Do postsurgical interventions optimize ultimate scar cosmesis?

Giornale Italiano di Dermatologia e Venereologia

Volumn 144, Issue 3, 2009, Pages 243-257

  Viera, M H ^a   Amini, S ^a   Konda, S ^a   Berman, B ^a  

^a UNIVERSITY OF MIAMI MILLER SCHOOL OF MEDICINE   (United States)

Author keywords

Cicatrix; Cosmetic techniques; Wound healig

Indexed keywords

ALPHA TOCOPHEROL; AMINOLEVULINIC ACID; AVOTERMIN; BEVACIZUMAB; BLEOMYCIN; CORTICOSTEROID; CRYSTAL VIOLET; DOXORUBICIN; EMLA; FLUOROURACIL; HYDROCORTISONE; IMIQUIMOD; JUVIDEX; JUVISTA; LIDOCAINE; LIQUID NITROGEN; MANNOSE 6 PHOSPHATE; NITROUS OXIDE; ONION EXTRACT; PREVASCAR; RAPAMYCIN; RECOMBINANT ALPHA2B INTERFERON; RECOMBINANT GAMMA INTERFERON; RECOMBINANT INTERLEUKIN 10; RESIQUIMOD; RETINOIC ACID; SCARGUARD; SILICONE; TACROLIMUS; TRANSFORMING GROWTH FACTOR BETA3; TRIAMCINOLONE ACETONIDE; TUMOR NECROSIS FACTOR ALPHA INHIBITOR; UNCLASSIFIED DRUG; UNINDEXED DRUG; VASCULOTROPIN INHIBITOR; VERAPAMIL;

ATOPIC DERMATITIS; CARBON DIOXIDE LASER; CHILL; CLINICAL TRIAL; COMPRESSION THERAPY; CRYOSURGERY; DERMATITIS; DRUG COST; ERBIUM YAG LASER; ESTHETICS; FATIGUE; FEVER; FLU LIKE SYNDROME; HEADACHE; HUMAN; HYPERTROPHIC SCAR; HYPOPIGMENTATION; INJECTION SITE PAIN; KELOID; LOW LEVEL LASER THERAPY; MONOTHERAPY; MYALGIA; NECROSIS; NIGHT SWEAT; NONHUMAN; PHOTODYNAMIC THERAPY; PHOTOSENSITIVITY; POSTOPERATIVE CARE; RECURRENT DISEASE; REVIEW; SCAR; SIDE EFFECT; SKIN ATROPHY; SKIN GRAFT; SKIN IRRITATION; SKIN PIGMENTATION; SURGICAL TECHNIQUE; TELANGIECTASIA; ULCER; ULTRAVIOLET A RADIATION; ULTRAVIOLET B RADIATION; WOUND HEALING;

EID: 68849108432     PISSN: 03920488     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (192)

1. Butler PD, Longaker MT, Yang GP. Current progress in keloid research and treatment. J Am Coll Surg 2008;206:731-741
2. Leventhal D, Furr M, Reiter D. Treatment of keloids and hypertrophic scars: a meta-analysis and review of the literature. Arch Facial Plast Surg 2006;8:362-368 (Pubitemid 44862494)
3. Duncan MR, Berman B. Differential regulation of glycosaminoglycan, fibronectin, and collagenase production in cultured human dermal fibroblasts by interferon-alpha, -beta, and -gamma. Arch Dermatol Res 1989;281:11-18 (Pubitemid 19064133)
4. Chodon T, Sugihara T, Igawa HH, Funayama E, Furukawa H. Keloid-derived fibroblasts are refractory to Fas-mediated apoptosis and neutralization of autocrine transforming growth factor-beta 1 can abrogate this resistance. Am J Pathol 2000;157:1661-1669 (Pubitemid 30943223)
5. Berman B, Amini S, Viera MH. Keloid and hypertrophic scar. eMedicine [Internet] Available from: http://emedicine.medscape.com/article/1057599- overview. [cited 2009, Feb 27]
6. Berman B, Viera MH, Amini S, Huo R, Jones IS. Prevention and management of hypertrophic scars and keloids after burns in children. J Craniofac Surg 2008;19:989-1006.
7. th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005:979-1013.
8. Thomas JR, Ehlert TK. Scar revision and camouflage. Otolaryngol Clin North Am 1990;23:963-973
9. Bradley DT, Park SS. Scar revision via resurfacing. Facial Plast Surg 2001;17:253-262
10. McGillis ST, Lucas AR. Scar revision. Dermatol Clin 1998;16:165-80.
11. Harmon CB. Dermabrasion. Dermatol Clin 2001;19:439-42, viii.
12. Berman B, Bieley HC. Keloids. J Am Acad Dermatol 1995;33:117-23.
13. Berman B, Bieley HC. Adjunct therapies to surgical management of keloids. Dermatol Surg 1996;22:126-130 (Pubitemid 26069616)
14. Lawrence WT. In search of the optimal treatment of keloids: report of a series and a review of the literature. Ann Plast Surg 1991;27: 164-178
15. Cosman B, Wolff M. Correlation of keloid recurrence with com-pleteness of local excision. A negative report. Plast Reconstr Surg 1972;50:163-166
16. Salasche SJ, Grabski WJ. Keloids of the earlobes: a surgical technique. J Dermatol Surg Oncol 1983;9:552-556
17. Al-Attar A, Mess S, Thomassen JM, Kauffman CL, Davison SP. Keloid pathogenesis and treatment. Plast Reconstr Surg 2006; 117:286-300.
18. Kelly AP. Medical and surgical therapies for keloids. Dermatol Ther. 2004;17:212-218
19. Tardy ME Jr, Thomas JR, Pashcow MS. The camouflage of cutaneous scars. Ear Nose Throat J 1981;60:61-70.
20. Engrav LH, Gottlieb JR, Millard SP, Walkinshaw MD, Heimbach DM, Marvin JA. A comparison of intramarginal and extramarginal excision of hypertrophic burn scars. Plast Reconstr Surg 1988;81: 40-5.
21. Yang JY. Intrascar excision for persistent perioral hypertrophic scar. Plast Reconstr Surg 1996;98:1200-1205 (Pubitemid 126754940)
22. Lee KK, Mehrany K, Swanson NA. Surgical revision. Dermatol Clin 2005;23:141-50, vii.
23. English RS, Shenefelt PD. Keloids and hypertrophic scars. Dermatol Surg 1999;25:631-638
24. Borges AF. The W-plastic versus the Z-plastic scar revision. Plast Reconstr Surg 1969;44:58-62.
25. Layton AM, Yip J. Cunliffe WJ. A comparison of intralesional triamcinolone and cryosurgery in the treatment of acne keloids. Br J Dermatol 1994;130:498-501. (Pubitemid 24204671)
26. Shepherd JP, Dawber RP. The response of keloid scars to cryosurgery. Plast Reconstr Surg 1982;70:677-682
27. Zouboulis CC, Blume U, Buttner P, Orfanos CE. Outcomes of cryosurgery in keloids and hypertrophic scars. A prospective consecutive trial of case series. Arch Dermatol 1993;129:1146-1151
28. Rusciani L, Rossi G, Bono R. Use of cryotherapy in the treatment of keloids. J Dermatol Surg Oncol 1993;19:529-534
29. Har-Shai Y, Amar M, Sabo E. Intralesional cryotherapy for enhancing the involution of hypertrophic scars and keloids. Plast Reconstr Surg 2003;111:1841-1852 (Pubitemid 36532336)
30. Nowak KC, McCormack M, Koch RJ. The effect of superpulsed carbon dioxide laser energy on keloid and normal dermal fibroblast secretion of growth factors: a serum-free study. Plast Reconstr Surg 2000;105:2039-2048 (Pubitemid 30244008)
31. Niessen FB, Spauwen PH, Schalkwijk J, Kon M. On the nature of hypertrophic scars and keloids: a review. Plast Reconstr Surg 1999;104:1435-1458 (Pubitemid 29466295)
32. Norris JE. The effect of carbon dioxide laser surgery on the recurrence of keloids. Plast Reconstr Surg 1991;87:44-49
33. Berman B, Villa A, Ramirez C. Novel opportunities in the treatment and prevention of scarring. J Cutan Med Surg 2005;8:32-36
34. Eberlein A, Schepler H, Spilker G, Altmeyer P, Hartmann B. Erbium: YAG laser treatment of post-burn scars: potentials and limitations. Burns 2005;31:15-24. (Pubitemid 40082644)
35. Cheng ET, Nowak KC, Koch RJ. Effect of blended carbon dioxide and erbium: YAG laser energy on preauricular and ear lobule keloid fibroblast secretion of growth factors: a serum-free study. Arch Facial Plast Surg 2001;3:252-257
36. Cheng ET, Pollard JD, Koch RJ. Effect of blended C02 and erbium:YAG laser irradiation on normal and keloid fibroblasts: a serum-free study. J Clin Laser Med Surg 2003;21:337-343
37. KuoYR, Wu WS, Jeng SF, Huang HC, Yang KD, Sacks JM etal. Activation of ERK and p38 kinase mediated keloid fibroblast apoptosis after flashlamp pulsed-dye laser treatment. Lasers Surg Med 2005;36:31-37
38. Kuo YR, Wu WS, Jeng SF,Wang FS, Huang HC, Lin CZ et al. Suppressed TGF-betal expression is correlated with up-regulation of matrix metalloproteinase-13 in keloid regression after flashlamp pulsed-dye laser treatment. Lasers Surg Med 2005;36:38-42.
39. Alster TS. Improvement of erythematous and hypertrophic scars by the 585-nm flashlamp-pumped pulsed dye laser. Ann Plast Surg 1994;32:186-190
40. Goldman MP, Fitzpatrick RE. Laser treatment of scars. Dermatol Surg 1995;21:685-687
41. Shaffer JJ, Taylor SC, Cook-Bolden F. Keloidal scars: a review with a critical look at therapeutic options. J Am Acad Dermatol 2002;46(2 Suppl):S63-97. (Pubitemid 41127933)
42. Alster TS, Williams CM. Treatment of keloid sternotomy scars with 585 nm flashlamp-pumped pulsed-dye laser. Lancet 1995;345: 1198-1200
43. Manuskiatti W, Wanitphakdeedecha R, Fitzpatrick RE. Effect of pulse width of a 595-nm flashlamp-pumped pulsed dye laser on the treatment response of keloidal and hypertrophic sternotomy scars. Dermatol Surg 2007;33:152-161 (Pubitemid 46208105)
44. Kono T, Erçöçen AR, Nakazawa H, Nozaki M. Treatment of hypertrophic scars using a long-pulsed dye laser with cryogen-spray cooling. Ann Plast Surg 2005;54:487-493 (Pubitemid 40571555)
45. Conologue TD, Norwood C. Treatment of surgical scars with the cryogen-cooled 595 nm pulsed dye laser starting on the day of suture removal. Dermatol Surg 2006;32:13-20.
46. Bellew SG, Weiss MA, Weiss RA. Comparison of intense pulsed light to 595-nm long-pulsed pulsed dye laser for treatment of hypertrophic surgical scars: a pilot study. J Drugs Dermatol 2005;4: 448-452
47. Alam M, Pon K, Van Laborde S, Kaminer MS, Arndt KA, Dover JS. Clinical effect of a single pulsed dye laser treatment of fresh surgical scars: randomized controlled trial. Dermatol Surg 2006;32:21-5.
48. Abergel RP, Meeker CA, Lam TS, Dwyer RM, Lesavoy MA, Uitto J. Control of connective tissue metabolism by lasers: recent developments and future prospects. J Am Acad Dermatol. 1984 Dec;11(6):1142-1150
49. Sherman R, Rosenfeld H. Experience with the Nd:YAG laser in the treatment of keloid scars. Ann Plast Surg 1988;21:231-235 (Pubitemid 18222698)
50. Kumar K, Kapoor BS, Rai P, Shukla HS. In-situ irradiation of keloid scars with Nd:YAG laser. J Wound Care 2000;9:213-215
51. 51- Bowes LE, Nouri K, Berman B, Jimenez G, Pardo R, Rodriguez L et al. Treatment of pigmented hypertrophic scars with the 585 nm pulsed dye laser and the 532 nm frequency-doubled Nd: YAG laser in the Q-switched and variable pulse modes: a comparative study. Dermatol Surg 2002;28:714-719 (Pubitemid 34913281)
52. Tredget EE, Nedelec B, Scott PG, Ghahary A. Hypertrophic scars, keloids, and contractures, the cellular and molecular basis for therapy. Surg Clin North Am 1997;77:701-730 (Pubitemid 27256042)
53. Apfelberg DB, Maser MR, Lash H. The use of epidermis over a keloid as an autograft after resection of the keloid. J Dermatol Surg 1976;2:409-411
54. Burke JF, Yannas IV, Quinby WC Jr, Bondoc CC, Jung WK. Successful use of a physiologically acceptable artificial skin in the treatment of extensive burn injury. Ann Surg 1981;194:413-428
55. Ismail A, Jarvi K, Canal AC. Successful resurfacing of scars from previous deliberate self-harm using Integra dermal matrix substitute. J Plast Reconstr Aesthet Surg 2008;61:839-841 (Pubitemid 351970468)
56. Groos N, Guillot M, Zilliox R, Braye FM. Use of an artificial dermis (Integra) for the reconstruction of extensive burn scars in children. About 22 grafts. Eur J Pediatr Surg 2005;15:187-192 (Pubitemid 40992007)
57. Woolery-Lloyd H et al. A Prospective, randomized, controlled pilot study of apligraf for the treatment and prevention of recurrence of excised keloids. ClinicalTrials.gov Identifier: NCT00587587 [Internet] Available at: http://www.clinicaltrials.gov/ct2/show/ NCTO0587587?term=NCTOO587587&rank=1 [cited 2009, Feb 27]
58. Sawada Y, Sone K. Hydration and occlusion treatment for hypertrophic scars and keloids. Br J Plast Surg 1992;45:599-603.
59. Bieley HC, Berman B. Effects of a water-impermeable, non-silicone-based occlusive dressing on keloids. J Am Acad Dermatol 1996;35:113-114 (Pubitemid 26231338)
60. Lindberg M, Forslind B. The effects of occlusion of the skin on the langerhans' cell and the epidermal mononuclear cells. Acta Derm Venereol 1981;61:201-205 (Pubitemid 11107475)
61. Duncan MR, Berman B. Stimulation of collagen and glycosaminoglycan production in cultured human adult dermal fibroblasts by recombinant human interleukin 6. J Invest Dermatol 1991;97: 686-692
62. George PA. Compression treatment for hypertrophic scars. Physiotherapy. 1975;61:215-216
63. Robertson JC, Hodgson B, Druett JE, Druett J. Pressure therapy for hypertrophic scarring: Preliminary communication. J R Soc Med 1980;73:348-354 (Pubitemid 10031252)
64. Reid WH, Evans JH, Naismith RS, Tully AE, Sherwin S. Hypertrophic scarring and pressure therapy. Burns Incl Therm Inj 1987;(13 Suppl):S29-32.
65. Linares HA, Larson DL, Willis-Galstaun BA. Historical notes on the use of pressure in the treatment of hypertrophic scars or keloids. Burns 1993;19:17-21. (Pubitemid 23059384)
66. Macintyre L, Baird M. Pressure garments for use in the treatment of hypertrophic scars-a review of the problems associated with their use. Burns 2006;32:10-15 (Pubitemid 43082266)
67. Diegelmann RF, Bryant CP, Cohen IK. Tissue alpha-globulins in keloid formation. Plast Reconstr Surg 1977;59:418-423
68. Haq MA, Haq A. Pressure therapy in treatment of hypertrophic scar, burn contracture and keloid: The kenyan experience. East Afr Med J. 1990;67:785-793.
69. Gold MH. A controlled clinical trial of topical silicone gel sheeting in the treatment of hypertrophic scars and keloids. J Am Acad Dermatol 1994;30:506-507
70. Musgrave MA, Umraw N, Fish JS, Gomez M, Cartotto RC. The effect of silicone gel sheets on perfusion of hypertrophic burn scars. J Burn Care Rehabil 2002;23:208-214 (Pubitemid 34547761)
71. Branagan M, Chenery DH, Nicholson S. Use of infrared attenuated total reflectance spectroscopy for the in vivo measurement of hydration level and silicone distribution in the stratum corneum following skin coverage by polymeric dressings. Skin Pharmacol Appl Skin Physiol 2000;13:157-164 (Pubitemid 30339294)
72. Chang CC, KuoYF, Chiu HC, Lee JL, Wong TW, Jee SH. Hydration, not silicone, modulates the effects of keratinocytes on fibroblasts. J Surg Res 1995;59:705-711.
73. Suetak T, Sasai S, Zhen YX, Tagami H. Effects of silicone gel sheet on the stratum corneum hydration. Br J Plast Surg 2000;53:503-507 (Pubitemid 30649045)
74. Gilman TH. Silicone sheet for treatment and prevention of hypertrophic scar: A new proposal for the mechanism of efficacy. Wound Repair Regen 2003;11:235-236
75. Quinn KJ, Evans JH, Courtney JM, Gaylor JD, Reid WH. Non-pressure treatment of hypertrophic scars. Burns Incl Therm Inj 1985; 12:102-108
76. Hirshowitz B, Lindenbaum E, Har-Shai Y, Feitelberg L, Tendier M, Katz D. Static-electric field induction by a silicone cushion for the treatment of hypertrophic and keloid scars. Plast Reconstr Surg 1998;101:1173-1183 (Pubitemid 28152689)
77. Kuhn MA, Moffit MR, Smith PD, Lyle WG, Ko F, Meltzer DD et al. Silicone sheeting decreases fibroblast activity and downregulates TGFbeta2 in hypertrophic scar model. Int J Surg Investig 2001;2: 467-474
78. Hanasono MM, Lum J, Carroll LA, Mikulec AA, Koch RJ. The effect of silicone gel on basic fibroblast growth factor levels in fibroblast cell culture. Arch Facial Plast Surg 2004;6:88-93.
79. Sauder DN, Smith MH, Senta-McMillian T, Soria I, Meng TC. Randomized, single-blind, placebo-controlled study of topical application of the immune response modulator resiquimod in healthy adults. Antimicrob Agents Chemother 2003;47:3846-3852 (Pubitemid 37484999)
80. Jimenez SA, Freundlich B, Rosenbloom J. Selective inhibition of human diploid fibroblast collagen synthesis by interferons. J Clin Invest 1984;74:1112-1116 (Pubitemid 14031053)
81. Tomai MA, Gibson SJ, Imbertson LM, et al. Immunomodulating and antiviral activities of the imidazoquinoline S-28463. Antiviral Res 1995;28:253-264
82. Berman B, Kaufman J. Pilot study of the effect of postoperative imiquimod 5% cream on the recurrence rate of excised keloids. J Am Acad Dermatol 2002;47:S209-11.
83. Martin-Garcia RF, Busquets AC. Postsurgical use of imiquimod 5% cream in the prevention of earlobe keloid recurrences: Results of an open-label, pilot study. Dermatol Surg 2005;31:1394-1398
84. Stashower ME. Successful treatment of earlobe keloids with imiquimod after tangential shave excision. Dermatol Surg 2006;32:380-386
85. Jacob SE, Berman B, Nassiri M, Vincek V. Topical application of imiquimod 5% cream to keloids alters expression genes associated with apoptosis. Br J Dermatol 2003;149(Suppl 66):62-65 (Pubitemid 38064523)
86. Meyer T, Nindl I, Schmook T, Ulrich C, Sterry W, Stockfleth E. Induction of apoptosis by toll-like receptor-7 agonist in tissue cultures. Br J Dermatol 2003;149(Suppl 66):9-14. (Pubitemid 38064506)
87. Daly TJ, Weston WL. Retinoid effects on fibroblast proliferation and collagen synthesis in vitro and on fibrotic disease in vivo. J Am Acad Dermatol 1986;15:900-902
88. Abergel RP, Meeker CA, Oikarinen H, Oikarinen AI, Uitto J. Retinoid modulation of connective tissue metabolism in keloid fibroblast cultures. Arch Dermatol 1985;121:632-635 (Pubitemid 15062716)
89. Oikarinen H, Oikarinen AI, Tan EM, Abergel RP, Meeker CA, Chu ML et al. Modulation of procollagen gene expression by retinoids, inhibition of collagen production by retinoic acid accompanied by reduced type I procollagen messenger ribonucleic acid levels in human skin fibroblast cultures. J Clin Invest 1985;75:1545-1553 (Pubitemid 15041447)
90. Cruz NI, Korchin L. Inhibition of human keloid fibroblast growth by isotretinoin and triamcinolone acetonide in vitro. Ann Plast Surg 1994;33:401-405 (Pubitemid 24320710)
91. Janssen de Limpens AM. The local treatment of hypertrophic scars and keloids with topical retinoic acid. Br J Dermatol 1980;103: 319-323 (Pubitemid 10056505)
92. Panabiere-Castaings MH. Retinoic acid in the treatment of keloids. J Dermatol Surg Oncol 1988;14:1275-1276
93. Hansen DA. Treatment of hypertrophic scars with retinoic acid. S Afr Med J 1979;56:1114. (Pubitemid 10142117)
94. Ong CT, Khoo YT, Mukhopadhyay A, Do DV, Lim IJ, Aalami O et al. mTOR as a potential therapeutic target for treatment of keloids and excessive scars. Exp Dermatol 2007;16:394-404. (Pubitemid 46585367)
95. Kim A, DiCarlo J, Cohen C, McCall C, Johnson D, McAlpine B et al. Are keloids really "gli-loids"?: High-level expression of gli-1 oncogene in keloids. J Am Acad Dermatol 2001;45:707-711
96. Ong CT, Khoo YT, Tan EK, Mukhopadhyay A, Do DV, Han HC et al. Epithelial-mesenchymal interactions in keloid pathogenesis modulate vascular endothelial growth factor expression and secretion. J Pathol 2007;211:95-108. (Pubitemid 46092034)
97. Augusti KT. Therapeutic values of onion (allium cepa L.) and garlic (allium sativum L.). Indian J Exp Biol 1996;34:634-640
98. Saulis AS, Mogford JH, Mustoe TA. Effect of mederma on hypertrophic scarring in the rabbit ear model. Plast Reconstr Surg 2002;110:177-83; discussion 184-186 (Pubitemid 34686267)
99. Jackson BA, Shelton AJ. Pilot study evaluating topical onion extract as treatment for postsurgical scars. Dermatol Surg 1999;25:267-269
100. Clarke L, Baker B, Trahan C, Myers L. Metzinger SE. A prospective double-blinded study of mederma skin care vs placebo for post-traumatic scar reduction. Cosmetic Dermatol 1999;12:19-26.
101. Chung VQ, Kelley L, Marra D, Jiang SB. Onion extract gel versus petrolatum emollient on new surgical scars: Prospective double-blinded study. Dermatol Surg 2006;32:193-197
102. Draelos ZD. The ability of onion extract gel to improve the cosmetic appearance of postsurgical scars. J Cosmet Dermatol 2008;7: 101-104
103. Hosnuter M, Payasli C, Isikdemir A. Tekerekoglu B. The effects of onion extract on hypertrophic and keloid scars. J Wound Care 2007;16:251-254
104. Drore Eisen: A Pilot Study to Evaluate the Efficacy of Scarguard in the Prevention of Scars. The Internet Journal of Dermatology. 2004. Volume 5 Number 2.
105. Berman B, Patel JK, Perez OA, Viera MH, Viera MH, Amini S, Block S et al. A prospective, randomized, investigator-blinded, place-bo-controlled, comparative study evaluating the tolerability and efficacy of two topical medications vs. placebo for the treatment of keloids and hypertrophic scars. Poster #500 presented at AAD 66th Annual Meeting 2008, San Antonio, TX. J Am Acad Dermatol 2008;58(2 Suppl 2):AB45.
106. Ehrlich HP, Tarver H, Hunt TK. Inhibitory effects of vitamin E on collagen synthesis and wound repair. Ann Surg 1972;175:235-240
107. MacKay D, Miller AL. Nutritional support for wound healing. Altern Med Rev 2003;8:359-377
108. Musalmah M, Fairuz AH, Gapor MT, Ngah WZ. Effect of vitamin E on plasma malondialdehyde, antioxidant enzyme levels and the rates of wound closures during wound healing in normal and diabetic rats. Asia Pac J Clin Nutr 2002; 11 (Suppl 7):S448-51.
109. Baumann LS, Spencer J. The effects of topical vitamin E on the cosmetic appearance of scars. Dermatol Surg 1999;25:311-315 (Pubitemid 29191320)
110. Palmieri B, Gozzi G, Palmieri G. Vitamin E added silicone gel sheets for treatment of hypertrophic scars and keloids. Int J Dermatol 1995;34:506-509
111. Sherris DA, Larrabee WF Jr, Murakami CS. Management of scar contractures, hypertrophic scars, and keloids. Otolaryngol Clin North Am 1995;28:1057-1068
112. Boyadjiev C, Popchristova E, Mazgalova J. Histomorphologic changes in keloids treated with Kenacort. J Trauma 1995;38(2): 299-302.
113. Alaish SM,Yager DR, Diegelmann RF, Cohen IK. Hyaluronic acid metabolism in keloid fibroblasts. J Pediatr Surg 1995;30:949-952
114. Gadson PF, Russell JD, Russell SB. Glucocorticoid receptors in human fibroblasts derived from normal dermis and keloid tissue. J Biol Chem 1984;259:11236-11241 (Pubitemid 14007773)
115. Krusche T, Worret WI. Mechanical properties of keloids in vivo during treatment with intralesional triamcinolone acetonide. Arch Dermatol Res 1995;287:289-293
116. McCoy BJ, Diegelmann RF, Cohen IK. In vitro inhibition of cell growth, collagen synthesis, and prolyl hydroxylase activity by triamcinolone acetonide. Proc Soc Exp Biol Med 1980; 163:216-22.
117. Kauh YC, Rouda S, Mondragon G, Tokarek R, diLeonardo M, Tuan RS et al. Major suppression of pro-alpha 1(1) type I collagen gene expression in the dermis after keloid excision and immediate intrawound injection of triamcinolone acetonide. J Am Acad Dermatol 1997;37:586-589
118. Darzi MA, Chowdri NA, Kaul SK, Khan M. Evaluation of various methods of treating keloids and hypertrophic scars: a 10-year follow up study. Br J Plast Surg 1992;45:374-379
119. Tang YW. Intra- and postoperative steroid injections for keloids and hypertrophic scars. Br J Plast Surg 1992;45:371-373
120. Kiil J. Keloids treated with topical injections of triamcinolone acetonide (kenalog). Immediate and long-term results. Scand J Plast Reconstr Surg 1977;11:169-172 (Pubitemid 8289059)
121. Berman B, Flores F. Recurrence rates of excised keloids treated with postoperative triamcinolone acetonide injections or interferon alfa2b injections. J Am Acad Dermatol 1997,37(5 Pt 1):755-757 (Pubitemid 27500320)
122. Jenkins M, Alexander JW, MacMillan BG, Waymack JP, Kopcha R. Failure of topical steroids and vitamin E to reduce postoperative scar formation following reconstructive surgery. J Burn Care Rehabil 1986;7:309-312 (Pubitemid 16010121)
123. Ratzer MA. A clinical trial of flurandrenolone tape. Br J Clin Pract 1970:24:185-189
124. Rauscher GE, Kolmer WL. Treatment of recurrent earlobe keloids. Cutis 1986:37:67-68
125. Koc E, Arca E, Surucu B, Kurumlu Z. An open, randomized, controlled, comparative study of the combined effect of intralesional triamcinolone acetonide and onion extract gel and intralesional triamcinolone acetonide alone in the treatment of hypertrophic scars and keloids. Dermatol Surg 2008;34:1507-1514
126. Apikian M, Goodman G. Intralesional 5-fluorouracil in the treatment of keloid scars. Australas J Dermatol 2004;45:140-143 (Pubitemid 38607932)
127. Fitzpatrick RE. Treatment of inflamed hypertrophic scars using intralesional 5-FU. Dermatol Surg 1999;25:224-232
128. Uppal RS, Khan U, Kakar S, Talas G, Chapman P, McGrouther AD. The effects of a single dose of 5-fluorouracil on keloid scars: a clinical trial of timed wound irrigation after extralesional excision. Plast Reconstr Surg 2001;108:1218-1224 (Pubitemid 32953059)
129. Manuskiatti W, Fitzpatrick RE. Treatment response of keloidal and hypertrophic sternotomy scars: comparison among intralesional corticosteroid, 5-fluorouracil, and 585-nm flashlamp-pumped pulseddye laser treatments. Arch Dermatol 2002;138:1149-1155 (Pubitemid 35025686)
130. Kontochristopoulos G, Stefanaki C, Panagiotopoulos A, Stefanaki K, Argyrakos T, Petridis A et al. Intralesional 5-fluorouracil in the treatment of keloids: an open clinical and histopathologic study. J Am Acad Dermatol 2005;52(3 Pt 1):474-479
131. Nanda S, Reddy BS. Intralesional 5-fluorouracil as a treatment modality of keloids. Dermatol Surg 2004;30:54-56 (Pubitemid 38174030)
132. Haurani MJ, Foreman K, Yang JJ, Siddiqui A. 5-Fluorouracil treatment of problematic scars. Plast Reconstr Surg 2009;123:139-48; discussion 149-151
133. Meier K, Nanney LB. Emerging new drugs for scar reduction. Expert Opin Emerg Drugs 2006; 11:39-47.
134. Larrabee WF Jr, East CA, Jaffe HS, Stephenson C, Peterson KE. Intralesional interferon gamma treatment for keloids and hypertrophic scars. Arch Otolaryngol Head Neck Surg 1990;116: 1159-1162 (Pubitemid 20328956)
135. Pittet B, Rubbia-Brandt L, Desmouliere A, Sappino AP, Roggero P, Guerret S et al. Effect of gamma-interferon on the clinical and biologic evolution of hypertrophic scars and Dupuytren's disease: an open pilot study. Plast Reconstr Surg 1994;93:1224-1235 (Pubitemid 24273751)
136. Yokozeki M, BabaY, Shimokawa H, Moriyama K, KurodaT. Interferon-gamma inhibits the myofibroblastic phenotype of rat palatal fibroblasts induced by transforming growth factor-betal in vitro. FEBS Lett 1999;442:61-64 (Pubitemid 29065379)
137. Rumalla VK, Borah GL. Cytokines, growth factors, and plastic surgery. Plast Reconstr Surg 2001;108:719-733
138. Tredget EE, Wang R, Shen Q, Scott PG, Ghahary A. Transforming growth factor-beta mRNA and protein in hypertrophic scar tissues and fibroblasts: antagonism by IFN-alpha and IFN-gamma in vitro and in vivo. J Interferon Cytokine Res 2000;20:143-151 (Pubitemid 30123742)
139. Wong TW, Chiu HC, Yip KM. Intralesional interferon alpha-2b has no effect in the treatment of keloids. Br J Dermatol 1994;130: 683-685
140. al-Khawajah MM. Failure of interferon-alpha 2b in the treatment of mature keloids. Int J Dermatol 1996;35:515-517
141. Espinassouze F, Heid E, Grosshans E. Treatment of keloid by intralesional injections of interferon alfa-2B. Ann Dermatol Venereol 1993;120:629-630
142. Conejo-Mir JS, Corbi R, Linares M. Carbon dioxide laser ablation associated with interferon alfa-2b injections reduces the recurrence of keloids. J Am Acad Dermatol 1998;39:1039-1040 (Pubitemid 28547751)
143. Granstein RD, Rook A, Flotte TJ, Haas A, Gallo RL, Jaffe HS et al. A controlled trial of intralesional recombinant interferon-gamma in the treatment of keloidal scarring. Clinical and histologic findings. Arch Dermatol 1990;126:1295-1302
144. Broker BJ, Rosen D, Amsberry J, Schmidt R, Sailor L, Pribitkin EA et al. Keloid excision and recurrence prophylaxis via intradermal interferon-gamma injections: a pilot study. Laryngoscope 1996;106(12 Pt 1): 1497-1501 (Pubitemid 26415257)
145. Brissett AE, Sherris DA. Scar contractures, hypertrophic scars, and keloids. Facial Plast Surg 2001;17:263-272
146. Poochareon VN, Berman B. New therapies for the management of keloids. J Craniofac Surg 2003;14:654-657
147. Lee JH, Kim SE, Lee AY. Effects of interferon-alpha2b on keloid treatment with triamcinolone acetonide intralesional injection. Int J Dermatol 2008;47:183-186
148. D'Andrea F, Brongo S, Ferraro G, Baroni A. Prevention and treatment of keloids with intralesional verapamil. Dermatology 2002;204: 60-62 (Pubitemid 34136816)
149. Skaria AM. Prevention and treatment of keloids with intralesional verapamil. Dermatology 2004;209:71. (Pubitemid 39179113)
150. Copcu E, Sivrioglu N, Oztan Y. Combination of surgery and intralesional verapamil injection in the treatment of the keloid. J Burn Care Rehabil 2004;25:1-7. (Pubitemid 38120353)
151. Lawrence WT. Treatment of earlobe keloids with surgery plus adjuvant intralesional verapamil and pressure earrings. Ann Plast Surg 1996;37:167-169
152. Wu WS, Wang FS, Yang KD, Huang CC, Kuo YR. Dexamethasone induction of keloid regression through effective suppression of VEGF expression and keloid fibroblast proliferation. J Invest Dermatol 2006;126:1264-1271
153. Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature 2000;407:249-257
154. Gira AK, Brown LF, Washington CV, Cohen C Arbiser JL. Keloids demonstrate high-level epidermal expression of vascular endothelial growth factor. J Am Acad Dermatol 2004;50:850-853 (Pubitemid 38685763)
155. Steinbrech DS, Mehrara BJ, Chau D, Rowe NM, Chin G, Lee T et al. Hypoxia upregulates VEGF production in keloid fibroblasts. Ann Plast Surg 1999;42:514-519 (Pubitemid 29218317)
156. Juvista. Products in development [Internet]. Available from www.renovo.com [cuted 2009, Feb 27].
157. Bush J. (Principal Investigator). A double-blind, placebo-controlled, randomised dose ranging trial to investigate the efficacy of two different dosing regimens of Avotermin (Juvista) in the improvement of scar appearance when applied to approximated wound margins in healthy volunteers [Internet] ClinicalTrials.gov Identifier NCT00629811. [cited 2009, Feb 27]. Available from:http://www.clinicaltrials.gov/ct2/show/ NCT00629811?term= NCT00629811&rank=1
158. Young VV. (Principal Investigator). A single-centre, double blind, randomised, tolerance study to investigate the safety of Juvista 500ng/100μL/Linear cm when administered following excision of ear lobe keloids [Internet]. ClinicalTrials.gov Identifier: NCT00710333. [cited 2009, Feb 27]. Available from http://www.clinicaltrials.gov/ ct2/show/NCT00710333?term= NCT00710333&rank=1
159. Young L. (Principal Investigator). A single-centre, double blind, randomised, rising dose tolerance study to investigate the safety of juvista when administered following excision of ear lobe keloids [Internet]. ClinicalTrials.gov Identifier: NCT00469235. [cited 2009, Feb 27). Available from http://www.clinicaltrials.gov/ct2/show/ NCT00469235?term=NCT00469235&rank=1
160. McGrouther DA. (Principal Investigator). A double blind, within patient, placebo controlled trial to confirm the efficacy of Juvista (Avotermin) in conjunction with scar revision surgery for the improvement of disfiguring scars [Internet]. ClinicalTrials.gov Identifier: NCT00742443. [cited 2009, Feb 27]. Available from:http://www.clinicaltrials.gov/ct2/show/ NCT00742443?term= NCT00742443&rank=1
161. Bush J. (Principal Investigator). A double blind, placebo controlled randomised trial to investigate the scar improvement efficacy of a single intradermal application of RN1001 (Avotermin) in subjects undergoing excision of benign head and neck naevi [Internet]. Clinical-Trials.gov Identifier: NCT00656227 [cited 2009, Feb 27].Available from:http://www.clinicaltrials.gov/ ct2/show/NCT006562277term= NCT00656227&rank=1
162. McGrouther DA. (Principal Investigator). A double blind, placebo controlled, randomised trial to investigate the efficacy of Juvista (Avotermin) in the prevention or improvement of scar appearance following scar revision surgery [Intermet]. ClinicalTrials.gov Identifier: NCT00432211. [cited 2009, Feb 27]. Available from: http://www.clinicaltrials.gov/ct2/show/NCT00432211? term=NCT00432211&rank=1
163. McCollum P. (Principal Investigator). A dose response trial to investigate the efficacy of Juvista (Avotermin) in the improvement of scar appearance when applied to approximated wound margins following bilateral varicose vein removal [Internet]. ClinicalTrials.gov Identifier: NCT00430326. [cited 2009, Feb 27] Available from: http://www.clinicaltrials.gov/ct2/show/ NCT00430326?term=NCT004 30326&rank=1
164. Gilbert P. (Principal Investigator). A double blind, placebo controlled, randomised trial to investigate the efficacy of Juvista (Avotermin) in the improvement of scar appearance in patients undergoing bilateral reduction mammaplasty [Internet]. ClinicalTrials.gov Identifier: NCT00432328. [cited 2009, Feb 27]. Available from:http://www.clin- icaltrials.gov/ct2/show/NCT00432328? term=NCT00432328&rank=1
165. Xue H, McCauley RL, Zhang W. Elevated interleukin-6 expression in keloid fibroblasts. J Surg Res 2000;89:74-77 (Pubitemid 30127445)
166. Feghali CA, Bost KL, Boulware DW, Levy LS. Control of IL-6 expression and response in fibroblasts from patients with systemic sclerosis. Autoimmunity 1994;17:309-318 (Pubitemid 24238337)
167. Prevascar. Products in development [Internet]. Available at: www.renovo.com. [cited 2009, Jan 29]
168. Sato Y et al. Regulatory role of endogenous interleukin-10 in cutaneous inflammatory response of murine wound healing. Biochem Biophys Res Commun 1999;265:194-199
169. Peranteau WH, Zhang L, Muvarak N, Badillo AT, Radu A, Zoltick PW, Liechty KW. IL-10 overexpression decreases inflammatory mediators and promotes regenerative healing in an adult model of scar formation. J. Invest Dermatol 2008;128:1852-1860 (Pubitemid 351847365)
170. Brown PD, Wakefield LM, Levinson AD, Sporn MB. Physicochemical activation of recombinant latent transforming growth factor-beta's 1,2, and 3. Growth Factors 1990;3:35-43.
171. Harpel JG, Metz CN, Kojima S, Rifkin DB. Control of transforming growth factor-beta activity: latency vs. activation. Prog Growth Factor Res 1992;4:321-335
172. Juvidex. Products in development [Internet] Available from www.renovo.com [cited 2009, Feb 27].
173. Bush J et al. A double blind, placebo controlled trial to investigate the efficacy and safety of two concentrations of Juvidex (Mannose-6-Phosphate) in accelerating the healing of split thickness skin graft donor sites using different dosing regimes [Internet] ClinicalTrials.gov Identifier: NCT00664352. Available from http://www.clinicaltrials.gov/ct2/show/NCT00664352?term= NCT00664352&rank=1 [cited 2009, Feb 27].
174. Borok TL, Bray M, Sinclair I, Plafker J, LaBirth L, Rollins C. Role of ionizing irradiation for 393 keloids. Int J Radiat Oncol Biol Phys 1998:;15:836-870
175. Norris JE. Superficial x-ray therapy in keloid management: a retrospective study of 24 cases and literature review. Plast Reconstr Surg 1995;95:1051-1055
176. Escarmant P, Zimmerman S, Amar A, Ratoanina JL, Moris A, Azaloux H et al. The treatment of 783 keloid scars by iridium 192 interstitial irradiation after surgical excision. Int J Radiat Oncol Biol Phys 1993;26:245-251 (Pubitemid 23156971)
177. Levitt WM, Gillies H. Radiotherapy in the prophylaxis and treatment of keloids. Lancet 1942;1:440-443
178. Cornbleet T. Treatment of keloids with hyaluronidase. JAMA 1954;134:1161-1163
179. Guix B, Henríquez I, Andrés A, Finestres F, Tello JI, Martínez A. Treatment of keloids by high-dose-rate brachy therapy: a seven-year study. Int J Radiat Oncol Biol Phys 2001;50:167-172
180. Mang R, Krutmann J. UVA-1 Phototherapy. Photodermatol Photoimmunol Photomed 2005;21:103-108
181. Asawanonda P, Khoo LS, Fitzpatrick TB, Taylor CR. UV-A1 for keloid. Arch Dermatol 1999;135:348-349
182. Chvapil M, Peacock EE Jr, Carlson EC, Blau S, Steinbronn K, Morton D. Colchicine and wound healing. J Surg Res 1980;28:49-56.
183. No authors listed. Effects of UVA1 radiation on the formation of hypertrophic scar in rabbits. Chinese J Dermatol 2008;41:367-370 Available at: http://www.pifukezazhi.com/cmazp/EN/volumn-l 143-abs.shtml. Accessed on May 21,2009.
184. KangS. (Principal Investigator). The effectiveness of UVA1 irradiation in the treatment of skin conditions with altered dermal matrix: a controlled, cross-over study [Internet] ainicalTrials.gov Identifier:NCT00476801. [cited 2009, Feb 27]. Available from:http://www.clinicaltrials.gov/ct2 /show/NCT00476801?term=NCT00476801&rank=1
185. Kang S. (Principal Investigator).The effectiveness of uval irradiation in the treatment of skin conditions with altered dermal matrix: an open pilot study [Internet] ClinicalTrials.gov Identifier NCT00476697. [cited 2009, Feb 27]. Available from: http://www.clinicaltrials.gov /ct2/show/NCT00476697?term= NCT00476697&rank= 1
186. Voorhees JJ. The effectiveness of UVB irradiation in the treatment of skin conditions with altered dermal matrix: an open pilot study [Internet] ClinicalTrials.gov Identifier:NCT00129428. [cited 2009, Feb 22]. Available from:http://www.clinicaltrials.gov/ct2/show/ NCT00129428?term= NCT00129428&rank=1
187. Choi CP, Kim YI, Lee JW, Lee MH. The effect of narrowband ultraviolet B on the expression of matrix metalloproteinase-1, transforming growth factor-betal and type I collagen in human skin fibroblasts. Clin Exp Dermatol 2007;32:180-185
188. Gambichler T, Breuckmann F, Boms S, Altmeyer P, Kreuter A. Narrowband UVB phototherapy in skin conditions beyond psoriasis J Am Acad Dermatol 2005;52:660-670
189. Oiso N, Kawara S, Kawada A. The effectiveness of narrowband ultraviolet B on hypertrophic scar in a patient having an isomorphic phenomenon and vitiligo. J Eur Acad Dermatol Venereol 2008; 22:1004.
190. Cartier H. Use of intense pulsed light in the treatment of scars. J Cosmet Dermatol 2005;4:34-40.
191. Erol OO, Gurlek A, Agaoglu G, Topcuoglu E, Oz H. Treatment of hypertrophic scars and keloids using intense pulsed light (IPL). Aesthetic Plast Surg 2008;32:902-909
192. Chiu LL, Sun CH, Yeh AT, Torkian B, Karamzadeh A, Tromberg B et al. Photodynamic therapy on keloid fibroblasts in tissue-engineered keratinocyte-fibroblast co-culture. Lasers Surg Med 2005;37:231-244 (Pubitemid 41464825)