Abstract: Objective: Keloids are exuberant cutaneous scars that form due to abnormal growth of fibrous tissue following an injury. The primary aim of this study was to assess the efficacy and mechanism of hyperbaric oxygen therapy (HBOT) to reduce the keloid recurrence rate after surgical excision and radiotherapy. Methods: (1) A total of 240 patients were randomly divided into two groups. Patients in the HBOT group (O group) received HBOT after surgical excision and radiotherapy. Patients in the other group were treated with only surgical excision and radiotherapy (K group). (2) Scar tissue from recurrent patients was collected after a second operation. Hematoxylin and eosin (H&E) staining was used to observe keloid morphology. Certain inflammatory factors (interleukin-6 (IL-6), hypoxia-inducible factor-1α (HIF-1α), tumor necrosis factor-α (TNF-α), nuclear factor κB (NF-κB), and vascular endothelial growth factor (VEGF)) were measured using immunohistochemical staining. Results: (1) The recurrence rate of the O group (5.97%) was significantly lower than that of the K group (14.15%), P<0.05. Moreover, patients in the O group reported greater satisfaction than those in the K group (P<0.05). (2) Compared with the recurrent scar tissue of the K group, the expression levels of the inflammatory factors were lower in the recurrent scar tissue of the O group. Conclusions: Adjunctive HBOT effectively reduces the keloid recurrence rate after surgical excision and radiotherapy by improving the oxygen level of the tissue and alleviating the inflammatory process.

高压氧治疗降低瘢痕疙瘩切除联合放疗后的复发率

[1]Alexandrescu D, Fabi S, Yeh LC, et al., 2016. Comparative results in treatment of keloids with intralesional 5-FU/ kenalog, 5-FU/verapamil, enalapril alone, verapamil alone, and laser: a case report and review of the literature. J Drugs Dermatol, 15(11):1442-1447.

[2]Arno AI, Amini-Nik S, Blit PH, et al., 2014. Effect of human Wharton’s jelly mesenchymal stem cell paracrine signaling on keloid fibroblasts. Stem Cells Transl Med, 3(3):299-307.

[3]Balestri R, Misciali C, Zampatti C, et al., 2013. Keloidal basal cell carcinoma: should it be considered a distinct entity? J Dtsch Dermatol Ges, 11(12):1196-1198.

[4]Berman B, Perez OA, Konda S, et al., 2007. A review of the biologic effects, clinical efficacy, and safety of silicone elastomer sheeting for hypertrophic and keloid scar treatment and management. Dermatol Surg, 33(11):1291-1303.

[5]Bloemen MCT, van der Veer WM, Ulrich MMW, et al., 2009. Prevention and curative management of hypertrophic scar formation. Burns, 35(4):463-475.

[6]Chen W, Fu XB, Sun XQ, et al., 2003. Analysis of differentially expressed genes in keloids and normal skin with cDNA microarray. J Surg Res, 113(2):208-216.

[7]Darzi MA, Chowdri NA, Kaul SK, et al., 1992. Evaluation of various methods of treating keloids and hypertrophic scars: a 10-year follow-up study. Br J Plast Surg, 45(5):374-379.

[8]Datubo-Brown DD, 1990. Keloids: a review of the literature. Br J Plast Surg, 43(1):70-77.

[9]de Felice B, Guida M, Boccia L, et al., 2015. Ingenol mebutate treatment in keloids. BMC Res Notes, 8:466.

[10]Demirtaş A, Azboy I, Bulut M, et al., 2014. The effect of hyperbaric oxygen therapy on fracture healing in nicotinized rats. Ulus Travma Acil Cerrahi Derg, 20(3):161-166.

[11]Dhani N, Fyles A, Hedley D, et al., 2015. The clinical significance of hypoxia in human cancers. Semin Nucl Med, 45(2):110-121.

[12]Dong XL, Mao SL, Wen H, 2013. Upregulation of proinflammatory genes in skin lesions may be the cause of keloid formation (Review). Biomed Rep, 1(6):833-836.

[13]Doornbos JF, Stoffel TJ, Hass AC, et al., 1990. The role of kilovoltage irradiation in the treatment of keloids. Int J Radiat Oncol Biol Phys, 18(4):833-839.

[14]Emad M, Omidvari S, Dastgheib L, et al., 2010. Surgical excision and immediate postoperative radiotherapy versus cryotherapy and intralesional steroids in the management of keloids: a prospective clinical trial. Med Princ Pract, 19(5):402-405.

[15]Froelich K, Staudenmaier R, Kleinsasser N, et al., 2007. Therapy of auricular keloids: review of different treatment modalities and proposal for a therapeutic algorithm. Eur Arch Otorhinolaryngol, 264(12):1497-1508.

[16]Goldenberg G, Luber AJ, 2013. Use of intralesional cryosurgery as an innovative therapy for keloid scars and a review of current treatments. J Clin Aesthet Dermatol, 6(7):23-26.

[17]Kovalic JJ, Perez CA, 1989. Radiation therapy following keloidectomy: a 20-year experience jeffrey. Int J Radiat Oncol Biol Phys, 17(1):77-80.

[18]Kutzner J, Schneider L, Seegenschmiedt MH, 2003. Radiotherapy of keloids. Patterns of care study-results. Strahlenther Onkol, 179(1):54-58.

[19]Liu QL, Wang XJ, Jia YH, et al., 2016. Increased blood flow in keloids and adjacent skin revealed by laser speckle contrast imaging. Lasers Surg Med, 48(4):360-364.

[20]Makino S, Mitsutake N, Nakashima M, et al., 2008. DHMEQ, a novel NF-kappaB inhibitor, suppresses growth and type I collagen accumulation in keloid fibroblasts. J Dermatol Sci, 51(3):171-180.

[21]Manresa MC, Godson C, Taylor CT, 2014. Hypoxia-sensitive pathways in inflammation-driven fibrosis. Am J Physiol Regul Integr Comp Physiol, 307(12):R1369-R1380.

[22]Niessen FB, Spauwen PHM, Schalkwijk J, et al., 1999. On the nature of hypertrophic scars and keloids: a review. Plast Reconstr Surg, 104(5):1435-1458.

[23]Ogawa R, 2017. Keloid and hypertrophic scars are the result of chronic inflammation in the reticular dermis. Int J Mol Sci, 18(3):606.

[24]Ogawa R, Akaishi S, 2016. Endothelial dysfunction may play a key role in keloid and hypertrophic scar pathogenesis— keloids and hypertrophic scars may be vascular disorders. Med Hypotheses, 96:51-60.

[25]O'Reilly D, Linden R, Fedorko L, et al., 2011. A prospective, double-blind, randomized, controlled clinical trial comparing standard wound care with adjunctive hyperbaric oxygen therapy (HBOT) to standard wound care only for the treatment of chronic, non-healing ulcers of the lower limb in patients with diabetes mellitus: a study protocol. Trials, 12:69.

[26]Park TH, Park JH, Chang CH, 2013. Clinical features and outcomes of foot keloids treated using complete surgical excision and full thickness skin grafting followed by corticosteroid injections. J Foot Ankle Res, 6:26.

[27]Perez CA, Lockett MA, Young G, 2001. Radiation therapy for keloids and plantar warts. Front Radiat Ther Oncol, 35: 135-146.

[28]Ragoowansi R, Cornes PG, Moss AL, et al., 2003. Treatment of keloids by surgical excision and immediate postoperative single-fraction radiotherapy. Plast Reconstr Surg, 111(6):1853-1859.

[29]Ueda K, Yasuda Y, Furuya E, et al., 2004. Inadequate blood supply persists in keloids. Scand J Plast Reconstr Surg Hand Surg, 38(5):267-271.

[30]Wang Y, Chen DD, Chen G, 2014. Hyperbaric oxygen therapy applied research in traumatic brain injury: from mechanisms to clinical investigation. Med Gas Res, 4:18.

[31]Yang Y, Zhang YG, Lin GA, et al., 2014. The effects of different hyperbaric oxygen manipulations in rats after traumatic brain injury. Neurosci Lett, 563:38-43.

[32]Zhang QZ, Wu YD, Ann DK, et al., 2003. Mechanisms of hypoxic regulation of plasminogen activator inhibitor-1 gene expression in keloid fibroblasts. J Invest Dermatol, 121(5):1005-1012.

[33]Zhang T, Gong W, Li Z, et al., 2007. Efficacy of hyperbaric oxygen on survival of random pattern skin flap in diabetic rats. Undersea Hyperb Med, 34(5):335-339.