Morphine Analgesia, Cannabinoid Receptor 2, and Opioid Growth Factor Receptor Cancer Tissue Expression Improve Survival after Pancreatic Cancer Surgery.

Simple Summary: Pancreatic carcinomas are among the most aggressive cancers and have a poor prognosis. The influence of postoperative analgesia on the prognosis of these patients has recently drawn considerable attention. We therefore conducted a retrospective study to evaluate the effect of postoperative analgesia on cancer-specific survival among patients after radical surgery for pancreatic cancer. We also investigated the effect of opioid and cannabinoid receptor gene expressions on overall survival. Our results showed that cancer-specific survival was increased by postoperative analgesia with morphine, cannabinoid receptor 2, and opioid growth factor receptor cancer tissue gene expressions but was reduced by delta opioid receptor gene expressions. The determination of opioid and cannabinoid receptor gene expression levels in pancreatic cancer cells and possibly also other cancer cells could thus provide important guidance on the selection of postoperative analgesia regimes and the prognosis of overall survival. Pancreatic cancer (PDAC) has a poor prognosis despite surgical removal and adjuvant therapy. Additionally, the effects of postoperative analgesia with morphine and piritramide on survival among PDAC patients are unknown, as are their interactions with opioid/cannabinoid receptor gene expressions in PDAC tissue. Cancer-specific survival data for 71 PDAC patients who underwent radical surgery followed by postoperative analgesia with morphine (n = 48) or piritramide (n = 23) were therefore analyzed in conjunction with opioid/cannabinoid receptor gene expressions in the patients' tumors. Receptor gene expressions were determined using the quantitative real-time polymerase chain reaction. Patients receiving morphine had significantly longer cancer-specific survival (CSS) than those receiving piritramide postoperative analgesia (median 22.4 vs. 15 months; p = 0.038). This finding was supported by multivariate modelling (p < 0.001). The morphine and piritramide groups had similar morphine equipotent doses, receptor expression, and baseline characteristics. The opioid/cannabinoid receptor gene expression was analyzed in a group of 130 pancreatic cancer patients. Of the studied receptors, high cannabinoid receptor 2 (CB2) and opioid growth factor receptor (OGFR) gene expressions have a positive influence on the length of overall survival (OS; p = 0.029, resp. p = 0.01). Conversely, high delta opioid receptor gene expression shortened OS (p = 0.043). Multivariate modelling indicated that high CB2 and OGFR expression improved OS (HR = 0.538, p = 0.011, resp. HR = 0.435, p = 0.001), while high OPRD receptor expression shortened OS (HR = 2.264, p = 0.002). Morphine analgesia, CB2, and OGFR cancer tissue gene expression thus improved CSS resp. OS after radical PDAC surgery, whereas delta opioid receptor expression shortened OS. [ABSTRACT FROM AUTHOR]