The synergistic mechanisms of propofol with cisplatin or doxorubicin in human ovarian cancer cells.

BACKGROUND: Most ovarian cancer cases are diagnosed at an advanced stage, leading to poor outcomes and a relatively low 5-year survival rate. While tumor resection in the early stages can be highly effective, recurrence following primary treatment remains a significant cause of mortality. Propofol is a commonly used intravenous anesthetic agent in cancer resection surgery. Previous research has shown that propofol anesthesia was associated with improved survival in patients undergoing elective surgery for epithelial ovarian cancer. However, the underlying antitumor mechanisms are not yet fully understood. METHODS: This study aimed to uncover the antitumor properties of propofol alone and combined with cisplatin or doxorubicin, in human SKOV3 and OVCAR3 ovarian cancer cells. We applied flowcytometry analysis for mitochondrial membrane potential, apoptosis, and autophagy, colony formation, migration, and western blotting analysis. RESULTS: Given that chemotherapy is a primary clinical approach for managing advanced and recurrent ovarian cancer, it is essential to address the limitations of current chemotherapy, particularly in the use of cisplatin and doxorubicin, which are often constrained by their side effects and the development of resistance. First of all, propofol acted synergistically with cisplatin and doxorubicin in SKOV3 cells. Moreover, our data further showed that propofol suppressed colony formation, disrupted mitochondrial membrane potential, and induced apoptosis and autophagy in SKOV3 and OVCAR3 cells. Finally, the effects of combined propofol with cisplatin or doxorubicin on mitochondrial membrane potential, apoptosis, autophagy, and epithelial-mesenchymal transition were different in SKOV3 and OVCAR3 cells, depending on the p53 status. CONCLUSION: In summary, repurposing propofol could provide novel insights into the existing chemotherapy strategies for ovarian cancer. It holds promise for overcoming resistance to cisplatin or doxorubicin and may potentially reduce the required chemotherapy dosages and associated side effects, thus improving treatment outcomes.

Predicting the optimal concentration of remifentanil for skull pin fixation with hemodynamic and analgesia nociception index monitoring.

Inadequate antinociception during skull pin fixation may cause hemodynamic instability in intracranial surgery. The optimal concentration of remifentanil to provide adequate antinociception and stable hemodynamics during skull pin fixation under analgesia nociception index monitoring is unknown. This study is to assess the 90% effective concentration of remifentanil for skull pin fixation under hemodynamic and analgesia nociception index monitoring. Twenty-six patients were enrolled for intracranial surgery, anesthesia was induced and maintained under total intravenous anesthesia using target-controlled infusion for remifentanil and propofol under analgesia nociception index and bispectral index monitoring. Skull pin fixation was performed at different effect-site concentrations of remifentanil required for Dixon's up-and-down method with a step size of 0.5 ng/ml under bispectral index 40-60. Inadequate antinociception is defined when either ANI < 30 or > 20% in hemodynamic changes from baseline (e.g. heart rate > 100 beats/min, or blood pressure > 180/100 mmHg) and the effect-site concentration of remifentanil is considered as failure. It is considered success as ANI > 30 and < 20% hemodynamic changes from baseline simultaneously. Seven pairs of failure/success were used for probit analysis. The 90% effective concentration of remifentanil for skull pin fixation with adequate antinociception and hemodynamic stability was 4.7 ng/ml.

Propofol-based total intravenous anesthesia is associated with less postoperative recurrence than desflurane anesthesia in thyroid cancer surgery.

BACKGROUND: The effects of anesthesia in patients undergoing thyroid cancer surgery are still not known. We investigated the relationship between the type of anesthesia and patient outcomes following elective thyroid cancer surgery. METHODS: This was a retrospective cohort study of patients who underwent elective surgical resection for papillary thyroid carcinoma between January 2009 and December 2019. Patients were grouped according to the type of anesthesia they received, desflurane or propofol. A Kaplan-Meier analysis was conducted, and survival/recurrence curves were presented from the date of surgery to death/recurrence. Univariable and multivariable Cox regression models were used to compare hazard ratios for recurrence after propensity matching. RESULTS: A total of 621 patients (22 deaths, 3.5%) under desflurane anesthesia and 588 patients (32 deaths, 5.4%) under propofol anesthesia were included. Five hundred and eighty-eight patients remained in each group after propensity matching. Propofol anesthesia was not associated with better survival compared to desflurane anesthesia in the matched analysis (P = 0.086). However, propofol anesthesia was associated with less recurrence (hazard ratio, 0.38; 95% confidence interval, 0.25-0.56; P < 0.001) in the matched analysis. CONCLUSIONS: Propofol anesthesia was associated with less recurrence, but not mortality, following surgery for papillary thyroid carcinoma than desflurane anesthesia. Further prospective investigation is needed to examine the influence of propofol anesthesia on patient outcomes following thyroid cancer surgery.

Tumor Necrosis Factor Alpha: Implications of Anesthesia on Cancers.

Cancer remains a major public health issue and a leading cause of death worldwide. Despite advancements in chemotherapy, radiation therapy, and immunotherapy, surgery is the mainstay of cancer treatment for solid tumors. However, tumor cells are known to disseminate into the vascular and lymphatic systems during surgical manipulation. Additionally, surgery-induced stress responses can produce an immunosuppressive environment that is favorable for cancer relapse. Up to 90% of cancer-related deaths are the result of metastatic disease after surgical resection. Emerging evidence shows that the interactions between tumor cells and the tumor microenvironment (TME) not only play decisive roles in tumor initiation, progression, and metastasis but also have profound effects on therapeutic efficacy. Tumor necrosis factor alpha (TNF-α), a pleiotropic cytokine contributing to both physiological and pathological processes, is one of the main mediators of inflammation-associated carcinogenesis in the TME. Because TNF-α signaling may modulate the course of cancer, it can be therapeutically targeted to ameliorate clinical outcomes. As the incidence of cancer continues to grow, approximately 80% of cancer patients require anesthesia during cancer care for diagnostic, therapeutic, or palliative procedures, and over 60% of cancer patients receive anesthesia for primary surgical resection. Numerous studies have demonstrated that perioperative management, including surgical manipulation, anesthetics/analgesics, and other supportive care, may alter the TME and cancer progression by affecting inflammatory or immune responses during cancer surgery, but the literature about the impact of anesthesia on the TNF-α production and cancer progression is limited. Therefore, this review summarizes the current knowledge of the implications of anesthesia on cancers from the insights of TNF-α release and provides future anesthetic strategies for improving oncological survival.

Comparison of Single Target-Controlled Infusion Pump-Delivered Mixed Propofol and Remifentanil with Two Target-Controlled Infusion Pumps-Delivered Propofol and Remifentanil in Patients Undergoing Breast Cancer Surgery-A Prospective Study.

Total intravenous anesthesia (TIVA) with remifentanil and propofol (RP) is considered to be an ideal type of general anesthesia (GA) for pediatric and adult patients undergoing medical procedures. However, delivery of an RP mixture by target-controlled infusion (TCI) for GA in surgical procedures has not been described. We investigated the merit of this approach for breast cancer surgery. Eighty-four patients (n = 42 per group) were randomly allocated to propofol and remifentanil either delivered by separate TCI pumps (S group) or in an RP mixture by a single TCI pump (M group). Dosages were adjusted based on the bispectral index (BIS) and the analgesia nociception index (ANI). The primary outcomes were adequate anesthesia (BIS 40-60 and ANI 50-70, respectively), acceptable hemodynamic fluctuations (<30% of baseline) with less frequent TCI pump adjustments, bolus injections of anesthetics, and total consumption of anesthetics during the procedure. The secondary endpoints included time of emergence from anesthesia, patient satisfaction, postoperative pain, rescue with opioids, and adverse events. The characteristics of patients, hemodynamic parameters, BIS and ANI scores, duration of surgery, anesthesia, and emergence were not significantly different between groups. The adjustment frequency of TCI was significantly higher in the S group (3 (range 0-6) vs. 2 (0-6) times; p = 0.005). The total dosage of anesthetics, pain rating, patient satisfaction, need for opioids postoperatively, and incidence of adverse events were not significantly different. We have demonstrated that this RP mixture provided adequate hypnotic and analgesic effects under BIS and ANI monitoring in patients undergoing breast cancer surgery within 1 h.

Apoptosis, Proliferation, and Autophagy Are Involved in Local Anesthetic-Induced Cytotoxicity of Human Breast Cancer Cells.

Breast cancer accounts for almost one quarter of all female cancers worldwide, and more than 90% of those who are diagnosed with breast cancer undergo mastectomy or breast conservation surgery. Local anesthetics effectively inhibit the invasion of cancer cells at concentrations that are used in surgical procedures. The limited treatment options for triple-negative breast cancer (TNBC) demonstrate unmet clinical needs. In this study, four local anesthetics, lidocaine, levobupivacaine, bupivacaine, and ropivacaine, were applied to two breast tumor cell types, TNBC MDA-MB-231 cells and triple-positive breast cancer BT-474 cells. In addition to the induction of apoptosis and the suppression of the cellular proliferation rate, the four local anesthetics decreased the levels of reactive oxygen species and increased the autophagy elongation indicator in both cell types. Our combination index analysis with doxorubicin showed that ropivacaine had a synergistic effect on the two cell types, and lidocaine had a synergistic effect only in MDA-MB-231 cells; the others had no synergistic effects on doxorubicin. Lidocaine contributed significantly to the formation of autophagolysosomes in a dose-dependent manner in MDA-MB-231 cells but not in BT-474 cells. Our study demonstrated that the four local anesthetics can reduce tumor growth and proliferation and promote apoptosis and autophagy.

Propofol-based total intravenous anesthesia is associated with better survival than desflurane anesthesia in limb-salvage surgery for osteosarcoma: A retrospective analysis.

Previous studies have demonstrated that anesthetic techniques can affect the outcomes of cancer surgery. We investigated the association between anesthetic techniques and patient outcomes after elective limb-salvage surgery for osteosarcoma (OS). This was a retrospective cohort study of patients who underwent elective limb-salvage surgery for OS between January 2007 and December 2018. Patients were grouped according to the administration of propofol-based total intravenous anesthesia (TIVA) or desflurane (DES) anesthesia. Kaplan-Meier analysis was performed, and survival curves were constructed from the date of surgery to death. Univariate and multivariate Cox regression models were applied to compare the hazard ratios (HRs) for death after propensity matching. Subgroup analyses were done for postoperative recurrence, metastasis, and tumor-node-metastasis (TNM) staging. A total of 30 patients (17 deaths, 56.7%) who received DES anesthesia and 26 (4 deaths, 15.4%) who received TIVA were eligible for analysis. After propensity matching, 22 patients were included in each group. In the matched analysis, patients who received TIVA had better survival with a HR of 0.30 (95% confidence interval [CI], 0.11-0.81; P = .018). Subgroup analyses also showed significantly better survival in the presence of postoperative metastasis (HR, 0.24; 95% CI, 0.06-0.87; P = .030) and with TNM stage II to III (HR, 0.26; 95% CI, 0.09-0.73; P = .011) in the matched TIVA group. In addition, patients administered with TIVA had lower risks of postoperative recurrence and metastasis than those administered with DES anesthesia in the matched analyses. Propofol-based TIVA was associated with better survival in patients who underwent elective limb-salvage surgery for OS than DES anesthesia. Prospective studies are needed to assess the effects of TIVA on oncological outcomes in patients with OS.

Comparison of 2 effect-site concentrations of remifentanil with midazolam during transrectal ultrasound-guided prostate biopsy under procedural analgesia and sedation: A randomized controlled study.

BACKGROUND: Until now, target-controlled infusion of remifentanil with midazolam for transrectal ultrasound-guided prostate biopsy has not been described. Here, we investigate 2 effect-site concentrations of remifentanil with intermittent bolus midazolam for transrectal ultrasound-guided prostate biopsy under procedural analgesia and sedation. METHODS: A prospective, randomized controlled trial including patients who received a transrectal ultrasound-guided prostate biopsy between February 2019 and January 2021 was conducted. Group 1 and Group 2 were respectively administered an initial effect-site concentration of remifentanil of 1.0 ng/mL and 2.0 ng/mL by a target-controlled infusion pump with Minto model. In both groups, maintenance of the effect-site concentration of remifentanil was adjusted upward and downward by 0.5 ng/mL to keep patient comfort with acceptable pain (remaining moveless), and mean arterial pressure and heart rate within baseline levels ±â€…30%, and using intermittent bolus midazolam to keep the Observer's Assessment of Alertness/Sedation scale between 2 and 4. The primary outcome was to determine which effect-site concentration of remifentanil provide adequate patient comfort with acceptable pain (remaining moveless) during the procedure. RESULTS: A total of 40 patients in Group 1 and 40 patients in Group 2 were eligible for analysis. Most parameters were insignificantly different between Group 1 and Group 2, except Group 1 having higher peripheral oxygen saturation while probe insertion compared with Group 2. Group 2 patients had less intraoperative movements affecting the procedure (2 vs 18; P < .001), and less total times of target-controlled infusion pump adjustment (0 [0-1] vs 1 [0-3], P < .001) compared with group 1. However, group 1 patients had less apnea with desaturation (peripheral oxygen saturation < 90%; 0 vs 9, P = .002) and less remifentanil consumption (94.9 ±â€…25.5 µg vs 106.2 ±â€…21.2 µg, P = .034) compared to Group 2. CONCLUSION: In transrectal ultrasound-guided prostate biopsy, target-controlled infusion with remifentanil Minto model target 2.0 ng/mL with 3 to 4 mg midazolam use provided sufficient analgesia and sedation, and appropriate hemodynamic and respiratory conditions.

Pancreatic Cancer and Microenvironments: Implications of Anesthesia.

Pancreatic malignancy is a lethal neoplasm, as well as one of the leading causes of cancer-associated mortality, having a 5-year overall survival rate of less than 10%. The average life expectancy of patients with advanced pancreatic cancer does not exceed six months. Although surgical excision is a favorable modality for long-term survival of pancreatic neoplasm, metastasis is initially identified in nearly 80% of the patients by the time of diagnosis, making the development of therapeutic policy for pancreatic cancer extremely daunting. Emerging evidence shows that pancreatic neoplastic cells interact intimately with a complicated microenvironment that can foster drug resistance, metastasis, or relapse in pancreatic cancer. As a result, the necessity of gaining further insight should be focused on the pancreatic microenvironment contributing to cancer progression. Numerous evidence reveals that perioperative factors, including surgical manipulation and anesthetics (e.g., propofol, volatile anesthetics, local anesthetics, epidural anesthesia/analgesia, midazolam), analgesics (e.g., opioids, non-steroidal anti-inflammatory drugs, tramadol), and anesthetic adjuvants (such as ketamine and dexmedetomidine), might alter the tumor microenvironment and cancer progression by affecting perioperative inflammatory or immune responses during cancer surgery. Therefore, the anesthesiologist plays an important role in perioperative management and may affect surgical outcomes. However, the literature on the impact of anesthesia on the pancreatic cancer microenvironment and progression is limited. This review summarizes the current knowledge of the implications of anesthesia in the pancreatic microenvironment and provides future anesthetic strategies for improving pancreatic cancer survival rates.

Association between General Anesthesia and Root Canal Treatment Outcomes in Patients with Mental Disability: A Retrospective Cohort Study.

In the population of individuals with a disability, mental illness patients can be uncooperative during dental treatment; thus, general anesthesia has been widely applied during dental procedures. This study aims to investigate the association between general anesthesia and the outcomes of root canal treatment in patients with disability. Teeth treatment records of patients with disability from Kaohsiung Medical University Hospital Research Database and electronic database from January 2005 to December 2018 were used in this retrospective cohort study. The authors conducted analysis comparing root canal treatment outcomes under general anesthesia and non-general anesthesia, indicated by endodontic re-treatment or post-treatment teeth extraction. Over the 9-year follow-up period, root canal treatment outcomes representing a cumulative survival rate of 87.68% and 74.51% in the general anesthesia group and non-general anesthesia group, respectively, were found. After adjustment for potential confounders, the teeth with general anesthesia showed a substantially and significantly reduced HR of root canal treatment failure at 0.24 (95% confidence interval, 0.12 to 0.49). Our study supported the notion that root canal treatment with general anesthesia may entail substantial reduction of treatment failure in patients with disability.

Antitumorigenic Effect of Tramadol and Synergistic Effect With Doxorubicin in Human Breast Cancer Cells.

BACKGROUND: Breast cancer in women is one of the leading causes of cancer mortality worldwide, and curative therapy is the main focus of clinical treatment. Anesthetic-analgesic techniques might alter stress responses and immunity and thereby influence outcomes in cancer patients. This study investigated the effect of tramadol on breast cancer progression and metastasis. METHODS: The effects of tramadol on two different subtypes of human breast adenocarcinoma cell lines, MDA-MB-231 and MCF-7, were studied with regard to cell growth, migration, colony formation and invasion and normoxic or hypoxic microenvironment for the expression of hypoxia-inducible factor-1α, reactive oxygen species, epithelial-mesenchymal transition related and cyclin-related proteins. The co-administration of tramadol and doxorubicin was studied to determine whether the effective doxorubicin dose might be reduced in combination with tramadol. RESULTS: The results showed that tramadol inhibited cell growth at concentrations more than 0.5 and more than 1.0 mg/mL in MDA-MB-231 and MCF-7 cells, respectively. Additionally, cell migration, colony formation and invasion were inhibited in a dose-dependent manner by tramadol in both cell lines. The combination of tramadol and doxorubicin induced synergistic effects in MDA-MD-231 cells and, with specific dosage combinations in MCF-7 cells. CONCLUSIONS: Tramadol may regulate epithelial-mesenchymal transition and possess cytotoxic effects in breast cancer cells. Tramadol inhibits the progression of breast cancer cells and might be a candidate for combination therapy, especially for triple-negative breast cancer, and is a promising treatment strategy for breast cancer.