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Hyperbaric oxygen therapy improves the effect of keloid surgery and radiotherapy by reducing the recurrence rate

高压氧治疗降低瘢痕疙瘩切除联合放疗后的复发率

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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.

中文概要

目的

研究高压氧治疗降低瘢痕疙瘩切除联合放疗后复发率的效果及作用机制。

创新点

将高压氧治疗应用于瘢痕疙瘩的辅助治疗。

方法

(1)将240例瘢痕疙瘩患者随机分成两组(高压氧治疗组和非高压氧治疗组), 高压氧治疗组接受瘢痕疙瘩切除术、放疗及高压氧治疗非高压氧治疗接受瘢痕疙瘩切除及放疗。(2)收集两组复发病人二次手术切下的瘢痕疙瘩标本及正常皮肤标本, 通过免疫组化染色观察三组组织标本因子白细胞介质-6(IL-6)、缺氧诱导因子-1α(HIF-1α)、肿瘤坏死因子-α(TNF-α)、核因子-κB(NF-κB)和血管内皮生长因子(VEGF)的表达量。

结论

高压氧治疗通过提高瘢痕疙瘩组织氧含量及减少炎症反应来降低瘢痕疙瘩切除联合放疗后的复发率。

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References

  • 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.

    PubMed  Google Scholar 

  • 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. https://doi.org/10.5966/sctm.2013-0120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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. https://doi.org/10.1111/ddg.12168

    PubMed  Google Scholar 

  • 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. https://doi.org/10.1111/j.1524-4725.2007.33280.x

    CAS  PubMed  Google Scholar 

  • Bloemen MCT, van der Veer WM, Ulrich MMW, et al., 2009. Prevention and curative management of hypertrophic scar formation. Burns, 35(4):463–475. https://doi.org/10.1016/j.burns.2008.07.016

    Article  PubMed  Google Scholar 

  • 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. https://doi.org/10.1016/S0022-4804(03)00188-4

    Article  CAS  PubMed  Google Scholar 

  • 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. https://doi.org/10.1016/0007-1226(92)90008-L

    Article  CAS  PubMed  Google Scholar 

  • Datubo-Brown DD, 1990. Keloids: a review of the literature. Br J Plast Surg, 43(1):70–77. https://doi.org/10.1016/0007-1226(90)90047-4

    Article  CAS  PubMed  Google Scholar 

  • de Felice B, Guida M, Boccia L, et al., 2015. Ingenol mebutate treatment in keloids. BMC Res Notes, 8:466. https://doi.org/10.1186/s13104-015-1429-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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. https://doi.org/10.5505/tjtes.2014.52323

    Article  PubMed  Google Scholar 

  • Dhani N, Fyles A, Hedley D, et al., 2015. The clinical significance of hypoxia in human cancers. Semin Nucl Med, 45(2):110–121. https://doi.org/10.1053/j.semnuclmed.2014.11.002

    Article  PubMed  Google Scholar 

  • 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. https://doi.org/10.3892/br.2013.169

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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. https://doi.org/10.1016/0360-3016(90)90405-9

    Article  CAS  PubMed  Google Scholar 

  • 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. https://doi.org/10.1159/000316381

    Article  PubMed  Google Scholar 

  • 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. https://doi.org/10.1007/s00405-007-0383-0

    Article  CAS  PubMed  Google Scholar 

  • 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.

    PubMed  PubMed Central  Google Scholar 

  • Kovalic JJ, Perez CA, 1989. Radiation therapy following keloidectomy: a 20-year experience jeffrey. Int J Radiat Oncol Biol Phys, 17(1):77–80. https://doi.org/10.1016/0360-3016(89)90373-8

    Article  CAS  PubMed  Google Scholar 

  • Kutzner J, Schneider L, Seegenschmiedt MH, 2003. Radiotherapy of keloids. Patterns of care study-results. Strahlenther Onkol, 179(1):54–58. https://doi.org/10.1007/s00066-003-1023-2

    Article  PubMed  Google Scholar 

  • 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. https://doi.org/10.1002/lsm.22470

    Article  PubMed  Google Scholar 

  • 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. https://doi.org/10.1016/j.jdermsci.2008.03.003

    Article  CAS  PubMed  Google Scholar 

  • 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. https://doi.org/10.1152/ajpregu.00349.2014

    Google Scholar 

  • 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. https://doi.org/10.1097/00006534-199910000-00031

    Article  CAS  PubMed  Google Scholar 

  • Ogawa R, 2017. Keloid and hypertrophic scars are the result of chronic inflammation in the reticular dermis. Int J Mol Sci, 18(3):606. https://doi.org/10.3390/ijms18030606

    Article  PubMed Central  Google Scholar 

  • 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. https://doi.org/10.1016/j.mehy.2016.09.024

    Article  CAS  PubMed  Google Scholar 

  • 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. https://doi.org/10.1186/1745-6215-12-69

    Article  PubMed  PubMed Central  Google Scholar 

  • 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. https://doi.org/10.1186/1757-1146-6-26

    Article  PubMed  PubMed Central  Google Scholar 

  • Perez CA, Lockett MA, Young G, 2001. Radiation therapy for keloids and plantar warts. Front Radiat Ther Oncol, 35: 135–146. https://doi.org/10.1159/000061273

    Article  CAS  PubMed  Google Scholar 

  • 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. https://doi.org/10.1097/01.PRS.0000056869.31142.DE

    Article  PubMed  Google Scholar 

  • 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. https://doi.org/10.1080/02844310410029552

    Article  PubMed  Google Scholar 

  • 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. https://doi.org/10.1186/2045-9912-4-18

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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. https://doi.org/10.1016/j.neulet.2014.01.002

    Article  CAS  PubMed  Google Scholar 

  • 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. https://doi.org/10.1046/j.1523-1747.2003.12564.x

    Article  CAS  PubMed  Google Scholar 

  • 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.

    CAS  PubMed  Google Scholar 

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Author notes

  1. The two authors contributed equally to this work

Authors and Affiliations

  1. Department of Plastic Surgery, Peking Union Medical College Hospital, Beijing, 100730, China

    Ke-xin Song, Ming-zi Zhang, Hao Liu, Xin-hang Dong, You-bin Wang & Xiao-jun Wang

  2. School of Medicine, North China University of Science and Technology, Tangshan, 063000, China

    Shu Liu

  3. Department of Plastic Surgery, China Meitan General Hospital, Beijing, 100028, China

    Wei-zhong Liang

Authors
  1. Ke-xin Song
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  2. Shu Liu
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  3. Ming-zi Zhang
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  4. Wei-zhong Liang
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  5. Hao Liu
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  6. Xin-hang Dong
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  7. You-bin Wang
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  8. Xiao-jun Wang
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Corresponding authors

Correspondence to You-bin Wang or Xiao-jun Wang.

Additional information

Project supported by the National Natural Science Foundation of China (No. 81471885) and the Beijing Natural Science Foundation (No. 7172172), China

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Song, Kx., Liu, S., Zhang, Mz. et al. Hyperbaric oxygen therapy improves the effect of keloid surgery and radiotherapy by reducing the recurrence rate. J. Zhejiang Univ. Sci. B 19, 853–862 (2018). https://doi.org/10.1631/jzus.B1800132

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  • DOI: https://doi.org/10.1631/jzus.B1800132

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