| 1. |
- Enlund, Mats, et al.
(författare)
-
Impact of general anaesthesia on breast cancer survival: a 5-year follow up of a pragmatic, randomised, controlled trial, the CAN-study, comparing propofol and sevoflurane
- 2023
-
Ingår i: EClinicalMedicine. - : Elsevier. - 2589-5370. ; 60
-
Tidskriftsartikel (refereegranskat)abstract
- Background Anaesthesia may impact long-term cancer survival. In the Cancer and Anaesthesia study, we hypothesised that the hypnotic drug propofol will have an advantage of at least five percentage points in five-year survival over the inhalational anaesthetic sevoflurane for breast cancer surgery. Methods From 2118 eligible breast cancer patients scheduled for primary curable, invasive breast cancer surgery, 1764 were recruited after ethical approval and individual informed consent to this open label, single-blind, randomised trial at four county- and three university hospitals in Sweden and one Chinese university hospital. Of surveyed patients, 354 were excluded, mainly due to refusal to participate. Patients were randomised by computer at the monitoring organisation to general anaesthesia maintenance with either intravenous propofol or inhaled sevoflurane in a 1:1 ratio in permuted blocks. Data related to anaesthesia, surgery, oncology, and demographics were registered. The primary endpoint was five-year overall survival. Data are presented as Kaplan-Meier survival curves and Hazard Ratios based on Cox univariable regression analyses by both intention-to-treat and perprotocol. EudraCT, 2013-002380-25 and ClinicalTrials.gov, NCT01975064. Findings Of 1764 patients, included from December 3, 2013, to September 29, 2017, 1670 remained for analysis. The numbers who survived at least five years were 773/841 (91.9% (95% CI 90.1-93.8)) in the propofol group and 764/829 (92.2% (90.3-94.0)) in the sevoflurane group, (HR 1.03 (0.73-1.44); P = 0.875); the corresponding results in the per-protocol-analysis were: 733/798 (91.9% (90.0-93.8)) and 653/710 (92.0% (90.0-94.0)) (HR = 1.01 (0.71-1.44); P = 0.955). Survival after a median follow-up of 76.7 months did not indicate any difference between the groups (HR 0.97, 0.72-1.29; P = 0.829, log rank test). Interpretation No difference in overall survival was found between general anaesthesia with propofol or sevoflurane for breast cancer surgery. Copyright (c) 2023 The Author(s). Published by Elsevier Ltd.
|
|
| 2. |
- Enlund, Mats, et al.
(författare)
-
Long-term survival after volatile or propofol general anesthesia for bladder cancer surgery : a retrospective national registry cohort study
- 2024
-
Ingår i: Anesthesiology. - : American Society of Anesthesiologists. - 0003-3022 .- 1528-1175. ; 140:6, s. 1126-1133
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Prospective interventional trials and retrospective observational analyses provide conflicting evidence regarding the relationship between propofol versus inhaled volatile general anesthesia and long-term survival after cancer surgery. In specific, bladder cancer surgery lacks prospective clinical trial evidence.METHODS: Data on bladder cancer surgery performed under general anesthesia between 2014 and 2021 from The National Quality Registry for Urinary Tract and Bladder Cancer and the Swedish Perioperative Registry were record-linked. Overall survival was compared between patients receiving propofol or inhaled volatile for anesthesia maintenance. The minimum clinically important difference was defined as a five-percentage point difference in five-year survival.RESULTS: Of 7,571 subjects, 4,519 (59.7%) received an inhaled volatile anesthetic and 3,052 (40.3%) received propofol for general anesthesia maintenance. The two groups were quite similar in most respects but differed in ASA physical status and tumor stage. Propensity score matching was used to address treatment bias. Survival did not differ during follow-up (median 45 months [interquartile range, 33 to 62]) in neither the full unmatched cohort, nor following 1:1 propensity score matching (3,052 matched pairs). The Kaplan-Meier adjusted five-year survival rates in the matched cohort were 898/3,052, 67.5% (65.7-69.3) for propofol and 852/3,052, 68.5% (66.7-70.4) for inhaled volatile general anesthesia, respectively (hazard ratio 1.05 [95% CI: 0.96 to 1.15], P = 0.332). A sensitivity analysis restricted to 1,766 propensity score matched pairs of patients who received only one general anesthetic during the study period did not demonstrate a difference in survival; Kaplan-Meier adjusted five-year-survival rates were 521/1,766, 67.1% (64.7-69.7) and 482/1,766, 68.9% (66.5-71.4) for propofol and inhaled volatile general anesthesia, respectively (hazard ratio 1.09 [95% CI: 0.97 to 1.23], P = 0.139).CONCLUSIONS: Among patients undergoing bladder cancer surgery under general anesthesia, there was no statistically significant difference in long-term overall survival associated with the choice of propofol or an inhaled volatile maintenance.
|
|
| 3. |
- Enlund, Mats, et al.
(författare)
-
Rationale and Design of the CAN Study : An RCT of Survival after Propofol- or Sevoflurane-based Anesthesia for Cancer Surgery
- 2019
-
Ingår i: Current pharmaceutical design. - : BENTHAM SCIENCE PUBL LTD. - 1381-6128 .- 1873-4286. ; 25:28, s. 3028-3033
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Based on animal data only, some clinicians have adopted pmpofol-based anesthesia for cancer surgery with the aim of increased survival.Objective: Our objective is to verify or refute the hypothesis that survival increases after cancer surgery with propofol compared with sevoflurane for anesthesia maintenance. This aim deserves a large-scale randomized study. The primary hypothesis is an absolute increase of minimum 5%-units in 1- and 5-year survival with propofol-based anesthesia for breast or colorectal cancer after radical surgery, compared with sevoflurane-based anesthesia.Method: Ethics and medical agency approvals were received and pre-study registrations at clinicaltrial.gov and EudraCT were made for our now ongoing prospective, randomized, open-label, multicenter study. A power analysis based on a retrospective study, including a safety margin for drop outs, resulted in a total requirement of 8,000 patients. The initial inclusion period constituted a feasibility phase with an emphasis on the functionality of the infrastructure at the contributing centers and at the monitoring organization, as well as on protocol adherence.Conclusion: The infrastructure and organization work smoothly at the different contributing centers. Protocol adherence is good, and the monitors are satisfied. We expect this trial to be able to either verify or refute that propofol is better than sevoflurane for cancer surgery.
|
|
| 4. |
- Enlund, Mats, et al.
(författare)
-
Survival after primary breast cancer surgery following propofol or sevoflurane general anesthesia-A retrospective, multicenter, database analysis of 6305 Swedish patients
- 2020
-
Ingår i: Acta Anaesthesiologica Scandinavica. - : John Wiley & Sons. - 0001-5172 .- 1399-6576. ; 64:8, s. 1048-1054
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Retrospective studies indicate that the choice of anesthetic can affect long-term cancer survival. Propofol seems to have an advantage over sevoflurane. However, this is questioned for breast cancer. We gathered a large cohort of breast cancer surgery patients from seven Swedish hospitals and hypothesized that general anesthesia with propofol would be superior to sevoflurane anesthesia regarding long-term breast cancer survival.Methods: We identified all patients who were anaesthetized for breast cancer surgery between 2006 and 2012. The patients were matched to the Swedish Breast Cancer Quality Register, to retrieve tumor characteristics, prognostic factors, and adjuvant treatment as well as date of death. Overall survival between patients undergoing sevoflurane and propofol anesthesia was analyzed with different statistical approaches: (a) multiple Cox regression models adjusted for demographic, oncological, and multiple control variables, (b) propensity score matching on the same variables, but also including the participating centers as a cofactor in a separate analysis.Results: The database analysis identified 6305 patients. The 5-year survival rates were 91.0% and 81.8% for the propofol and sevoflurane group, respectively, in the final model (P = .126). Depending on the statistical adjustment method used, different results were obtained, from a non-significant to a "proposed" and even a "determined" difference in survival that favored propofol, with a maximum of 9.2 percentage points higher survival rate at 5 years (hazard ratio 1.46, 95% CI 1.10-1.95).Conclusions: It seems that propofol may have a survival advantage compared with sevoflurane among breast cancer patients, but the inherent weaknesses of retrospective analyses were made apparent.
|
|
| 5. |
- Enlund, Mats, et al.
(författare)
-
The choice of anaesthetic - sevoflurane or propofol - and outcome from cancer surgery : a retrospective analysis
- 2014
-
Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 119:3, s. 251-261
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Commonly used inhalational hypnotics, such as sevoflurane, are pro-inflammatory, whereas the intravenously administered hypnotic agent propofol is anti-inflammatory and anti-oxidative. A few clinical studies have indicated similar effects in patients. We examined the possible association between patient survival after radical cancer surgery and the use of sevoflurane or propofol anaesthesia.PATIENTS AND METHODS:Demographic, anaesthetic, and surgical data from 2,838 patients registered for surgery for breast, colon, or rectal cancers were included in a database. This was record-linked to regional clinical quality registers. Cumulative 1- and 5-year overall survival rates were assessed using the Kaplan-Meier method, and estimates were compared between patients given propofol (n = 903) or sevoflurane (n = 1,935). In a second step, Cox proportional hazard models were calculated to assess the risk of death adjusted for potential effect modifiers and confounders.RESULTS:Differences in overall 1- and 5-year survival rates for all three sites combined were 4.7% (p = 0.004) and 5.6% (p < 0.001), respectively, in favour of propofol. The 1-year survival for patients operated for colon cancer was almost 10% higher after propofol anaesthesia. However, after adjustment for several confounders, the observed differences were not statistically significant.CONCLUSION:Propofol anaesthesia might be better in surgery for some cancer types, but the retrospective design of this study, with uneven distributions of several confounders, distorted the picture. These uncertainties emphasize the need for a randomized controlled trial.
|
|
| 6. |
- Enlund, Mats, et al.
(författare)
-
Volatile versus Propofol General Anesthesia and Long-term Survival after Breast Cancer Surgery : A National Registry Retrospective Cohort Study
- 2022
-
Ingår i: Anesthesiology. - : Lippincott Williams & Wilkins. - 0003-3022 .- 1528-1175. ; 137:3, s. 315-326
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Several retrospective studies using administrative or single-center data have failed to show any difference between general anesthesia using propofol versus inhaled volatiles on long-term survival after breast cancer surgery. Although randomized controlled trials are ongoing, validated data from national clinical registries may advance the reliability of existing knowledge.Methods: Data on breast cancer surgery performed under general anesthesia between 2013 and 2019 from the Swedish PeriOperative Registry and the National Quality Registry for Breast Cancer were record-linked. Overall survival was compared between patients receiving propofol and patients receiving inhaled volatile for anesthesia maintenance.Results: Of 18,674 subjects, 13,873 patients (74.3%) received propofol and 4,801 (25.7%) received an inhaled volatile for general anesthesia maintenance. The two cohorts differed in most respects. Patients receiving inhaled volatile were older (67 yr vs. 65 yr), sicker (888 [19.0%] American Society of Anesthesiologists status 3 to 5 vs. 1,742 [12.8%]), and the breast cancer to be more advanced. Median follow-up was 33 months (interquartile range, 19 to 48). In the full, unmatched cohort, there was a statistically significantly higher overall survival among patients receiving propofol (13,489 of 13,873 [97.2%]) versus inhaled volatile ( 4,039 of 4,801 [84.1%]; hazard ratio, 0.80; 95% CI, 0.70 to 0.90; P < 0.001). After 1:1 propensity score matching (4,658 matched pairs), there was no statistically significant difference in overall survival (propofol 4,284 of 4,658 [92.0%]) versus inhaled volatile (4,288 of 4,658 [92.1%]; hazard ratio, 0.98; 95% CI, 0.85 to 1.13; P = 0.756).Conclusions: Among patients undergoing breast cancer surgery under general anesthesia, no association was observed between the choice of propofol or an inhaled volatile maintenance and overall survival.
|
|
| 7. |
- Rhodin, Annica, 1949-
(författare)
-
Long-term Effects of Opioids in the Treatment of Chronic Pain : Investigation of Problems and Hazards on Clinical, Biochemical, Cellular and Genetic Levels
- 2010
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- After two decades of liberal prescribing of opioids, there has been an increasing recognition of problems connected to the prolonged use of opioids for chronic pain. The aim of my thesis was to explore some consequences of long-term opioid treatment for chronic pain such as problematic opioid use, endocrine disorders, tolerance and genetic variations in pain and opioid response. Sixty patients with severe pain and problematic opioid use were treated with a structured methadone programme. Risk factors were musculoskeletal pain, psychiatric co-morbidity and previous addiction. Treatment resulted in good pain relief and improved quality of life, but function was impaired by side effects indicating endocrine dysregulation. The possibility of opioid-induced endocrine dysfunction was explored in the second paper, where 40 pain patients treated with strong opioids and 20 pain patients without treatment of strong opioids were investigated. The opioid-treated patients had significantly higher incidence of endocrine disturbance affecting gonadal and adrenal function and prolactin levels. The functionality of the μ-receptor after long-term treatment with morphine, saline and naloxone was explored in a cell-line expressing the μ-receptor. After one and four weeks of treatment the binding was tested with morphine, methadone, fentanyl and DAMGO and function measured by GTP γ-assay. The binding of DAMGO was significantly diminished after 4 weeks in cells treated with morphine compared with saline and naloxone. Genetic variation in three genes with functional impact on opioid response and pain sensitivity was investigated in 80 patients with chronic low-back pain and differential opioid sensitivity and in 56 healthy controls. The results indicated a higher incidence of opioid-related side effects and gender differences in patients with the minor allele of the ABCB1 gene, a correlation between increased opioid sensitivity and the major CACNA2D2 allele and a possible relationship between intrinsic protection against chronic pain and the minor allele of OPRM1.
|
|
| 8. |
- Adman, Per, et al.
(författare)
-
171 forskare: ”Vi vuxna bör också klimatprotestera”
- 2019
-
Ingår i: Dagens nyheter (DN debatt). - Stockholm. - 1101-2447.
-
Tidskriftsartikel (populärvet., debatt m.m.)abstract
- DN DEBATT 26/9. Vuxna bör följa uppmaningen från ungdomarna i Fridays for future-rörelsen och protestera eftersom det politiska ledarskapet är otillräckligt. Omfattande och långvariga påtryckningar från hela samhället behövs för att få de politiskt ansvariga att utöva det ledarskap som klimatkrisen kräver, skriver 171 forskare i samhällsvetenskap och humaniora.
|
|
| 9. |
|
|
| 10. |
- Arbin, Linn, et al.
(författare)
-
Post-tonsillectomy pain after using bipolar diathermy scissors or the harmonic scalpel : a randomised blinded study
- 2017
-
Ingår i: European Archives of Oto-Rhino-Laryngology. - : Springer Science and Business Media LLC. - 0937-4477 .- 1434-4726. ; 274:5, s. 2281-2285
-
Tidskriftsartikel (refereegranskat)abstract
- To compare the postoperative pain following bipolar diathermy scissors tonsillectomy (higher temperature dissection) with harmonic scalpel tonsillectomy (lower temperature dissection). Sixty patients aged 7-40 years planned for tonsillectomy with no other concurrent surgery were randomised to either bipolar diathermy scissors or harmonic scalpel as surgical technique. Blinded to the surgical technique, the patients recorded their pain scores (VAS, 0-10) at awakening and the worst pain level of the day in the postoperative period. All intake of pain medication was also recorded. No statistically significant differences were found between the two groups regarding postoperative pain levels or consumption of pain medication. Usage of the harmonic scalpel does not render less postoperative pain following tonsillectomy when compared with usage of the bipolar diathermy scissors.
|
|
