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

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.

Influence of opioid analgesia type on circulating tumor cells in open colorectal cancer surgery (POACC-1): study protocol for a prospective randomized multicenter controlled trial.

BACKGROUND: Opioids and epidural analgesia are a mainstay of perioperative analgesia but their influence on cancer recurrence remains unclear. Based on retrospective data, we found that cancer recurrence following colorectal cancer surgery correlates with the number of circulating tumor cells (CTCs) in the early postoperative period. Also, morphine- but not piritramide-based postoperative analgesia increases the presence of CTCs and shortens cancer-specific survival. The influence of epidural analgesia on CTCs has not been studied yet. METHODS: We intend to enroll 120 patients in four centers in this prospective randomized controlled trial. The study protocol has been approved by Ethics Committees in all participating centers. Patients undergoing radical open colorectal cancer surgery are randomized into epidural, morphine, and piritramide groups for perioperative analgesia. The primary outcome is the difference in the number of CTCs in the peripheral blood before surgery, on the second postoperative day, and 2-4 weeks after surgery. The number of CTCs is measured using molecular biology methods. Perioperative care is standardized, and relevant data is recorded. A secondary outcome, if feasible, would be the expression and activity of various receptor subtypes in cancer tissue. We intend to perform a 5-year follow-up with regard to metastasis development. DISCUSSION: The mode of perioperative analgesia favorably affecting cancer recurrence would decrease morbidity/mortality. To identify such techniques, trials with long-term follow-up periods seem suboptimal. Given complex oncological therapeutic strategies, such trials likely disable the separation of perioperative analgesia effects from other factors. We believe that early postoperative CTCs presence/dynamics may serve as a sensitive marker of various perioperative interventions´ influences on cancer recurrence. Importantly, it is unbiased to the influence of long-term factors and minimally invasive. Analysis of opioid/cannabinoid receptor subtypes in cancer tissue would improve understanding of underlying mechanisms and promote personalization of treatment. We are not aware of any similar ongoing studies. TRIAL REGISTRATION NUMBER: NCT03700411, registration date: October 3, 2018. STUDY STATUS: recruiting.

Cannabinoid receptor 2 expression in early-stage non-small cell lung cancers identifies patients with good prognosis and longer survival.

Background: Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related death with a 5-year survival of only 21%. Reliable prognostic and/or predictive biomarkers are needed to improve NSCLC patient stratification, particularly in curative disease stages. Since the endogenous cannabinoid system is involved in both carcinogenesis and anticancer immune defense, we hypothesized that tumor tissue expression of cannabinoid 1 and 2 receptors (CB1 and CB2) may affect survival. Methods: Tumor tissue samples collected from 100 NSCLC patients undergoing radical surgery were analyzed for CB1 and CB2 gene and protein expression using the quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). The gene and protein expression data were correlated with disease stage, histology, tumor grading, application of chemotherapy, and survival. Additional paired tumor and normal tissue samples of 10 NSCLC patients were analyzed independently for comparative analysis of CB1 and CB2 gene expression. Results: Patients with tumors expressing the CB2 gene had significantly longer overall survival (OS) (P<0.001), cancer specific survival (CSS) (P=0.002), and disease-free survival (DFS) (P<0.001). They also presented with fewer lymph node metastases at the time of surgery (P=0.011). A multivariate analysis identified CB2 tumor tissue gene expression as a positive prognostic factor for CSS [hazard ratio (HR) =0.274; P=0.013] and DFS (HR =0.322; P=0.009), and increased CSS. High CB2 gene and protein expression were detected in 79.6% and 31.5% of the tested tumor tissue samples, respectively. Neither CB1 gene nor CB1 or CB2 protein expression affected survival. When comparing paired tumor and tumor-free lung tissue samples, we observed reduced CB1 (P=0.008) and CB1 (P=0.056) gene expression in tumor tissues. Conclusions: In NSCLC patients undergoing radical surgery, expression of the CB1 and CB2 receptor genes is significantly decreased in neoplastic versus tumor-free lung tissue. CB2 tumor tissue gene expression is strongly associated with longer survival (OS, CSS, DFS) and fewer lymph node metastases at the time of surgery. More studies are needed to evaluate its role as a biomarker in NSCLC and to investigate the potential use of CB2 modulators to treat or prevent lung cancers.

Percutaneous upper thoracic radiofrequency sympathectomy in Raynaud phenomenon: a comparison of T2/T3 procedure versus T2 lesion with phenol application.

BACKGROUND AND OBJECTIVES: Percutaneous radiofrequency (RF) thoracic sympathectomy is an alternative method to surgical procedures for the treatment of acral ischemia in Raynaud phenomenon. The procedure is indicated if conservative therapy fails to provide sufficient relief. The aim of this study was to compare classic T2 and T3 RF thermolesioning with a less invasive procedure at the level of T2 only. METHODS: Fifty adult patients, American Society of Anesthesiologists (ASA) classification I to III, were randomly assigned to 1 of 2 groups. T2 and T3 thoracic RF thermolesion was performed in 1 group, whereas T2 thermolesion with local application of 0.5 mL of 6% phenol was delivered in the second group. Changes in cold perception, pain, and quality of life were assessed using a questionnaire. Blood circulation in the upper extremity was evaluated using infrared thermography. Patients were observed for a period of 3 months. RESULTS: A significant decrease in pain according to visual analog scale (P < 0.001), increase in peripheral temperature in the upper extremities (P < 0.001), and improvement in quality of life were observed in both groups of patients after the procedure. Susceptibility to cold-provoked vasospasm was not significantly affected in either group. There was no significant difference between the 2 groups in any parameter apart from the duration of the procedure. CONCLUSIONS: Thoracic RF upper sympathectomy is an effective method in the treatment of resistant forms of Raynaud phenomenon. A single-shot procedure at the level of T2 may be preferable because of the shorter procedure duration of this technique.

Single injection paravertebral block for renal surgery in children.

BACKGROUND: Continuous paravertebral block (PVB) has been successfully used for postoperative analgesia in children. However, data regarding the efficacy of a single injection technique for major renal surgery are still lacking. METHODS: Following the ethics committee approval and parent informed consent, 24 children (median 10.3 months; range: 2.9-26.8) undergoing major renal surgery were included in a prospective observational pilot study. Following a standardized general anesthetic the patients were administered a single injection low thoracic PVB (loss-of-resistance technique; 0.5 ml.kg(-1) of levobupivacaine 2.5 mg.ml(-1) with epinephrine 5 mug.ml(-1)) at the end of surgery. Postoperative pain was assessed by Face, Legs, Activity, Cry, Consolability (FLACC) score at predetermined time points and in case of apparent patients' discomfort during the first 12 postoperative hours. The duration of postoperative analgesia was defined as the interval between PVB and the first supplemental administration of a rescue opioid analgesic. The incidence of complications and postoperative vomiting (POV) was also recorded. RESULTS: A successful PVB was achieved in 23/24 patients (95.8%). The median duration of the block was 600 min (range: 180-720 min) with 10 children not requiring any supplemental analgesia during the 12-h observation period. Vascular puncture was observed in 2/24 children (8.3%) and POV occurred in 4/24 children (16.7%). All complications were considered minor and did not influence recovery. CONCLUSIONS: Single injection PVB provided clinically relevant postoperative analgesia in children undergoing major renal surgery.