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Open Access 01-12-2012 | Review

Wound healing after radiation therapy: Review of the literature

Authors: Frank Haubner, Elisabeth Ohmann, Fabian Pohl, Jürgen Strutz, Holger G Gassner

Published in: Radiation Oncology | Issue 1/2012

Abstract

Radiation therapy is an established modality in the treatment of head and neck cancer patients. Compromised wound healing in irradiated tissues is a common and challenging clinical problem. The pathophysiology and underlying cellular mechanisms including the complex interaction of cytokines and growth factors are still not understood completely. In this review, the current state of research regarding the pathomechanisms of compromised wound healing in irradiated tissues is presented. Current and possible future treatment strategies are critically reviewed.

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Marks JE, Freeman RB, Lee F, Ogura JH: Pharyngeal wall cancer: an analysis of treatment results complications and patterns of failure. Int J Radiat Oncol Biol Phys 1978, 4: 587-593. 10.1016/0360-3016(78)90179-7CrossRefPubMed

Tang Y, Shen Q, Wang Y, Lu K, Peng Y: A randomized prospective study of rehabilitation therapy in the treatment of radiation-induced dysphagia and trismus. Strahlenther Onkol 2011, 187: 39-44. 10.1007/s00066-010-2151-0CrossRefPubMed

Melan'in VD, Rybak RF, Senkevich VM: Prophylaxis of the postop complications in combined treatment of patients with laryngeal cancer. Vestn Otorinolaringol 1998, 46: 8.

Girod DA, McCulloch TM, Tsue TT, Weymuller EA Jr: Risk factors for complications in clean-contaminated head and neck surgical procedures. Head Neck 1995, 17: 7-13. 10.1002/hed.2880170103CrossRefPubMed

Lee S, Thiele C: Factors associated with free flap complications after head and neck reconstruction and the molecular basis of fibrotic tissue rearrangement in preirradiated soft tissue. J Oral Maxillofac Surg 2010, 68: 2169-2178. 10.1016/j.joms.2009.08.026CrossRefPubMed

Hom DB, Adams G, Koreis M, Maisel R: Choosing the optimal wound dressing for irradiated soft tissue wounds. Otolaryngol Head Neck Surg 1999, 121: 591-598. 10.1016/S0194-5998(99)70062-8CrossRefPubMed

Lambert PM, Patel M, Gutman E, Campana HA: Dermal grafts to bony defects in irradiated and nonirradiated tissues. Arch Otolaryngol 1984, 110: 657-659. 10.1001/archotol.1984.00800360029006CrossRefPubMed

Hunt TK KD, Thakral KK: Cellular control of repair. In Soft and hard tissue repair: biological and clinical aspects. Edited by: Hunt TK Heppenstall RB, Pines E, Rovee D. Praeger, New York 1984:3-19.

Beaudry VG, Ihrie RA, Jacobs SB, et al.: Loss of the desmosomal component perp impairs wound healing in vivo. Dermatol Res Pract 2010, 2010: 759731.PubMedCentralPubMed

10.

Scheithauer M, Riechelmann H: Review part I: basic mechanisms of cutaneous woundhealing. Laryngorhinootologie 2003, 82: 31-35. 10.1055/s-2003-36908CrossRefPubMed

11.

Scheithauer M, Riechelmann H: Review part II: disorders in cutaneous woundhealing. Laryngorhinootologie 2003, 82: 36-39. 10.1055/s-2003-36909CrossRefPubMed

12.

Dormand EL, Banwell PE, Goodacre TE: Radiotherapy and wound healing. Int Wound J 2005, 2: 112-127. 10.1111/j.1742-4801.2005.00079.xCrossRefPubMed

13.

Albers-Schonberg: Beitrag zur therapeutischen Verwendung der Roentgenstrahlen in der Behandlung des Lupus. Fortschritte a d Geb d Roentgen 1897, 1: 72-75.

14.

Hom DHV, Lee C: Irradiatid Skin and Its Postsurgical Management. In Essential Tissue Healing of the Face and the Neck Edited by: Hom H, Gosain F. 2009, 224-238.

15.

Herskind C, Bamberg M, Rodemann HP: The role of cytokines in the development of normal-tissue reactions after radiotherapy. Strahlenther Onkol 1998,174(Suppl 3):12-15.PubMed

16.

Shi HP, Most D, Efron DT, Tantry U, Fischel MH, Barbul A: The role of iNOS in wound healing. Surgery 2001, 130: 225-229. 10.1067/msy.2001.115837CrossRefPubMed

17.

Schaffer M, Weimer W, Wider S, et al.: Differential expression of inflammatory mediators in radiation-impaired wound healing. J Surg Res 2002, 107: 93-100.CrossRefPubMed

18.

Illsley MC, Peacock JH, McAnulty RJ, Yarnold JR: Increased collagen production in fibroblasts cultured from irradiated skin and effect of TGF beta(1)- clinical study. Br J Cancer 2000, 83: 650-654. 10.1054/bjoc.2000.1321PubMedCentralCrossRefPubMed

19.

Gu Q, Wang D, Gao Y, et al.: Expression of MMP1 in surgical and radiation-impaired wound healing and its effects on the healing process. J Environ Pathol Toxicol Oncol 2002, 21: 71-78.CrossRefPubMed

20.

Goessler UR, Bugert P, Kassner S, et al.: In vitro analysis of radiation-induced dermal wounds. Otolaryngol Head Neck Surg 2010, 142: 845-850. 10.1016/j.otohns.2010.01.033CrossRefPubMed

21.

Medrado AP, Soares AP, Santos ET, Reis SR, Andrade ZA: Influence of laser photobiomodulation upon connective tissue remodeling during wound healing. J Photochem Photobiol B 2008, 92: 144-152. 10.1016/j.jphotobiol.2008.05.008CrossRefPubMed

22.

Johnson LB, Jorgensen LN, Adawi D, et al.: The effect of preoperative radiotherapy on systemic collagen deposition and postoperative infective complications in rectal cancer patients. Dis Colon Rectum 2005, 48: 1573-1580. 10.1007/s10350-005-0066-0CrossRefPubMed

23.

Harris A, Komray RR: Cost-effective management of pharyngocutaneous fistulas following laryngectomy. Ostomy Wound Manage 1993, 39: 36–7-40–2. 4

24.

Jacobson AS, Buchbinder D, Hu K: Urken ML. Paradigm shifts in the management of osteoradionecrosis of the mandible, Oral Oncol; 2010.

25.

Delanian S, Chatel C, Porcher R, Depondt J, Lefaix JL: Complete Restoration of Refractory Mandibular Osteoradionecrosis by Prolonged Treatment with a Pentoxifylline-Tocopherol-Clodronate Combination (PENTOCLO): A Phase II Trial. Int J Radiat Oncol Biol Phys 2010,80(3):832-839.CrossRefPubMed

26.

Freiberger JJ, Yoo DS, de Lisle Dear G, et al.: Multimodality surgical and hyperbaric management of mandibular osteoradionecrosis. Int J Radiat Oncol Biol Phys 2009, 75: 717-724. 10.1016/j.ijrobp.2008.11.025CrossRefPubMed

27.

Peleg M, Lopez EA: The treatment of osteoradionecrosis of the mandible: the case for hyperbaric oxygen and bone graft reconstruction. J Oral Maxillofac Surg 2006, 64: 956-960. 10.1016/j.joms.2006.02.017CrossRefPubMed

28.

Tai YJ, Birely BC, Im MJ, Hoopes JE, Manson PN: The use of hyperbaric oxygen for preservation of free flaps. Ann Plast Surg 1992, 28: 284-287. 10.1097/00000637-199203000-00016CrossRefPubMed

29.

Mayer R, Hamilton-Farrell MR, van der Kleij AJ, et al.: Hyperbaric oxygen and radiotherapy. Strahlenther Onkol 2005, 181: 113-123. 10.1007/s00066-005-1277-yCrossRefPubMed

30.

Narozny W, Sicko Z, Stankiewicz C, Przewozny T, Kot J, Kuczkowski J: An application of hyperbaric oxygen therapy in otolaryngological oncology. Otolaryngol Pol 2003, 57: 799-807.PubMed

31.

Grundmann T, Jaehne M, Fritze G: The value of hyperbaric oxygen therapy (HBO) in treatment of problem wounds in the area of plastic-reconstructive head and neck surgery. Laryngorhinootologie 2000, 79: 304-310. 10.1055/s-2000-8802CrossRefPubMed

32.

Neovius EB, Lind MG, Lind FG: Hyperbaric oxygen therapy for wound complications after surgery in the irradiated head and neck: a review of the literature and a report of 15 consecutive patients. Head Neck 1997, 19: 315-322. 10.1002/(SICI)1097-0347(199707)19:4<315::AID-HED10>3.0.CO;2-8CrossRefPubMed

33.

Mathes SJ, Alexander J: Radiation injury. Surg Oncol Clin N Am 1996, 5: 809-824.PubMed

34.

Kendall AC, Whatmore JL, Harries LW, Winyard PG, Smerdon GR: Eggleton P. Changes in inflammatory gene expression induced by hyperbaric oxygen treatment in human endothelial cells under chronic wound conditions, Exp Cell Res; 2011.

35.

Thom SR: Hyperbaric oxygen: its mechanisms and efficacy. Plast Reconstr Surg 2011,127(Suppl 1):131S-141S.PubMedCentralCrossRefPubMed

36.

Friedman HI, Fitzmaurice M, Lefaivre JF, Vecchiolla T, Clarke D: An evidence-based appraisal of the use of hyperbaric oxygen on flaps and grafts. Plast Reconstr Surg 2006, 117: 175S-90S. discussion 91S-92S 10.1097/01.prs.0000222555.84962.86CrossRefPubMed

37.

Lu G, Ling K, Zhao P, et al.: A novel in situ-formed hydrogel wound dressing by the photocross-linking of a chitosan derivative. Wound Repair Regen 2010, 18: 70-79. 10.1111/j.1524-475X.2009.00557.xCrossRefPubMed

38.

Brown CD, Zitelli JA: Choice of wound dressing and ointments. In Essential Tissue Healing of the Face and the Neck. Edited by: Hebda , Hom , Friedman , Gosain . BC Decker, Shelton, CT; 2009:409-433.

39.

Legeza VI, Galenko-Yaroshevskii VP, Zinov'ev EV, et al.: Effects of new wound dressings on healing of thermal burns of the skin in acute radiation disease. Bull Exp Biol Med 2004, 138: 311-315.CrossRefPubMed

40.

Kwan Delta KH, Liu Delta X, Yeung KW, Ho CM, To MK, Wong KK: Modulation of collagen alignment by silver nanoparticles results in better mechanical properties in wound healing. Nanomedicine 2011,7(4):497-504. 10.1016/j.nano.2011.01.003CrossRef

41.

Leon-Villapalos J, Eldardiri M, Dziewulski P: The use of human deceased donor skin allograft in burn care. Cell Tissue Bank 2010, 11: 99-104. 10.1007/s10561-009-9152-1CrossRefPubMed

42.

Ferguson PC, Boynton EL, Wunder JS, et al.: Intradermal injection of autologous dermal fibroblasts improves wound healing in irradiated skin. J Surg Res 1999, 85: 331-338. 10.1006/jsre.1999.5664CrossRefPubMed

43.

Gorodetsky R, McBride WH, Withers HR, Miller GG: Effect of fibroblast implants on wound healing of irradiated skin: assay of wound strength and quantitative immunohistology of collagen. Radiat Res 1991, 125: 181-186. 10.2307/3577886CrossRefPubMed

44.

Chunmeng S, Tianmin C, Yongping S, et al.: Effects of dermal multipotent cell transplantation on skin wound healing. J Surg Res 2004, 121: 13-9. 10.1016/j.jss.2004.04.008CrossRefPubMed

45.

Rigotti G, Marchi A, Galie M, et al.: Clinical treatment of radiotherapy tissue damage by lipoaspirate transplant: a healing process mediated by adipose-derived adult stem cells. Plast Reconstr Surg 2007, 119: 1409-1422. discussion 23–4 10.1097/01.prs.0000256047.47909.71CrossRefPubMed

46.

Akita S, Akino K, Hirano A, Ohtsuru A, Yamashita S: Noncultured autologous adipose-derived stem cells therapy for chronic radiation injury. Stem Cells Int 2010, 2010: 532704.PubMedCentralCrossRefPubMed

47.

Hadad I, Johnstone BH, Brabham JG, et al.: Development of a porcine delayed wound-healing model and its use in testing a novel cell-based therapy. Int J Radiat Oncol Biol Phys 2010, 78: 888-896. 10.1016/j.ijrobp.2010.05.002CrossRefPubMed

48.

Hom DB, Unger GM, Pernell KJ, Manivel JC: Improving surgical wound healing with basic fibroblast growth factor after radiation. Laryngoscope 2005, 115: 412-422. 10.1097/01.mlg.0000157852.01402.12CrossRefPubMed

49.

Forcheron F, Agay D, Scherthan H, et al.: Autologous adipocyte derived stem cells favour healing in a minipig model of cutaneous radiation syndrome. PLoS One 2012, 7: e31694. 10.1371/journal.pone.0031694PubMedCentralCrossRefPubMed

50.

Kim WS, Park BS, Sung JH: The wound-healing and antioxidant effects of adipose-derived stem cells. Expert Opin Biol Ther 2009, 9: 879-987. 10.1517/14712590903039684CrossRefPubMed

51.

Kim WS, Park BS, Park SH, Kim HK, Sung JH: Antiwrinkle effect of adipose-derived stem cell: activation of dermal fibroblast by secretory factors. J Dermatol Sci 2009, 53: 96-102. 10.1016/j.jdermsci.2008.08.007CrossRefPubMed

52.

Kim JH, Jung M, Kim HS, Kim YM, Choi EH: Adipose-derived stem cells as a new therapeutic modality for ageing skin. Exp Dermatol 2011, 20: 383-387. 10.1111/j.1600-0625.2010.01221.xCrossRefPubMed

53.

Lee SH, Jin SY, Song JS, Seo KK, Cho KH: Paracrine effects of adipose-derived stem cells on keratinocytes and dermal fibroblasts. Ann Dermatol 2012, 24: 136-143. 10.5021/ad.2012.24.2.136PubMedCentralCrossRefPubMed

54.

Khanna S, Roy S, Bagchi D, Bagchi M, Sen CK: Upregulation of oxidant-induced VEGF expression in cultured keratinocytes by a grape seed proanthocyanidin extract. Free Radic Biol Med 2001, 31: 38-42. 10.1016/S0891-5849(01)00544-5CrossRefPubMed

55.

Chung YL, Wang AJ, Yao LF: Antitumor histone deacetylase inhibitors suppress cutaneous radiation syndrome: Implications for increasing therapeutic gain in cancer radiotherapy. Mol Cancer Ther 2004, 3: 317-325. 10.4161/cbt.3.3.698CrossRefPubMed

56.

Jagetia GC, Rajanikant GK, Rao SK: Evaluation of the effect of ascorbic acid treatment on wound healing in mice exposed to different doses of fractionated gamma radiation. Radiat Res 2003, 159: 371-380. 10.1667/0033-7587(2003)159[0371:EOTEOA]2.0.CO;2CrossRefPubMed

57.

Pollard JD, Quan S, Kang T, Koch RJ: Effects of copper tripeptide on the growth and expression of growth factors by normal and irradiated fibroblasts. Arch Facial Plast Surg 2005, 7: 27-31. 10.1001/archfaci.7.1.27CrossRefPubMed

58.

Cromack DT, Porras-Reyes BH, Wee SS, et al.: Acceleration of soft tissue repair by a thrombin-derived oligopeptide. J Surg Res 1992, 53: 117-122. 10.1016/0022-4804(92)90022-RCrossRefPubMed

59.

Bourke SL, Al-Khalili M, Briggs T, Michniak BB, Kohn J, Poole-Warren LA: A photo-crosslinked poly(vinyl alcohol) hydrogel growth factor release vehicle for wound healing applications. AAPS PharmSci 2003, 5: E33.CrossRefPubMed

60.

Sugiyama K, Ishii G, Ochiai A, Esumi H: Improvement of the breaking strength of wound by combined treatment with recombinant human G-CSF, recombinant human M-CSF, and a TGF-beta1 receptor kinase inhibitor in rat skin. Cancer Sci 2008, 99: 1021-1028. 10.1111/j.1349-7006.2008.00761.xCrossRefPubMed

61.

Masucci G: New clinical applications of granulocyte-macrophage colony-stimulating factor. Med Oncol 1996, 13: 149-154.PubMed

62.

Garnick MB, Stoudemire JB: Preclinical and clinical evaluation of recombinant human macrophage colony-stimulating factor (rhM-CSF). Int J Cell Cloning 1990,8(Suppl 1):356-371. discussion 71–3CrossRefPubMed

63.

Vegesna V, McBride WH, Taylor JM, Withers HR: The effect of interleukin-1 beta or transforming growth factor-beta on radiation-impaired murine skin wound healing. J Surg Res 1995, 59: 699-704. 10.1006/jsre.1995.1226CrossRefPubMed

64.

Amento EP, Beck LS: TGF-beta and wound healing. Ciba Found Symp 1991, 157: 115-123. discussion 23–9PubMed

65.

Lonergan DM, Mikulec AA, Hanasono MM, Kita M, Koch RJ: Growth factor profile of irradiated human dermal fibroblasts using a serum-free method. Plast Reconstr Surg 2003, 111: 1960-1968. 10.1097/01.PRS.0000055065.41599.75CrossRefPubMed

66.

Schultze-Mosgau S, Wehrhan F, Amann K, Radespiel-Troger M, Rodel F, Grabenbauer GG: In Vivo TGF-beta 3 expression during wound healing in irradiated tissue. An experimental study. Strahlenther Onkol 2003, 179: 410-416.PubMed

67.

Cromack DT, Porras-Reyes B, Purdy JA, Pierce GF, Mustoe TA: Acceleration of tissue repair by transforming growth factor beta 1: identification of in vivo mechanism of action with radiotherapy-induced specific healing deficits. Surgery 1993, 113: 36-42.PubMed

68.

Philipp K, Riedel F, Germann G, Hormann K, Sauerbier M: TGF-beta antisense oligonucleotides reduce mRNA expression of matrix metalloproteinases in cultured wound-healing-related cells. Int J Mol Med 2005, 15: 299-303.PubMed

69.

Cordeiro MF, Mead A, Ali RR, et al.: Novel antisense oligonucleotides targeting TGF-beta inhibit in vivo scarring and improve surgical outcome. Gene Ther 2003, 10: 59-71. 10.1038/sj.gt.3301865CrossRefPubMed

70.

Riedel K, Koellensperger E, Ryssel H, et al.: Abrogation of TGF-beta by antisense oligonucleotides modulates expression of VEGF and increases angiogenic potential in isolated fibroblasts from radiated skin. Int J Mol Med 2008, 22: 473-480.PubMed

71.

Riedel K, Kremer T, Ryssel H, et al.: TGF-beta antisense oligonucleotides modulate expression of matrix metalloproteinases in isolated fibroblasts from radiated skin. In Vivo 2008, 22: 1-7.PubMed

72.

Mustoe TA, Purdy J, Gramates P, Deuel TF, Thomason A, Pierce GF: Reversal of impaired wound healing in irradiated rats by platelet-derived growth factor-BB. Am J Surg 1989, 158: 345-350. 10.1016/0002-9610(89)90131-1CrossRefPubMed

73.

Hom DB, Linzie BM, Huang TC: The healing effects of autologous platelet gel on acute human skin wounds. Arch Facial Plast Surg 2007, 9: 174-183. 10.1001/archfaci.9.3.174CrossRefPubMed

74.

Hom DB, Manivel JC: Promoting healing with recombinant human platelet-derived growth factor–BB in a previously irradiated problem wound. Laryngoscope 2003, 113: 1566-1571. 10.1097/00005537-200309000-00029CrossRefPubMed

75.

Kilic D, Sayan H, Gonul B, Egehan I: The effect of granulocyte macrophage-colony stimulating factor on glutathione and lipid peroxidation in a rat model. Eur J Surg Oncol 2000, 26: 701-4. 10.1053/ejso.2000.0984CrossRefPubMed

76.

Glaspy JA, Golde DW: Clinical applications of the myeloid growth factors. Semin Hematol 1989, 26: 14-7.PubMed

77.

Ryu SH, Kim YH, Lee SW, Hong JP: The preventive effect of recombinant human growth factor (rhEGF) on the recurrence of radiodermatitis. J Radiat Res (Tokyo) 2010, 51: 511-517. 10.1269/jrr.10010CrossRef

78.

Riedel F, Philipp K, Sadick H, Goessler U, Hormann K, Verse T: Immunohistochemical analysis of radiation-induced non-healing dermal wounds of the head and neck. In Vivo 2005, 19: 343-350.PubMed

79.

Avanzi GC, Gallicchio M, Saglio G: Hematopoietic growth factors in autologous transplantation. Biotherapy 1998, 10: 299-308. 10.1007/BF02678550CrossRefPubMed

Title: Wound healing after radiation therapy: Review of the literature
Authors: Frank Haubner
Elisabeth Ohmann
Fabian Pohl
Jürgen Strutz
Holger G Gassner
Publication date: 01-12-2012
Publisher: BioMed Central
Published in: Radiation Oncology / Issue 1/2012
Electronic ISSN: 1748-717X
DOI: https://doi.org/10.1186/1748-717X-7-162

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Wound healing after radiation therapy: Review of the literature

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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