Annals of Surgical Oncology

, Volume 14, Issue 10, pp 2887–2895 | Cite as

Post Operative Infection and Increased Survival in Osteosarcoma Patients: Are They Associated?

  • L. M. Jeys
  • R. J. Grimer
  • S. R. Carter
  • R. M Tillman
  • A. Abudu
Bone and Soft Tissue Sarcomas



Despite neo-adjuvant chemotherapy osteosarcomas having significant mortality, recent studies have shown survival advantages following infections for some tumour types. This study investigates the effect of post-operative infection in patients treated for osteosarcoma using endoprosthetic replacement and neo-adjuvant chemotherapy.

Material and Methods

A consecutive series of 547 patients underwent surgery between 1981 and 2001 for osteosarcoma. Patients were excluded from the study if over 60 years old at diagnosis (n = 14) as they would not routinely receive chemotherapy. Studies showed that 70% of deep infections occur within one year from reconstruction. Therefore landmark analysis was performed; all patients infected after 12 months of reconstruction were excluded (15 patients, 2.7%) and those who died within 12 months from diagnosis due to metastases were excluded (105 patients, 19.2%), leaving 412 patients. Any survival advantage of early infection was analysed by Kaplan-Meier survival analysis from this landmark point.


Overall population survival was 65% at 10 years after landmarking. There were 41 patients (10%) who developed an infection within one year of implantation. These patients had significantly better survival (p = 0.017). The 10-year survival for patients with osteosarcoma with infection was 84.5% compared to 62.3% in the non-infected group after landmarking. There was no significant difference in the percentage post-chemotherapy specimen necrosis between the two groups (p = 0.36). Infection was an independent prognostic factor on cox regression analysis.


There was evidence for increased survival after deep post-operative infection in osteosarcoma patients, in keeping with other research. The authors feel this warrants further investigation.


Osteosarcoma Deep Infection Infected Group Isolate Limb Perfusion Landmark Point 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Virkus WW, Marshall D, Enneking WF, Scarborough MT. The effect of contaminated surgical margins revisited. Clin Orthop Relat Res 2002;397:89–94PubMedCrossRefGoogle Scholar
  2. 2.
    Rech A, Castro CG Jr, Mattei J, Gregianin L, Di Leone L, David A, Rivero LF, Tarrago R, Abreu A, Brunetto AL. Clinical features in osteosarcoma and prognostic implications. J Pediatr (Rio J) 2004; 80(1):65–70CrossRefGoogle Scholar
  3. 3.
    Bacci G, Longhi A, Versari M, Mercuri M, Briccoli A, Picci P. Prognostic factors for osteosarcoma of the extremity treated with neoadjuvant chemotherapy: 15-year experience in 789 patients treated at a single institution. Cancer 2006; 106(5):1154–61PubMedCrossRefGoogle Scholar
  4. 4.
    Scully SP, Ghert MA, Zurakowski D, Thompson RC, Gebhardt MC. Pathologic fracture in osteosarcoma: prognostic importance and treatment implications. J Bone Joint Surg Am 2002; 84-A(1):49–57PubMedGoogle Scholar
  5. 5.
    Bramer JA, Abudu AA, Tillman RM, Carter SR, Sumathi VP, Grimer RJ. Pre- and post-chemotherapy alkaline phosphatase levels as prognostic indicators in adults with localised osteosarcoma. Eur J Cancer 2005; 41(18):2846–52. Epub 2005 Nov 7PubMedCrossRefGoogle Scholar
  6. 6.
    Kawai A, Healey JH, Boland PJ, Lin PP, Huvos AG, Meyers PA. Prognostic factors for patients with sarcomas of the pelvic bones. Cancer 1998; 82(5):851–9PubMedCrossRefGoogle Scholar
  7. 7.
    Bieling P, Rehan N, Winkler P, Helmke K, Maas R, Fuchs N, Bielack S, Heise U, Jurgens H, Treuner J, Romanowski R, Exner U, Kotz R, Winkler K. Tumor size and prognosis in aggressively treated osteosarcoma. J Clin Oncol 1996; 14(3):848–58PubMedGoogle Scholar
  8. 8.
    Raymond AK, Chawla SP, Carrasco CH, Ayala AG, Fanning CV, Grice B, Armen T, Plager C, Papadopoulos NE, Edeiken J. Osteosarcoma chemotherapy effect: a prognostic factor. Semin Diagn Pathol 1987; 4(3):212–36PubMedGoogle Scholar
  9. 9.
    Juergens H, Kosloff C, Nirenberg A, Mehta BM, Huvos AG, Rosen G. Prognostic factors in the response of primary osteogenic sarcoma to preoperative chemotherapy (high-dose methotrexate with citrovorum factor). Natl Cancer Inst Monogr. 1981; (56):221–6PubMedGoogle Scholar
  10. 10.
    Bacci G, Ferrari S, Lari S, Mercuri M, Donati D, Longhi A, Forni C, Bertoni F, Versari M, Pignotti E. Osteosarcoma of the limb. Amputation or limb salvage in patients treated by neoadjuvant chemotherapy. J Bone Joint Surg Br 2002; 84(1):88–92PubMedCrossRefGoogle Scholar
  11. 11.
    Rodriguez-Galindo C, Shah N, McCarville MB, Billups CA, Neel MN, Rao BN, Daw NC. Outcome after local recurrence of osteosarcoma: the St. Jude Children’s Research Hospital experience (1970–2000). Cancer 2004; 100(9):1928–35PubMedCrossRefGoogle Scholar
  12. 12.
    Grimer RJ, Sommerville S, Warnock D, Carter S, Tillman R, Abudu A, Spooner D. Management and outcome after local recurrence of osteosarcoma. Eur J Cancer 2005; 41(4):578–83; Epub 2005 Jan 5PubMedCrossRefGoogle Scholar
  13. 13.
    Davis AM, Bell RS, Goodwin PJ. Prognostic factors in osteosarcoma: a critical review. J Clin Oncol 1994; 12(2):423–31PubMedGoogle Scholar
  14. 14.
    Jeys LM, Grimer RJ, Carter SR, Tillman RM. Periprosthetic infection in patients treated for an orthopaedic oncological condition’. J Bone Joint Surg Am 2005; 87-A(4):842–9CrossRefGoogle Scholar
  15. 15.
    Lascelles BD, Dernell WS, Correa MT, Lafferty M, Devitt CM, Kuntz CA, Straw RC, Withrow SJ. Improved survival associated with postoperative wound infection in dogs treated with limb-salvage surgery for osteosarcoma. Ann Surg Oncol 2005; 12(12):1073–83.; Epub 2005 Oct 28PubMedCrossRefGoogle Scholar
  16. 16.
    Weeden S, Grimer RJ, Cannon SR, Taminiau AH, Uscinska BM. European Osteosarcoma Intergroup; The effect of local recurrence on survival in resected osteosarcoma. Eur J Cancer 2001; 37(1):39–46PubMedCrossRefGoogle Scholar
  17. 17.
    Schoenfeld DA, Richter JR. Nomograms for calculating the number of patients needed for a clinical trial with survival as an endpoint. Biometrics 1982; 38:163–170PubMedCrossRefGoogle Scholar
  18. 18.
    Dupont WD, Plummer WD. Power and sample size calculations: a review and computer orogram. Controlled Clinical Trials 1990;11:116–28PubMedCrossRefGoogle Scholar
  19. 19.
    Thrall DE, Withrow SJ, Powers BE, Straw RC, Page RL, Heidner GL, Richardson DC, Bissonnette KW, Betts CW, DeYoung DJ. Radiotherapy prior to cortical allograft limb sparing in dogs with osteosarcoma: a dose response assay. Int J Radiat Oncol Biol Phys 1990; 18(6):1351–7PubMedGoogle Scholar
  20. 20.
    Wiemann B, Starnes CO. Coley’s toxins, tumour necrosis factor and cancer research: a historical perspective. Pharmacol Ther 1994; 64(3): 529–64PubMedCrossRefGoogle Scholar
  21. 21.
    American Cancer Society. Guide to complementary & alternative cancer methods. Atlanta: American Cancer Society Inc.; 2000Google Scholar
  22. 22.
    Shear MJ, Turner FC. Chemical treatment of tumours; isolation of hemorrhagic-producing fraction from Serratia marcescens (Bacillus prodigious) culture filtrate. J Natl Cancer Inst 1943; 4:81–7Google Scholar
  23. 23.
    Algire GH, Legallais FY, Park HD. Vascular reactions of normaland malignant tissues in vivo. II. The vascular reaction of normal and neoplastic tissues of mice to a bacterial polysaccharide from Serratia marcescens (Bacillus prodigious) culture filtrates. J Natl Cancer Inst 1947; 8:53–62Google Scholar
  24. 24.
    Carswell EA, Old LJ, Kassel RL, Green S, Fiore N, Williamson B. An endotoxin-induced serum factor that causes necrosis of tumours. Proc Natl Acad Sci USA 1975; 72:3666–70PubMedCrossRefGoogle Scholar
  25. 25.
    Pennica D, Nedwin GE, Hayflick JS, Seeburg PH, Derynck R, Palladino MA, et al. Human tumour necrosis factor: precursor structure, expression and homology to lymphotoxin. Nature 1984; 312:724–9PubMedCrossRefGoogle Scholar
  26. 26.
    Hobohm U. Fever therapy revisited. Br J Cancer 2005; 92:421–5PubMedGoogle Scholar
  27. 27.
    Challis G, Stam H. The spontaneous regression of cancer. A review of cases from 1900 to 1987. Acta Oncol 1990; 29(5):545–50PubMedGoogle Scholar
  28. 28.
    Vermeire K, Schols D. Specific CD-4 down-modulating compounds with potent anti-HIV activity. J Leukoc Biol 2003; 74(5):667–75PubMedCrossRefGoogle Scholar
  29. 29.
    Sensenig DM, Rossi NP, Ehrenhaft JL. Pulmonary resection for bronchogenic carcinoma in geriatric patients. Ann Thorac Surg 1966; 2:508–13PubMedCrossRefGoogle Scholar
  30. 30.
    Ruckdesche l JC, Codish SD, Stranahan A, McKneally MF. Postoperative empyema improves survival in lung cancer. Documentation and analysis of a natural experiment. N Engl J Med 1972; 287:1013–7CrossRefGoogle Scholar
  31. 31.
    Schantz SP, Skolnik EM, O’Neill JV. Improved survival associated with postoperative wound infection in laryngeal cancer: an analysis of its therapeutic implications. Otolaryngol Head Neck Surg 1980; 88:412–7PubMedGoogle Scholar
  32. 32.
    Koelmel K, Pfahlberg A, Mastrangelo G, Niin M, Botev I, Seebacher C, Schneider D, Lambert D, Shafir R, Kokoschka E, Kleeberg U, Henz B, Gefeller O. Infections and melanoma risk: results of a multicenter EORTC case study. Melanoma Res 1999; 9:511–519CrossRefGoogle Scholar
  33. 33.
    Krone B, Kolmel KF, Grange JM, Mastrangelo G, Hez BM, Botev IN, Niin M, Seebacher C, Lambert D, Shafir R, Kokoschka EM, Kleeberg UR, Gefeller O, Pfahlberg A. Impact of vaccinations and infectious diseases on the risk of melanoma – evaluation of an EORTC case control study. Eur J Cancer. 2004; 39(16):2372–8CrossRefGoogle Scholar
  34. 34.
    Alexandroff AB, Jackson AM, O’Donnell MA, James K. BCG immunotherapy of bladder cancer: 20 years on. Lancet 1999; 353:1689–94PubMedCrossRefGoogle Scholar
  35. 35.
    Grunhagen DJ, de Wilt JH, Graveland WJ, van Geel AN, Eggermont AM. The palliative value of tumour necrosis alpha based isolated limb perfusion in patients with metastatic sarcoma and melanoma. Cancer. 2006; 106(1):156–62PubMedCrossRefGoogle Scholar
  36. 36.
    Grunhagen DJ, de Wilt JH, Graveland WJ, van Geel AN, Eggermont AM. TNF-based isolated limb perfusion of unresectable extremity desmoid tumours. Eur J Surg Oncol 2005; 31(8):912–8PubMedCrossRefGoogle Scholar
  37. 37.
    Pennica D, Nedwin GE, Hayflick JS, Seeburg PH, Derynck R, Palladino MA, et al. Human tumour necrosis factor: precursor structure, expression and homology to lymphotoxin. Nature 1984; 312:724–9PubMedCrossRefGoogle Scholar
  38. 38.
    Tracey KJ, Cerami A. Tumor necrosis factor: a pleiotropic cytokine and therapeutic target. Annu Rev Med 1994; 45:491–503PubMedCrossRefGoogle Scholar
  39. 39.
    Hibbs Jr JB, Lambert Jr LH, Remington JS. Resistance to murine tumours conferred by chronic infection with intracellular protozoa, Toxoplasma gondii and Besnoitia jellisoni. J Infect Dis 1971; 124:587–92PubMedGoogle Scholar
  40. 40.
    Hibbs Jr JB, Lambert Jr LH, Remington JS. Control of carcinogenesis: a possible role for the activated macrophage. Science 1972; 177:998–1000PubMedCrossRefGoogle Scholar
  41. 41.
    Hibbs Jr JB, Lambert Jr LH, Remington JS. Possible role of macrophage mediated nonspecific cytotoxicity in tumour resistance. Nat New Biol 1972; 235:48–50PubMedGoogle Scholar
  42. 42.
    Hibbs Jr JB. Infection and nitric oxide. J Infect Dis 2002; 185:S9–S17PubMedCrossRefGoogle Scholar
  43. 43.
    North RJ, Kirstein DP. T-cell-mediated concomitant immunity to syngeneic tumours. I. Activated macrophages as the expressors of nonspecific immunity to unrelated tumours and bacterial parasites. J Exp Med 1977; 145:275–92PubMedCrossRefGoogle Scholar
  44. 44.
    Youdim S, Sharman M. Resistance to tumor growth mediated by Listeria monocytogenes: collaborative and suppressive macrophagelymphocyte interactions in vitro. J Immunol 1976; 117:1860–5PubMedGoogle Scholar
  45. 45.
    Keller R, Keist R, Leist TP, van der Meide PH. Resistance to a non-immunogenic tumor, induced by Corynebacterium parvum or Listeria monocytogenes, is abrogated by anti-interferon γ. Int J Cancer 1990; 46:687–90PubMedCrossRefGoogle Scholar
  46. 46.
    Hunter CA, Yu D, Gee M, Ngo C, Sevignani C, Goldscmidt M. Cutting edge: systemic inhibition of angiogenesis underlies resistance to tumours during acute toxoplasmosis. J Immunol 2001; 166:5878–81PubMedGoogle Scholar
  47. 47.
    Thomas-Tikhonenko A, Hunter CA. Infection and cancer: the common vein Cytokine Growth Factor Rev. 2003; 14:67–77CrossRefGoogle Scholar
  48. 48.
    Mori K, Redini F, Gouin F, Cherrier B, Heymann D. Osteosarcoma: current status of immunotherapy and future trends (Review). Oncol Rep 2006; 15(3):693–700PubMedGoogle Scholar
  49. 49.
    Muller R, Sigbjorn S, Bauer H, Saeter G, Strander H. Interferon-a as the only adjuvant treatment in high-grade Osteosarcoma: Long term results of the Karolinska Hospital series. Acta Oncologica 2005; 44:475–80PubMedCrossRefGoogle Scholar
  50. 50.
    Inaba H, Glibetic M, Buck S, Ravindranath Y, Kaplan J. Interferon-gamma sensitizes osteosarcoma cells to Fas-induced apoptosis by up regulating Fas receptors and caspase-8. Pediatr Blood Cancer 2004; 43(7):729–36PubMedCrossRefGoogle Scholar
  51. 51.
    Pritchard-Jones K, Spendlove I, Wilton C, Whelan J, Weeden S, Lewis I, Hale J, Douglas C, Pagonis C, Campbell B, Alvarez P, Halbert G, Durrant LG. Immune responses to the 105AD7 human anti-idiotypic vaccine after intensive chemotherapy, for osteosarcoma. Br J Cancer 2005; 92(8):1358–65PubMedCrossRefGoogle Scholar
  52. 52.
    Anderson P. Liposomal muramyl tripeptide phosphatidyl ethanolamine: ifosfamide-containing chemotherapy in osteosarcoma. Future Oncol 2006; 2(3):333–43. ReviewPubMedCrossRefGoogle Scholar
  53. 53.
    Nardin A, Lefebvre ML, Labroquere K, Faure O, Abastado JP. Liposomal muramyl tripeptide phosphatidylethanolamine: Targeting and activating macrophages for adjuvant treatment of osteosarcoma. Curr Cancer Drug Targets 2006; 6(2):123–33. ReviewPubMedCrossRefGoogle Scholar
  54. 54.
    Meyers PA, Schwartz CL, Krailo M, Kleinerman ES, Betcher D, Bernstein ML,Conrad E, Ferguson W, Gebhardt M, Goorin AM, Harris MB, Healey J, Huvos A, Link M, Montebello J, Nadel H, Nieder M, Sato J, Siegal G, Weiner M, Wells R, Wold L, Womer R, Grier H. Osteosarcoma: a randomized, prospective trial of the addition of ifosfamide and/or muramyl tripeptide to cisplatin, doxorubicin, and high-dose methotrexate. J Clin Oncol 2005; 23(9):2004–11PubMedCrossRefGoogle Scholar
  55. 55.
    Kurzman ID, Shi F, Vail DM, MacEwen EG. In vitro and in vivo enhancement of canine pulmonary alveolar macrophage cytotoxic activity against canine osteosarcoma cells. Cancer Biother Radiopharm 1999; 14(2):121–8PubMedCrossRefGoogle Scholar
  56. 56.
    Kurzman ID, MacEwen EG, Rosenthal RC, Fox LE, Keller ET, Helfand SC, Vail DM, Dubielzig RR, Madewell BR, Rodriguez CO Jr, et al. Adjuvant therapy for osteosarcoma in dogs: results of randomized clinical trials using combined liposome-encapsulated muramyl tripeptide and cisplatin. Clin Cancer Res 1995; 1(12):1595–601PubMedGoogle Scholar

Copyright information

© Society of Surgical Oncology 2007

Authors and Affiliations

  • L. M. Jeys
    • 1
    • 2
  • R. J. Grimer
    • 1
  • S. R. Carter
    • 1
  • R. M Tillman
    • 1
  • A. Abudu
    • 1
  1. 1.Royal Orthopaedic Hospital Oncology ServiceNorthfieldUnited Kingdom
  2. 2.Royal Orthopaedic Hospital Oncology ServiceHolmfirthUnited Kingdom

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