Morphine Analgesia, Cannabinoid Receptor 2, and Opioid Growth Factor Receptor Cancer Tissue Expression Improve Survival after Pancreatic Cancer Surgery
Lubomir Vecera 1 2, Petr Prasil 3, Josef Srovnal 4 5, Emil Berta 4 6, Monika Vidlarova 4 5, Tomas Gabrhelik 7, Pavla Kourilova 4 5, Martin Lovecek 8, Pavel Skalicky 8, Jozef Skarda 9, Zdenek Kala 10, Pavel Michalek 11, Marian Hajduch 4 5 12
- 1Department of Emergency Medicine, The Tomas Bata Regional Hospital in Zlin, 762 75 Zlin, Czech Republic.
- 2Department of Paediatric Anaesthesiology and Intensive Care Medicine, University Hospital Brno, Medical Faculty of Masaryk University, 625 00 Brno, Czech Republic.
- 3Department of Anesthesiology and Intensive Medicine, Landesklinikum Amstetten, 3300 Amstetten, Austria.
- 4Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, 779 00 Olomouc, Czech Republic.
- 5Laboratory of Experimental Medicine, Olomouc University Hospital, 779 00 Olomouc, Czech Republic.
- 6Department of Anaesthesia and Intensive Care, Ringerike Hospital, 3511 Hønefoss, Norway.
- 7Department of Anaesthesiology, Resuscitation and Intensive Care, The Tomas Bata Regional Hospital in Zlin, 762 75 Zlin, Czech Republic.
- 8Department of Surgery I, University Hospital Olomouc, Faculty of Medicine and Dentistry, Palacky University, 779 00 Olomouc, Czech Republic.
- 9Institute of Molecular and Clinical Pathology and Medical Genetics, Faculty of Medicine, University Hospital Ostrava, University of Ostrava, 703 00 Ostrava, Czech Republic.
- 10Department of Surgery, Faculty of Medicine, University Hospital Brno, Masaryk University, 625 00 Brno, Czech Republic.
- 11Department of Anesthesiology and Intensive Medicine, General University Hospital, First Medical Faculty of the Charles University, 128 00 Prague, Czech Republic.
- 12Cancer Research Czech Republic Foundation, 779 00 Olomouc, Czech Republic.
Affiliationer
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.
