Potential Influence of the Anesthetic Technique Used during Open Radical Prostatectomy on Prostate Cancer-Related Outcome

University Department of Anaesthesiology and Pain Therapy, University Hospital Bern, and Institute of Mathematical Statistics and Actuarial Science, University of Bern, Berne, Switzerland.
Anesthesiology (Impact Factor: 5.88). 09/2010; 113(3):570-6. DOI: 10.1097/ALN.0b013e3181e4f6ec
Source: PubMed


Recently published studies suggest that the anesthetic technique used during oncologic surgery affects cancer recurrence. To evaluate the effect of anesthetic technique on disease progression and long-term survival, we compared patients receiving general anesthesia plus intraoperative and postoperative thoracic epidural analgesia with patients receiving general anesthesia alone undergoing open retropubic radical prostatectomy with extended pelvic lymph node dissection.
Two sequential series were studied. Patients receiving general anesthesia combined with epidural analgesia (January 1994-June 1997, n=103) were retrospectively compared with a group given general anesthesia combined with ketorolac-morphine analgesia (July 1997-December 2000, n=158). Biochemical recurrence-free survival, clinical progression-free survival, cancer-specific survival, and overall survival were assessed using the Kaplan-Meier technique and compared using a multivariate Cox-proportional-hazards regression model and an alternative model with inverse probability weights to adjust for propensity score.
Using propensity score adjustment with inverse probability weights, general anesthesia combined with epidural analgesia resulted in improved clinical progression-free survival (hazard ratio, 0.45; 95% confidence interval, 0.27-0.75, P=0.002). No significant differences in the two groups were found for biochemical recurrence-free survival, cancer-specific survival, or overall survival. Higher preoperative serum values for prostate-specific antigen, specimen Gleason score of at least 7, non-organ-confined tumor stage, and positive lymph node status were independent predictors of biochemical recurrence-free survival.
General anesthesia with epidural analgesia was associated with a reduced risk of clinical cancer progression. However, no significant difference was found between general anesthesia plus postoperative ketorolac-morphine analgesia and general anesthesia plus intraoperative and postoperative thoracic epidural analgesia in biochemical recurrence-free survival, cancer-specific survival, or overall survival.

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    • "Experimental studies also suggest that EA may protect intestinal barrier function, improve mucosal capillary perfusion in acute experimental pancreatitis and in sepsis [8], as well as increase anastomotic mucosal blood flow after oesophageal resection [9]. Furthermore, EA may influence tumour progression after oncological surgery [10] [11] [12] [13]. Many of these benefits, including EA's analgesic effects, may be relevant to the intensive care unit (ICU) patient. "
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    ABSTRACT: Epidural analgesia (EA) has been more investigated during the perioperative period than in the intensive care unit (ICU) setting. Recent studies support beneficial effects for EA beyond analgesia itself. However, data on feasibility and safety are still lacking in the ICU. Our goal was to assess the feasibility and practice of EA in ICU patients. Multicentre observational study in 3 ICUs over a 10-month period. Goals were to report the incidence of EA-related complications and EA duration. All ICU patients receiving EA were included, whether EA was initiated in the ICU or elsewhere, e.g. in the operating room. Demographics, clinical and biological data were prospectively recorded. Epidural catheter tips were sent to the microbiology laboratory for culture. One hundred and twenty-one patients were included (mean age 60years), with mean SOFA and median SAPS II scores of 3.2 and 32, respectively. Reasons for EA initiation included trauma (14%), postoperative pain management after major surgery (42%), and pancreatitis (31%). No EA-related neurologic complication was recorded, and one case of epidural abscess is discussed. No other EA-related infectious complications were observed. Median duration of EA was 11days. Reasons for EA discontinuation included efficient analgesia without EA (60%) and accidental catheter removal (17%). 22% of epidural catheter cultures were positive for skin flora bacteria. EA seems feasible in the ICU. Its apparent safety should be further validated in larger cohorts, but these preliminary results may stimulate more interest in the assessment of potential benefits associated with EA in the ICU setting. Copyright © 2015 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.
    05/2015; DOI:10.1016/j.accpm.2014.12.002
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    • "[10] [11] [12] Opioids Perioperative morphine induces immunosuppression. Hydromorphone, oxycodone, and buprenorphine have lower immunosuppressive activity, and tramadol does not suppress immune functions [28] [29] [30] [31] [32] [33] Opioids have proangiogenic effect [34] [35] [36] Methylnaltrexone inhibits angiogenesis and immune response, attenuates tumor growth, and reduces lung metastasis in mice inoculated with cancer cells [39] [40] The higher MOR expression and opioid dose requirement is associated with shorter survival [43] Anesthesia Some general anesthetics (ketamine, thiopental, and halothane) suppress NK cell activity and increase metastases [15] Inhaled anesthetics up-regulate HIF, which can facilitate cancer spread and contribute to cancer recurrence [16] [17] [18] Propofol is better than inhaled anesthesia in terms of immunity and induces apoptosis in breast cancer cells [19] [20] [21] [22] [23] [24] [25] [26] General anesthesia combined with regional anesthesia/analgesia improves immune outcome and reduces metastatic burden in animals, risk of metastasis in breast cancer, VEGF and TGF-β expression [7] [44] [45] [46] [47] [48] [49] Some studies have shown controversial results in terms of survival with epidural anesthesia/analgesia [51] [52] [53] [54] Prospective ongoing clinical trials are investigating influence of regional anesthesia in some tumor outcomes [55] [56] [57] 6 Anesthesia, cancer progression, cancer outcome, substance P F. Cassinello et al. Dibucaine was the most cytotoxic, followed by tetracaine, bupivacaine, or ethylaminobenzoate, whereas lidocaine, procaine, and mepivacaine were much less cytotoxic. "
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    ABSTRACT: To review the published literature regarding the effects of anesthesia on cancer surgery to prevent tumor cell proliferation/migration or induce apoptosis. Surgery is the main treatment for potentially curable solid tumors, but most cancer-related deaths in patients who have received previous surgical treatment are caused by metastatic disease. There is increasing evidence that anesthetic technique has the potential to affect long-term outcome after cancer surgery. This work reviews the English published literature that was obtained by performing a search of the PubMed database up to January 2014. We selected articles that provided evidence or reviewed the possible actions of anesthetics on cancer cells or the influence of anesthesia in recurrence/outcome. Inhaled anesthetics induce immunosuppression and activate inflammatory cascade activation, whereas propofol has a protective action. Opioids might promote cancer recurrence and metastasis. In vitro and in vivo studies have demonstrated that local anesthetics inhibit proliferation and migration of cancer cells and induce apoptosis. Anesthesiologists should follow current best clinical practice and include all strategies that effectively decrease pain and attenuate stress. Regional anesthesia and multimodal analgesia, adding anti-inflammatory drugs, play an unquestionable role in the control of perioperative pain and may improve recurrence-free survival. Copyright © 2015. Published by Elsevier Inc.
    03/2015; 27(3). DOI:10.1016/j.jclinane.2015.02.007
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    • "General anesthesia in combination with epidural analgesia seemed to improve disease clinical progression-free survival. However, they did not find significant differences in the two groups in terms of disease biochemical recurrence-free survival, cancer-specific survival, and overall survival [76]. "
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    ABSTRACT: Many of the most common anesthetics are used in surgical oncology, yet effects on cancer cells are still not known. Anesthesia technique could differentially affect cancer recurrence in oncologic patients undergoing surgery, due to immunosuppression, stimulation of angiogenesis, and dissemination of residual cancer cells. Data support the use of intravenous anesthetics, such as propofol anesthesia, thanks to antitumoral protective effects inhibiting cyclooxygenase 2 and prostaglandins E2 in cancer cells, and stimulation of immunity response; a restriction in the use of volatile anesthetics; restriction in the use of opioids as they suppress humoral and cellular immunity, and their chronic use favors angiogenesis and development of metastases; use of locoregional anesthesia compared with general anesthesia, as locoregional appears to reduce cancer recurrence after surgery. However, these findings must be interpreted cautiously as there is no evidence that simple changes in the practice of anesthesia can have a positive impact on postsurgical survival of cancer patients.
    02/2014; 2014(5):328513. DOI:10.1155/2014/328513
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