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.


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.

Introduction
Implant-based breast reconstruction is the most applied reconstructive option after mastectomy in the USA and Europe [1,2]. Capsular contracture (CC) is a clinical condition that typically affects breast-implanted patients in which an excessive fibrous tissue formed around prostheses causes implant firmness, deformation, dislocation, patient discomfort, and pain with adverse impact on patients' quality of life and psychological well-being. Baker classified it in four clinical grades [3,4]. Most patients usually complain about symptoms in the first 12-24 months after primary surgery even if there is a lack of agreement regarding the time of CC development [5,6].
CC still represents one of the most challenging complications of breast reconstruction affecting 13.7 to 45% of patients, and it is the most common reason of re-operation [7]. However, it is considered a multifactorial event depending on patient/surgery/implant-based risk factors with unknown etiology [3,8,9].
Surgical intervention is usually indicated for the treatment of grades III and IV CC according to Baker's classification, respectively, characterized by moderate, palpable and visible prosthesis or severe, hard, painful contraction with prosthesis distortion [15].
The best approach to reduce the risk of recurrence is still a matter of debate. Polyurethane devices [16], implants substitution using smaller size [15], the association of fat grafting, precaution in preventing the contact between the skin and the prosthesis, anterior capsulectomy (as described by Ganon et al. and Lam et al. [15,17]) and implants coverage with acellular dermal matrices (ADM) [18,19] have been associated with reduced risk of recurrence.
The use of ADMs for the treatment of capsular contracture is gaining popularity, with many papers describing the use of human-derived ADM with complete or partial implant coverage [28]. Cheng et al. in 2013 reported a novel technique with improved results in reducing capsular contracture [18]. Among many ADMs available in the market, not all of them are available worldwide. In particular, the use of human-derived ADM is limited by law in some countries. Therefore, porcine-derived ADM can be used.
We aimed in evaluating the role of complete implant wrapping with porcine-derived ADM in reducing capsular contraction recurrence and improving patients' reported outcomes with validated Breast Q questionnaire [29].

Patients and Methods
A retrospective case-control study was conducted in accordance with the World Medical Association Declaration of Helsinki (June 1964) and subsequent amendments.
We performed a case-control study with 42 breast reconstruction patients affected by capsular contracture grades 3 and 4 according to Baker's classification who underwent a revision surgery to treat capsular contracture at the Division of Plastic Surgery, at our University-Hospital, from May 2018th to May 2019th. Institutional review board approval was granted for this study.

Surgical Technique and Peri-operative Indications
The breast implant exchange was performed with complete anterior capsulectomy without plane change. The final implant size was selected after pocket measurement. Patient received prophylactic peri-operative intravenous antibiotics in the form of cefazolin, or clindamycin in case of allergy. If indicated, simultaneous contralateral surgery was performed with symmetrization or with bilateral CC treatment.
In the control group were collected patients undergoing only breast implant exchange while in the ADM group were collected patients in which a 0.6 mm porcine patented-shaped ADM BraxonÒ (Decomed S.r.l) was wrapped all around the prosthesis to achieve a total implant coverage after ADM hydration (Fig. 2) The prostheses covered with ADM were then inserted in the pocket and sutured to the thoracic fascia with Vicryl TM 2-0 (Ethicon Inc., the USA), without glue (Fig. 3). In case of bilateral CC, the same surgical solution with or without ADM was applied for both breasts.   Patients of both groups were discharged the day after surgery. Post operative oral antibiotic prophylaxis was continued until drainage removal (output \ 30 mL in a 24-hour period). Post-operative bra was recommended for 3 months.

Clinical Data and Follow-Up
Age, preoperative BMI, smoke, comorbidities, history of RT and chemotherapy as well as implant volume and type, operative time were collected retrospectively from patients' chart.
In our Unit, all patients are followed up with periodic controls during the first month and at 3, 6, 12, 18, 24 months after surgery, and Breast-Q Questionnaires (BQ) are administrated.
Post-operative complications were divided in minor complications, implant loss and CC relapse. Minor complications considered were ulcerations/necrosis not requiring revision, fever, infection, edema, hematoma not requiring re-operation, type IV delayed hypersensitivity reactions (red breast syndrome). CC was diagnosed in patients who developed a Baker III or IV grade.
Data on patients' demographics and history, breast characteristics, surgery, implant specificity, recovery time and complications were analyzed and compared in the 2 groups in order to find potential risk factors for capsular contracture recurrence and/or implant loss.
Patients' perceived outcomes were compared based on the data collected from the registered-trademark BREAST-Q Reconstructive Module, which includes multiple scales concerning specific aspects of Patient Satisfaction and No statistical significant differences were observed between the two groups Health-related Quality of Life and that has a specific approved Italian translation.
Breast Q values before and after surgery were compared within and between the two groups using the paired t test and the ANOVA test, respectively.

Statistical Analysis
Statistical analysis was carried out using MicrosoftÒ ExcelÒ software (version 16.35 for Mac) and IBMÒ SPSSÒ software (version 25 for Windows).
Categorical variables were described by number and percentage and continuous variables by mean, standard deviation, median, minimum and maximum. For test of differences between the two groups, Fisher's exact test was used for dichotomous variables, the chi-square test for nonordered categorical variables and the ANOVA test for continuous variables.
The prediction of complications during the study with baseline characteristic variables was performed by using logistic regression. Odds ratio (OR) and 95% confidence intervals (CIs) were presented from these analyses with associated p value. All tests were two-tailed and conducted at a 0.05 significance level.

Ethical Statement
The displayed study was carried out with respect of high ethical standards. All the studies have been approved, when required, by the appropriate ethics committee and have, therefore, been performed in accordance and in conformity to the World Medical Association Declaration of Helsinki (June 1964) and sub-sequent amendments.

Informed Consent
All patients signed an informed consent for the procedures. For this type of study, formal consent is not required.

Results
42 patients who underwent surgical treatment of CC affecting 46 breasts after reconstruction with breast implant were collected in the two groups (Control vs. ADM group). No differences were observed in patients' demographics (Table 1), surgical details, post-operative management and follow-up data ( Table 2) between the two groups. The mean follow-up time was 28 ± 3 months in the ADM group and 30 ± 4 months in the control group (Fig. 4).

Capsular Contracture and Complications
The CC recurrence was lower in the ADM group (11.7%-2/17) compared to the control group (25 %-6/23) even if without statistical significance (p = 0.261). On the contrary, the rate of complication was higher in the ADM group. Implant losses were higher in the ADM group even if without statistical significance (22.7%-5/22 cases in the ADM group vs. 4.2%-1/24 in the control group, p = 0.075). On the other hand, a significant statistical difference was observed in the rate of minor complications such as red breast syndrome (Fig. 5) and skin ulceration rate (Figs. 6 and 7).
Univariable logistic regressions recognized previous radiation as a significant predictor for developing both CC recurrence and implant loss (OR 6, p = 0.046 and OR  As for intra-group differences before and after surgery, both groups showed improvement in all items. A statistical significant difference in the improvement of breast Q values, in favor of the ADM group, was observed in the Physical Well-Being of the Chest Scale (relief from thorax muscles pain, tension, discomfort on the breast, difficulties in arms moving) and in the Satisfaction of Breast Scale, (normality in clothes, size of the reconstructed breast, being able to wear clothes that are more fitted, how breasts are lined up in relation to each other, how comfortably bras fit, how equal in size are breast to each other) (Table 3A). On the contrary, the improvement in the Sexual Well-Being Scale (satisfaction of sexual life, comfort while having sex and sexual attractiveness without clothes) was higher in the control group (Table 3B).

Discussion
Capsular contracture is a problematic issue that has affected and is still affecting plastic surgery practice for a long time. Acellular dermal matrixes placed in various manners have been proposed to decrease the rate of CC recurrence. Clinical and patients' reported outcomes were retrospectively compared in the present study in order to define the impact of a porcine-derived ADM in improving CC treatment. Anterior ''complete'' ADM implant coverage showed promising results in limiting capsular contracture recurrence and improving patients' satisfaction in breast reconstruction patients [18]. As reported by Liu et al. [30], previous studies demonstrated the role of partial and anterior ADM coverage in reducing CC formation and recurrence both in breast reconstruction and breast augmentation [18,19,27,31]. Indeed, we postulated that a complete isolation of the prosthesis also from the posterior capsule, left in place after anterior capsulectomy to reduce post-operative complications, could be beneficial to further reduce CC recurrence, improving patient well-being. A complete ADM coverage could limit the pathologic process of capsule formation tridimensionally [27].
Even if non-statistically significant, the results confirmed the role of ADM in reducing the risk capsular contracture development and recurrence, according to previous studies [18,19]. A larger study could corroborate the significance of the results. Capsular contracture recurrence of grade III and IV showed significant relation with history of RT and implant volume greater than 400 cc. Both RT and high implant volume are known risk factors for CC recurrence [5,30,32]. Even though ADM application is considered a protective factor before adjuvant RT [26], its protective effects appeared limited when the reconstruction with ADM is performed after RT [33,34].
Indeed, according to previous studies, the use of ADM was associated with higher rates of complication (ulceration and red breast syndrome) with significant correlation between RT and implant loss [35,36]. No other factor alone showed association with implant loss in univariate analysis.
Our results confirmed that preoperative RT is a significant predictor of both implants loss and CC recurrence after surgical revision with and without ADM. Proper  selection of patients and indication for autologous breast reconstruction should be considered in previously irradiated breasts [37].
As for patients reported outcome, the ADM improved Breast Q scores in tools such as general satisfaction, chest well-being and implants satisfaction when compared to breast implant exchange alone. A scarce literature dealing 11 [38]. According to previous study, ADM-assisted breast reconstruction is associated with high satisfaction rates when performed in a selected group of patients [39].
As for the enhanced post-operative results in the ADM group, they could be explained by the improved quality of soft tissue covering prosthesis anteriorly and with the application of a dermal matrix over the posterior capsule, left in place after anterior capsulectomy. In addition, an efficacious unloading of the weight of the prostheses over the suture of the matrix could explain the improved chest well-being score in the ADM group [28,40]. On the contrary, the significant improvement of sexual well-being after surgery in the control group could be related to the differences in preoperative sexual well-being, which was lower in the control group.
The benefits in terms of improved patients' reported outcome and protection against CC recurrence should be carefully weighed with the risk of complications and reconstructive failure and discussed with patients through a thorough discussion.
The main limitations of the present study include its retrospective nature, and the relative low number of patients involved. In addition, we report a clinical experience with a porcine-derived ADM and studies performed with different ADM should be performed. Moreover, the role of complete and partial coverage with ADM in preventing CC recurrence could be compared.
Further studies based on larger cohorts performing cost analysis should be done in long term to define the impact of different confounders in capsular contracture development and the effect of this technique in the overall costs of the procedure.

Conclusion
Complete implant coverage by ADM may reduce the risk of CC recurrence in breast reconstruction. An accurate patient selection allows to minimize complications improving patient well-being and satisfaction.
Previous RT represents the main contraindication, as a risk factor for implant loss and capsular contracture recurrence. These results may represent the basis for future studies to determine an ideal flow chart to accomplish optimal outcomes in the treatment of CC and to achieve improved aesthetic and functional results breast reconstruction.
Funding Open access funding provided by Università degli Studi di Padova within the CRUI-CARE Agreement.

Declarations
Conflict of interest The authors have no conflict of interest regarding the submitted work.
Ethical standard The displayed study was carried out with respect of high ethical standards. All the studies have been approved, when required, by the appropriate ethics committee and have, therefore, been performed in accordance and in conformity to the World Medical Association Declaration of Helsinki (June 1964) and subsequent amendments.
Informed consent All patients signed an informed consent for the procedures. For this type of study, formal consent is not required.
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons. org/licenses/by/4.0/.