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      The Preventive Effect of Topical Zafirlukast Instillation for Peri-Implant Capsule Formation in Rabbits

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          Abstract

          Background

          Capsular contracture is the most troublesome complication in breast implant surgery. Although capsule formation can be seen as a normal reaction to a foreign body, it can induce pain, hardness, deformity, and other pathologic problems. Surgical intervention is required in severe cases, but even surgery cannot guarantee a successful outcome without recurrence. This experimental study confirms that single topical administration of leukotriene antagonist zafirlukast (Accolate, Astrazeneca) reduces peri-implant capsule formation and prevents capsular contracture.

          Methods

          Twelve smooth-surfaced cohesive gel implants were implanted in New Zealand White rabbits. These miniature implants were designed to be identical to currently used products for breast augmentation. The rabbits were divided into 2 groups. In the experimental group (n=6), the implant and normal saline with zafirlukast were inserted in the submuscular pocket. In the control group (n=6), the implant and normal saline alone were used. Two months later, the implants with peri-implant capsule were excised. We evaluated capsule thickness and collagen pattern and performed immunohistochemical staining of myofibroblasts, transforming growth factor (TGF)-β1, 2.

          Results

          The thickness of the capsules in the experimental group was reduced in both dorsal and ventral directions. The collagen pattern showed parallel alignment with low density, and the number of myofibroblasts as well as the amounts of TGF-β1 and TGF-β2 were reduced in the experimental group.

          Conclusions

          We suggest that single topical administration of leukotriene antagonist zafirlukast can be helpful in reducing capsule formation and preventing capsular contracture via myofibroblast suppression, modulation of fibroblastic cytokines, and anti-inflammatory effect.

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          Most cited references25

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          On the nature of hypertrophic scars and keloids: a review.

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            Neutralising antibody to TGF-beta 1,2 reduces cutaneous scarring in adult rodents.

            Scarring is a major cause of many clinical problems. Scar tissue interferes with growth, impairs function and is aesthetically unpleasant. However, scarring does not appear to be a problem of embryonic life. Embryonic wounds heal with a lower inflammatory and angiogenic response and have a different growth factor profile compared to adult wounds. We have used neutralising antibody to transforming growth factor-beta 1,2 (TGF-beta 1,2) to alter the growth factor profile of cutaneous wounds in adult rodents and studied the effect on scar tissue formation. This paper extends our preliminary report that neutralising antibody to TGF-beta reduces cutaneous scarring in adult rodents. To be effective, the neutralising antibody to TGF-beta needs to be administered at the time of wounding or soon thereafter. The antiscarring effects of this neutralising antibody to TGF-beta were dose dependent. Exogenous addition of neutralising antibody to TGF-beta to incisional wounds reduced the inflammatory and angiogenic responses and reduced the extracellular matrix deposition in the early stages of wound healing without reducing the tensile strength of the wounds. Importantly, the architecture of the neodermis of wounds treated with neutralising antibody to TGF-beta resembled more closely that of normal dermis compared to the unmanipulated control wounds, which healed with an abnormal neodermal architecture resulting in obvious scarring. This study suggests a novel therapeutic approach to reducing scarring in post-natal life.
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              A rabbit model for capsular contracture: development and clinical implications.

              Capsular contracture remains one of the most common complications involving aesthetic and reconstructive breast surgery; however, its cause, prevention, and treatment remain to be fully elucidated. Presently, there is no accurate and reproducible pathologic in vitro or in vivo model examining capsular contracture. The purpose of this study was to establish an effective pathologic capsular contracture animal model that mimics the formation of capsular contracture response in humans. New Zealand White rabbits (n = 32) were subdivided into experimental (n = 16) and control groups (n = 16). Each subgroup underwent placement of smooth saline mini implants (30 cc) beneath the panniculus carnosus in the dorsal region of the back. In addition, the experimental group underwent instillation of fibrin glue into the implant pocket as a capsular contracture-inducing agent. Rabbits were euthanized from 2 to 8 weeks after the procedure. Before the animals were euthanized, each implant was serially inflated with saline and a pressure-volume curve was developed using a Stryker device to assess the degree of contracture. Representative capsule samples were collected and histologically examined. Normal and contracted human capsular tissue samples were also collected from patients undergoing breast implant revision and replacement procedures. Tissue samples were assessed histologically. Pressure-volume curves demonstrated a statistically significantly increased intracapsular pressure in the experimental group compared with the control group. The experimental subgroup had thicker, less transparent capsules than the control group. Histologic evaluation of the rabbit capsule was similar to that of the human capsule for the control and experimental subgroups. The authors conclude that pathologic capsular contracture can be reliably induced in the rabbit. This animal model provides the framework for future investigations testing the effects of various systemic or local agents on reduction of capsular contracture.
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                Author and article information

                Journal
                Arch Plast Surg
                Arch Plast Surg
                APS
                Archives of Plastic Surgery
                The Korean Society of Plastic and Reconstructive Surgeons
                2234-6163
                2234-6171
                March 2015
                16 March 2015
                : 42
                : 2
                : 179-185
                Affiliations
                [1 ]Department of Plastic and Reconstructive Surgery, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea.
                [2 ]Department of Pathology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea.
                Author notes
                Correspondence: Woo Seob Kim. Department of Plastic and Reconstructive Surgery, Chung-Ang University Hospital, Chung-Ang University College of Medicine, 102 Heukseok-ro, Dongjak-gu, Seoul 156-755, Korea. Tel: +82-2-6299-1615, Fax: +82-2-825-9880, kimws@ 123456cau.ac.kr
                Article
                10.5999/aps.2015.42.2.179
                4366699
                cbf465fc-1644-4c1f-985c-deac50cefa7a
                Copyright © 2015 The Korean Society of Plastic and Reconstructive Surgeons

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 22 September 2014
                : 20 October 2014
                : 28 October 2014
                Categories
                Original Article

                Surgery
                breast implants,implant capsular contracture,zafirlukast,prevention
                Surgery
                breast implants, implant capsular contracture, zafirlukast, prevention

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