An acellular dermal matrix (ADM) is a decellularized soft tissue material derived from a biological source. In breast surgery, ADMs have been used as an alternative to autologous myocutaneous flap grafts to bridge defects following aesthetic or oncoplastic breast reconstruction [
A variety of human derived ADMs (HADMs) are commercially available: Epiflex by DIZG (Berlin, Germany), Alloderm® by LifeCell Corporation (Bridgewater, NJ, USA), and DermaMatrix® by Synthes CMF (West Chester, PA, USA). However, Alloderm is not currently licensed for use in Germany. Strattice by LifeCell Corporation (Bridgewater, NJ, USA) is derived from porcine dermis/corium (PADM) and Tutomesh by RTI Surgical (Alachua, FL, USA) is derived from bovine pericardium.
Reported complications of ADM reconstruction techniques include skin necrosis, seroma, haematoma, infection, and Red Breast Syndrome (RBS). RBS is erythematous change occurring superficially to the area of ADM implantation without any specific signs of local infection; its mechanism is not well understood [
The aim of this study is to assess the incidence of short- and long-term complications of implantation of various kinds of ADMs in our centre.
Our analysis followed 41 female patients with a total of 52 ADM-based breast reconstructions between 2010 and 2015, using matrices such as Epiflex by DIZG (Berlin, Germany), Strattice by LifeCell Corporation (Bridgewater, NJ, USA), and Tutomesh by RTI Surgical (Alachua, FL, USA). Indications for reconstruction included secondary oncologic breast reconstructions (delayed), primary augmentations (in large breasts), or secondary breast augmentations (revision). In further detail, 15 HADMs (Epiflex), 21 PADMs (Strattice), and 16 BADMs (Tutomesh) were applied. Detailed information about the patient demographics with respect to type of ADM used is shown in Table
Patient collective with ADM-implementation.
ADM | Product | Number of ADM implants used | Number of treated patients | Avg. patient age (years) | Avg. follow-up time (months) |
---|---|---|---|---|---|
HADM | Epiflex/DIZG | 15 | 12 | 46 (36–76) | 40 (20–50) |
PADM | Strattice/LifeCell | 21 | 16 | 56 (44–66) | 43 (30–54) |
BADM | Tutomesh/RTI Surgical | 16 | 13 | 53 (33–74) | 20 (12–31) |
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Total |
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Listing of matrix, name of ADM-product and its fabricant, amount of breast reconstructions (BR)/augmentations with usage of ADMs, number of patients treated with ADMs, average patient age and range in years, and average follow-up time + range in months of the given patient collective, which received a breast reconstruction with ADM; HADM: human ADM, PADM: porcine ADM, and BADM: bovine ADM.
Indications for ADM implementation.
ADM | Product | BR with ADM ( |
Oncologic indication | Aesthetic indication |
| ||
---|---|---|---|---|---|---|---|
BR with no capsular |
BR with capsular |
Primary |
Secondary augmentation after capsular |
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HADM | Epiflex/DIZG | 15 | 1 | 3 | 9 | 2 | 0 |
PADM | Strattice/LifeCell | 21 | 6 | 8 | 5 | 2 | 0 |
BADM | Tutomesh/RTI Surgical | 16 | 2 | 5 | 3 | 2 | 4 |
Listing of kind of matrix used, name of product, number of breast reconstructions with certain ADMs, and indications for ADM usage (breast reconstruction (BR) with no capsular contracture, BR with capsular contracture, primary augmentation, secondary augmentation after capsular contracture). Oncologic patients made up 27% of the HADM group, 67% of the BADM group, and 44% of the BADM group; HADM: human ADM, PADM: porcine ADM, and BADM: bovine ADM;
Complications after ADM implementation.
ADM | Product | Complication |
Skin necrosis | Seroma | Haematoma | Infection | Recurrence of capsular contracture | Implant malposition | Implant loss |
|
---|---|---|---|---|---|---|---|---|---|---|
HADM | Epiflex/DIZG | 7% | — | — | — | 1 | — | — | — | — |
PADM | Strattice/LifeCell | 14% | 1 | 1 | — | — | 1 | — | — | 1 |
BADM | Tutomesh/RTI Surgical | 31% |
|
— | — | 1 |
|
— | 1 | 2 |
Complications following ADM implantation for breast reconstruction with type of matrix, product, complications requiring further medical treatment (in %), infection, seroma, haematoma, skin necrosis, recurrence of capsular contracture, implant malposition, implant loss, and Red Breast Syndrome (RBS); HADM: human ADM, PADM: porcine ADM, and BADM: bovine ADM;
Retrospective data analysis was performed using our hospital information system (HIS), median follow-up of 36 months (range: 12–54 months). Only patients with at least one year of follow-up time were included in our study. Patients were followed up at intervals of one week, two weeks, one month, three months, six months, and one year and then annually thereafter or if complications occurred. Assessment of short-term complications such as infection, seroma, haematoma, or skin necrosis and long-term complications such as capsular contracture (>Baker-St. II), implant malposition, or implant loss was made. Red Breast Syndrome (RBS) was the only complication occurring shortly after ADM usage in which no further medical treatment was indicated, though differential diagnosis might be challenging. Ultrasound imaging was performed in all patients with suspicion of RBS. Histopathological samples of the ADM implementation area were taken in four cases (
Continuous variables were expressed as median (range) and categorical variables as percentages (frequencies) if not other specified. Primary endpoints were skin necrosis, seroma, haematoma, infection, recurrence of capsular contracture, implant malposition, and implant loss. The composite endpoint included all complications as well as the Red Breast Syndrome. In order to analyze whether a trend exists regarding the endpoints between HADM, PADM, and BADM, Mantel-Haenszel Chi-Square was applied. Further, Chi-Square analysis allowed direct comparison between two kinds of ADMs. Statistical analysis was performed using the software SAS (Version 9.4, SAS Institute Inc., Cary, NC). A two-sided
All documented complications after implementations of ADMs occurring during the follow-up interval are demonstrated in Table
Three out of 15 patients, who were treated with Epiflex, required revision breast surgery: three patients received a mastopexy with contralateral breast refinement after 4, 7, or 8 months postoperatively. One month after breast reconstruction with ADM, an infection occurred in a patient with a history of radiotherapy; this was managed conservatively with antibiotics.
Five out of 21 patients, who received a Strattice implant, required revision surgery.
One patient needed revision surgery due to capsular contracture after 11 months postoperatively, and another with a history of radiotherapy had to be surgically revised due to skin necrosis after four months. One patient required ultrasound-guided drainage of a seroma after two months. After 5, 13, and 17 months postoperatively, three patients received a mastopexy with a contralateral mammary adaptation.
Four out of 16 patients, who were treated with Tutomesh, received a surgical revision.
one patient, with a history of chemotherapy, had a skin necrosis plus recurrence of capsular contracture after 6 months postoperatively, resulting in a DIEP-flap coverage. Another had a shell rupture of an implant after two months postoperatively, leading to a breast implant loss. After 10 months postoperatively, one patient with a recurrence of capsular contracture and a history of radiotherapy received a capsulotomy and implant exchange. After two months postoperatively, one patient with infection and loss of IMF underwent a surgical debridement followed by IMF-reconstruction and reaugmentation. In this group, there were no mastopexies with contralateral mammary adaptation during the given follow-up interval. Overall complications, after usage of all three given ADMs, are demonstrated in Table
Overall complication probabilities for used ADMs.
ADM | HADM (Epiflex/DIZG), PADM (Strattice/LifeCell), BADM (Tutomesh/RTI Surgical) |
Breasts (total) | 52 |
Avg. follow-up time (in months) | 36 (12–54) |
Complications (total) | 9 (17%) |
Short-term complications | |
Skin necrosis | 2 (4%) |
Seroma | 1 (2%) |
Haematoma | 0 (0%) |
Infection | 2 (4%) |
|
3 |
Long-term complications | |
Capsular |
3 (6%) |
Implant malposition | 0 (0%) |
Implant loss | 1 (2%) |
Short-term (skin necrosis, seroma, haematoma, infection, and Red Breast Syndrome (RBS)) and long-term complications (capsular contracture, implant malposition, and implant loss) for all breasts with usage of ADMs (human ADM (HADM), porcine ADM (PADM), bovine ADM (BADM)), median follow-up time for all patients, total complications of all breasts being reconstructed with ADMs;
In four patients, who had undergone revision procedures, histopathologic biopsy samples could be taken within HADM-implementation zone (Figures
Histological slide within area of ADM implementation, H&E stain. Vascular invasion within the BADM (Strattice/LifeCell) after 6 months postoperatively. P = patient’s side with breast tissue; ADM = acellular dermal matrix; I = implant side;
Histological slide within area of ADM implementation, CD34 stain. No histological evidence of capsular contracture in sample taken 6 months after BADM-implementation (Strattice/LifeCell). Immunohistochemistry showing strong expression of CD34 in endothelial cells within new grown vessels. P = patient’s side with breast tissue; ADM = acellular dermal matrix; I = implant side;
Case I: 57-year-old female patient suffering from implant malposition with lateral deviation, bottoming-out, rippling, ptosis with different nipple-areola complex (NAC) and IMF positions preoperatively; (a) frontal view; (b) lateral view; one-year postoperative results after BADM implantation (Strattice/LifeCell) with frontal (c) and lateral view (d).
Case II: skin sparing mastectomy and breast augmentation performed in 54-year-old female patient with a history of breast carcinoma, complicated by shell rupture of the left-sided implant and subsequent breast-expander implantation; (a) frontal view; (b) lateral view; three-month postoperative results after HADM usage (Epiflex/DIZG) with frontal (c) and lateral view (d).
ADM-based techniques are now well established for breast reconstruction. There are various products available on the market: Epiflex is a cell-free dermis allograft, which is up to now the only licensed medicinal HADM product in German-speaking countries; Strattice is a sterile, acellular reconstructive tissue matrix, which is derived from porcine dermis; Tutomesh (BADM) is an avital, acellular, and xenogeneic membrane made from bovine pericardium. All manufacturers advertise their acellular matrices to rapidly integrate into the surrounding tissue without causing any immune response. Due to a special treatment of the human or animal source materials, cells, which may cause an autoimmune reaction, are washed out, leaving only a natural collagen membrane behind. But certainly, ADMs generated out of human, porcine, or bovine tissue might still have different qualities concerning tissue integration and postoperative outcomes.
According to the available literature, several studies have demonstrated reduction of capsular contracture [
The incidence of RBS in our cohort was 6% (3/52 patients), with one case in the Strattice and two cases in the Tutomesh group.
In comparison to previously published data, we demonstrate a higher overall complication rate after the implantation of ADM summing up to 17%. In detail, BADM (Tutomesh) had the highest complication probability with 31%, followed by PADM (Strattice) with 14%, and HADM (Epiflex) with 7%. A statistically increased complication probability was noted between the HADM and BADM group, if RBS was included to the other complications requiring further medical treatment. The inclusion of oncologic patients with breast reconstruction after/without radio- and/or chemotherapy may have resulted in greater heterogeneity and therefore increased complication rates.
Furthermore, it has already been shown that radio- or chemotherapy had an influence on implanted ADMs (Alloderm), resulting in a limited ADM modeling [
Salzberg et al. listed an overall complication rate of 3.9% in patients treated with prophylactic or oncologic SSM/NSM in combination with direct-to-implant immediate breast reconstruction using Alloderm (median follow-up: 28.9 months) [
In a recent publication by Mendenhall et al., outcomes from time of tissue expander and HADM placement (Alloderm and DermaMatrix) to definitive reconstruction after simple and total skin and nipple-areola complex-sparing mastectomy were assessed [
Other limitations of our study include the relative brevity of follow-up with a mean time period of 36 months. Many of the complications occurred early in the follow-up interval. Statements about the incidence of long-term complications such as capsular contractures are limited. Certainly, a larger patient collective and a longer follow-up interval are needed to obtain statistically significant results concerning complication rates.
As a result, indications for the use of ADMs should be considered on a case-by-case basis. Surely product costs may influence the surgeon’s decision from time to time: from all three ADMs compared in our study, Strattice was the most expensive matrix and Tutomesh the one with the lowest price.
In our experience, ADMs are useful to correct these problems: loss of the IMF, implantation of high-volume implants, slight capsular contracture, bottoming-out, or other forms of implant malposition.
In this study, Epiflex (HADM) had the lowest complication rate, which may be due to allogenicity; nevertheless our detected total complication rate is greater than rates published within the available literature. In terms of preventing capsular contracture, thicker ADMs, such as Epiflex or Strattice, might be more appropriate for breast reconstruction. This effect could be explained due to prolonged vascular ingrowth time throughout the matrix and a delayed autoimmune response, caused by a longer isolation of the implant from the surrounding tissue. When aesthetic considerations are the greatest concern with loss of the IMF or bottoming-out of the implant, Tutomesh, which is made out of thinner bovine pericardium (offering a greater plasticity), may be favored. But an increased complication rate following BADM application has to be taken into account and should be discussed with the patient preoperatively.
Our retrospective study demonstrated that the use of HADMs is associated with the lowest complication risk (7%) among the three ADMs tested. In comparison with the available literature, the total complication rate of 17% was high. In our study, the capsular contracture rate after ADM reconstruction was 6% at a median follow-up interval of 36 months, that is also increased in comparison to other literature. The authors recommend a judicial use of ADM, taking into account costs, condition after radiotherapy, and uncertain long-term results. The flexible properties of BADMs have advantages in tissue handling and aesthetic properties but had the highest complication probability compared to the other subgroups within our study. Treatment of recurring capsular contracture calls for thicker ADMs such as Epiflex or Strattice. Overall, Epiflex (HADM) had the lowest complication rate within our study, whereas Tutomesh (BADM) showed the highest complication rate. In the case of loss of the IMF, large-volume implants, slight capsular contracture, bottoming-out, and implant malposition, the authors recommend in selected cases HADMs as primary and PADM as secondary treatment options. Due to the small amount of patients included in this retrospective study, a larger patient collective is urgently needed for further evaluation; therefore we suggest a prospective randomised study in order to receive more distinct results.
The research project with all its procedures was granted by the Local Ethics Committee (medical association of Lower Saxony, Germany) and is in accordance with national law and the World Medical Association Declaration of Helsinki (1964) with its ethical principles for medical research involving human subjects and subsequent amendments.
The authors received no payment, compensation, or funding for the current study and thus have no conflicts of interest to declare. Highest ethical and scientific standards were applied. After the study was completed and reviewed, DIZG (Berlin, Germany) was approached and agreed to pay the Article Processing Charge for open access publication.
The authors declare that they have no conflicts of interest.