April 2020 HSC Section 4 - Plastic and Reconstructive Problems

Reprinted by permission of Ann Plast Surg. 2019; 83(2):154-162.

B URN S URGERY AND R ESEARCH

Keloid Excision and Adjuvant Treatments A Network Meta-analysis

Charalampos Siotos, MD,* Akachimere C. Uzosike, BA,* Hwanhee Hong, PhD, † Stella M. Seal, MLS, ‡ Gedge D. Rosson, MD,* Carisa M. Cooney, MPH,* and Damon S. Cooney, MD, PhD*

groups are more frequently affected, particularly African Americans and Asians. 7 Although keloids and hypertrophic scars are not life-threatening, great morbidity can be associated with these pathologies. A recent study provides evidence that patients with keloid scars have lower emotional and mental health quality-of-life scores in comparison to the reference keloid-free group. Pruritus and pain were among the significant factors affecting patient scores. 8 Following intramarginal keloid excision and steroid injection, quality-of-life scores were significantly improved in recurrence-free patients, whereas patients with recurrences did not achieve the same improvement. 9 Research has revealed that the pathophysiology of the disease lies in the wound healing process 10 and is the result of chronic inflammation within the reticular dermis. 11 Excess deposition of extracellular matrix by fibroblasts or decreased degradation and remodeling by metalloprotein- ases of the matrix result in keloid and hypertrophic scar formation. 12 Animal keloid models exhibit an exaggerated inflammatory response to any skin trauma, including increased transforming growth factor β (TGF- β ), vascular endothelial growth factor, and connective tissue growth factor. 13 Despite remarkable medical and surgical developments over the past century, the treatment of keloids remains controversial. 14 Medical regimens introduced for the treatment of keloids/hypertrophic scars are intralesional corticosteroids, 15 antineoplastic drugs such as 5-fluorouracil (5-FU), 16 silicone gel sheets, 17 and pressure therapy. 18 Interventional treatments include surgical excision, cryotherapy, radiation, and laser therapy. 19 Although various treatments have been employed either as single regimen or as combined regimen, 20 recurrence rates remain high and no criterion-standard therapy has been established. 21 In light of this, we sought to evaluate the success rates of different adjuvant treatments employed immediately after surgical excision of keloids by conducting a systematic review and network meta-analysis. This type of analysis enabled us to simultaneously take into account and compare directly and indirectly the recurrence rates among multiple treatment modalities. 22 To our knowledge, this is the first network meta-analysis assessing the effects of different adjuvant treatments after surgical excision for the management of keloids. We conducted the present systematic review and meta-analysis using the guidelines suggested by the Preferred Reporting Items for Sys- tematic ReviewandMeta-analyses. 23 Additional guidelines for conducting network meta-analyses were employed. 24,25 We did not register a protocol. The present study conforms to the Declaration of Helsinki, and approval by the institutional review board was waived. A qualified informaticist (S.M.S.) performed the search of the databases PubMed, EMBASE, Cochrane Library, and Scopus through November 29, 2016, using specific terms available as online supplemental material (Table, Supplemental Digital Content 1, http://links.lww.com/SAP/A364). We included studies with an experimental or observational controlled design that were pub- lished in English. We did not apply restrictions on number of participants, MATERIALS AND METHODS Literature Search

Background: Keloid disease treatment continues to be unsatisfactorywith high recur- rence rates. We evaluated the literature regarding the effectiveness of keloid excision with various adjuvant treatments following surgery and assessed recurrence rates. Methods: We systematically searched databases through November 2016. We performed pairwise meta-analyses and Bayesian network meta-analyses on the number of recurrences. Results: Following screening, 14 studies including 996 patients with various types of keloids were eligible for inclusion. Patients were categorized based on the receipt of surgery and the type of adjuvant treatment employed afterward. Paired meta-analysis (6 meta-analyses) showed that “ excision + 1 adjuvant drug ” led to statistically significantly higher odds of recurrence compared to “ excision + radiation ” (odds ratio [OR], 3.22; 95% confidence interval [CI], 1.35 – 7.67). Based on the network meta-analyses, the ORs of keloid recurrence following var- ious treatments compared to no excision were as follows: “ excision + pressure, 0.18 (95% CI, 0.01 – 7.07); excision + 2 adjuvants drugs, 0.47 (95% CI, 0.02 – 12.82); excision + radiation, 0.39 (95% CI, 0.04 – 3.31); excision + skin grafting, 0.58 (95% CI, 0.00 – 76.10); excision + 1 adjuvant drug, 1.76 (95% CI, 0.17 – 21.35); and excision only, 2.17 (95% CI, 0.23 – 23.95). Conclusions: According to our results, “ excision + radiation ” had significantly better outcomes than excision alone. “ Excision + pressure ” had better outcomes than excision + any other treatment modality, and excision + nonradiation adjuvant therapies were also better than “ excision only, ” although these findings did not reach statistical significance. Key Words: keloid, meta-analysis, reconstruction, review, scar ( Ann Plast Surg 2019;83: 154 – 162) K eloids and hypertrophic scars are chronic skin pathologies that affect approximately 15 new patients per 10,000 people every year. 1 These conditions may result from skin trauma including any injury, burn, sur- gical procedure, or acne, or they may grow spontaneously in genetically predisposed patients. 2 Keloids are created by deposition of collagen, glycosaminoglycans, and acidic mucopolysaccharides that normally exist in the skin. 3 In the case of keloids, this deposition is disorganized, in excess, and enriched in collagen type I rather than collagen type III. 4 Hypertrophic scars present with the same characteristics as keloids but are milder because, unlike keloids, hypertrophic scars do not grow beyond scar borders. 4 Additionally, keloids tend to recur and do not regress. 5 In both cases, the development of keloids or hypertrophic scars often runs in families, implying a genetic background to the disease. 6 Specific ethnic Received November 2, 2018, and accepted for publication, after revision March 4, 2019. From the *Department of Plastic & Reconstructive Surgery, Johns Hopkins University School of Medicine; and † Bloomberg School of Public Health and ‡ Welch Medical Library, Johns Hopkins University, Baltimore, MD. Conflicts of interest and sources of funding: none declared. Reprints: Damon S. Cooney, MD, PhD, Johns Hopkins University School of Medicine, 601 N Caroline St, Baltimore, MD 21205. E-mail: dcooney2@jhmi.edu. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal ’ s Web site (www.annalsplasticsurgery.com). Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0148-7043/19/8302 – 0154 DOI: 10.1097/SAP.0000000000001951

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Annals of Plastic Surgery • Volume 83, Number 2, August 2019

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