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      Effects of Postoperative Pain Management on Immune Function After Laparoscopic Resection of Colorectal Cancer : A Randomized Study

      research-article
      , MD, PhD, , MD, PhD, , MD, PhD, , MD, PhD, , MD, , PhD, , MD, , PhD, , MD, PhD
      Medicine
      Wolters Kluwer Health

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          Abstract

          There has been a rising interest in the possible association between perioperative opioid use and postoperative outcomes in cancer patients. Continuous surgical wound infiltration with local anesthetics is a nonopioid analgesic technique that can be used as a postoperative pain management alternative to opioid-based intravenous patient-controlled analgesia (IV PCA). The aim of this study was to compare the effects of an opioid-based analgesic regimen versus a local anesthetic wound infiltration-based analgesic regimen on immune modulation and short-term cancer recurrence or metastasis in patients undergoing laparoscopic resection of colorectal cancer.

          Sixty patients undergoing laparoscopic resection of colorectal cancer were randomly assigned to either the opioid group or the ON-Q group. For postoperative analgesia during the first 48 hours, the opioid group (n = 30) received fentanyl via IV PCA, whereas the ON-Q group (n = 30) received continuous wound infiltration of 0.5% ropivacaine with an ON-Q pump and tramadol via IV PCA. Pethidine for the opioid group and ketorolac or propacetamol for the ON-Q group were used as rescue analgesics. Anesthesia was induced and maintained with propofol and remifentanil. The primary outcome was postoperative immune function assessed by natural killer cell cytotoxicity (NKCC) and interleukin-2. Secondary outcomes were postoperative complications, cancer recurrence, or metastasis within 1 year after surgery, and postoperative inflammatory responses measured by white blood cell count, neutrophil percentage, and C-reactive protein. Immune function and inflammatory responses were measured before surgery and 24 and 48 hours after surgery.

          Fifty-nine patients completed the study. In the circumstance of similar pain control efficacy between the opioid group and the ON-Q group, postoperative NKCC and interleukin-2 levels did not differ between the 2 groups. The incidence of postoperative complications and recurrence or metastasis within 1 year after surgery was comparable between the groups. Postoperative inflammatory responses were also similar between the groups.

          When compared with ropivacaine wound infiltration-based analgesia, fentanyl-based analgesia did not further decrease NKCC or affect short-term cancer recurrence or metastasis. Thus, a fentanyl-based analgesic regimen and a ropivacaine wound infiltration-based analgesic regimen can both be used for postoperative pain management in laparoscopic resection of colorectal cancer.

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          Laparoscopy-assisted colectomy versus open colectomy for treatment of non-metastatic colon cancer: a randomised trial.

          Although early reports on laparoscopy-assisted colectomy (LAC) in patients with colon cancer suggested that it reduces perioperative morbidity, its influence on long-term results is unknown. Our study aimed to compare efficacy of LAC and open colectomy (OC) for treatment of non-metastatic colon cancer in terms of tumour recurrence and survival. From November, 1993, to July, 1998, all patients with adenocarcinoma of the colon were assessed for entry in this randomised trial. Adjuvant therapy and postoperative follow-up were the same in both groups. The main endpoint was cancer-related survival. Data were analysed according to the intention-to-treat principle. 219 patients took part in the study (111 LAC group, 108 OC group). Patients in the LAC group recovered faster than those in the OC group, with shorter peristalsis-detection (p=0.001) and oral-intake times (p=0.001), and shorter hospital stays (p=0.005). Morbidity was lower in the LAC group (p=0.001), although LAC did not influence perioperative mortality. Probability of cancer-related survival was higher in the LAC group (p=0.02). The Cox model showed that LAC was independently associated with reduced risk of tumour relapse (hazard ratio 0.39, 95% CI 0.19-0.82), death from any cause (0.48, 0.23-1.01), and death from a cancer-related cause (0.38, 0.16-0.91) compared with OC. This superiority of LAC was due to differences in patients with stage III tumours (p=0.04, p=0.02, and p=0.006, respectively). LAC is more effective than OC for treatment of colon cancer in terms of morbidity, hospital stay, tumour recurrence, and cancer-related survival.
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            Anesthetic technique for radical prostatectomy surgery affects cancer recurrence: a retrospective analysis.

            Regional anesthesia and analgesia attenuate or prevent perioperative factors that favor minimal residual disease after removal of the primary carcinoma. Therefore, the authors evaluated prostate cancer recurrence in patients who received either general anesthesia with epidural anesthesia/analgesia or general anesthesia with postoperative opioid analgesia. In a retrospective review of medical records, patients with invasive prostatic carcinoma who underwent open radical prostatectomy between January 1994 and December 2003 and had either general anesthesia-epidural analgesia or general anesthesia-opioid analgesia were evaluated through October 2006. The endpoint was an increase in postoperative prostate-specific antigen. After adjusting for tumor size, Gleason score, preoperative prostate-specific antigen, margin, and date of surgery, the epidural plus general anesthesia group had an estimated 57% (95% confidence interval, 17-78%) lower risk of recurrence compared with the general anesthesia plus opioids group, with a corresponding hazard ratio of 0.43 (95% confidence interval, 0.22-0.83; P = 0.012) in a multivariable Cox regression model. Gleason score and tumor size (percent of prostate involved) were also independent predictors of recurrence (hazards ratios of 1.19 [1.08, 1.52], P = 0.004, and 1.17 [1.03, 1.34] for 10% size difference, P = 0.01, respectively). A similar association between epidural use and recurrence was obtained by comparing patients matched on the propensity to receive epidural versus general anesthesia. Open prostatectomy surgery with general anesthesia, substituting epidural analgesia for postoperative opioids, was associated with substantially less risk of biochemical cancer recurrence. Prospective randomized trials to evaluate this association seem warranted.
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              Suppression of natural killer cell activity and promotion of tumor metastasis by ketamine, thiopental, and halothane, but not by propofol: mediating mechanisms and prophylactic measures.

              Postoperative immunosuppression is partly ascribed to anesthesia and has been suggested to compromise patients' resistance to infection and tumor metastasis. We compared the effects of various anesthetics on natural killer (NK) cell activity and on resistance to experimental metastasis, and studied mediating mechanisms and prophylactic measures. Fischer 344 rats served as controls or were anesthetized for 1 h with ketamine, thiopental, halothane, or propofol. Anesthetized rats were either maintained in normothermia or left to spontaneously reach 33 degrees C-35 degrees C. Rats were then injected IV with MADB106 tumor cells, and 24 h later lung tumor retention was assessed, or 3 wk later, lung metastases were counted. Additionally, the number and activity of circulating NK cells were assessed after anesthesia. All anesthetics, except propofol, significantly reduced NK activity and increased MADB106 lung tumor retention or lung metastases. Hypothermia had no significant effects. Ketamine increased metastasis most potently, and this effect was markedly reduced in rats pretreated with a beta-adrenergic antagonist (nadolol) or with chronic small doses of an immunostimulator (polyriboinosinic:polyribocytidylic acid). Overall, the marked variation in the NK-suppressive effects of anesthetics seems to underlie their differential promotion of MADB106 metastasis. Prophylactic measures may include perioperative immunostimulation and the use of beta-blockers. This study in a rat model of pulmonary metastasis demonstrates that some anesthetics, but not others, increase susceptibility to tumor metastasis, apparently by suppressing natural killer cell activity. Ketamine was most deleterious, and its effects were prevented by peripheral blockade of beta-adrenoceptors combined with low levels of immunostimulation.
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                Author and article information

                Journal
                Medicine (Baltimore)
                Medicine (Baltimore)
                MEDI
                Medicine
                Wolters Kluwer Health
                0025-7974
                1536-5964
                May 2016
                13 May 2016
                : 95
                : 19
                : e3602
                Affiliations
                From the Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine (SYK, H-YN, B-NK); Department of Surgery, Division of Colon and Rectal Surgery, Yonsei University College of Medicine (NKK, SHB, BSM, HH); Biostatistics Collaboration Unit, Yonsei University College of Medicine (JL); and Research Center for Silver Science, Institute of Symbiotic Life-TECH, National Leading Research Laboratory of Clinical Nutrigenetics/Nutrigenomics, Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University (JHL), Seoul, Republic of Korea.
                Author notes
                Correspondence: Jong Ho Lee, Research Center for Silver Science, Institute of Symbiotic Life-TECH, National Leading Research Laboratory of Clinical Nutrigenetics/Nutrigenomics, Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea (e-mail: jhleeb@ 123456younsei.ac.kr ).
                Co-correspondence: Bon-Neyo Koo, Department of Anesthesiology and Pain Medicine, Severance Hospital, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, 50–1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea (e-mail: KOOBN@ 123456yuhs.ac ).
                Article
                03602
                10.1097/MD.0000000000003602
                4902506
                27175664
                9f83e340-5476-4924-ae4c-b331486ecdca
                Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.

                This is an open access article distributed under the Creative Commons Attribution License 4.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0

                History
                : 11 January 2016
                : 24 March 2016
                : 12 April 2016
                Categories
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                Research Article
                Clinical Trial/Experimental Study
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