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Influence of the Anesthetic Technique on Circulating Extracellular Vesicles in Bladder Cancer Patients Undergoing Radical Cystectomy: A Prospective, Randomized Trial.

ABSTRACT: Anesthetics have been shown to alter tumor progression and seem to influence surgical cancer outcome. Circulating extracellular vesicles as mediators of intercellular communication are involved in cancer progression and may be influenced by anesthetics. In this prospective, randomized study, effects of anesthetics on extracellular vesicles and associated micro-RNAs in bladder cancer patients undergoing radical cystectomy were tested. Extracellular vesicles from 51 patients at four perioperative time points receiving Propofol or Sevoflurane were extracted with polymer-based methods and quantified with a nanoparticle-tracking analysis. Vesicle-associated micro-RNAs were analyzed with a real-time polymerase chain reaction using array cards and single assays for tumor-associated miR-21-5p, miR-15a-5p, miR-17-5p and miR-451a. Plasma extracellular vesicle concentration (suture: fold change (fc) in Propofol at 4.1 ± 3.9 vs. Sevoflurane at 0.8 ± 0.5; p = 0.003) and associated miRNAs increased significantly (+30% post induction, +9% 30 Min surgery) in the Propofol group. Tumor-associated miRNAs increased during surgery in both groups (fc in miR-21-5p: 24.3 ± 10.2, p = 0.029; fc in miR-15a-5p: 9.7 ± 3.8, p = 0.027; fc in miR-17-5p: 5.4 ± 1.7, p = 0.014), whereas antitumor miR-451a increased in the Propofol group only (fc: 2.5 ± 0.6 vs. 1.0 ± 0.2; p = 0.022). Anesthetics influence extracellular vesicles and associated micro-RNAs of bladder cancer patients during surgery. Increased expression of antitumor micro-RNA may be an explanatory approach for decreased tumor cell viability after Propofol.

SUBMITTER: Gluth L

PROVIDER: S-EPMC10605791 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Influence of the Anesthetic Technique on Circulating Extracellular Vesicles in Bladder Cancer Patients Undergoing Radical Cystectomy: A Prospective, Randomized Trial.

Gluth Luisa L Ochsenfarth Crista C Pham Phuong Nam Viet PNV Wischermann Jan M JM Komanek Thomas T Roghmann Florian F Frey Ulrich H UH

Cells 20231023 20

Anesthetics have been shown to alter tumor progression and seem to influence surgical cancer outcome. Circulating extracellular vesicles as mediators of intercellular communication are involved in cancer progression and may be influenced by anesthetics. In this prospective, randomized study, effects of anesthetics on extracellular vesicles and associated micro-RNAs in bladder cancer patients undergoing radical cystectomy were tested. Extracellular vesicles from 51 patients at four perioperative ...[more]

PMID: 37887347

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Project description:Radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC) is an extensive and morbid operation, often associated with permanent alteration of body image and disability. Combined with the aggressive malignant potential of MIBC and considerable risk of complications, it poses a serious threat to the psychological well-being of patients. Educational deficiencies causing uncertainty and confusion aggravate surgery-related anxiety and may lead to depression along with further social disability. We conceived a preoperative supportive program named "Cystocare" held by urologists, psychologists, stoma therapists and cancer survivors to facilitate patients' adaptation and coping. We aimed to evaluate whether participation in Cystocare meetings would alleviate emotional distress in patients undergoing RC. We included 95 consecutive patients who filled Hospital Anxiety and Depression Score questionnaires before RC and on discharge. The intervention arm (A) comprised 32 Cystocare participants. The remaining 63 patients who received standard preparation constituted the control arm (B). Whilst there were no differences in median anxiety and depression scores preoperatively, in postoperative measurement, the intervention arm showed a lower median depression score than controls: 3 vs. 8 points, p = 0.015. On multivariate analysis we confirmed lower risk of postoperative depression in Cystocare participants: OR = 0.215 (95%CI: 0.066-0.699), p = 0.011, along with lower odds of preoperative anxiety in patients undergoing laparoscopic RC: OR = 0.365 (95%CI: 0.136-0.978), p = 0.045, and higher risk of prolonged hospital stay in patients experiencing postoperative anxiety OR = 17.114 (95%CI: 1.283-228.234) p = 0.032. Preoperative educational and supportive intervention complements laparoscopic RC in the alleviation of surgery-related anxiety and depression. The support group meetings provide an attractive and cost-effective opportunity to moderate emotional response in patients undergoing RC, and as such, deserve widespread adoption.

Project description:PurposeTo assess the prognostic value of acidic urine (low urine pH) in patients with bladder cancer undergoing radical cystectomy.Materials and methodsWe reviewed patients enrolled in the Seoul National University Prospectively Enrolled Registry for Urothelial Cancer-Cystectomy (SUPER-UC-Cx) who underwent radical cystectomy for bladder cancer between March 2016 and December 2020 at the Seoul National University Hospital. During this period, 368 patients were registered in our database. To eliminate confounding factors, we excluded patients diagnosed with non-urothelial cancer and end-stage renal disease.ResultsA total of 351 patients with a mean age of 69.8 ± 10.5 years and median follow-up of 16.0 months were eligible for the analysis. The mean preoperative urine pH was 6.0. The patients were divided into low (pH ≤ 5.5) and high (pH≥6.0) urine pH groups for comparison. All clinicopathological features, including the tumor size, grade, and stage were comparable between the low and high urine pH groups. A Cox regression analysis was performed to assess the independent effect of acidic urine on patient survival. A multivariate analysis showed that high T stage (T3-4) (hazard ratio (HR) 5.18, P<0.001), decreased renal function (estimated glomerular filtration rate <60 mL/min/1.73 m2) (HR 2.29, P=0.003), and low urine pH (≤5.5) (HR 1.69, P=0.05) were associated with shortened recurrence-free survival (RFS). Regarding the overall survival (OS), high T stage (T3-4) (HR 7.15, P<0.001) and low urine pH (≤5.5) (HR 2.66, P=0.029) were significantly associated with shortened survival. A Kaplan-Meier analysis demonstrated that the acidic urine group showed shorter RFS (P=0.04) and OS (P=0.028) than the other groups.ConclusionsAcidic urine was independently associated with reduced RFS and OS in patients with bladder cancer undergoing radical cystectomy. Acidic urine contributing to an acidic tumor environment may promote aggressive behavior in bladder cancer.

Project description:ImportanceThe value to payers of robot-assisted radical cystectomy with intracorporeal urinary diversion (iRARC) when compared with open radical cystectomy (ORC) for patients with bladder cancer is unclear.ObjectivesTo compare the cost-effectiveness of iRARC with that of ORC.Design, setting, and participantsThis economic evaluation used individual patient data from a randomized clinical trial at 9 surgical centers in the United Kingdom. Patients with nonmetastatic bladder cancer were recruited from March 20, 2017, to January 29, 2020. The analysis used a health service perspective and a 90-day time horizon, with supplementary analyses exploring patient benefits up to 1 year. Deterministic and probabilistic sensitivity analyses were undertaken. Data were analyzed from January 13, 2022, to March 10, 2023.InterventionsPatients were randomized to receive either iRARC (n = 169) or ORC (n = 169).Main outcomes and measuresCosts of surgery were calculated using surgery timings and equipment costs, with other hospital data based on counts of activity. Quality-adjusted life-years were calculated from European Quality of Life 5-Dimension 5-Level instrument responses. Prespecified subgroup analyses were undertaken based on patient characteristics and type of diversion.ResultsA total of 305 patients with available outcome data were included in the analysis, with a mean (SD) age of 68.3 (8.1) years, and of whom 241 (79.0%) were men. Robot-assisted radical cystectomy was associated with statistically significant reductions in admissions to intensive therapy (6.35% [95% CI, 0.42%-12.28%]), and readmissions to hospital (14.56% [95% CI, 5.00%-24.11%]), but increases in theater time (31.35 [95% CI, 13.67-49.02] minutes). The additional cost of iRARC per patient was £1124 (95% CI, -£576 to £2824 [US $1622 (95% CI, -$831 to $4075)]) with an associated gain in quality-adjusted life-years of 0.01124 (95% CI, 0.00391-0.01857). The incremental cost-effectiveness ratio was £100 008 (US $144 312) per quality-adjusted life-year gained. Robot-assisted radical cystectomy had a much higher probability of being cost-effective for subgroups defined by age, tumor stage, and performance status.Conclusions and relevanceIn this economic evaluation of surgery for patients with bladder cancer, iRARC reduced short-term morbidity and some associated costs. While the resulting cost-effectiveness ratio was in excess of thresholds used by many publicly funded health systems, patient subgroups were identified for which iRARC had a high probability of being cost-effective.Trial registrationClinicalTrials.gov Identifier: NCT03049410.

Project description:ObjectivesTo assess the comparative effectiveness of robot-assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) vs open radical cystectomy (ORC) for bladder cancer (BC).Patients and methodsWe conducted a real-life monocentric study including all consecutive patients who underwent RARC with ICUD or ORC for BC at our institution from 2014 to 2023. Uni- and multivariable logistic and Cox regression analyses were used to compare perioperative, oncological and stricture outcomes between both groups by calculating odds (ORs) and hazard (HRs) ratios with their corresponding 95% confidence intervals (CIs), respectively.ResultsOverall, 316 patients underwent either RARC with ICUD (n = 228 [72.2%]) or ORC (n = 88 [27.8%]). The perioperative benefits of RARC vs ORC included decreased risks of major blood loss (OR 0.10, 95% CI 0.04-0.23; P < 0.001), perioperative transfusion (OR 0.30, 95% CI 0.16-0.57; P < 0.001), 90-day major complications (OR 0.56, 95% CI 0.29-0.99; P = 0.04), and prolonged initial length of hospital stay (OR 0.20, 95% CI 0.09-0.35; P < 0.001), as well as more days alive and out of the hospital within 90 days of surgery (OR 2.56, 95% CI 1.46-4.6; P < 0.01). In addition, the use of RARC vs ORC was associated with a higher lymph node (LN) count (OR 3.35, 95% CI 1.83-6.30; P < 0.001), while there was no significant difference in recurrence-free (HR 0.72, 95% CI 0.49-1.07; P = 0.1), cancer-specific (HR 0.69, 95% CI 0.43-1.10; P = 0.1), overall (HR 0.76, 95% CI 0.47-1.20; P = 0.3) and uretero-ileal stricture-free (HR 1.18, 95% CI 0.62-2.25; P = 0.6) survival between both groups after a median (interquartile range) follow-up of 42.3 (16.4-73.8) months.ConclusionOur real-world study supports the effectiveness of RARC with ICUD vs ORC for BC. We generally observed better perioperative outcomes, as well as similar oncological-except for higher LN count-and uretero-ileal stricture outcomes after RARC with ICUD vs ORC.

Dataset Information

Influence of the Anesthetic Technique on Circulating Extracellular Vesicles in Bladder Cancer Patients Undergoing Radical Cystectomy: A Prospective, Randomized Trial.

Publications

Influence of the Anesthetic Technique on Circulating Extracellular Vesicles in Bladder Cancer Patients Undergoing Radical Cystectomy: A Prospective, Randomized Trial.

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