Suppressive Effect of Leukotriene Antagonists on Capsular Contracture in Patients Who Underwent Breast Surgery with Prosthesis: A Meta-Analysis.

Abstract

Sir: As breast surgery continues to progress, capsular contracture continues to be one of the most concerning complications regarding prosthetic breast surgery. As a result, studies regarding this topic keep progressing, aiming to effectively prevent or cure capsular contraction postoperatively. We read with interest the recently published article by Wang et al.1 entitled “Suppressive Effect of Leukotriene Antagonists on Capsular Contracture in Patients Who Underwent Breast Surgery with Prosthesis: A Meta-Analysis.” The authors presented a comprehensive analysis demonstrating the suppressive effect of leukotriene antagonists on capsular contracture. In this communication, we would like to raise a few questions regarding this analysis, possibly to benefit further studies. First, we did not find the time limit for literature searching, which is considered an important element of a comprehensive meta-analysis. Particularly in the field of prosthetic breast surgery, the development of technology is not homogeneous, resulting in different incidence rates of capsular contracture over different periods.2 We hope that, through a more rigorous literature search, the result of this analysis could be more reliable, which would increase its clinical reference value. Second, the Baker grading system, although it serves as a well-recognized standard for evaluating the severity of capsular contracture after implant breast surgery, is not an objective method. Instead, it merely complies with the subjective feeling of the examiner,3 which will unavoidably cause measurement bias. This type of bias is acceptable when the experiment is carried out in a single center with limited examiners. However, in this meta-analysis, five publications were included, which means different examiners from different centers were included, thus exacerbating measurement bias, and this is without effective statistical solution. In addition, in the five studies included, the classification standards of capsular contracture are inconsistent: some used Baker grade greater than 1.5, whereas others recognized Baker grade over 2 or 3 as the standards of capsular contracture. This inconsistency of judgment standards will inevitably bias the final result. If this is added in the discussion section of the article, it can better help the reader to correctly understand the result and better guide clinical application. Third, both leukotriene antagonists mentioned in this article, zafirlukast and montelukast, are oral medicines that act on the whole body rather than locally. As a result, we think it is more appropriate that, one patient, instead of one side of breast, should be considered as one sample, regardless of whether the patient was operated on unilaterally or bilaterally. This way should bring us more accurate and objective evaluation results. Moreover, a subgroup analysis based on patients operated on unilaterally and bilaterally might be more beneficial to the outcome. Furthermore, the authors concluded that leukotriene antagonists have both preventive and therapeutic effects on capsular contracture. However, we failed to find subgroup analysis performed based on these two effects in this meta-analysis. The preventive effect of leukotriene antagonists focuses on its inhibitory effect on the formation of the periprosthetic envelope, whereas its therapeutic effect focuses on the reduction in thickness of an already formed capsule. We are confused regarding the conclusion the authors drew without addressing the evidence. Thus, we look forward to a further analysis of the two respective effects of leukotriene antagonists on capsular contracture carried out. Last but not least, the risk of neuropsychiatric reactions regarding the use of montelukast (Singulair; Merck & Co., Inc., Kenilworth, N.J.) has raised our attention recently and was not well-addressed in this article. The UK Medicines and Healthcare Products Regulatory Agency warned doctors on September 20, 2019, that they should be alert for neuropsychiatric reactions in patients taking montelukast and evaluate carefully the risks and benefits of continuing treatment.4 Immediately thereafter, on September 27, 2019, the U.S. Food and Drug Administration Affairs Committee held a joint meeting to review the safety of montelukast for the occurrence of neuropsychiatric events in patients taking it. There is a survey showing that this type of side effects is more common than is currently reported.5 Considering the side effect mentioned above, we consider it obligatory to emphasize this point and think it might be safer to use zafirlukast instead in the future. DISCLOSURE The authors have no financial interest to declare in relation to the content of this study. No funding was received for this communication. Ziying Zhang, M.D.Chenglong Wang, M.D.Zixuan Zhang, M.D.Minqiang Xin, M.D.Department of Aesthetic and Reconstructive Breast SurgeryPlastic Surgery HospitalChinese Academy of Medical SciencesPeking Union Medical CollegeBeijing, People’s Republic of China