The Effect of 3-Dimensional-Printed Sequential Dual Drug-Releasing Patch on the Capsule Formation Around the Silicone Implant in a Rat Model.

BACKGROUND: Implant-based breast reconstruction is associated with increased risk of early infection and late-stage capsular contracture. OBJECTIVES: We evaluated the feasibility of a dual drug-releasing patch that enabled the controlled delivery of antibiotics and immunosuppressants in a temporally and spatially appropriate manner to the implant site. METHODS: The efficacy of a dual drug-releasing patch, which was 3-dimensional-printed (3D-printed) with tissue-derived biomaterial ink, was evaluated in rats with silicone implants. The groups included implant only (n = 10); implant plus bacterial inoculation (n = 14); implant, bacterial inoculation, and patch loaded with gentamycin placed on the ventral side of the implant (n = 10), and implant, bacterial inoculation, and patch loaded with gentamycin and triamcinolone acetonide (n = 9). Histologic and immunohistochemical analyses were performed 8 weeks after implantation. RESULTS: The 2 drugs were sequentially released from the dual drug-releasing patch and exhibited different release profiles. Compared to the animals with bacterial inoculation, those with the antibiotic-only and the dual drug-releasing patch exhibited thinner capsules and lower myofibroblast activity and inflammation, indicating better tissue integration and less foreign body response. These effects were more pronounced with the dual drug-releasing patch than with the antibiotic-only patch. CONCLUSIONS: The 3D-printed dual drug-releasing patch effectively reduced inflammation and capsule formation in a rat model of silicone breast reconstruction. The beneficial effect of the dual drug-releasing patch was better than that of the antibiotic-only patch, indicating its therapeutic potential as a novel approach to preventing capsular contracture while reducing concerns of systemic side effects.

Devil's Advocate: Evidence-Based Recommendation for "One Breast-One Insertion Funnel" Policy.

BACKGROUND: Rates of capsular contracture have reduced significantly since the use of insertion funnels to place breast implants became routine. However, due to financial constraints, the same funnel is usually used for implantation of both sides. OBJECTIVES: The aim of this study was to determine whether the risk of capsular contracture is higher for the second breast when the same insertion funnel is used for both breasts. METHODS: The authors collected a sample of the insertion funnel tip immediately after removing the funnel from its sterile packaging and another tip sample after the funnel had been used to insert the first implant. These samples were sent for microbiological culture evaluations. Capsular contracture rates in the first implanted breast vs the second implanted breast were then retrospectively analyzed. RESULTS: All samples taken from the funnel before the first implantation showed no bacterial growth. All 10 samples taken from the funnel after the first implantation showed organism growth (8 were positive for Staphylococcus epidermidis and 2 for Cutibacterium acnes). Retrospective analysis of the results revealed that the overall capsular contracture rate had reduced after the authors began to use insertion funnels. However, this complication was still more common on the second implanted breast. CONCLUSIONS: Surgeons should consider the use of separate insertion funnels for each breast. This might help to slightly reduce the incidence of capsular contracture.See the abstract translated into Hindi, Portuguese, Korean, German, Italian, Arabic, and Chinese (Simplified and Traditional) online here: https://doi.org/10.1093/asj/sjad288.

Use of Antimicrobial Irrigation and Incidence of Capsular Contracture in Breast Augmentation and Immediate Implant-Based Breast Reconstruction.

Capsular contracture (CC) is one of the most common complications of implant-based breast reconstruction or augmentation surgery. Common risk factors of CC include biofilm, surgical site infections, history of prior CC or fibrosis, history of radiation therapy, and implant characteristics. Though bacterial contamination of breast protheses is associated with adverse sequelae, there are not universally accepted guidelines and limited best practice recommendations for antimicrobial breast pocket irrigation. Despite advanced molecular biology, the exact mechanism of this complication is not fully understood. Interventions that decrease the rate of CC include antibiotic prophylaxis or irrigation, acellular dermal matrix, leukotriene inhibitors, surgical techniques, and others. However, there is inconsistent evidence supporting these risk factors, and the current data was based on broad heterogeneous studies. The objective of this review was to provide a summary of the current data of contributing risk factors as well as preventative and treatment measures for CC.Level of Evidence III This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266.

Reducing Peri-implant Capsule Thickness in Submuscular Rodent Model of Breast Reconstruction With Delayed Radiotherapy.

INTRODUCTION: Capsular contracture remains the most common complication following device-based breast reconstruction, occurring in up to 50% of women who also undergo adjuvant radiotherapy either before or after device-based reconstruction. While certain risk factors for capsular contracture have been identified, there remains no clinically effective method of prevention. The purpose of the present study is to determine the effect of coating the implant with the novel small molecule Met-Z2-Y12, with and without delayed, targeted radiotherapy, on capsule thickness and morphologic change around smooth silicone implants placed under the latissimus dorsi in a rodent model. METHODS: Twenty-four female Sprague Dawley rats each had 2 mL smooth round silicone breast implants implanted bilaterally under the latissimus dorsi muscle. Twelve received uncoated implants and twelve received implants coated with Met-Z2-Y12. Half of the animals from each group received targeted radiotherapy (20 Gray) on postoperative day ten. At three and 6 months after implantation, the tissue surrounding the implants was harvested for analysis of capsular histology including capsule thickness. Additionally, microCT scans were qualitatively analyzed for morphologic change. RESULTS: Capsules surrounding Met-Z2-Y12-coated implants were significantly thinner (P = 0.006). The greatest difference in capsule thickness was seen in the irradiated 6-month groups, where mean capsule thickness was 79.1 ± 27.3 µm for uncoated versus 50.9 ± 9.6 µm for Met-Z2-Y12-coated implants (P = 0.038). At the time of explant, there were no capsular morphologic differences between the groups either grossly or per microCT. CONCLUSIONS: Met-Z2-Y12 coating of smooth silicone breast implants significantly reduces capsule thickness in a rodent model of submuscular breast reconstruction with delayed radiotherapy.

Difference in the Occurrence of Capsular Contracture According to Tissue Characteristics in an Irradiated Rat Model.

BACKGROUND: This study was performed to evaluate the hypothesis that capsule formation varies according to the radiation dose in muscle tissues; chest wall tissues, including the ribs; and acellular dermal matrices (ADM) that are in contact with the silicone implant. METHODS: In this study, 20 Sprague-Dawley rats underwent submuscular plane implant reconstruction using ADM. They were divided into four groups: an unradiated control group ( n = 5), nonfractionated radiation at a dose of 10 Gy ( n = 5), nonfractionated radiation at a dose of 20 Gy ( n = 5), and fractionated radiation at a dose of 35 Gy ( n = 5). Three months after surgery, hardness was measured, and histologic and immunochemical analyses of the capsule tissues of the ADM, muscle tissues, and chest wall tissues were analyzed. RESULTS: As the radiation dose increased, the silicone implant became harder, but no significant difference in capsule thickness according to the radiation dose was observed. Based on the tissue in contact with the silicone implant, ADM had a thinner capsule thickness than the muscle tissues, as well as less inflammation and less neovascularization compared with the other tissues. CONCLUSIONS: This study describes a new rat model of clinically relevant implant-based breast reconstruction using a submuscular plane and ADM with irradiation. The ADM in contact with the silicone implant, even after irradiation, was protected from radiation compared with the other tissues. CLINICAL RELEVANCE STATEMENT: These research results could support the use of ADM in implant-based breast reconstruction for prevention of the capsular contracture, even after radiation.

An Antifibrotic Breast Implant Surface Coating Significantly Reduces Periprosthetic Capsule Formation.

BACKGROUND: The body responds to prosthetic materials with an inflammatory foreign body response and deposition of a fibrous capsule, which may be deleterious to the function of the device and cause significant discomfort for the patient. Capsular contracture (CC) is the most common complication of aesthetic and reconstructive breast surgery. The source of significant patient morbidity, it can result in pain, suboptimal aesthetic outcomes, implant failure, and increased costs. The underlying mechanism remains unknown. Treatment is limited to reoperation and capsule excision, but recurrence rates remain high. In this study, the authors altered the surface chemistry of silicone implants with a proprietary anti-inflammatory coating to reduce capsule formation. METHODS: Silicone implants were coated with Met-Z2-Y12, a biocompatible, anti-inflammatory surface modification. Uncoated and Met-Z2-Y12-coated implants were implanted in C57BL/6 mice. After 21, 90, or 180 days, periprosthetic tissue was removed for histologic analysis. RESULTS: The authors compared mean capsule thickness at three time points. At 21, 90, and 180 days, there was a statistically significant reduction in capsule thickness of Met-Z2-Y12-coated implants compared with uncoated implants ( P < 0.05). CONCLUSIONS: Coating the surface of silicone implants with Met-Z2-Y12 significantly reduced acute and chronic capsule formation in a mouse model for implant-based breast augmentation and reconstruction. As capsule formation obligatorily precedes CC, these results suggest contracture itself may be significantly attenuated. Furthermore, as periprosthetic capsule formation is a complication without anatomical boundaries, this chemistry may have additional applications beyond breast implants, to a myriad of other implantable medical devices. CLINICAL RELEVANCE STATEMENT: Coating of the silicone implant surface with Met-Z2-Y12 alters the periprosthetic capsule architecture and significantly reduces capsule thickness for at least 6 months postoperatively in a murine model. This is a promising step forward in the development of a therapy to prevent capsular contracture.

Stem Cell-Enriched Hybrid Breast Reconstruction Reduces Risk for Capsular Contracture in a Hybrid Breast Model.

BACKGROUND: Hybrid breast reconstruction (HBR) combines silicone implants with fat grafting to improve implant coverage, treating local tissue deficiencies and leading to a more natural breast appearance. Recent data also indicated less capsular contracture after HBR. The authors developed a novel technique and animal model of cell-assisted (CA) HBR to illuminate its effects on capsular contracture. METHODS: Animals received silicone implants in a dorsal submuscular pocket. Although animals of the HBR group received fat grafting around the implant without stem cell enrichment, rats of the CA-HBR1 and the CA-HBR2 groups received stem cell-enriched fat grafting with 2 × 10 6 and 4 × 10 6 adipose-derived stem cells immediately after implant insertion. On day 60, animals underwent sonography and elastography imaging and were euthanized, and outcome analysis was performed by means of histology, immunohistochemistry, chemical collagen quantification, and gene expression analysis. RESULTS: With this novel technique, long-term survival of adipose-derived stem cells within the implant pocket was demonstrated after 60 days after implant insertion. CA-HBR led to significantly reduced thickness and collagen density of capsular contractures. In addition, CA-HBR resulted in reduced fibrotic responses with less occurrence of collagen type I and transforming growth factor-ß in capsule tissue. Moreover, the addition of stem cells suppressed fibrotic and inflammatory responses on a genetic level with significant underexpression of collagen type I and transforming growth factor-ß1. CONCLUSIONS: With this new technique and animal model, the authors observed a preventive effect on capsular contracture substantiating the basis of clinical outcomes of HBR. The authors propose that the addition of stem cells to HBR might booster its beneficial results. CLINICAL RELEVANCE STATEMENT: Stem cell-enriched fat grafting around silicone implants may reduce the risk for capsular contracture after silicone breast implantation. While fat grafting alone already shows beneficial effects, the addition of stem cells to the fat graft can potentiate this effect.

Histologic and Immunohistochemical Evaluation of Human Breast Capsules Formed around Five Different Expander Surfaces.

BACKGROUND: Polyurethane (PU) coating and implant texturization were designed to reduce the incidence of capsular contracture (CC), even if the link between surface type and CC remains unclear. To date, the etiopathogenetic aspects have not been fully clarified. The aim of this study was to evaluate capsules formed around five different breast expanders. METHODS: Thirty patients were divided into randomized groups implanted with five different expanders: smooth, coated with PU foam (poly), with a low-microtextured, high-microtextured, and macrotextured surface (L-micro, H-micro, macro). Specimens of the capsules were removed at implant reconstruction and evaluated for morphology and immunohistochemistry expression of α-smooth muscle actin (α-SMA), collagen type I and III, CD68, CD34, and CD3. Remodeling Combined Index was also evaluated. RESULTS: Expression of α-SMA was significantly increased in smooth capsules versus poly, low-microtextured, and high-microtextured groups ( P = 0.007; P = 0.010; P = 0.028), whereas the prevalence of collagen type I in smooth capsules and collagen type III in poly capsules identified a stable versus an unstable tissue. Remodeling Combined Index and α-SMA showed an inverted correlation. CD68 and CD34 cellular expression increased significantly in poly capsules with respect to smooth ( P < 0.001; P < 0.001) and macrotextured groups ( P < 0.001; P < 0.001). CD3 showed no significant difference among the groups. CONCLUSION: In this human study, the authors observed that increased tissue remodeling and reduced myofibroblast activation, along with the inflammatory infiltration and neoangiogenesis, especially in the poly and low-microtextured groups, might promote the formation of an unstable and less fibrotic capsule, lowering the risk of CC. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Enhancing Patient Outcomes in Aesthetic Breast Implant Procedures Using Proven Antimicrobial Breast Pocket Irrigations: A 20-Year Follow-up.

BACKGROUND: Capsular contracture (CC) remains the most common complication of implant-based aesthetic and reconstructive breast surgery. With subclinical infection proven to be the primary etiology, antimicrobial breast pocket irrigation has been recommended as the key step to reduce CC but has not been universally adopted. OBJECTIVES: The purpose of this study was to review the rates of CC observed when applying proven antimicrobial breast pocket irrigations. METHODS: Data from patients undergoing cosmetic breast augmentation were recorded prospectively from 1997 to 2017. The irrigation was performed with either a Betadine-containing (50% Betadine or "Betadine triple") or a non-Betadine triple antibiotic regimen. The database was assessed to determine the type of implant used, the incidence of CC, and possible contributing factors. The degree of CC was recorded according to the Baker classification. RESULTS: A 20-year prospective data collection yielded 2088 patients with 4176 implants; of these patients, 826 had textured implants and 1262 had smooth implants. The incidence of Grade III/IV CC was found to be 0.57% in all patients undergoing primary breast augmentation (1.21% in textured implants and 0.16% in smooth implants). CONCLUSIONS: This study constitutes the largest and longest review of CC in a controlled, single-surgeon setting. The incidence of CC is low and reinforces the efficacy/utility of antimicrobial breast pocket irrigation. Both the Betadine and non-Betadine antibiotic regimens were found to be effective, with the Betadine regimen being preferred. Universal adoption of Betadine-containing antimicrobial breast pocket irrigation is recommended to reduce CC and other device-associated infections.

Pharmacological Approaches for the Prevention of Breast Implant Capsular Contracture.

Capsular contracture is a common complication associated with breast implants following reconstructive or aesthetic surgery in which a tight or constricting scar tissue capsule forms around the implant, often distorting the breast shape and resulting in chronic pain. Capsulectomy (involving full removal of the capsule surrounding the implant) and capsulotomy (where the capsule is released and/or partly removed to create more space for the implant) are the most common surgical procedures used to treat capsular contracture. Various structural modifications of the implant device (including use of textured implants, submuscular placement of the implant, and the use of polyurethane-coated implants) and surgical strategies (including pre-operative skin washing and irrigation of the implant pocket with antibiotics) have been and/or are currently used to help reduce the incidence of capsular contracture. In this article, we review the pharmacological approaches-both commonly practiced in the clinic and experimental-reported in the scientific and clinical literature aimed at either preventing or treating capsular contracture, including (i) pre- and post-operative intravenous administration of drug substances, (ii) systemic (usually oral) administration of drugs before and after surgery, (iii) modification of the implant surface with grafted drug substances, (iv) irrigation of the implant or peri-implant tissue with drugs prior to implantation, and (v) incorporation of drugs into the implant shell or filler prior to surgery followed by drug release in situ after implantation.

Comparison of Cromolyn Sodium, Montelukast, and Zafirlukast Prophylaxis for Capsular Contracture.

BACKGROUND: Capsular contracture is the most common complication following breast augmentation. Recently, prophylaxis studies aiming to inhibit the release of profibrotic substances to prevent capsular contracture have gained in importance. This study investigated the effects of cromolyn sodium, montelukast, and zafirlukast on capsular contracture in a rat model. METHODS: Thirty female Wistar albino rats were randomly divided into five groups: control, sham, cromolyn sodium, montelukast, and zafirlukast. Intraperitoneal injections were administered daily to the sham (1 ml per day), cromolyn sodium (10 mg/kg per day), montelukast (10 mg/kg per day), and zafirlukast (1.25 mg/kg per day) groups 1 month before surgery. Miniature breast implants were then placed on the backs of the rats in each group. Injections were continued for the next 3 months. The rats were subsequently killed, and the capsules were harvested and assessed histopathologically. The histopathologic outcomes were acute inflammation status, inflammation severity, synovial metaplasia, foreign body reaction, mast cell count, and capsular thickness. RESULTS: The cromolyn sodium, montelukast, and zafirlukast groups had less acute inflammation and lower mean inflammation severity scores, foreign body reaction occurrence, mast cell counts, and capsular thickness than the control and sham groups ( p < 0.05). These parameters were better in the cromolyn sodium group than in the montelukast and zafirlukast groups ( p < 0.05). CONCLUSIONS: Cromolyn sodium appears to inhibit capsular contracture more efficiently than montelukast and zafirlukast. This report may be a pioneer study for the prophylactic use of cromolyn sodium in capsular contracture. CLINICAL RELEVANCE STATEMENT: The prophylactic administration of cromolyn sodium appears to reduce capsular contracture more efficiently than that of montelukast and zafirlukast. This report might constitute a pioneer study for the prophylactic use of cromolyn sodium in capsular contracture.

The Role of Verteporfin in Prevention of Periprosthetic Capsular Fibrosis: An Experimental Study.

BACKGROUND: Capsular contracture (CC) characterized by excessive fibrosis is one of the most common complications after silicone implant surgery. Verteporfin (VP), an inhibitor of Yes-associated protein 1 (YAP1), has recently been found to reduce the fibrotic process. OBJECTIVES: The aim of this study was to use an in vivo rabbit model to evaluate the efficacy of VP for the prevention of CC. METHODS: Twenty-four New Zealand rabbits received 10-cc smooth saline silicone implants inserted in the dorsal skin and were randomly divided into 2 groups to receive 2 mL VP (1.5 mg/mL) or 2 mL phosphate-buffered saline solution instillation in the implant pocket. When the animals were killed on Day 60, capsule formation was observed both macroscopically and microscopically. Histologic evaluation included capsule thickness, fibrosis degree, and myofibroblast (α smooth muscle actin positive) content. In addition, the YAP1 expression level was examined by immunofluorescence staining. Transforming growth factor ß1, collagen I, and connective tissue growth factor expression were measured by real-time quantitative polymerase chain reaction. RESULTS: The VP-treated group exhibited thinner, more transparent capsules and less fibrosis than the control group at 60 days postsurgery (P < 0.05). Moreover, the VP treatment significantly reduced α smooth muscle actin, YAP1, transforming growth factor ß1, collagen I, and connective tissue growth factor expression levels in the capsular tissues (P < 0.05). CONCLUSIONS: VP reduced capsule formation after silicone implantation by inhibiting YAP1-mediated mechanical signaling, thereby attenuating excessive collagen deposition in the rabbit model. This preclinical study may provide a feasible strategy to prevent periprosthetic capsular fibrosis in clinical application.

In Vivo and In Vitro Fibroblasts' Behavior and Capsular Formation in Correlation with Smooth and Textured Silicone Surfaces.

BACKGROUND: As the most principal complication following breast augmentation with silicone breast implants, capsular contracture is greatly influenced by surface texture. However, there have long been widespread debates on the function of smooth or textured surface implants in reducing capsular contracture. MATERIALS AND METHODS: Three commercially available silicone breast implants with smooth and textured surfaces were subjected to surface characterization, and in vitro and in vivo assessments were then implemented to investigate the effect of these different surfaces on the biological behaviors of fibroblasts and capsular formation in rat models. RESULTS: Surface characterization demonstrated that all three samples were hydrophobic with distinct roughness values. Comparing the interactions of fibroblasts or tissues with different surfaces, we observed that as surface roughness increased, the adhesion and cell spreading of fibroblasts, the level of echogenicity, the density of collagen and α-SMA-positive immunoreactivity decreased, while the proliferation of fibroblasts and capsule thickness increased. CONCLUSIONS: Our findings elucidated that the effect of silicone implant surface texture on fibroblasts' behaviors and capsular formation was associated with variations in surface roughness, and the number of myofibroblasts may have a more significant influence on the process of contracture than capsule thickness in the early stage of capsular formation. These results highlight that targeting myofibroblasts may be wielded in the prevention and treatment strategies of capsular contracture clinically. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Complete Implant Wrapping with Porcine-Derived Acellular Dermal Matrix for the Treatment of Capsular Contracture in Breast Reconstruction: A Case-Control Study.

BACKGROUND: Capsular contracture (CC) represents one of the most common complications in breast reconstruction surgery, impairing final result and patients' well-being. The role of acellular dermal matrixes (ADM) has been widely described for the treatment and prevention of contracture. The aim of the study was to evaluate the efficacy and safety of complete implant coverage with porcine-derived ADM in preventing CC limiting complications. In addition, patients' reported outcomes were evaluated in order to define the role of ADM in improving sexual, physical and psychosocial well-being and satisfaction. METHODS: 42 patients who underwent surgical treatment of 46 contracted reconstructed breasts from May 2018th to May 2019th were collected in the two groups (ADM group vs. Control group). RESULTS: The ADM group showed lower rate of CC recurrence and a higher rate of implant losses and minor complications. A significant difference was observed in red breast syndrome (27.3% in the ADM group vs. absent in control the group) and skin ulceration rates (18.2% in the ADM group vs. 4.18% in the control group). As for patients' perceived outcomes, the ADM group showed a statistically significant higher postoperative Satisfaction of Breast Scale score compared to the control group. In addition, a significant difference was observed in the improvement of Physical Well-Being of the Chest Scale and the Satisfaction of Breast Scale after surgery, in favor to the ADM group. CONCLUSION: Complete implant coverage with ADM may reduce the risk of CC recurrence in breast reconstruction. An accurate patient selection allows minimizing complications improving patient well-being and satisfaction. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Implants and Breast Pocket Irrigation: Outcomes of Antibiotic, Antiseptic, and Saline Irrigation.

BACKGROUND: Breast implant-associated infection and capsular contracture are challenging complications that can result in poor outcomes following implant-based breast surgery. Antimicrobial irrigation of the breast pocket or implant is a widely accepted strategy to prevent these complications, but the literature lacks an evidence-based consensus on the optimal irrigation solution. OBJECTIVES: The objective of this systematic review was to compare clinical outcomes, specifically capsular contracture, infection, and reoperation rates, associated with the use of antibiotic, antiseptic, and saline irrigation. METHODS: A systematic review was performed in March 2020 based on the following search terms: "breast implant," "irrigation," "antibiotic," "bacitracin," "antiseptic," "povidone iodine," "betadine," "low concentration chlorhexidine," and "hypochlorous acid." Capsular contracture, infection, and reoperation rates were compared by analysis of forest plots. RESULTS: Out of the 104 articles screened, 14 met the inclusion criteria. There was no significant difference in capsular contracture rates between antibiotic and povidone-iodine irrigation, although the data comparing these 2 groups were limited and confounded by the concurrent use of steroids. Antibiotic irrigation showed a significantly lower rate of capsular contracture compared with saline irrigation and a lower rate of capsular contracture and reoperation compared with no irrigation at all. Povidone-iodine was associated with lower rates of capsular contracture and reoperation compared with saline irrigation but there were no data on infection rates specific to povidone-iodine irrigation. CONCLUSIONS: Our study supports the use of antibiotics or povidone-iodine for breast implant irrigation. Further research is required to better determine which of these 2 irrigation types is superior.

Treatment and Prevention of Periprosthetic Capsular Contracture in Breast Surgery With Prosthesis Using Leukotriene Receptor Antagonists: A Meta-Analysis.

BACKGROUND: Capsular contracture (CC) is the most common long-term complication of breast surgery with prosthesis. Leukotriene receptor antagonists (LRAs) have been tested as a potential treatment; however, mixed results have been observed. OBJECTIVES: The aim of this study was to undertake a meta-analysis to clarify the treatment and prophylactic capabilities of LRAs in the management of CC. METHODS: A systematic literature search of the most popular English-language databases was performed to identify relevant primary publications. We included all studies that used the Baker scale to evaluate the treatment and preventive capabilities of LRAs. RESULTS: Six eligible studies were included based on predefined inclusion and exclusion criteria, totalling 2276 breasts, of which 775 did not receive LRAs and 1501 did. Final pooled results showed that LRAs could help manage CC with a risk difference (RD) of -0.38 with a corresponding 95% CI of -0.69 to -0.08, showing statistical significance at a Z value of 2.48, P = 0.01. Subgroup analysis based on the type of drug showed that only montelukast yielded statistical significance (RD = -0.27, 95% CI = -0.51 to -0.03, Z = 2.20, P = 0.03). Zafirlukast did not seem to influence CC. Further subgroup analysis based on treatment timing showed that prophylaxis was ineffective and only treatment for ongoing CC yielded statistically significant improvements. CONCLUSIONS: The current meta-analysis proved that LRAs could be used in the management of CC. Only treatment for ongoing CC showed statistically significant improvements. Montelukast seemed to be more efficient with a safer profile for adverse effects, whereas zafirlukast yielded no statistically significant results.