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Published in: Clinical Orthopaedics and Related Research® 5/2014

01-05-2014 | Symposium: Perioperative Pain Management in Orthopaedic Surgery

Can Regional Anesthesia and Analgesia Prolong Cancer Survival After Orthopaedic Oncologic Surgery?

Authors: Juan P. Cata, MD, Mike Hernandez, MS, Valerae O. Lewis, MD, Andrea Kurz, MD

Published in: Clinical Orthopaedics and Related Research® | Issue 5/2014

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Abstract

Background

The perioperative period of major oncologic surgery is characterized by immunosuppression, angiogenesis, and an increased load of circulating malignant cells. It is a window period in which cancer cells may seed, invade, and proliferate. Thus, it has been hypothesized that the use of regional anesthesia with the goal of reducing surgical stress and opioid and volatile anesthetic consumption would avoid perioperative immune suppression and angiogenesis and ultimately cancer recurrence.

Questions/purposes

We performed a systematic review of the literature on the use of regional anesthesia and postoperative analgesia to improve cancer-related survival after oncologic surgery. Our primary topic of interest is survival after orthopaedic oncologic surgery, but because that literature is limited, we also have systematically reviewed the question of survival after breast, gastrointestinal, and genitourologic cancers.

Methods

We searched the PubMed and Embase databases with the search terms: “anesthesia and analgesia”, “local neoplasm recurrence”, “cancer recurrence”, “loco-regional neoplasm recurrence”, “disease-free survival”, and “cumulative survival rates”. Our initial search of the two databases provided 836 studies of which 693 were rejected. Of the remaining 143 studies, only 13 articles qualified for inclusion in this systematic review, based on defined inclusion criteria. All these studies had retrospective design. Due to the high heterogeneity among the identified studies and the complete absence of randomized controlled trials from the literature on this topic, the results of a meta-analysis would be heavily confounded; hence, we instead performed a systematic review of the literature.

Results

No eligible studies addressed the question of whether regional anesthesia and analgesia have an impact on survival after musculoskeletal cancer surgery. Only one relevant clinical study was identified on regional breast cancer survival; it suggested a benefit. The literature on gastrointestinal and genitourinary surgery was larger but mixed, although some preliminary studies do suggest a benefit of regional anesthesia on survival after oncologic surgery in those patient populations.

Conclusions

Although basic science studies suggest a potential benefit of regional anesthesia and stress response reduction in cancer formation, we found little clinical evidence to support the theory that regional anesthesia and analgesia improve overall patient survival after oncologic surgery.
Literature
1.
go back to reference Bielack SS, Kempf-Bielack B, Delling G, Exner GU, Flege S, Helmke K, Kotz R, Salzer-Kuntschik M, Werner M, Winkelmann W, Zoubek A, Jürgens H, Winkler K. Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J Clinical Oncol. 2002;20:776–790.CrossRef Bielack SS, Kempf-Bielack B, Delling G, Exner GU, Flege S, Helmke K, Kotz R, Salzer-Kuntschik M, Werner M, Winkelmann W, Zoubek A, Jürgens H, Winkler K. Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J Clinical Oncol. 2002;20:776–790.CrossRef
2.
go back to reference Biki B, Mascha E, Moriarty DC, Fitzpatrick JM, Sessler DI, Buggy DJ. Anesthetic technique for radical prostatectomy surgery affects cancer recurrence: a retrospective analysis. Anesthesiology. 2008;109:180–187.PubMedCrossRef Biki B, Mascha E, Moriarty DC, Fitzpatrick JM, Sessler DI, Buggy DJ. Anesthetic technique for radical prostatectomy surgery affects cancer recurrence: a retrospective analysis. Anesthesiology. 2008;109:180–187.PubMedCrossRef
3.
go back to reference Capmas P, Billard V, Gouy S, Lhommé C, Pautier P, Morice P, Uzan C. Impact of epidural analgesia on survival in patients undergoing complete cytoreductive surgery for ovarian cancer. Anticancer Res. 2012;32:1537–1542.PubMed Capmas P, Billard V, Gouy S, Lhommé C, Pautier P, Morice P, Uzan C. Impact of epidural analgesia on survival in patients undergoing complete cytoreductive surgery for ovarian cancer. Anticancer Res. 2012;32:1537–1542.PubMed
4.
go back to reference Cata JP, Gottumukkala V, Sessler DI. How regional analgesia might reduce postoperative cancer recurrence. Eur J Pain Suppl. 2011;5:345–355.CrossRef Cata JP, Gottumukkala V, Sessler DI. How regional analgesia might reduce postoperative cancer recurrence. Eur J Pain Suppl. 2011;5:345–355.CrossRef
5.
go back to reference Chen WK, Miao CH. The effect of anesthetic technique on survival in human cancers: a meta-analysis of retrospective and prospective studies. PloS One. 2013;8:e56540.PubMedCentralPubMedCrossRef Chen WK, Miao CH. The effect of anesthetic technique on survival in human cancers: a meta-analysis of retrospective and prospective studies. PloS One. 2013;8:e56540.PubMedCentralPubMedCrossRef
6.
go back to reference Christopherson R, James KE, Tableman M, Marshall P, Johnson FE. Long-term survival after colon cancer surgery: a variation associated with choice of anesthesia. Anesth Analg. 2008;107:325–332.PubMedCrossRef Christopherson R, James KE, Tableman M, Marshall P, Johnson FE. Long-term survival after colon cancer surgery: a variation associated with choice of anesthesia. Anesth Analg. 2008;107:325–332.PubMedCrossRef
7.
go back to reference Cummings KC 3rd, Xu F, Cummings LC, Cooper GS. A comparison of epidural analgesia and traditional pain management effects on survival and cancer recurrence after colectomy: a population-based study. Anesthesiology. 2012;116:797–806.PubMedCrossRef Cummings KC 3rd, Xu F, Cummings LC, Cooper GS. A comparison of epidural analgesia and traditional pain management effects on survival and cancer recurrence after colectomy: a population-based study. Anesthesiology. 2012;116:797–806.PubMedCrossRef
8.
go back to reference Day A, Smith R, Jourdan I, Fawcett W, Scott M, Rockall T. Retrospective analysis of the effect of postoperative analgesia on survival in patients after laparoscopic resection of colorectal cancer. Br J Anaesth. 2012;109:185–190.PubMedCrossRef Day A, Smith R, Jourdan I, Fawcett W, Scott M, Rockall T. Retrospective analysis of the effect of postoperative analgesia on survival in patients after laparoscopic resection of colorectal cancer. Br J Anaesth. 2012;109:185–190.PubMedCrossRef
9.
go back to reference Deegan CA, Murray D, Doran P, Ecimovic P, Moriarty DC, Buggy DJ. Effect of anaesthetic technique on oestrogen receptor-negative breast cancer cell function in vitro. Br J Anaesth. 2009;103:685–690.PubMedCrossRef Deegan CA, Murray D, Doran P, Ecimovic P, Moriarty DC, Buggy DJ. Effect of anaesthetic technique on oestrogen receptor-negative breast cancer cell function in vitro. Br J Anaesth. 2009;103:685–690.PubMedCrossRef
10.
go back to reference Deegan CA, Murray D, Doran P, Moriarty DC, Sessler DI, Mascha E, Kavanagh BP, Buggy DJ. Anesthetic technique and the cytokine and matrix metalloproteinase response to primary breast cancer surgery. Reg Anesth Pain Med. 2010;35:490–495.PubMedCrossRef Deegan CA, Murray D, Doran P, Moriarty DC, Sessler DI, Mascha E, Kavanagh BP, Buggy DJ. Anesthetic technique and the cytokine and matrix metalloproteinase response to primary breast cancer surgery. Reg Anesth Pain Med. 2010;35:490–495.PubMedCrossRef
11.
go back to reference de Oliveira GS Jr, Ahmad S, Schink JC, Singh DK, Fitzgerald PC, McCarthy RJ. Intraoperative neuraxial anesthesia but not postoperative neuraxial analgesia is associated with increased relapse-free survival in ovarian cancer patients after primary cytoreductive surgery. Reg Anesth Pain Med. 2011;36:271–277.PubMedCrossRef de Oliveira GS Jr, Ahmad S, Schink JC, Singh DK, Fitzgerald PC, McCarthy RJ. Intraoperative neuraxial anesthesia but not postoperative neuraxial analgesia is associated with increased relapse-free survival in ovarian cancer patients after primary cytoreductive surgery. Reg Anesth Pain Med. 2011;36:271–277.PubMedCrossRef
12.
go back to reference Ecimovic P, Murray D, Doran P, McDonald J, Lambert DG, Buggy DJ. Direct effect of morphine on breast cancer cell function in vitro: role of the NET1 gene. Br J Anaesth. 2011;107:916–923.PubMedCrossRef Ecimovic P, Murray D, Doran P, McDonald J, Lambert DG, Buggy DJ. Direct effect of morphine on breast cancer cell function in vitro: role of the NET1 gene. Br J Anaesth. 2011;107:916–923.PubMedCrossRef
13.
go back to reference Exadaktylos AK, Buggy DJ, Moriarty DC, Mascha E, Sessler DI. Can anesthetic technique for primary breast cancer surgery affect recurrence or metastasis? Anesthesiology. 2006;105:660–664.PubMedCentralPubMedCrossRef Exadaktylos AK, Buggy DJ, Moriarty DC, Mascha E, Sessler DI. Can anesthetic technique for primary breast cancer surgery affect recurrence or metastasis? Anesthesiology. 2006;105:660–664.PubMedCentralPubMedCrossRef
14.
go back to reference Federman N, Bernthal N, Eilber FC, Tap WD. The multidisciplinary management of osteosarcoma. Curr Treat Options Oncol. 2009;10:82–93.PubMedCrossRef Federman N, Bernthal N, Eilber FC, Tap WD. The multidisciplinary management of osteosarcoma. Curr Treat Options Oncol. 2009;10:82–93.PubMedCrossRef
15.
go back to reference Forget P, Tombal B, Scholtes JL, Nzimbala J, Meulders C, Legrand C, Van Cangh P, Cosyns JP, De Kock M. Do intraoperative analgesics influence oncological outcomes after radical prostatectomy for prostate cancer? Eur J Anaesth. 2011;28:830–835.CrossRef Forget P, Tombal B, Scholtes JL, Nzimbala J, Meulders C, Legrand C, Van Cangh P, Cosyns JP, De Kock M. Do intraoperative analgesics influence oncological outcomes after radical prostatectomy for prostate cancer? Eur J Anaesth. 2011;28:830–835.CrossRef
16.
go back to reference Goldfarb Y, Sorski L, Benish M, Levi B, Melamed R, Ben-Eliyahu S. Improving postoperative immune status and resistance to cancer metastasis: a combined perioperative approach of immunostimulation and prevention of excessive surgical stress responses. Ann Surg. 2011;253:798–810.PubMedCrossRef Goldfarb Y, Sorski L, Benish M, Levi B, Melamed R, Ben-Eliyahu S. Improving postoperative immune status and resistance to cancer metastasis: a combined perioperative approach of immunostimulation and prevention of excessive surgical stress responses. Ann Surg. 2011;253:798–810.PubMedCrossRef
17.
go back to reference Gupta A, Bjornsson A, Fredriksson M, Hallböök O, Eintrei C. Reduction in mortality after epidural anaesthesia and analgesia in patients undergoing rectal but not colonic cancer surgery: a retrospective analysis of data from 655 patients in central Sweden. Br J Anaesth. 2011;107:164–170.PubMedCrossRef Gupta A, Bjornsson A, Fredriksson M, Hallböök O, Eintrei C. Reduction in mortality after epidural anaesthesia and analgesia in patients undergoing rectal but not colonic cancer surgery: a retrospective analysis of data from 655 patients in central Sweden. Br J Anaesth. 2011;107:164–170.PubMedCrossRef
18.
go back to reference Hatsukari I, Hitosugi N, Matsumoto I, Nagasaka H, Sakagami H. Induction of early apoptosis marker by morphine in human lung and breast carcinoma cell lines. Anticancer Res. 2003;23:2413–2417.PubMed Hatsukari I, Hitosugi N, Matsumoto I, Nagasaka H, Sakagami H. Induction of early apoptosis marker by morphine in human lung and breast carcinoma cell lines. Anticancer Res. 2003;23:2413–2417.PubMed
19.
go back to reference Hatsukari I, Hitosugi N, Ohno R, Hashimoto K, Nakamura S, Satoh K, Nagasaka H, Matsumoto I, Sakagami H. Induction of apoptosis by morphine in human tumor cell lines in vitro. Anticancer Res. 2007;27:857–864.PubMed Hatsukari I, Hitosugi N, Ohno R, Hashimoto K, Nakamura S, Satoh K, Nagasaka H, Matsumoto I, Sakagami H. Induction of apoptosis by morphine in human tumor cell lines in vitro. Anticancer Res. 2007;27:857–864.PubMed
20.
go back to reference Honda K. Interleukin-6 and soluble interleukin-6 receptor suppress osteoclastic differentiation by inducing PGE(2) production in chondrocytes. J Oral Sci. 2011;53:87–96.PubMedCrossRef Honda K. Interleukin-6 and soluble interleukin-6 receptor suppress osteoclastic differentiation by inducing PGE(2) production in chondrocytes. J Oral Sci. 2011;53:87–96.PubMedCrossRef
21.
go back to reference Kim MH, Hahm TS. Plasma levels of interleukin-6 and interleukin-10 are affected by ketorolac as an adjunct to patient-controlled morphine after abdominal hysterectomy. Clin J Pain. 2001;17:72–77.PubMedCrossRef Kim MH, Hahm TS. Plasma levels of interleukin-6 and interleukin-10 are affected by ketorolac as an adjunct to patient-controlled morphine after abdominal hysterectomy. Clin J Pain. 2001;17:72–77.PubMedCrossRef
22.
go back to reference King T, Vardanyan A, Majuta L, Melemedjian O, Nagle R, Cress AE, Vanderah TW, Lai J, Porreca F. Morphine treatment accelerates sarcoma-induced bone pain, bone loss, and spontaneous fracture in a murine model of bone cancer. Pain. 2007;132:154–168.PubMedCentralPubMedCrossRef King T, Vardanyan A, Majuta L, Melemedjian O, Nagle R, Cress AE, Vanderah TW, Lai J, Porreca F. Morphine treatment accelerates sarcoma-induced bone pain, bone loss, and spontaneous fracture in a murine model of bone cancer. Pain. 2007;132:154–168.PubMedCentralPubMedCrossRef
23.
go back to reference Lai R, Peng Z, Chen D, Wang X, Xing W, Zeng W, Chen M. The effects of anesthetic technique on cancer recurrence in percutaneous radiofrequency ablation of small hepatocellular carcinoma. Anesth Analg. 2012;114:290–296.PubMedCrossRef Lai R, Peng Z, Chen D, Wang X, Xing W, Zeng W, Chen M. The effects of anesthetic technique on cancer recurrence in percutaneous radiofrequency ablation of small hepatocellular carcinoma. Anesth Analg. 2012;114:290–296.PubMedCrossRef
24.
go back to reference Lennon FE, Mirzapoiazova T, Mambetsariev B, Salgia R, Moss J, Singleton PA. Overexpression of the mu-opioid receptor in human non-small cell lung cancer promotes Akt and mTOR activation, tumor growth, and metastasis. Anesthesiology. 2012;116:857–867.PubMedCrossRef Lennon FE, Mirzapoiazova T, Mambetsariev B, Salgia R, Moss J, Singleton PA. Overexpression of the mu-opioid receptor in human non-small cell lung cancer promotes Akt and mTOR activation, tumor growth, and metastasis. Anesthesiology. 2012;116:857–867.PubMedCrossRef
25.
go back to reference Lin L, Liu C, Tan H, Ouyang H, Zhang Y, Zeng W. Anaesthetic technique may affect prognosis for ovarian serous adenocarcinoma: a retrospective analysis. Br J Anaesth. 2011;106:814–822.PubMedCrossRef Lin L, Liu C, Tan H, Ouyang H, Zhang Y, Zeng W. Anaesthetic technique may affect prognosis for ovarian serous adenocarcinoma: a retrospective analysis. Br J Anaesth. 2011;106:814–822.PubMedCrossRef
26.
go back to reference Looney M, Doran P, Buggy DJ. Effect of anesthetic technique on serum vascular endothelial growth factor C and transforming growth factor beta in women undergoing anesthesia and surgery for breast cancer. Anesthesiology. 2010;113:1118–1125.PubMedCrossRef Looney M, Doran P, Buggy DJ. Effect of anesthetic technique on serum vascular endothelial growth factor C and transforming growth factor beta in women undergoing anesthesia and surgery for breast cancer. Anesthesiology. 2010;113:1118–1125.PubMedCrossRef
27.
go back to reference Mammoto T, Higashiyama S, Mukai M, Mammoto A, Ayaki M, Mashimo T, Hayashi Y, Kishi Y, Nakamura H, Akedo H. Infiltration anesthetic lidocaine inhibits cancer cell invasion by modulating ectodomain shedding of heparin-binding epidermal growth factor-like growth factor (HB-EGF). J Cell Physiol. 2002;192:351–358.PubMedCrossRef Mammoto T, Higashiyama S, Mukai M, Mammoto A, Ayaki M, Mashimo T, Hayashi Y, Kishi Y, Nakamura H, Akedo H. Infiltration anesthetic lidocaine inhibits cancer cell invasion by modulating ectodomain shedding of heparin-binding epidermal growth factor-like growth factor (HB-EGF). J Cell Physiol. 2002;192:351–358.PubMedCrossRef
28.
go back to reference Myles PS, Peyton P, Silbert B, Hunt J, Rigg JR, Sessler DI; ANZCA Trials Group Investigators. Perioperative epidural analgesia for major abdominal surgery for cancer and recurrence-free survival: randomised trial. BMJ. 2011;342:d1491.PubMedCrossRef Myles PS, Peyton P, Silbert B, Hunt J, Rigg JR, Sessler DI; ANZCA Trials Group Investigators. Perioperative epidural analgesia for major abdominal surgery for cancer and recurrence-free survival: randomised trial. BMJ. 2011;342:d1491.PubMedCrossRef
29.
go back to reference Narita S, Tsuchiya N, Kumazawa T, Maita S, Numakura K, Obara T, Tsuruta H, Saito M, Inoue T, Horikawa Y, Satoh S, Habuchi T. Comparison of surgical stress in patients undergoing open versus laparoscopic radical prostatectomy by measuring perioperative serum cytokine levels. J Laparoendosc Adv Surg Tech A. 2013;23:33–37.PubMedCrossRef Narita S, Tsuchiya N, Kumazawa T, Maita S, Numakura K, Obara T, Tsuruta H, Saito M, Inoue T, Horikawa Y, Satoh S, Habuchi T. Comparison of surgical stress in patients undergoing open versus laparoscopic radical prostatectomy by measuring perioperative serum cytokine levels. J Laparoendosc Adv Surg Tech A. 2013;23:33–37.PubMedCrossRef
30.
go back to reference Naruse T, Nishida Y, Hosono K, Ishiguro N. Meloxicam inhibits osteosarcoma growth, invasiveness and metastasis by COX-2-dependent and independent routes. Carcinogenesis. 2006;27:584–592.PubMedCrossRef Naruse T, Nishida Y, Hosono K, Ishiguro N. Meloxicam inhibits osteosarcoma growth, invasiveness and metastasis by COX-2-dependent and independent routes. Carcinogenesis. 2006;27:584–592.PubMedCrossRef
31.
go back to reference O’Riain SC, Buggy DJ, Kerin MJ, Watson RW, Moriarty DC. Inhibition of the stress response to breast cancer surgery by regional anesthesia and analgesia does not affect vascular endothelial growth factor and prostaglandin E2. Anesth Analg. 2005;100:244–249.PubMedCrossRef O’Riain SC, Buggy DJ, Kerin MJ, Watson RW, Moriarty DC. Inhibition of the stress response to breast cancer surgery by regional anesthesia and analgesia does not affect vascular endothelial growth factor and prostaglandin E2. Anesth Analg. 2005;100:244–249.PubMedCrossRef
33.
go back to reference Sloan EK, Priceman SJ, Cox BF, Yu S, Pimentel MA, Tangkanangnukul V, Arevalo JM, Morizono K, Karanikolas BD, Wu L, Sood AK, Cole SW. The sympathetic nervous system induces a metastatic switch in primary breast cancer. Cancer Res. 2010;70:7042–7052.PubMedCentralPubMedCrossRef Sloan EK, Priceman SJ, Cox BF, Yu S, Pimentel MA, Tangkanangnukul V, Arevalo JM, Morizono K, Karanikolas BD, Wu L, Sood AK, Cole SW. The sympathetic nervous system induces a metastatic switch in primary breast cancer. Cancer Res. 2010;70:7042–7052.PubMedCentralPubMedCrossRef
34.
go back to reference Sood AK, Bhatty R, Kamat AA, Landen CN, Han L, Thaker PH, Li Y, Gershenson DM, Lutgendorf S, Cole SW. Stress hormone-mediated invasion of ovarian cancer cells. Clin Cancer Res. 2006;12:369–375.PubMedCentralPubMedCrossRef Sood AK, Bhatty R, Kamat AA, Landen CN, Han L, Thaker PH, Li Y, Gershenson DM, Lutgendorf S, Cole SW. Stress hormone-mediated invasion of ovarian cancer cells. Clin Cancer Res. 2006;12:369–375.PubMedCentralPubMedCrossRef
35.
go back to reference von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP; STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007;370:1453–1457.CrossRef von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP; STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007;370:1453–1457.CrossRef
36.
go back to reference Wong IH, Chan AT, Johnson PJ. Quantitative analysis of circulating tumor cells in peripheral blood of osteosarcoma patients using osteoblast-specific messenger RNA markers: a pilot study. Clin Cancer Res. 2000;6:2183–2188.PubMed Wong IH, Chan AT, Johnson PJ. Quantitative analysis of circulating tumor cells in peripheral blood of osteosarcoma patients using osteoblast-specific messenger RNA markers: a pilot study. Clin Cancer Res. 2000;6:2183–2188.PubMed
37.
go back to reference Wuethrich PY, Hsu Schmitz SF, Kessler TM, Thalmann GN, Studer UE, Stueber F, Burkhard FC. Potential influence of the anesthetic technique used during open radical prostatectomy on prostate cancer-related outcome: a retrospective study. Anesthesiology. 2010;113:570–576.PubMed Wuethrich PY, Hsu Schmitz SF, Kessler TM, Thalmann GN, Studer UE, Stueber F, Burkhard FC. Potential influence of the anesthetic technique used during open radical prostatectomy on prostate cancer-related outcome: a retrospective study. Anesthesiology. 2010;113:570–576.PubMed
38.
go back to reference Yardeni IZ, Beilin B, Mayburd E, Alcalay Y, Bessler H. Relationship between fentanyl dosage and immune function in the postoperative period. J Opioid Manag. 2008;4:27–33.PubMed Yardeni IZ, Beilin B, Mayburd E, Alcalay Y, Bessler H. Relationship between fentanyl dosage and immune function in the postoperative period. J Opioid Manag. 2008;4:27–33.PubMed
Metadata
Title
Can Regional Anesthesia and Analgesia Prolong Cancer Survival After Orthopaedic Oncologic Surgery?
Authors
Juan P. Cata, MD
Mike Hernandez, MS
Valerae O. Lewis, MD
Andrea Kurz, MD
Publication date
01-05-2014
Publisher
Springer US
Published in
Clinical Orthopaedics and Related Research® / Issue 5/2014
Print ISSN: 0009-921X
Electronic ISSN: 1528-1132
DOI
https://doi.org/10.1007/s11999-013-3306-y

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