In other terms, the original study was not designed to investigate the impact of dexmedetomidine on cancer progression – which can be viewed as an important limitation. ...while the study shows a ...strong association in the benefit of the use of dexmedetomidine, it should not be interpreted as a cause-effect. Furthermore, no data was presented on cancer histological subtypes. ...they pooled multiple cancers in the survival analysis. ...it remains unknown whether dexmedetomidine significantly improved patients' quality of life immediately after surgery, which was certainly not the case in Li’s follow-up study.
The theory that the perioperative period is critical for oncological outcomes has been a matter of extensive preclinical and clinical research. Basic science research strongly supports the notion ...that surgical stress, anesthetics, and analgesics influence the mechanisms of cancer progression. Hence, it is hypothesized that perioperative interventions that impact mechanisms or predictors of tumor progression can also affect patients' survival. As a result of that hypothesis, clinical researchers have conducted many retrospective studies. However, much fewer randomized controlled trials have been performed to investigate whether surgery itself (minimally invasive versus open procedures), anesthetics (volatile anesthetics versus propofol-based anesthesia), analgesics (opioids versus opioid-free anesthesia), and blood transfusions (transfusions versus no transfusions) modify the survival of patients with cancer. Unfortunately, randomized controlled trials have failed to translate the preclinical results into clinical outcomes. In this review, I will highlight the challenges of translating basic science to clinical outcomes. We will also point out opportunities for future research.
Intravenous lidocaine has been shown to reduce opioid consumption and is associated with favourable outcomes after surgery. In this study, we explored whether intraoperative lidocaine reduces ...intraoperative opioid use and length of stay (LOS) and improves long-term survival after pancreatic cancer surgery.
This retrospective study included 2239 patients who underwent pancreatectomy from January 2014 to December 2017. The patients were divided into non-lidocaine and lidocaine (bolus injection of 1.5 mg kg−1 at the induction of anaesthesia followed by a continuous infusion of 2 mg kg−1 h−1 intraoperatively) groups. The overall use of postoperative rescue analgesia and LOS were recorded. Propensity score matching was used to minimise bias, and disease-free survival and overall survival were compared between the two groups.
After propensity score matching, patient characteristics were not significantly different between groups. Intraoperative sufentanil consumption and use of postoperative rescue analgesia in the lidocaine group were significantly lower than those in the non-lidocaine group. The LOS was similar between groups. There was no significant difference in disease-free survival between groups (hazard ratio HR=0.913; 95% confidence interval CI, 0.821–1.612; P=0.316). The overall survival rates at 1 and 3 yr were significantly higher in the lidocaine group than in the non-lidocaine group (68.0% vs 62.6%, P<0.001; 34.1% vs 27.2%, P=0.011). The multivariable analysis indicated that intraoperative lidocaine infusion was associated with a prolonged overall survival (HR=0.616; 95% CI, 0.290–0.783; P=0.013).
Intraoperative intravenous lidocaine infusion was associated with improved overall survival in patients undergoing pancreatectomy.
To summarize the current evidence on the impact of regional anesthesia or analgesia on cancer recurrence.
Preclinical investigations suggest that regional anesthesia could have a positive impact on ...reducing cancer growth and progression. Regional anesthesia is also associated with better immunological and stress-related outcomes in patients undergoing major oncological surgery. Most recent retrospective studies do not show any benefit of regional anesthesia or analgesia on cancer recurrence or recurrence-free survival.
The available clinical evidence does not support the use of any anesthesia technique to improve the cancer-related survival after major oncological surgery. The results from four randomized controlled trials will shed light on this critical topic in perioperative medicine.
Peripheral neuropathy is dose limiting in paclitaxel cancer chemotherapy and can result in both acute pain during treatment and chronic persistent pain in cancer survivors. The hypothesis tested was ...that paclitaxel produces these adverse effects at least in part by sensitizing transient receptor potential vanilloid subtype 1 (TRPV1) through Toll-like receptor 4 (TLR4) signaling. The data show that paclitaxel-induced behavioral hypersensitivity is prevented and reversed by spinal administration of a TRPV1 antagonist. The number of TRPV1(+) neurons is increased in the dorsal root ganglia (DRG) in paclitaxel-treated rats and is colocalized with TLR4 in rat and human DRG neurons. Cotreatment of rats with lipopolysaccharide from the photosynthetic bacterium Rhodobacter sphaeroides (LPS-RS), a TLR4 inhibitor, prevents the increase in numbers of TRPV1(+) neurons by paclitaxel treatment. Perfusion of paclitaxel or the archetypal TLR4 agonist LPS activated both rat DRG and spinal neurons directly and produced acute sensitization of TRPV1 in both groups of cells via a TLR4-mediated mechanism. Paclitaxel and LPS sensitize TRPV1 in HEK293 cells stably expressing human TLR4 and transiently expressing human TRPV1. These physiological effects also are prevented by LPS-RS. Finally, paclitaxel activates and sensitizes TRPV1 responses directly in dissociated human DRG neurons. In summary, TLR4 was activated by paclitaxel and led to sensitization of TRPV1. This mechanism could contribute to paclitaxel-induced acute pain and chronic painful neuropathy. Significance statement: In this original work, it is shown for the first time that paclitaxel activates peripheral sensory and spinal neurons directly and sensitizes these cells to transient receptor potential vanilloid subtype 1 (TRPV1)-mediated capsaicin responses via Toll-like receptor 4 (TLR4) in multiple species. A direct functional interaction between TLR4 and TRPV1 is shown in rat and human dorsal root ganglion neurons, TLR4/TRPV1-coexpressing HEK293 cells, and in both rat and mouse spinal cord slices. Moreover, this is the first study to show that this interaction plays an important role in the generation of behavioral hypersensitivity in paclitaxel-related neuropathy. The key translational implications are that TLR4 and TRPV1 antagonists may be useful in the prevention and treatment of chemotherapy-induced peripheral neuropathy in humans.
The major goal of translational research is to evaluate the efficacy and effectiveness of treatments and interventions that have emerged from exhaustive preclinical evidence. In 2007, a major ...clinical trial was started to investigate the impact of paravertebral analgesia on breast cancer recurrence. The trial was based on preclinical evidence demonstrating that spinal anesthesia suppressed metastatic dissemination by inhibiting surgical stress, boosting the immunological response, avoiding volatile anesthetics, and reducing opioid use. However, that trial and three more recent randomized trials with a total of 4,770 patients demonstrate that regional analgesia does not improve survival outcomes after breast, lung, and abdominal cancers. An obvious question is why there was an almost complete disconnect between the copious preclinical investigations suggesting benefit and robust clinical trials showing no benefit? The answer is complex but may result from preclinical research being mechanistically driven and based on reductionist models. Both basic scientists and clinical investigators underestimated the limitations of various preclinical models, leading to the apparently incorrect hypothesis that regional anesthesia reduces cancer recurrence. This article reviews factors that contributed to the discordance between the laboratory science, suggesting that regional analgesia might reduce cancer recurrence and clinical trials showing that it does not-and what can be learned from the disconnect.
•Opium use is associated with an increased risk of cancer development.•Prescription opioid use have not convincingly showed to increase the risk of new cancers.•The mu opioid receptor could be used ...as an actionable target for the treatment of malignancies expressing the receptor.
Pain is a common and devastating symptom among cancer patients. It can be caused by the cancer itself or by certain therapies like surgery, radiation or chemotherapy. Opioids are the first line of treatment for moderate to severe cancer-related pain. Opioids alone or in combination with non-opioid analgesics and adjuvant medications are important components for pain management during the perioperative period for cancer patients. Opioids act on the μ-opioid receptor (MOR), which is expressed in cancer cells and non-malignant cells of the tumor microenvironment. Retrospective studies suggest an association between the expression of MOR in cancers and shorter survival. In addition, recent evidence suggests that opium use and prescription opioids can influence clinical oncological outcomes. In this review, we will summarize the clinical evidence regarding the effect of opioid administration and survival in patients with cancer as well as the current evidence involving MOR expression and cancer progression.
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