Evaluation of Topical Sclerosant Agents for Minimization of Postmastectomy Seroma: A Placebo-Controlled, Double-Blind, Randomized Trial.

Original Article Eur J Breast Health 2023; 19(2): 134-139 DOI: 10.4274/ejbh.galenos.2023.2022-11-1 Evaluation of Topical Sclerosant Agents for Minimization of Postmastectomy Seroma: A Placebo-Controlled, Double-Blind, Randomized Trial Ashraf Khater, Ahmed Hassan, Osama Eldamshety Omar Farouk, Ahmed Sinbel, Saleh Saleh, Mahmoud Abdelaziz, Department of Surgery, Oncology Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt ABSTRACT Objective: Seroma after mastectomy is a bothersome problem. Topical sclerosants are one method used to reduce seroma. The aim of this study was to evaluate if spraying flaps before closure with doxycycline or bleomycin after total mastectomy can prevent seroma. Materials and Methods: After institutional review board approval, using a computer-based randomization program, a prospective, double-blind, placebo-controlled randomized, superiority study was conducted during the period from the first of August 2017 to the first of August 2018. IRB proposal code was MS/17.08.66 and the trial was approved at 15/8/2017. The trial is available publicly at http://www.eulc.edu.eg/eulc_v5/Libraries/Thesis/ BrowseThesisPages.aspx?fn=PublicDrawThesis&BibID=12553049. The primary outcome of the study was to assess the incidence of seroma following total mastectomy after intervention comprising spraying of skin flaps with doxycycline or bleomycin versus placebo. Patients who were candidates for total mastectomy were randomized into control, doxycycline, and bleomycin groups. The postoperative data included length of the hospital stay, pain score among the three groups, post-operative drained fluid volume, post-operative day of drain removal, complication rates including infection, flap necrosis and hematoma, the incidence of seroma and aspirated seroma volume, and total number of postoperative visits. Results: Of 125 patients, 90 were candidates for total mastectomy. Analysis of these 90 showed that the incidence of seroma was similar; 43.4%, 40% and 40% in the control, doxycycline, and bleomycin groups, respectively (p = 0.99). Furthermore, wound complication rates were similar among all groups. Conclusion: Despite improved recognition and management of risk factors, seromas remain a common clinical concern in the postoperative setting of total mastectomy. These results suggest that sclerosant agents, specifically bleomycin and doxycycline, have no utility for prevention of post mastectomy seroma. Keywords: Mastectomy, seroma, sclerosant Cite this article as: Khater A, Hassan A, Farouk O, Sinbel A, Saleh S, Abdelaziz M, Eldamshety O. Evaluation of Topical Sclerosant Agents for Minimization of Postmastectomy Seroma: A Placebo-Controlled, Double-Blind, Randomized Trial. Eur J Breast Health 2023; 19(2): 134-139 Key Points • Mastectomy. • Seroma. • Sclerosant. Introduction Since mastectomy was first described by Halsted in 1894, surgeons have faced several problems, such as necrosis of the skin flaps, breakdown of the wound, hematoma, seroma, and infection (1). Seromas can disrupt the healing process, lengthen the convalescence, be upsetting for the patient, and delay adjuvant therapy (2). The incidence of post-mastectomy seroma has been reported to vary widely from 15% to 81% (1). Various methods have been tried aiming to decrease the occurrence of seroma, with limited success. These include insertion of suction drains, obliteration of mastectomy or the axillary space by sutures, topical application of sclerotherapy 134 Corresponding Author: Ashraf Khater, with tetracycline, application of fibrin glue, and external application of compressive dressings. Spraying of mastectomy flaps with doxycyclines and bleomycin were previously reported as having a positive effect in seroma prevention (3). The aim of this study was to evaluate if seroma can be prevented after total mastectomy by the spraying of flaps before closure with doxycycline or bleomycin. The primary outcome was to assess the incidence of seroma after total mastectomy when flaps were sprayed with doxycycline or bleomycin versus placebo. The secondary endpoints were the operative outcomes and complication rates, including hematoma, flap necrosis and wound infection. Received: 01.11.2022 Accepted: 09.02.2023 Available Online Date: 01.04.2023 ©Copyright 2023 by the Turkish Federation of Breast Diseases Societies / European Journal of Breast Health published by Galenos Publishing House. Khater et al. Sclerosants for Post-Mastectomy Seroma Materials and Methods After Institutional Review Board approval, a prospective, double-blind, placebo-controlled randomized, superiority study was conducted during the period from the first of August 2017 to the first of August 2018. After obtaining informed consent, ninety female patients, aged between 25 and 75 years old who were candidates for elective total mastectomy were enrolled. Patients were included if they had operable breast cancer with no distant metastases and consented to participate. Those with incapacitating cardiac disease, uncontrolled diabetes, advanced liver disease, coagulopathy, or collagen vascular disease were excluded. Exclusion criteria also included patients aged less than 25 years, patients using steroids or anticoagulants, patients with ongoing systemic infection at the time of surgery, those with history of chest irradiation or prior axillary surgery, patients with planned immediate breast reconstruction, pregnant and lactating patients, those who were unfit for general anesthesia, patients with locally advanced cancer with no neoadjuvant chemotherapy, patients with metastatic cancer and those unwilling to participate in the trial. After using a computer-based randomization program, patients were assigned to groups by a closed envelope method (Figure 1). Patients were divided into three groups: Doxycycline, bleomycin, and placebo control. Participants in the doxycycline group were sprayed with 500 mg doxycycline [5x100 mg tablets of Doxymycin (EL-NILE CO) diluted in 100 mL saline] onto the undersurface of the skin flaps after the mastectomy and after achieving hemostasis. Patients in the bleomycin group were sprayed with 60 units of bleomycin (2 ampules of Bleomycin 30 IU; Salius Pharma), also diluted in 100 mL saline. Patients in the control group were sprayed with 100 mL of saline. Surgeons were blinded to the three preparations, which were prepared by a third party. Skin was closed routinely in all patients after placing two Nelaton catheters 18French drains, one in the axilla and the second underneath the mastectomy flaps. Drains were clamped for three hours postoperatively to keep solutions in contact with the skin flaps. In all patients, a dry light dressing was placed. Arm exercise was allowed from the first postoperative day but lifting more than 5 kg or lifting the arm above the shoulder was prohibited until two weeks after surgery. All participants were followed up by routine postoperative visits for 1-2 (...truncated)