opioid prescriptions recorded in CPRD. Multiple logistic regression will be employed to adjust for relevant confounders, and adjusted measures of association, with effect sizes, will be reported.
Health Outcomes to be Measured:
The following outcomes will be measured in this cohort: (1) postoperative anastomotic leak; and (2) prolonged opioid use.
HES Admitted Patient Care