Surgical excision of the primary tumor represents the most frequent and curative procedure for solid malignancies. Compelling evidence suggests that, despite its beneficial effects, surgery may impair immunosurveillance by triggering an immunosuppressive inflammatory stress response and favor recurrence by stimulating minimal residual disease. In addition, many factors interfere with the immune effectors before and after cancer procedures, such as malnutrition, anemia, or subsequent transfusion. Thus, the perioperative period plays a key role in determining oncological outcomes and represents a short phase to circumvent anesthetic and surgical deleterious factors by supporting the immune system through the use of synergistic pharmacological and non-pharmacological approaches. In line with this, accumulating studies indicate that anesthetic agents could drive both protumor or antitumor signaling pathways during or after cancer surgery. While preclinical investigations focusing on anesthetics’ impact on the behavior of cancer cells are quite convincing, limited clinical trials studying the consequences on survival and recurrences remain inconclusive. Herein, we highlight the main factors occurring during the perioperative period of cancer surgery and their potential impact on immunomodulation and cancer progression. We also discuss patient management prior to and during surgery, taking into consideration the latest advances in the literature.
The question of whether anesthetic, analgesic or other perioperative intervention during cancer resection surgery might influence long-term oncologic outcomes has generated much attention over the past 13 years. A wealth of experimental and observational clinical data have been published, but the results of prospective, randomized clinical trials are awaited. The European Union supports a pan-European network of researchers, clinicians and industry partners engaged in this question (COST Action 15204: Euro-Periscope). In this narrative review, members of the Euro-Periscope network briefly summarize the current state of evidence pertaining to the potential effects of the most commonly deployed anesthetic and analgesic techniques and other non-surgical interventions during cancer resection surgery on tumor recurrence or metastasis.
Pancreatic cancer (PC) is one of the deadliest malignancies worldwide, since patients rarely display symptoms until an advanced and unresectable stage of the disease. Current chemotherapy options are unsatisfactory and there is an urgent need for more effective and less toxic drugs to improve the dismal PC therapy. Repurposing of non-oncology drugs in PC treatment represents a very promising therapeutic option and different compounds are currently being considered as candidates for repurposing in the treatment of this tumor. In this review, we provide an update on some of the most promising FDA-approved, non-oncology, repurposed drug candidates that show prominent clinical and preclinical data in pancreatic cancer. We also focus on proposed mechanisms of action and known molecular targets that they modulate in PC. Furthermore, we provide an explorative bioinformatic analysis, which suggests that some of the PC repurposed drug candidates have additional, unexplored, oncology-relevant targets. Finally, we discuss recent developments regarding the immunomodulatory role displayed by some of these drugs, which may expand their potential application in synergy with approved anticancer immunomodulatory agents that are mostly ineffective as single agents in PC.
Background: Colorectal cancer (CRC) is a leading cause of mortality worldwide and in the UK. Surgical resection is the main curative treatment modality available and using a laparoscopic vs. an open approach may have a direct influence on the inflammatory response, influencing cancer biology and potentially the recurrence kinetics by promoting cancer growth. Methods: This systematic review aims to compare laparoscopic with open surgery for the treatment of colon cancer with a specific focus on the moment of the recurrence. We included randomised controlled trials in intended curative surgery for colon cancer in adults. Interventions: Studies investigating laparoscopic vs. open resection as an intended curative treatment for patients with confirmed carcinoma of the colon. The two co-primary outcomes were the time to recurrence and the overall survival (OS) and disease-free survival (DFS) at three and five years. Meta-analyses were done on the mean differences. Results: After selection, we reviewed ten randomised controlled trials. Most of the trials did not display a statistically significant difference in either DFS or OS at three or at five years when comparing laparoscopic to open surgery. Groups did not differ for the OS and DFS, especially regarding the time needed to observe the median recurrence rate. The quality of evidence (GRADE) was moderate to very low. Conclusion: We observed no difference in the recurrence kinetics, OS or DFS at three or five years when comparing laparoscopic to open surgery in colon cancer.
Background: Intra-operative nausea, vomiting and retching (NVR) are frequently associated with subarachnoid anesthesia (SA) in women undergoing cesarean section (CS). In this study performed in women undergoing CS under SA with a risk factor control strategy, we compared saline (placebo), propofol, metoclopramide and both drugs to prevent NVR. Methods: We recorded NVR events in 110 women undergoing CS who were randomized after umbilical cord clamping to receive saline (S; n = 27), metoclopramide 10 mg (M; n = 28), propofol 1 mg/kg/h (P; n = 27) or both drugs (PM; n = 28). Results: The proportion of women with intra-operative nausea was: S: 17/27 (63%); P: 15/27 (56%); M: 13/28 (46%); PM: 6/28 (21%) (p = 0.012, Cramér’s V = 0.31 (large effect). The proportion of women with intra-operative vomiting/retching was: S: 9/27 (33%); M: 7/27 (25%); P: 3/28 (11%); PM 2/28 (7%) (p = 0.049, Cramér’s V = 0.26 (medium effect). Post-hoc multiple comparisons revealed a significant reduction in NVR episodes and NRS scores between the PM group and control. Sedation scores did not differ among groups. Conclusion: In women undergoing CS under SA with a risk factor control strategy, combined propofol and metoclopramide reduce nausea and vomiting.
About Me
Dr. Zhirajr Mokini is an independent researcher and mentee of the ESAIC Mentorship Program.
Dr. Zhirajr Mokini is an independent researcher and mentee of the ESAIC Mentorship Program.