Tacrolimus action pathways in an ointment base for hypertrophic scar prevention in a rabbit ear model

Abstract Background: Tacrolimus is used to prevent unaesthetic scars due to its action on fibroblast activity and collagen production modulation. Objectives: To evaluate the action pathways, from the histopathological point of view and in cytokine control, of tacrolimus ointment in the prevention of hypertrophic scars. Methods: Twenty-two rabbits were submitted to the excision of two 1-cm fragments in each ear, including the perichondrium. The right ear received 0.1% and 0.03% tacrolimus in ointment base twice a day in the upper wound and in the lower wound respectively. The left ear, used as the control, was treated with petrolatum. After 30 days, collagen fibers were evaluated using special staining, and immunohistochemistry analyses for smooth muscle actin, TGF-β and VEGF were performed. Results: The wounds treated with 0.1% tacrolimus showed weak labeling and a lower percentage of labeling for smooth muscle actin, a higher proportion of mucin absence, weak staining, fine and organized fibers for Gomori's Trichrome, strong staining and organized fibers for Verhoeff when compared to controls. The wounds treated with 0.03% tacrolimus showed weak labeling for smooth muscle actin, a higher proportion of mucin absence, strong staining for Verhoeff when compared to the controls. There was absence of TGF-β and low VEGF expression. Study limitations: The analysis was performed by a single pathologist. Second-harmonic imaging microscopy was performed in 2 sample areas of the scar. Conclusions: Both drug concentrations were effective in suppressing TGF-β and smooth muscle actin, reducing mucin, improving the quality of collagen fibers, and the density of elastic fibers, but only the higher concentration influenced elastic fiber organization.

Evaluation of the use of tacrolimus ointment for the prevention of hypertrophic scars in experimental model

Abstract BACKGROUND: Tacrolimus, for its activity on modulation of collagen production and fibroblast activity, may have a role in the prevention of hypertrophic scars. OBJECTIVES: Evaluate macroscopic, microscopic, metabolic, laboratory effects and side effects of the use of topical tacrolimus ointment, in different concentrations, in the prevention of hypertrophic scars. METHODS: Twenty-two rabbits were submitted to the excision of 2 fragments of 1 cm of each ear, 4 cm apart, down to cartilage. The left ear of the animals was standardized as control and Vaseline applied twice a day. The right ear received tacrolimus ointment, at concentrations of 0.1% on the upper wound and 0.03% on the lower wound, also applied twice a day. Macroscopic, microscopic, laboratory criteria and the animals' weight were evaluated after 30 days of the experiment. RESULTS: Wounds treated with tacrolimus, at concentrations of 0.1% and 0.03%, when compared to control, showed a lower average degree of thickening (p = 0.048 and p <0.001, respectively). The average of scar thickness and lymphocyte, neutrophil and eosinophil concentrations are lower in the treated wounds compared to the control (p <0.001, p=0.022, p=0.007, p=0.044, respectively). The mean concentration of lymphocytes is lower in wounds treated with a higher concentration of the drug (p=0.01). STUDY LIMITATIONS: experiment lasted only 30 days. CONCLUSIONS: Tacrolimus at the 2 concentrations evaluated reduced the severity of inflammatory changes and positively altered the macroscopic aspect of the scar in the short term. Its use was shown to be safe, with no evidence of systemic or local adverse effects.

Wound natural healing in treatment of tumor-like hypertrophic scar

Abstract: Background: Surgical sutures, wound tension, additional skin incisions and other factors may result in recurrence of tumor-like scar. Objective: To investigate the role of wound natural healing therapy in tumor-like hypertrophic scar. Methods: In this study, tumor-like hypertrophic scars of 47 cases were excised completely and the residual wounds were treated with natural healing. The short-term and long-term effects of treatment were evaluated. Results: All cases were successfully cured by natural healing therapy. The healing time of the maximum wound (80mm × 20mm) and the minimal wound (5mm× 5mm) was 25 days and 7 days respectively. The size of new skin scars ranged from 3mm to 11 mm. Clinical followed-up was performed in 34 cases for 36 months. Among them, no recurrence happened in 31 cases and new scar size ranged from 2mm to 8mm, while local recurrence happened in 3 cases whose scar size were less than 5 mm. Study Limitations: The cure rate of the therapy was 91.2%. Conclusion: The wound natural healing therapy is effective in treating tumor-like hypertrophic scar, which can prevent recurrence and has good cosmetic results.

Efetividade do ácido hialurônico na terapia tópica de queimaduras de espessura parcial e/ou espessura parcial profunda: revisão sistemática / Effectiveness of hyaluronic acid in topical treatment of partial thickness burns and/or deep partial thickness: systematic review

Objetivo: Avaliar a efetividade e segurança do ácido hialurônico na cicatrização completa, cicatrização parcial, tempo médio de cicatrização e prevenção de formação de queloides e cicatrizes hipertróficas, em pacientes hospitalizados com queimaduras de espessura parcial e/ou espessura parcial profunda, comparado com outros tratamentos. Método: Revisão sistemática de ensaios clínicos randomizados, recuperados nas bases eletrônicas: (1) Medical Literature Analysis and Retrieval System Online, (2) Excerpta Medica Database, (3) Cumulative Index to Nursing and Health Literature, (4) Literatura Latino Americana e do Caribe em Ciências da Saúde, (5) Cochrane Central Register of Controlled Trials e (6) Web of Science. A busca foi realizada no período de junho e julho de 2015. Foram selecionados estudos que descreviam a aplicação de ácido hialurônico em pacientes hospitalizados, adultos ou crianças, que apresentavam queimaduras de espessura parcial ou parcial profunda, considerando diferentes formulações e associações de produtos. Os desfechos selecionados foram: (1) cicatrização completa, (2) cicatrização parcial ou redução da área da ferida, (3) prevenção de queloides e cicatrizes hipertróficas, (4) efeitos colaterais e efeitos adversos. Para a análise estatística utilizou-se o programa Review Manager 5.3. Dois revisores independentes avaliaram o risco de viés dos ensaios clínicos e determinaram a inclusão dos estudos. As divergências entre avaliadores foram resolvidas pela intervenção de terceiro revisor. A qualidade metodológica dos estudos foi definida com a utilização da Ferramenta de Risco de Viés da Colaboração Cochrane. Resultados: Foram recuperados 69 estudos, dos quais, 20 estavam replicados entre as bases. Quatro estudos foram pré-selecionados e avaliados na íntegra, e dois que associaram ácido hialurônico e sulfadiazina de prata em queimaduras de espessura parcial foram incluídos à revisão. A cicatrização completa, que representou o desfecho principal dos estudos, apresentou significância estatística em favor do grupo intervenção. O teste de inconsistência do programa Review Manager 5.3 da Colaboração Cochrane apontou para uma heterogeneidade de 97%, inviabilizando assim, a realização de metanálise entre os estudos para o desfecho "tempo médio de cicatrização". Como houve cicatrização completa de todas as lesões durante o tempo de segmento não foi possível realizar a análise das variáveis categóricas. Conclusão: Os resultados desta revisão sistemática apontam que são necessários novos ensaios clínicos aleatorizados devido à escassez de estudos identificados e ao número reduzido de pacientes avaliados. No entanto, a ação tópica de creme de ácido hialurônico em associação com sulfadiazina de prata apresentou resposta significativamente favorável no que tange a cicatrização de queimaduras de espessura parcial ou espessura parcial profunda, sugerindo assim, a possibilidade para a utilização clínica do produto.

Objective: This study aims to evaluate the effectiveness and safety of HA in complete healing, partial healing, average time of healing, and prevention of formation of keloid and hypertrophic scars in hospitalized patients with partial thickness burns and/or deep partial thickness burns, compared to other treatments. Methods: This study is based on a systematic review of randomized clinical trials retrieved in electronic databases: (1) Medical Literature Analysis and Retrieval System Online, (2) Excerpta Medica Database, (3) Cumulative Index to Nursing and Health Literature, (4) Latin American and Caribbean Health Sciences, (5) Cochrane Central Register of Controlled Trials, and (6) Web of Science. The search was carried out from June to July 2015. Studies selected reporting the application of hyaluronic acid in hospitalized, adults or children, who had burns of partial thickness or deep partial thickness, considering different formulations and products associations. The selected endpoints were: (1) complete healing; (2) partial healing or reduction of wound area; (3) prevention of keloid and hypertrophic scars; and (4) side effects and adverse effects. For statistical analysis, the Review Manager 5.3 software was used. Two independent reviewers determined the inclusion of studies and evaluated the risk of bias of clinical trials. Disagreements among reviewers were resolved by the intervention of a third reviewer. The methodological quality of the studies was determined by Cochrane Collaboration's tool for assessing risk of bias. Results: Sixty-nine studies were retrieved, from which twenty studies were replicated among the bases. Four studies were pre-selected and evaluated in full, including two which associated hyaluronic acid and silver sulfadiazine in partial thickness burns. Complete healing, which represented the main conclusion of the studies, showed statistically significant in favor of the intervention group. The Review Manager 5.3 inconsistency test of the Cochrane Collaboration indicated heterogeneity of 97%, thus impeding the holding of meta-analysis of studies for the outcome "mean time to healing". There was complete healing of all lesions during the segment time, therefore, analysis of categorical variables couldn't be performed. Conclusion: The results of this systematic review indicate that requires new randomized clinical trials due to scarcity of identified studies and the small number of evaluated patients. However, the topical action of hyaluronic acid cream in combination with silver sulfadiazine showed significantly a favorable response as it pertains the healing of partial-thickness or deep partialthickness burns, thus suggesting the possibility for the clinical use of the product.

Condutas atuais na prevenção da hipertrofia cicatricial pós-operatória / Current management for the prevention of postoperative scar hypertrophy

Introdução: Considerando um número estimado de cerca de 51 milhões de cirurgias a cada ano apenas nos EUA, podemos dizer que a hipertrofia cicatricial é um problema relevante, já que uma cicatriz fina, de boa qualidade, pode ser a linha divisória entre um bom resultado e uma cirurgia malsucedida. O objetivo é fazer uma revisão bibliográfica acerca dos métodos de tratamento não invasivos atualmente disponíveis para a prevenção da hipertrofia cicatricial pós-cirúrgica e discutir a sua eficácia baseada em evidências. Método: Foi realizada uma pesquisa nas bases de dados Pubmed, Lilacs e SciELO, utilizando os termos "scar prevention" and "hypertrophic scars", por ensaios clínicos, meta-análises e artigos de revisão publicados a partir de 2004, em inglês ou português. Resultados e Conclusões: Foram encontrados vários trabalhos utilizando o silicone, proporcionando alguma evidência acerca da sua eficácia; foram encontrados apenas três ensaios clínicos prospectivos relacionados ao uso do Contractubex®; dois ensaios clínicos prospectivos, controlados, randomizados, sendo apenas um deles duplo-cego, com o imiquimode a 5%; foi encontrado apenas um ensaio clínico bem desenhado utilizando o esparadrapo microporoso e outro trabalho relacionado ao uso da vitamina E, que não mostrou bons resultados; não foram encontrados ensaios clínicos sobre o uso da massagem e da pressão local. Apesar das deficiências dos estudos, o silicone é considerado a primeira opção na prevenção da hipertrofia cicatricial pós-cirúrgica. Não há evidências que comprovem a eficácia do esparadrapo microporoso, da massagem, da pressão local, do Contractubex, do imiquimode a 5% e da vitamina E.

Introduction: Considering that nearly 51 million surgeries are performed annually just in the USA, we can state that scar hypertrophy is a relevant problem, since a thin, good quality scar can be the dividing line between a good outcome and an unsuccessful surgery. The objective is to perform a bibliographic review of the noninvasive methods currently available to prevent postoperative hypertrophic scars and discuss their evidence-based effectiveness. Method: A search was performed in PubMed, LILACS, and SciELO databases, using the terms "scar prevention" and "hypertrophic scars," for clinical trials, meta-analyses, and review articles published since 2004 in English or Portuguese language. Results and Conclusions: Several studies using silicone were found, providing some evidence on its effectiveness; only 3 prospective clinical trials using Contractubex® were found; 2 controlled, randomized prospective clinical trials using 5% imiquimod were found, but only one was doubleblind; one well-designed clinical trial using a micropore adhesive tape was found; a similar clinical trial using vitamin E did not show good results. Clinical trials on the use of massage and local pressure were not found. Despite the limitations of the studies, silicone is considered the first treatment option for the prevention of postoperative hypertrophic scars. There is no evidence proving the effectiveness of micropore adhesive tape, massage, local pressure, Contractubex, 5% imiquimod, or vitamin E.

Overview of Surgical Scar Prevention and Management

Management of incisional scar is intimately connected to stages of wound healing. The management of an elective surgery patient begins with a thorough informed consent process in which the patient is made aware of personal and clinical circumstances that cannot be modified, such as age, ethnicity, and previous history of hypertrophic scars. In scar prevention, the single most important modifiable factor is wound tension during the proliferative and remodeling phases, and this is determined by the choice of incision design. Traditional incisions most often follow relaxed skin tension lines, but no such lines exist in high surface tension areas. If such incisions are unavoidable, the patient must be informed of this ahead of time. The management of a surgical incision does not end when the sutures are removed. Surgical scar care should be continued for one year. Patient participation is paramount in obtaining the optimal outcome. Postoperative visits should screen for signs of scar hypertrophy and has a dual purpose of continued patient education and reinforcement of proper care. Early intervention is a key to control hyperplastic response. Hypertrophic scars that do not improve by 6 months are keloids and should be managed aggressively with intralesional steroid injections and alternate modalities.

Estado actual del uso de silicona en cicatrices hipertróficas / Recent state of use of silicone in hypertrophic scars

Con la finalidad de prevenir o mejorar la apariencia de las cicatrices hipertróficas, sean éstas de origen quirúrgico o traumático, se ha desarrollado una gran variedad de tratamientos, tanto tópicos como sistémicos. Estas lesiones son notoriamente recurrentes y su manejo es poco satisfactorio. Ninguna medida en forma individual ha probado ser efectiva en evitar el proceso de la cicatrización hipertrófica (CH), con excepción tal vez de la silicona. El presente trabajo tiene como objetivo revisar la evidencia disponible en estudios prospectivos, controlados, descritos en la literatura acerca de la utilidad de la silicona en el tratamiento de las cicatrices hipertróficas