Current Problems in Surgery
Volume 44, Issue 11 , Pages 691-763 , November 2007

Optimizing Healing of the Acute Wound by Minimizing Complications

  • Michael G. Franz, MD

      Affiliations

    • Associate Professor of Surgery, University of Michigan School of Medicine, Ann Arbor, Michigan
  • ,
  • David L. Steed, MD

      Affiliations

    • Professor of Surgery, Director of the Wound Healing/Limb Preservation Clinic, University of Pittsburgh, Pittsburgh, Pennsylvania
  • ,
  • Martin C. Robson, MD

      Affiliations

    • Professor Emeritus of Surgery, Founder, Institute for Tissue Regeneration, Repair, and Rehabilitation, University of South Florida, Tampa, Florida

References 

  1. Robson MC. Exogenous growth factor application effect on human wound healing. Prog Dermatol. 1996;30:1–7
  2. Lazarus GS, Cooper DM, Knighton DR, et al. Definitions and guidelines for assessment of wounds and evaluation of healing. Arch Dermatol. 1994;130:489–493
  3. NHDS 1995. National Hospital Discharge Survey: Detailed Diagnoses and Procedures. Washington, D.C.: National Center for Health Statistics; 1995;
  4. Arrow AK. Biotechnology in wound care. In: Investment Outlook. Los Angeles: Wedbush Morgan Stanley Securities; 1999;p. 1–82
  5. Carlson MA. Acute wound failure. Surg Clin North Am. 1997;77:607–636
  6. Lionelli GT, Lawrence WT. Wound dressings. Surg Clin North Am. 2003;83:631–633
  7. Sheffield P. Tissue oxygen measurements with respect to soft tissue wound healing with normobaric and hyperbaric oxygen. HBO Rev. 1985;6:18–46
  8. Hopf HW, Viele M, Watson JJ, et al. Subcutaneous perfusion and oxygen during acute severe isovolemic hemodilution in healthy volunteers. Arch Surg. 2000;135(12):1443–1449
  9. Pollock AV, Evans M. Early prediction of late incisional hernias. Br J Surg. 1989;76:953–954
  10. Flum DR, Horvath K, Koepsell T. Have outcomes of incisional hernia repair improved with time? (A population based analysis). Ann Surg. 2003;237(1):129–135
  11. Luijendijk RW, Hop WCJ, van den Tol P, et al. A comparison of suture repair with mesh repair for incisional hernia. N Engl J Med. 2000;343(6):392–398
  12. Duepree HJ, Senagore AJ, Delaney CP, Fazio VW. Does means of access affect the incidence of small bowel obstruction and ventral hernia after bowel resection? (Laparoscopy versus laparotomy). J Am Coll Surg. 2003;197(2):177–181
  13. Cleveland RD, Zitsch RP, Laws HL. Incisional closure in morbidly obese patients. Am Surg. 1989;55(1):61–63
  14. Livingston EH. Procedure incidence and in-hospital complication rates of bariatric surgery in the United States. Am J Surg. 2004;188(2):105–110
  15. Hesselink VJ, Luijendijk RW, Dewilt JHW, Heide R, Jeekel J. An evaluation of risk factors in incisional hernia recurrence. Surg Gynecol Obstet. 1993;176(3):228–234
  16. Robson MC, Burns BF, Smith DJ. Acute management of the burned patient. Plast Reconstr Surg. 1992;89:1155–1168
  17. Pruett R. Wound Data and Munitions Effectiveness Team (WDMET) Study, Data Collection June 1967-June 1969, Statistical Analyses Completed 2002. Bethesda, MD: Uniformed Services University Health Sciences; 2002;
  18. Marshall TJ. The Alpha Surgical Company experiences during Operation Iraqi Freedom. Mil Med. 2005;170:469–472
  19. Gondusky JS, Reiter MP. Protecting military convoys in Iraq: an examination of battle injuries sustained by a mechanical battalion during Operation Iraqi Freedom II. Mil Med. 2005;170:546–549
  20. Romalingam T, Pathak G, Barker P. A method for determining the rates of major limb amputations in battle casualties: experiences of a British field hospital in Iraq. Ann R Coll Surg Engl. 2003;87:113–116
  21. Johnson BA, Carmack D, Neary M, Tenuta J, Chen J. Operation Iraqi Freedom: the Landstuhl Regional Medical Center experiences. J Foot Ankle Surg. 2005;44:177–183
  22. Cancio LC, Horvath EE, Barillo DJ, et al. Burn support for Operation Iraqi Freedom and related operations, 2003 to 2004. J Burn Care Rehabil. 2005;26:151–161
  23. Robson MC. Wound infection: a failure of wound healing caused by an imbalance of bacteria. Surg Clin N Am. 1997;77:637–650
  24. Cooper DM, Robson MC. Wound healing: infection. J fur Anasthesie Intensivbehandlung. 1996;13:25–28
  25. Robson MC. Disturbances in wound healing. Ann Emerg Med. 1988;17:1274–1278
  26. Majno G. The Healing Hand: Man and Wound in the Ancient World. Cambridge, MA: Harvard University Press; 1975;
  27. Major RH. A History of Medicine. Springfield, IL: Charles C. Thomas; 1954;
  28. Robson MC, Steed DL, Franz MG. Wound healing: biologic features and approaches to maximize healing trajectories. Curr Prob Surg. 2001;38:64–140
  29. Bhishagrama KKL. An English Translation of the Susruta Samhita Based on Original Sanskrit Text. Varanasi, India: Chowkhamba Sanskrit Office; 1963;
  30. Robson MC, Krizek TJ, Heggers JP. Biology of surgical infection. In:  Ravitch MM editors. Chicago: Year Book Medical; 1973;
  31. Haynes BW. The history of burn care. In:  Boswick JA editors. The Art and Science of Burn Care. Rockville, MD: Aspen Publishers Inc; 1987;
  32. Haller JD. Guy de Chauliac and his Chirurgia Magna. Surgery. 1964;55:337
  33. Clowes WA. A Profitable and Necessarie Booke of Observations for All Those Burnt with the Flame of Gunpowder. London: 1596.
  34. Paré A. The Workes of That Famous Chiurgian Ambrose Parey, trans. by T. Johnson, Cotes and Young, 1634. Pound Ridge, NY: Milford House; 1968;
  35. Hidanus F. De Combustionibus. Frankfort: 1646.
  36. Murray EGD. A synopsis of the history of medical bacteriology. In:  Dubos RJ editors. Bacterial and Mycotic Infections of Man. 2nd ed.. Philadelphia: JB Lippincott; 1952;
  37. Major RH. Classic Descriptions of Disease. 3rd ed.. Springfield, IL: Charles C. Thomas; 1959;
  38. Lister J. On a new method of treating compound fracture, abscess, etc. with observations on the conditions of suppuration. Lancet. 1867;1:326
  39. Earle AS. The germ theory in America: antisepsis and asepsis (1867-1900). Surgery. 1969;65:508–522
  40. Kentish J. An Essay on Burns Which Happen to Workmen in Mines. Edinburgh: Robinson; 1797;
  41. Earle J. Means of Lessening the Effect of Fire on the Human Body. London: Clarke; 1799;
  42. Pollack GD. Cases of skin grafting and skin transplantation. Trans Clin Soc. 1871;4:37
  43. Eaglstein WH. Historical aspects of wound healing. In:  Falabella AF,  Kirsner RS editor. Wound Healing. Boca Raton, FL: Taylor & Francis Group; 2005;
  44. Hunt TK. Physiology in wound healing. In:  Clowes GHA editors. Trauma, Sepsis and Shock: The Physiological Basis of Therapy. New York: Marcel Dekker; 1988;p. 443–471
  45. Bennett NT, Schultz GS. Growth factors and wound healing—biochemical properties of growth factors and their receptors. Am J Surg. 1993;165(6):728–737
  46. Dubay DA, Franz MG. Acute wound healing: the biology of acute wound failure. Surg Clin North Am. 2003;83(3):463–481
  47. Cromack DT, Sporn MB, Roberts AB, Merino MJ, Dart LL, Norton JA. Transforming growth factor beta levels in rat wound chambers. J Surg Res. 1987;42:622–628
  48. Wahl SM, Wong H, McCartney-Francis N. Role of growth factors in inflammation and repair. J Cell Biochem. 1989;40(2):193–199
  49. Robson MC, Dubay DA, Wang X, Franz MG. Effect of cytokine growth factors on the prevention of acute wound failure. Wound Repair Regen. 2004;12(1):38–43
  50. Evans PJ, Midha R, Mackinnon SE. The peripheral nerve allograft: a comprehensive review of regeneration and neuroimmunology. Prog Neurobiol. 1994;43(3):187–233
  51. Heggers JP, Robson MC, London MD, Raine TJ, Becker B. Cooling and the prostaglandin effect in the thermal injury. J Burn Care Rehabil. 1982;3:350–354
  52. Robson MC. Infected soft tissue wounds. In:  Cameron J editors. Current Therapy in Plastic and Reconstructive Surgery. Philadelphia: BC Decker; 1989;
  53. Rappolee DA, Mark D, Banda MJ, Werb Z. Wound macrophages express TGF-α and other growth factors in vivo: analysis by mRNA phenotyping. Science. 1988;241:708–712
  54. Adzick NS, Lorenz P. Cells, matrix, growth factors, and the surgeon: the biology of scarless fetal wound repair. Ann Surg. 1994;220:10–18
  55. Gosiewska A, Yi CF, Brown LJ, Cullen B, Silcock D, Geesen JC. Differential expression and regulation of extracellular matrix-associated genes in fetal and neonatal fibroblasts. Wound Repair Regen. 2001;9(3):213–222
  56. Ferguson MW, Whitby DJ, Shah M. Scar formation: the spectral nature of fetal and adult wound repair. Plast Reconstr Surg. 1996;97:854–860
  57. Gottrup F. Healing of incisional wounds in stomach and duodenum (Functional interaction between normal and wounded tissue). Am J Surg. 1981;141:706–711
  58. Viidik A, Gottrup F. Mechanics of healing soft tissue wounds. In:  Schmidt-Schonbein GW,  Woo SLY,  Zweifach BW editor. Frontiers in Biomechanics. New York: Springer; 1986;p. 263–279
  59. Clark RAF. The Molecular and Cellular Biology of Wound Repair. 2nd ed.. New York: Plenum Press; 1995;
  60. Kessler D, Dethlefsen S, Haase I, et al. Fibroblasts in mechanically stressed collagen lattices assume a “synthetic” phenotype. J Biol Chem. 2001;276(39):36575–36585
  61. Ingber DE. Tensegrity: the architectural basis of cellular mechanotransduction. Annu Rev Physiol. 1997;59:575–599
  62. Skutek M, van Griensven M, Zeichen J, Brauer N, Bosch U. Cyclic mechanical stretching modulates secretion pattern of growth factors in human tendon fibroblasts. Eur J App Physiol. 2001;86(1):48–52
  63. Dingfelder JR. Prostaglandin inhibitors: new treatment for an old nemesis. N Engl J Med. 1982;307:746–747
  64. Tzeng E, Billiar TR. Nitric oxide and the surgical patient: identifying therapeutic targets. Arch Surg. 1997;132:977–982
  65. Yamasaki K, Edington HD, McClosky C, Tzeng E, Lizanova A, Kovesdi I. Reversal of impaired wound repair in iNOS-deficient mice by topical adenoviral-mediated iNOS gene transfer. J Clin Invest. 1998;101:967–971
  66. Thornton FJ, Schaffer MR, Barbul A. Wound healing in sepsis and trauma. Shock. 1997;8(6):391–401
  67. Riches DWH. Macrophage involvement in wound repair, remodeling and fibrosis. In:  Clark RAF editors. 2nd ed.. New York: Plenum Press; 1995;p. 95–141
  68. Robson MC. Infection in the surgical patient: an imbalance in the normal equilibrium. Clin Plast Surg. 1979;6:493
  69. Leaper DJ, Gottrup F. Surgical wounds. In:  Leaper DJ,  Harding KG editor. Wounds: Biology and Management. 1st ed.. Oxford: Oxford University Press; 1998;p. 23–40
  70. Nielson EG, Phillips SM, Jimenez S. Lymphokine modulation of fibroblast proliferation. J Immunol. 1982;128(3):1484–1486
  71. Newman SL, Henson JE, Henson PM. Phagocytosis of senescent neutrophils by human monocyte-derived macrophages and rabbit inflammatory macrophages. J Exp Med. 1982;156(2):430–442
  72. Morgan CJ, Pledger WJ. Fibroblast proliferation. In:  Cohen IH,  Diegelmann RF,  Lindblad WJ editor. Wound Healing: Biochemical and Clinical Aspects. 1st ed.. Philadelphia: Saunders; 1992;p. 63–76
  73. Barry FP. Biology and clinical applications of mesenchymal stem cells. Birth Defects Res Part C Embryo Today Rev. 2003;69(3):250–256
  74. Hunt T, Hussain Z. Wound microenvironment. In:  Cohen IH,  Diegelmann RF,  Lindblad WJ editor. Wound Healing: Biochemical and Clinical Aspects. 1st ed.. Philadelphia: WB Saunders; 1992;p. 274–281
  75. Pajulo OT, Pulkki KJ, Lertola KK, et al. Hyaluronic acid in incision wound fluid: a clinical study with the cellstick device in children. Wound Repair Regen. 2001;9(3):200–204
  76. Lygoe KA, Norman JT, Marshall JF, Lewis MP. Alpha v integrins play an important role in myofibroblast differentiation. Wound Repair Regen. 2004;12(4):461–470
  77. Ehrlich HP. Wound closure: evidence of cooperation between fibroblasts and collagen matrix. Eye. 1988;2(pt 2):149–157
  78. Ehrlich HP, Keefer KA, Myers RL, Passaniti A. Vanadate and the absence of myofibroblasts in wound contraction. Arch Surg. 1999;134(5):494–501
  79. Prockop DJ, Kivirikko KI, Tuderman L, Guzman NA. The biosynthesis of collagen and its disorders. N Engl J Med. 1979;301:13–23
  80. Jorgensen LN, Kellehave F, Karlsmark T, Gottrup F. Reduced collagen accumulation after major surgery. Br J Surg. 1996;83:1591–1594
  81. Banda MJ, Dwyer KS, Beckmann A. Wound fluid angiogenesis factor stimulates the directed migration of capillary endothelial cells. J Cell Biochem. 1985;29:183–193
  82. Monaco JL, Lawrence WT. Acute wound healing an overview. Clin Plast Surg. 2003;30(1):1–12
  83. Gordillo GM, Sen CK. Revisiting the essential role of oxygen in wound healing. Am J Surg. 2003;186(3):259–263
  84. Hunt T. Disorders of wound healing. World J Surg. 1980;4:271–277
  85. Logerfo F, Goffman S. Vascular and microvascular disease of the foot in diabetes: implications for foot care. N Engl J Med. 1984;311:1615–1619
  86. Falanga V. Venous ulceration. Wounds. 1996;3:102–108
  87. Marti HH. Angiogenesis—a self-adapting principle in hypoxia. EXS. 2005;94:163–180
  88. Zhang F, Lei MP, Oswald TM, et al. The effect of vascular endothelial growth factor on the healing of ischemic skin wounds. Br J Plast Surg. 2003;56(4):334–341
  89. Hunt T, Pai M. The effect of variant ambient oxygen tensions on wound metabolism and collagen synthesis. Surg Gynecol Obstet. 1972;135:561–567
  90. Poredos P, Rakovec S, Guzic-Salobir B. Determination of amputation level in ischaemic limbs using TcPO2 measurement. Vasa. 2005;34(2):108–112
  91. Wutschert R, Bounameau XH. Determination of amputation level in ischemic limbs: reappraisal of the measurement of TcPO2. Diabetes Care. 1997;20(5):1315–1318
  92. Moosa H, Makaroun M, Peitzman A, Steed DL, Webster M. Transcutaneous oxygen measurements in limb ischemia: effects of regional blood flow and arterial oxygen tension. J Surg Res. 1986;40:482–487
  93. Murphy MO, Ghosa J, Fulford P, et al. Expression of growth factors and growth factor receptors in non-healing ischemic ulceration. Eur J Endovasc Surg. 2006;31(5):516–522
  94. Shesta LK, Hendricks D, Webster M. Indirect revascularization of the lower extremity by means of a microvascular free muscle flap: a preliminary report. J Vasc Surg. 1990;12:581–585
  95. Mustoe TA, O’Shaughnessy K, Kloeters O. Chronic wound pathogenesis and current treatment strategies: a unifying hypothesis. Plast Reconstr Surg. 2006;117(suppl 7):35S–41S
  96. Grayson ML, Gibbons GW, Balogh K, Levin E, Karchner AW. Probing to bone in infected pedal ulcers: a clinical sign of underlying osteomyelitis in diabetic patients. JAMA. 1995;273:7231–7233
  97. Swanson DL, Vetter RS. Bites of brown recluse spiders and suspected necrotic arachnidism. N Engl J Med. 2005;352:700–707
  98. Bohannon RW. Whirlpool versus whirlpool and rinse for removal of bacteria from a venous stasis ulcer. Phys Ther. 1982;62:304–306
  99. Lineaweaver WC, Howard R, Soucy D. Topical antimicrobial toxicity. Arch Surg. 1985;120:267–270
  100. Green VA, Carson HC, Briggs RL, Steward JL. A comparison of the efficacy of pulsed mechanical lavage with that of rubber-bulb syringe in removal of debris from avulsive wounds. Oral Surg Oral Med Oral Pathol. 1971;32:158–164
  101. Hamer ML, Robson MC, Krizek TJ, Southwick W. Quantitative bacterial analyses of comparative wound irrigations. Ann Surg. 1978;181:819–822
  102. Hebda P, Lo C. The effects of active ingredients of standard debriding agents—papain and collagenase—on digestion of nature and denatured collagenous substrates, fibrin, and elastin. Wounds. 2001;13(5):190–194
  103. Sherman RA. A new dressing design for treating pressure ulcers with maggot therapy. Plast Reconstr Surg. 1997;100:451–456
  104. Harding KG, Moore K, Phillips TJ. Wound chronicity and fibroblast senescence—implications for treatment. Int Wound J. 2005;2(4):364–368
  105. Steed DL, Donohoe D, Webster MW, Lindsley L. Diabetic Ulcer Study Group: effect of extensive debridement and treatment in the healing of diabetic foot ulcers. J Am Col Surg. 1996;183(1):61–64
  106. Robson MC, Stenberg BD, Heggers JP. Wound healing alterations caused by bacteria. Clin Plast Surg. 1990;17:485–492
  107. American College of SurgeonsCommittee on Control of Surgical Infections of the Committee on Pre and Postoperative Care of the American College of Surgeons. Manual on Control of Infection in Surgical Patients. 1st ed.. Philadelphia: JB Lippincott; 1976;
  108. Heggers JP, Robson MC. Quantitative Bacteriology: Its Role in the Armamentarium of the Surgeon. Boca Raton, FL: CRC Press; 1991;
  109. Robson MC, Heggers JP. Surgical infection II: the B-hemolytic streptococcus. J Surg Res. 1969;9:289–292
  110. Berard F, Gandon J. Postoperative wound infections: the influence of ultraviolet irradiation of the operating room and the influence of various other factors. Ann Surg. 1964;160(suppl):1–192
  111. Miles AA, Miles EM, Burke J. The value and duration of defense reactions to the primary lodgement of bacteria. Br J Exp Pathol. 1957;38:79
  112. Robson MC, Heggers JP. Surgical infection I: single bacterial species or polymicrobic in origin?. Surgery. 1969;65:608–610
  113. Altemeier WA, Gibbs EW. Bacterial flora of fresh accidental wounds. Surg Gynecol Obstet. 1944;78:164
  114. Robson MC, Duke WF, Krizek TJ. Rapid bacterial screening in the treatment of civilian wounds. J Surg Res. 1973;14:426–430
  115. Ricketts LR, Squire JE, Topley E, et al. Human skin lipids with particular reference to the self-sterilizing power of the skin. Clin Sci Mol Med. 1951;10:89–92
  116. Lyle WG, Outlaw K, Krizek TJ, Koss N, Payne WG, Robson MC. Prophylactic antibiotics in plastic surgery: trends of use over 25 years of an evolving specialty. Aesthetic Surg J. 2003;23:177–183
  117. Burke JF. The effective period of preventive antibiotic action in experimental incisions and dermal lesions. Surgery. 1961;50:161
  118. Cruse PS, Foord R. A five year study of 23,649 surgical wounds. Arch Surg. 1973;107:206–210
  119. Platt R, Zaleznik DF, Hopkins CC, et al. Perioperative antibiotic prophylaxis for herniorrhaphy and breast surgery. N Engl J Med. 1990;322:153–160
  120. Regina PL, Gold S, Meakins JL. Correspondence: antibiotic prophylaxis for herniorrhaphy and breast surgery. N Engl J Med. 1990;322:1884
  121. Wagman LD, Tegtmeier B, Beatty JD, et al. A prospective randomized double-blind study of the use of antibiotics at the time of mastectomy. Surg Gynecol Obstet. 1990;170:12–16
  122. Classen DC, Evans RS, Pestotnik SL, Horn SD, et al. The timing of prophylactic administration of antibiotics and the risk of surgical wound infection. N Engl J Med. 1992;326:281–286
  123. Dellinger EP, Gross PA, Barrett TL, Krause PJ, et al. Quality standard for antimicrobial prophylaxis is surgical procedures. Clin Infect Dis. 1994;18:422–427
  124. Page CP, Bohnen JMA, Fletcher JR, McManus AT, et al. Antimicrobial prophylaxis for surgical wounds: guidelines for clinical care. Arch Surg. 1993;128:79–88
  125. Barie PS. Modern surgical antibiotic prophylaxis and therapy: less is more. Surg Infect. 2000;1:23–29
  126. Robson MC, Zachary LS. Repair of traumatic cutaneous injuries involving the skin and soft tissue. In:  Georgiade GS,  Georgiade NG,  Riefkohl R, et al. editor. Textbook of Plastic Maxillofacial and Reconstructive Surgery. 2nd ed.. Baltimore: Williams & Wilkins; 1992;
  127. Edlich RF, Rogers W, Kasper G, et al. Studies in the management of the contaminated wound. I (Optimal time for closure of contaminated open wounds. II. Comparison of resistance to infection of open and closed wounds during healing). Am J Surg. 1969;117:323–329
  128. Robson MC, Heggers JP. Delayed wound closures based on bacterial counts. J Surg Oncol. 1970;2:379–383
  129. Robson MC. Burn sepsis. Crit Care Clin N Am. 1988;4:281–298
  130. Guay DR. Treatment of bacterial skin and skin structure infection. Expert Opin Pharmacother. 2003;4:1259–1275
  131. Dall L, Peterson S, Simmons T, et al. Rapid resolution of cellulitis in patients managed with combination antibiotic and anti-inflammatory therapy. Cutis. 2005;75:177–180
  132. Robson MC, Shaw RC, Heggers JP. The reclosure of postoperative incisional abscesses based on bacterial quantification of the wound. Ann Surg. 1970;171:279–282
  133. Krizek TJ, Robson MC, Kho E. Bacterial growth and skin graft survival. Surg Forum. 1967;18:518–519
  134. Serena T, Robson MC, Cooper DM, Ignatius J Human Genome Sciences Clinical Trial Group. Serena T, Robson MC, Cooper DM, The lack of reliability of clinical assessment of chronic wound infection: the incidence of biopsy-proven infection in venous leg ulcers. Wounds. 2006;18(7):197–202
  135. Robson MC, Edstrom LE, Krizek TJ, Groskin MG. The efficacy of systemic antibiotics in the treatment of granulating wounds. J Surg Res. 1974;16:299–306
  136. Geerts WH, Heit JA, Clagett GP, et al. Prevention of venous thromboembolism. Chest. 2001;119(suppl 1):132S–175S
  137. Hopkinson GB, Bullen BR. Removable subcuticular skin suture in acute appendicitis: a prospective comparative clinical trial. Br Med J (Clin Res Ed). 1982;284(6319):869
  138. Spotnitz WD, Dalton MS, Baker JW, Nolan SP. Reduction of perioperative hemorrhage by anterior mediastinal spray application of fibrin glue during cardiac operations. Ann Thorac Surg. 1987;44(5):529–531
  139. Cruse PJ, Foord R. A five-year prospective study of 23,649 surgical wounds. Arch Surg. 1973;107(2):206–210
  140. Best PJ, Daoud MS, Pittelkow MR, Petitt RM. Hydroxyurea-induced leg ulceration in 14 patients. Ann Intern Med. 1998;128(1):29–32
  141. Weinlich G, Fritsch P. Leg ulcers in patients treated with hydroxyurea for myeloproliferative disorders: what is the trigger?. Br J Dermatol. 1999;141(1):171–172
  142. Lauvin R, Miglianico L, Hellegouarc’h R. Skin cancer occurring 10 years after the extravasation of doxorubicin. N Engl J Med. 1995;332(11):754
  143. Coleman JJ, Walker AP, Didolkar MS. Treatment of adriamycin-induced skin ulcers: a prospective controlled study. J Surg Oncol. 1983;22(2):129–135
  144. Porock D. Factors influencing the severity of radiation skin and oral mucosal reactions: development of a conceptual framework. Eur J Cancer Care. 2002;11(1):33–43(Engl)
  145. Majeski J, Austin RM, Fitzgerald RH. Cutaneous angiosarcoma in an irradiated breast after breast conservation therapy for cancer: association with chronic breast lymphedema. J Surg Oncol. 2000;74(3):208–212
  146. Martin M, Vozenin MC, Gault N, Crechet F, Pfarr CM, Lefaix JL. Coactivation of AP-1 activity and TGF-beta1 gene expression in the stress response of normal skin cells to ionizing radiation. Oncogene. 1997;15(8):981–989
  147. Kouvaris JR, Kouloulias VE, Plataniotis GA, Balafouta EJ, Vlahos LJ. Dermatitis during radiation for vulvar carcinoma: prevention and treatment with granulocyte-macrophage colony-stimulating factor impregnated gauze. Wound Repair Regen. 2001;9(3):187–193May
  148. Halperin EC, Gaspar L, George S, Darr D, Pinnell S. A double-blind, randomized, prospective trial to evaluate topical vitamin C solution for the prevention of radiation dermatitis (CNS Cancer Consortium). Int J Radiat Oncol Biol Phys. 1993;26(3):413–416
  149. Michalowski AS. On radiation damage to normal tissues and its treatment. II (Anti-inflammatory drugs). Acta Oncol. 1994;33(2):139–157
  150. Svendsen MN, Werther K, Nielsen HJ, Kristjansen PE. VEGF and tumour angiogenesis: impact of surgery, wound healing, inflammation and blood transfusion. Scand J Gastroenterol. 2002;37:373–379
  151. Risau W. Mechanisms of angiogenesis. Nature. 1997;386:671–674
  152. Gallucci RM, Simeonova PP, Matheson JM, et al. Impaired cutaneous wound healing in interleukin-6-deficient and immunosuppressed mice. FASEB J. 2000;14(15):2525–2531
  153. Stephens FO, Dunphy JE, Hunt TK. Effect of delayed administration of corticosteroids on wound contraction. Ann Surg. 1971;173:214–218
  154. Hunt TK. Vitamin A and wound healing. Am Acad Dermatol. 1986;15:817–821
  155. Gupta A, Jain GK, Raghubir R. A time course study for the development for an immunocompromised wound model using hydrocortisone. J Pharmacol Toxicol Methods. 1999;41(4):183–187
  156. Schaffer MR, Barbul A. Lymphocyte function in wound healing and following injury. Br J Surg. 1998;85(4):444–460
  157. Davis PA, Corless DJ, Gazzard BG, Wastell C. Increased risk of wound complications and poor healing following laparotomy in HIV-seropositive and AIDS patients. Dig Surg. 1999;16(1):60–67
  158. Nadal SR, Manzione CR, Galvao VM, Salim VR, Speranzini MB. Healing after anal fistulotomy: a comparative study between HIV+ and HIV− patients. Dis Colon Rectum. 1998;41(2):177–179
  159. Lord RV. Anorectal surgery in patients infected with human immunodeficiency virus: factors associated with delayed wound healing. Ann Surg. 1997;226(1):92–99
  160. Luck JV. Orthopaedic surgery in the HIV positive patient: complications and outcome. Instr Course Lect. 1994;43:543–549
  161. Davis PA, Wastell D. A comparison of biomechanical properties of excised mature scars from HIV patients and non-HIV controls. Am J Surg. 2000;180(3):217–222
  162. Tartter PI. Immunologic effects of blood transfusion. Immunol Invest. 1995;24(1-2):277–288
  163. Tadros T, Wobbes T, Hendriks T. Blood transfusion impairs the healing of experimental intestinal anastomoses. Ann Surg. 1992;215(3):276–281
  164. Ohwada S, Sato Y, Sato N, et al. Effect of transfusion in gastrointestinal anastomotic wound healing and leucocyte function in rats. Eur Surg Res. 2000;32(6):353–358
  165. Apostolidis SA, Michalopoulos AA, Hytiroglou PM, et al. Prevention of blood-transfusion-induced impairment of anastomotic healing by leucocyte depletion in rats. Eur J Surg. 2000;166(7):562–567
  166. Mandia R, Equchi Y, Tanaka M, Sai Y, Nosaka S. Effects of profound hemodilution on small intestinal wound healing in rabbits. J Surg Res. 2001;99(1):107–113
  167. Cruse JM, Lewis RE, Dilioglou S, Roe DL, Wallace WF, Chen RS. Review of immune function, healing of pressure ulcers, and nutritional status in patients with spinal cord injury. J Spinal Cord Med. 2000;23(2):129–135
  168. Raine TJ, Heggers JP, Robson MC, London MD, Johns L. Cooling the burn wound to maintain microcirculation. J Trauma. 1981;21:394–397
  169. Robson MC, Smith DJ. Thermal injuries. In:  Jurkiewicz MJ,  Krizek TJ,  Mathes SJ,  Ariyan S editor. Plastic Surgery: Principles and Practice. St. Louis: Mosby; 1990;
  170. Hansbrough JF. The use of bioengineered skin for burn patients. In:  Falanga V editors. Cutaneous Wound Healing. London: Martin Dunitz Ltd; 2001;
  171. Fu X, Shen Z, Chen Y, et al. Randomized placebo-controlled trial of use of topical recombinant bovine basic fibroblast growth factor for second degree burns. Lancet. 1998;352:1661–1664
  172. Zawacki BE. Reversal of capillary stasis and prevention of necrosis in burns. Ann Surg. 1974;180:98–102
  173. Wilmore DW. Metabolic changes after thermal injury. In:  Boswick JA editors. The Art and Science of Burn Care. Rockville, MD: Aspen Publishers; 1987;
  174. Rovee DT, et al. Effect of local environment on epidermal healing. In:  Maibach HI,  Rovee DT editor. Epidermal Wound Healing. Chicago: Year Book Medical; 1972;
  175. Janzekovic Z. The burn wound from a surgical point of view. J Trauma. 1975;15:42–62
  176. Herndon DN, Barrow RE, Rutan RL, Rutan TC, Desai MH, Abston S. A comparison of conservative versus early excision: therapies in severely burned patients. Ann Surg. 1989;209:547–553
  177. Herndon DN, Barrow RE, Kunkel KR, Broemeling L, Rutan RL. Effects of recombinant human growth hormone on donor site healing in severely burned children. Ann Surg. 1990;212:424–431
  178. Soler PM, Wright TE, Smith PD, et al. In vivo characterization of keratinocyte growth factor-2 as a potential wound healing agent. Wound Rep Regen. 1999;7:172–178
  179. Smith PD, Polo M, Soler PM, et al. Efficacy of growth factors to accelerate closure of interstices in explanted human meshed skin grafts. J Burn Care Rehabil. 2000;231:773–777
  180. Lee JJ, Marvin JA, Heimbach DM, Grube BJ. Use of 5% sulfamylon (mafenide) solution after excision and grafting of burns. J Burn Care Rehabil. 1988;9:602–605
  181. Maggi SP, Soler PM, Smith PD, Hill DP, Ko F, Robson MC. The efficacy of 5% sulfamylon solution for the treatment of contaminated explanted human meshed skin grafts. Burns. 1999;25:237–241
  182. Krizek TJ. Topical therapy of burns: problems in wound healing. J Trauma. 1968;8:276–280
  183. Robson MC, Jellema A, Heggers JP, et al. Care of the healed burn wound: a prospective randomized study. Proc Am Burn Assoc. 1980;12:94–95
  184. Abrams RA, Tsai AM, Watson B, Jamali A, Lieber RL. Skeletal muscle recovery after tenotomy and 7-day delayed muscle length restoration. Muscle Nerve. 2000;23(5):707–714
  185. Arem AJ, Madden JW. Effects of stress on healing wounds: I (Intermittent noncyclical tension). J Surg Res. 1976;20(2):93–102
  186. DuBay DA, Choi W, Urbanchek MG, et al. Incisional herniation induces decreased abdominal wall compliance via oblique muscle atrophy and fibrosis. Ann Surg. 2007;245:140–146
  187. Levenson SM, Demetriou AA. Metabolic Factors. In:  Cohen IH,  Diegelmann RF,  Lindblad WJ editor. Wound Healing: Biochemical and Clinical Aspects. Philadelphia: Saunders; 2001;p. 248–273
  188. Demling RH, DeSanti L. The stress response to injury and infection: the role of nutritional support. Wounds. 2000;12:3
  189. Williams JG, Barbul A. Nutrition and wound healing. Surg Clin North Am. 2003;83:571–596
  190. Williams JZ, Abumrad N, Barbul A. Effect of a specialized amino acid mixture on human collagen deposition. Ann Surg. 2002;236(3):369–374
  191. Best WR, Khuri SF, Phelan . Identifying patient preoperative risk factors and postoperative adverse events in administrative databases: results from the Department of Veterans Affairs National Surgical Quality Improvement Program. J Am Coll Surg. 2002;194(3):257–266
  192. Cho K, Adamson LK, Greenhalgh DG. Parallel self-induction of TNF-α and apoptosis in the thymus of mice after burn injury. J Surg Res. 2001;98(1):9–15
  193. Burns JL, Mancoll JS, Phillips LG. Impairments to wound healing. Clin Plast Surg. 2003;30(1):47–56
  194. Knighton DR, Hunt TK, Scheuenstuhl H, Halliday BJ, Werb Z, Banda MJ. Oxygen tension regulates the expression of angiogenesis factor by macrophages. Science. 1983;221(4617):1283–1285
  195. McGinn FP. Effects of haemorrhage upon surgical operations. Br J Surg. 1976;63(10):742–746
  196. Peacock J. Fascia and muscle. In:  Peacock J editors. Wound Repair. 3rd ed.. Philadelphia: WB Saunders; 1984;p. 332–362
  197. Jenkins TPN. The burst abdominal wound: a mechanical approach. Br J Surg. 1976;63:873–876
  198. Devereux DF, Triche TJ, Webber BL, Thibault LE, Brennan MF. A study of adriamycin-reduced wound breaking strength in rats (An evaluation by light and electron microscopy, induction of collagen maturation, and hydroxyproline content). Cancer. 1980;45(11):2811–2815
  199. Jorgensen LN, Kallehave F, Christensen E, Siana JE, Gottrup F. Less collagen production in smokers. Surgery. 1998;123(4):450–455
  200. Lenhardt R, Hopf HW, Marker E, et al. Perioperative collagen deposition in elderly and young men and women. Arch Surg. 2000;135(1):71–74
  201. Reus WF, Colen LB, Straker DJ. Tobacco smoking and complications in elective microsurgery. Plast Reconstr Surg. 1992;89(3):490–494
  202. Deveci M, Gilmont RR, Dunham WR, Mudge BP, Smith DJ, Marcelo CL. Glutathione enhances fibroblast collagen contraction and protects keratinocytes from apoptosis in hyperglycemic culture. Br J Dermatol. 2005;152(2):217–224
  203. Greenhalgh DG. Wound healing and diabetes mellitus. Clin Plast Surg. 2003;30(1):37–45
  204. Robson MC. Proliferative scarring. Surg Clin North Am. 2003;83:557–569
  205. Cuono CB. Scars and keloids. In:  Jurkiewicz MJ,  Mathes SJ,  Krizek TJ,  Ariyan S editor. Plastic Surgery: Principles and Practice. St. Louis: Mosby; 1990;p. 1411–1428
  206. Linares HA. Hypertrophic healing: controversies and etiopathogenic review. In:  Carvajal HF,  Parks DH editor. Burns in Children: Pediatric Burn Management. Chicago: Year Book Medical; 1988;p. 348–362
  207. Robson MC, Barnett RA, Leitch IOW, Hayward PG. Prevention and treatment of postburn scars and contracture. World J Surg. 1992;16:87–96
  208. Ferguson MWJ, Howarth GF. Marsupial models of scarless wound healing. In:  Adzick NS,  Longaker MT editor. Fetal Wound Healing. New York: Elsevier Scientific Press; 1992;p. 95–124
  209. Mast BA, Nelson JM, Krummel TM. Tissue repair in the mammalian fetus. In:  Cohen IK,  Diegelmann RF,  Lindblad WJ editor. Wound Healing: Biochemical and Clinical Aspects. Philadelphia: WB Saunders; 1992;p. 326–341
  210. Murray JC, Pinnell SR. Keloids and excessive dermal scarring. In:  Cohen IK,  Diegelmann RF,  Lindblad WJ editor. Wound Healing: Biochemical and Clinical Aspects. Philadelphia: WB Saunders; 1992;p. 500–509
  211. Polo M, Ko F, Busillo F, Cruse CW, Krizek TJ, Robson MC. The 1997 Moyer Award: cytokine production in burn patients with hypertrophic scars. J Burn Care Rehabil. 1997;18:477–482
  212. Ketchum LD, Cohen IK, Masters FW. Hypertrophic scars and keloids: a collective review. Plast Reconstr Surg. 1974;53:140–154
  213. Border WA, Noble NA. Transforming growth factor beta in tissue fibrosis. N Engl J Med. 1994;321:1286–1292
  214. O’Kane S, Ferguson MWJ. Transforming growth factor-Bs and wound healing. Int J Biochem Cell Biol. 1997;29:63–78
  215. Roberts AB. Transforming growth factor beta: activity and efficacy in animal models of wound healing. Wound Repair Regen. 1995;3(4):408–418
  216. Shah M, Foremann DM, Ferguson MW. Neutralization of TGF-B1 and TGF-B2 or exogenous addition of TGF-B3 to cutaneous rat wounds reduces scarring. J Cell Sci. 1995;108:985–1002
  217. Wang X, Smith P, Pu LLQ, Kim YJ, Ko F, Robson MC. Exogenous TGF-B2 modulates collagen I and collagen III synthesis in proliferative scar xenografts in nude rats. J Surg Res. 1999;87:194–200
  218. Cox DA. Transforming growth factor beta-3. Cell Biol Int. 1995;19:357–370
  219. Wassermann RJ, Polo M, Smith PD, Wang X, Ko F, Robson MC. Differential production of apoptosis modulating proteins in patients with hypertrophic burn scar. J Surg Res. 1998;75:74–79
  220. Lawrence WT. In search of the optimal treatment of keloids: report of a series and review of the literature. Ann Plast Surg. 1991;27:164–178
  221. Ahn ST, Monafo WW, Mustoe TA. Topical silicone gel: a new treatment for hypertrophic scars. Surgery. 1989;106:781–787
  222. Ahn ST, Monafo WW, Mustoe TA. Topical silicone gel for the prevention and treatment of hypertrophic scar. Arch Surg. 1991;126:499–504
  223. Mercer NGS. Silicone gel in the treatment of keloid scars. Br J Plast Surg. 1989;42:83–87
  224. Kuhn MA, Moffitt MR, Smith PD, et al. Silicone sheeting decreases fibroblast activity and downregulates TGF-B2 in hypertrophic scar model. Int J Surg Invest. 2001;2:467–474
  225. Peacock EE. Pharmacologic control of surface scarring in human beings. Ann Surg. 1981;193:592–597
  226. Shah M, Foremann DM, Ferguson MWJ. Control of scarring in adult wounds by neutralizing antibody to transforming growth factor B. Lancet. 1992;339:213–214
  227. Smith P, Mosiello G, Deluca L, Ko F, Maggi S, Robson MC. TGF-B2 activates proliferative scar fibroblasts. J Surg Res. 1999;82:319–323
  228. Ferguson MW, O’Kane S. Scar-free healing: from embryonic mechanisms to adult therapeutic intervention. Philos Trans R Soc Lond B Biol Sci. 2004;359:839–850
  229. Tredget EE, Shankowsky HA, Pannu R, et al. Transforming growth factor-B in thermally injured patients with hypertrophic scars: effect of interferon alpha-2b. Plast Reconstr Surg. 1998;102:1317–1330
  230. McCallion RL, Ferguson MWJ. Fetal wound healing and the development of antiscarring therapies for adult wound healing. In:  Clark RAF editors. The Molecular and Cellular Biology of Wound Repair. New York: Plenum Press; 1996;p. 561–600
  231. Payne WG, Ko F, Anspaugh S, Wheeler CK, Wright TE, Robson MC. Down-regulating causes of fibrosis with tamoxifen: a possible cellular/molecular approach to treat rhinophyma. Ann Plast Surg. 2006;56:301–305
  232. Mancoll JS, Zhao J, McCauley RL, et al. The inhibitory effect of tamoxifen on keloid fibroblasts. Surg Forum. 1996;47:718–720
  233. Hu D, Hughes MA, Cherry GW. Topical tamoxifen—a potential therapeutic regime in treating excessive dermal scarring?. Br J Plast Surg. 1998;51:462–469
  234. Chau D, Mancoll JS, Lee S, et al. Tamoxifen downregulates TGF-B production in keloid fibroblasts. Ann Plast Surg. 1998;40:490–493
  235. Danielson KG, Baribault H, Holmes DF, et al. Targeted disruption of decorin leads to abnormal collagen fibril morphology and skin fragility. J Cell Biol. 1997;136:729–743
  236. Scott PG, Dodd CM, Ghahary A, et al. Fibroblasts from post-burn hypertrophic scar tissue synthesize less decorin than normal dermal fibroblasts. Clin Sci. 1998;94:541–547
  237. Hildebrand A, Romaris M, Rasmussen LM, et al. Interaction of the small interstitial proteoglycans biglycan, decorin, and fibromodulin with transforming growth factor beta. Biochem J. 1994;302:527–534
  238. Logan A, Berry M, Gonzalez M, et al. Effects of transforming growth factor-b1 on scar production in the injured central nervous system of the rat. Eur J Neurosci. 1994;6:355–363
  239. Younai S, Nichter LS, Wellisz T, et al. Modulation of collagen synthesis by transforming growth factor-beta in keloid and hypertrophic scar fibroblasts. Ann Plast Surg. 1994;33:148–151
  240. Kuhn MA, Payne WG, Kierney PC, et al. Cytokine manipulation of explanted Dupuytren’s affected human palmar fascia. Int J Surg Invest. 2001;2:443–456
  241. Kuhn MA, Wang X, Payne WG, Ko F, Robson MC. Tamoxifen decreases fibroblast function and downregulates TGF-B2 in Dupuytren’s affected palmar fascia. Surg Res. 2002;103:146–152
  242. Kuhn MA, Singh S, Smith PD, et al. Periprosthetic breast capsules contain the fibrogenic cytokines TGF-B1 and TGF-B2 suggesting possible new treatment approaches. Ann Plast Surg. 2000;44:387–391

PII: S0011-3840(07)00109-8

doi: 10.1067/j.cpsurg.2007.07.001

Current Problems in Surgery
Volume 44, Issue 11 , Pages 691-763 , November 2007