Opioids have been extensively used in cancer pain management because they can significantly improve the quality of life of patients with advanced cancer. However, recent evidence suggests that opioids can also modulate the tumor immune microenvironment by interacting with opioid receptors on immune cells, potentially regulating tumor progression and efficacy of cancer treatments. Notably, morphine can exhibit a dose-dependent effect on tumor immunity in pancreatic cancer and renal cell models, with lower doses potentially promoting tumor migration and invasion of pancreatic cancer cells, whereas higher doses shows the effect of inhibiting migration and invasion through distinct molecular pathways. The present review therefore comprehensively explored the mechanisms by which opioids can regulate the tumor immune microenvironment, focusing on their effects on immune cells, oxidative stress and angiogenesis. It also examined the interactions between opioids and other analgesics, along with their potential impact on immune modulation. All relevant articles and materials were retrieved from PubMed using the key words 'opioids', 'immune system', 'T cells', 'monocytes', 'macrophages', 'lymphocytes', 'natural killer cell', 'immunotherapy', 'immune cell function' and 'dose dependent effect'. The immunosuppressive effects of opioids, particularly through the µ-opioid receptor, can suppress the activity of natural killer cells, impair antigen presentation and promote the function of regulatory T cells (Tregs). These effects may contribute to tumor progression and metastasis. The severity of these immunosuppressive effects appears to be dose-dependent and can vary among different tumor types. There is evidence to suggest that tumors with higher immune responsiveness will experience more pronounced suppression, including the reduction of tumor angiogenesis, resulting in a decrease in tumor volume and decrease in tumor metastases. Furthermore, the combination of opioids with other analgesics, such as non-steroidal anti-inflammatory drugs, has the potential to exacerbate immunosuppression, which can in turn increase the risk of infections. Therefore, although opioids are essential for pain management in patients with cancer, their potential to modulate the immune microenvironment and promote tumor progression requires careful consideration. Clinicians should evaluate the advantages and disadvantages of opioids, especially regarding emerging immunotherapies, to minimize their potential negative effects on the outcomes of cancer treatments. Future studies are recommended to prioritize the development of strategies that optimize pain management whilst preserving immune function, such as receptor-specific opioid formulations or adjunctive therapies targeting immunosuppressive pathways.

Esophageal cancer constitutes one of the most aggressive malignant neoplasms associated with poor clinical outcomes. While surgical resection remains the cornerstone of curative intervention, optimization of perioperative care protocols has emerged as an essential strategy to reduce postoperative complications and potentially improve long-term survival rates in patients undergoing esophagectomy. However, substantial debate persists regarding the relative importance of various perioperative risk factors and their impact on post-resection outcomes.

To identify perioperative factors affecting prognosis after radical esophagectomy, aiming to improve patient outcomes through targeted interventions.

A retrospective study analyzed 378 patients with esophageal cancer who underwent radical esophagectomy (McKeown, Sweet, or Ivor-Lewis procedures) from January 2022 through December 2023. All operations were performed by experienced surgeons following standardized perioperative protocols. The investigation gathered data on patient demographics, surgical parameters, tumor pathology (using the 8th edition American Joint Committee on Cancer staging system), and survival outcomes. Statistical analyses utilized Kaplan-Meier estimates and Cox proportional hazards modeling, with adjustment for confounding variables.

Multivariate Cox proportional hazards analysis identified three independent predictors of survival: Tumor-node-metastasis staging [Hazard ratio (HR) = 2.31, 95% confidence interval (CI): 1.72-3.10, P < 0.001], tumor differentiation (moderate: HR = 1.46, 95%CI: 1.02-2.09, P = 0.038; poor: HR = 2.15, 95%CI: 1.47-3.14, P < 0.001), and extended postoperative analgesic use (> 5 days) (HR = 1.43, 95%CI: 1.08-1.89, P = 0.012). Kaplan-Meier analysis demonstrated significantly lower overall survival rates in patients requiring analgesics for > 5 days compared to ≤ 5 days (P = 0.003), with consistent patterns observed for both opioid (P = 0.019) and nonsteroidal anti-inflammatory drug use (P = 0.028). The extended analgesic group exhibited a higher proportion of elderly patients (48.47% vs 35.57%, P = 0.015), while other baseline characteristics and tumor features remained comparable between groups.

Tumor-node-metastasis staging, tumor differentiation, and duration of postoperative analgesic use independently predict survival following radical esophagectomy, underscoring the significance of optimal pain management protocols.

Gynecological cancers remain a leading cause of cancer among female patients, and surgery continues to be the primary therapeutic approach. Anesthesia is an indispensable component of perioperative period. In recent years, the influence of anesthesia drugs on cancer has become one of the focuses of anesthesiologists. Anesthetic drugs may influence cancer metabolic reprogramming and modulate immune function through the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS). Emerging evidence suggests that the choice of anesthetic agents could affect the prognosis of gynecological cancers. This review explores the relationship between anesthetic drugs and gynecological cancers (cervical cancer, ovarian cancer, and endometrial cancer), elucidating their effects on cancer prognosis through cellular pathways, metabolic regulation, and immune mechanisms. The findings aim to guide clinical decision-making and evaluate optimal perioperative anesthetic management strategies for gynecological cancer patients.

Potent analgesics such as sufentanil and remifentanil play a pivotal role in general anesthesia, but these medications have disadvantages, including respiratory depression, nausea, vomiting, immune system suppression, and gastrointestinal function inhibition. This study aimed to evaluate the effects of the transversus thoracic muscle plane-pectoral nerves (TTP-PECS) block on postoperative analgesia, immune function and early postoperative recovery quality in patients undergoing modified radical mastectomy under opioid-sparing general anesthesia.

A total of 100 patients scheduled for modified radical mastectomy under general anesthesia were randomly divided into the TTP-PECS block combined with opioid-sparing general anesthesia group (TO group, n = 50) or the conventional general anesthesia group (GA group, n = 50). The TO group underwent TTP-PECS block prior to induction, using oxycodone as the analgesic during induction instead of sufentanil, no additional continuous infusion of analgesic was performed intra-operatively. Visual analogue scale (VAS) scores at rest and during movement at different time points were recorded in both groups, and the levels of T cell subsets, natural killer (NK) cells were measured before the surgery and at 24 h and 48 h after the surgery. Quality of Recovery-40 (QoR-40) scores were assessed at 24 h postoperatively, and the incidence of peri-operative adverse reactions was also observed in both groups.

Except for 48 h postoperatively, patients in the TO group had significantly lower VAS scores than those in the GA group at 2 h, 6 h, 12 h, and 24 h postoperatively at rest and during movement (P < 0.05). At 24 h and 48 h postoperatively, the expression of CD4+ T cells and the CD4+/CD8+ ratio were significantly higher in the TO group than in the GA group (P < 0.05). The QoR-40 scale, assessed at 24 h postoperatively, showed that the TO group significantly outperformed the GA group in total scores as well as in sub-scores for emotional state, physical comfort, physical independence, psychological support, and pain (P < 0.05). In addition, systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) were lower at time points T1-T4 than at T0 in both groups (P < 0.05), but the differences between the two groups were not statistically significant(P > 0.05). The incidence of cough reflex during induction and postoperative nausea and vomiting were significantly lower in the TO group than in the GA group (P < 0.05). There was no statistically significant difference between the two groups in the incidence of other adverse reactions (P > 0.05).

The combination of TTP-PECS block and oxycodone-propofol opioid-sparing general anesthesia can provide superior postoperative analgesia and reduce the incidence of postoperative nausea and vomiting. It also alleviated the suppression of cellular immune function and improves the quality of early recovery in breast cancer patients. At the same time, opioid-sparing general anesthesia is a safe strategy for modified radical mastectomy.

Chinese Clinical Trial Registry; ChiCTR2200066753.

In the past decade, a variety of immune checkpoint inhibitors (ICIs) are currently approved for lung cancer in the world. As a new therapeutic approach, ICIs have shown significant clinical benefits in the first-line or second-line treatment for advanced lung cancer, improving the survival and quality of life of patients. Patients need to take multiple drugs in the meantime due to their own disease or side effects during treatment. In view of drug interactions, concomitant medications have a positive or negative impact on the prognosis of lung cancer patients. In this review, we reviewed the effects of multiple drugs on the prognosis of patients with lung cancer taking ICIs. Several studies indicate that antibiotics, proton pump inhibitors (PPIs), corticosteroids, and opioid analgesics can decrease the efficacy of ICIs. Aspirin and bone-targeting drugs can enhance the efficacy of ICIs and improve the survival rate. The effects of metformin (MET), renin-angiotensin-aldosterone system inhibitors (RASI), nonsteroidal anti-inflammatory drug (NSAIDS) (except aspirin), and statins on ICIs are controversial. Future research should further explore the effects of these concomitant medications on ICIs and develop personalized prescriptions based on the specific needs of patients.

Parecoxib, a well-recognized nonsteroidal anti-inflammatory drug, has been reported to possess anticancer properties in various tumor types. In this work, we aimed to investigate the potential anticancer effects of parecoxib on hepatocellular carcinoma (HCC) cells. To assess the impact of parecoxib on HCC cell proliferation, we employed Cell Counting Kit-8, colony formation, and 5-ethynyl-2'-deoxyuridine assays. Hoechst/propidium iodide (PI) double staining and flow cytometry were performed to evaluate apoptosis and cell cycle analysis. Wound healing and transwell assays were utilized to assess cell migration and invasion. Tube formation assay was employed to analyze angiogenesis. Protein levels were determined using western blotting, and mRNA expression levels were assessed using quantitative real-time polymerase chain reaction (PCR). A xenograft mouse model was used to confirm the antitumor effects of parecoxib on HCC tumors in vivo. Our data demonstrated that parecoxib effectively inhibited the proliferation of HCC cells in a dose- and time-dependent manner. In addition, parecoxib induced cell cycle arrest in the G2 phase and promoted apoptosis. Moreover, parecoxib hindered tumor migration and invasion by impeding the epithelial-mesenchymal transition process. Further investigation showed that parecoxib could significantly suppress angiogenesis through the inhibition of extracellular signal-regulated kinase (ERK)-vascular endothelial growth factor (VEGF) axis. Notably, treatment with the ERK activator phorbol myristate acetate upregulated the expression of matrix metalloproteinase (MMP)-2, MMP-9, and VEGF and reversed the function of parecoxib in HCC cells. Besides, parecoxib displayed its antitumor efficacy in vivo. Collectively, our results suggest that parecoxib ameliorates HCC progression by regulating proliferation, cell cycle, apoptosis, migration, invasion, and angiogenesis through the ERK-VEGF/MMPs signaling pathway.

Opioids are the most effective and widely used treatments for acute and chronic pain in patients with cancer. This review focuses on the impact of opioids and mu-opioid receptors (MORs) on the stages of oncologic metastasis. Studies have shown that opioids can facilitate tumor progression and are related to a poor prognosis in patients with cancer. As the primary receptor for opioids, MORs play a significant role in regulating malignant tumor transformation and are involved in processes, such as proliferation, angiogenesis, epithelial-mesenchymal transition (EMT), circulating tumor cells (CTCs) and the tumor microenvironment (TME). While clinical trials have investigated the relationship between opioids and patient prognosis, further research is needed to clarify the relationship between opioids, MORs and metastasis.

Opioid receptor agonists are often used when cancer patients undergo surgery or analgesic treatment. As analgesics in clinical care, opioids can provide intraoperative or to chronic cancer pain relief. Immune function plays an important role in anti-cancer therapy, with cellular immunity, comprised principally of T-lymphocytes and natural killer cells, representing the primary anti-cancer immune response. However, it remains unclear whether immune function is further affected with the use of opioids in already immunocompromised cancer patients. This article provides a review of the effects of commonly used clinical opioids, including morphine, oxycodone, fentanyl and tramadol, on immune function in cancer patients. It provides a summary of current evidence regarding the immunomodulatory effects of opioids in the cancer setting and mechanisms underlying these interactions.

Tramadol, a weak opioid anesthetic, is used for pain management in patients with cancer, but the effects of tramadol on cancer via µ-opioid receptor are still unknown. We assessed the effects of tramadol on pancreatic ductal adenocarcinoma using transgenic mice (LSL-KrasG12D/+; Trp53flox/flox; Pdx-1cre/+ ).

Six-week-old transgenic mice were orally administered 10 mg/kg/day tramadol (n=12), 10 mg/kg/day tramadol and 1 mg/kg/day naltrexone (n=9), or vehicle water (n=14) until the humane endpoint. Cancer-related pain and plasma cytokine levels were assessed by the mouse grimace scale and cytokine array, respectively. Tumor status was determined histopathologically. Tramadol's effects on proliferation and invasion in pancreatic ductal adenocarcinoma cell lines were studied in vitro.

Tramadol with/without naltrexone improved mouse grimace scale scores while decreasing inflammatory cytokines such as tumor necrosis factor-α and interleukin-6. Proliferative Ki-67 and cyclins decreased by tramadol, while local M1-like tumor-associated macrophages increased by tramadol, which was blocked by naltrexone. Meanwhile, tramadol with/without naltrexone reduced juxta-tumoral cancer-associated fibroblasts and M2-like tumor-associated macrophages. Tumor-associated neutrophils, natural killers, and cytotoxic T cells were not altered. Tramadol decreased the proliferative and invasive potentials of pancreatic ductal adenocarcinoma cell lines via decreasing cyclins/cyclin-dependent kinases, which was partially reversed by naltrexone.

These findings imply that tramadol might be a useful anesthetic for pancreatic ductal adenocarcinoma: inhibiting the proliferation and invasion along with increasing antitumor M1-like tumor-associated macrophages via the µ-opioid receptor, while improving cancer-associated pain possibly through the antitumor effects with the decrease of inflammatory cytokines.

Radical gastrectomy is a mainstay therapy for patients with locally resectable gastric cancer (GC). GC patients who are candidates for radical gastrectomy will experience at least part of the following perioperative events: surgery, anesthesia, pain, intraoperative blood loss, allogeneic blood transfusion, postoperative complications, and their related anxiety, depression and stress response. Considerable clinical studies have shown that these perioperative events can promote recurrence and decrease the long-term survival of GC patients. The mechanisms include activation of neural signaling and the inflammatory response, suppression of antimetastatic immunity, increased release of cancer cells into circulation, and delayed adjuvant therapy, which are involved in every step of the invasion-metastasis cascade. Having appreciated these perioperative events and their influence on the risk of GC recurrence, we can now use this knowledge to find strategies that might substantially prevent the deleterious recurrence-promoting effects of perioperative events, potentially increasing cancer-free survival in GC patients.