Relevant data from all studies were included in the meta-analysis. Seven studies reported on any necrosis or ischemia, 9 studies reported on NAC necrosis or ischemia, 6 studies reported on infection, 5 studies reported on hematoma, 4 studies reported on seroma, 4 studies reported on unplanned return to OR, and 5 studies reported on implant explantation (Table 1). Results from the meta-analysis were 9% for any necrosis or ischemia, 4% for NAC necrosis or ischemia, 12% for infection, 1% for hematoma, 5% for seroma, 4% experienced explantation, and 9% experienced unplanned return to OR. I2 statistic was above 80% in most analyses. The results and Forrest plots are shown in Supplemental Digital Content 1 (see pdf, Supplemental Digital Content 1, which displays the meta-analysis of complication rates related to nipple-sparing mastectomy with acellular dermal matrix presented individually, http://links.lww.com/PRSGO/A650).
The use of ADM has rapidly become a well-established part of breast reconstruction with NSM.6,29 In many institutions it has become an integrated part of the reconstructive procedure. However, the literature regarding benefits and complications from this method seems sparse. To our knowledge, this systematic review provides the first summarized data on complications specifically related to NSM and IBR with ADM. The results of our meta-analysis indicate that approximately 4% (9 studies, 778 procedures) of patients experienced nipple necrosis or ischemia when using ADM for NSM and IBR. Furthermore, our meta-analysis computed a 12% infection rate (6 studies, 616 procedures), a seroma rate of 5% (4 studies, 270 procedures), and a hematoma rate of 1% (5 studies, 551 procedures). Because of a large heterogeneity, it is difficult to compare these findings. Although 1 study reported a significant decrease in the rate of infection in patients reconstructed with ADM compared with those reconstructed without ADM,21 it is not possible to conclude whether or not the use of ADM significantly affects the risk of these complications. The infection rate remains 1 of the controversial issues related to the use of ADM and more studies specifically addressing this issue are warranted. Five of the included studies reported on explantation (362 procedures). Peled et al.21 found a decrease of explantation from 17.8% to 7% when ADM was introduced. Sbitany et al.22 reported a small decrease of approximately 1% in the rate of explantation. None of the studies elaborated on the cause of explantation.
The identification of possible risk factors as selection criteria is mandatory for successful reconstruction. Olson et al.26 reported smoking as a significant risk factor for postoperative infection and that women later scheduled for postoperative chemotherapy had significantly higher risk of postoperative necrosis. Radiotherapy is a known risk factor for postoperative complications in breast reconstructive surgery, which was supported by findings in several of the included studies. Rawlani et al. demonstrated a trend toward increased nipple necrosis and soft-tissue infection in mainly women receiving neoadjuvant radiotherapy.11 This was in concordance with findings by Olson et al.26 who reported increased risk of necrosis in women receiving premastectomy radiation. In addition, Boneti et al.23 reported increased rate of capsular contracture in irradiated breasts but did not distinguish between TSSM and SSM. Peled et al.21 is the only study that reports complication rates specifically in the setting of postoperative radiotherapy. They found significantly decreased rates of infection, expander-implant loss, and unplanned return to the operating room in women who consecutively received ADM compared with women who did not receive ADM. This point toward a protective effect of ADM in these patients.21 Gunnarsson et al.24 only included nonsmoking women treated with risk-reducing mastectomy and presented complication rates that were considerably lower than in all other studies included in this review. In contrast, Wong et al.27 only included cases treated therapeutically and presented considerably higher complication rates. This suggests that ADM use in NSM is a relatively safe procedure in healthy women. However, it also indicates that caution should be taken when considering ADM for women with significant risk factors even though ADM may have a protective effect in women scheduled for postmastectomy radiotherapy.
Choice of material may also influence complication rates. Higher complication rates when using the human-derived Alloderm in terms of seroma, infection, and necrosis have been reported in a recently published review.30 Some surgeons have argued that porcine-derived materials are safer to use in terms of complications compared with human-derived materials.31 However, it should be emphasized that Alloderm is by far the most thoroughly evaluated material and reporting bias preclude any firm conclusions.30 Due to few studies included in this review, we were not able to investigate differences between ADM materials.
To fully appreciate results of this review, some aspects needs to be addressed. Studies had to be excluded due to their vagueness regarding rates of complications in the respective subgroups. Although the studies did define the surgical methods and the proportion of patients reconstructed using ADM versus muscle coverage, they did not differentiate between subgroups. Several of the included studies lack clear definitions of the nature of complications. It is recommended that authors clearly define which signs determine the presence of infection to enhance comparability with other studies. Skin flap/nipple necrosis should be clearly described with regard to thickness, level, and appearance. In addition, the reporting of epidermolysis varies and some authors may have chosen not to report this as a complication. Therefore, the risk of observer bias could limit the certainty of the meta-analysis results. Only a few studies elaborate on patient characteristics such as radiotherapy, demographic factors, smoking, and BMI. Only 1 of the 9 included studies include predictor analysis for high risk patients.26 The heterogeneity of the included studies should also be considered when interpreting results of this review. As expected, the heterogeneity as expressed by the I2 statistic was high in most of the meta-analyses. Besides unclear definitions, other factors are likely to explain this. The populations vary from healthy relatively young women treated with risk-reducing mastectomy to older women with considerable comorbidities treated with therapeutic mastectomy, sometimes with a history of prior breast surgery. Moreover, some of the studies did not distinguish between 1- and 2-stage reconstructions in the reporting of data (Table 1). Surgeon experience will naturally influence complication rates as well. The quality of the skin flaps are important determining factors for reducing complication rates, especially NAC necrosis.32 Although it may be difficult to carry out in real life, it would be of great interest to document the quality of the skin flaps using objective measures.
Lastly, potential commercial bias is an important aspect that needs mentioning. Information on conflicts of interest was provided in all studies. Seven studies reported no conflicting interests among the authors.11,21,24–28 One author was a member of the speakers bureau for LifeCell Corporation but also states that he did not receive any compensation or financial support for the study.22 Another study reported 1 author receiving support from Fashion Footwear Association of New York.23
In summary, this review and meta-analysis regarding NSM and IBR using ADM revealed a skin necrosis rate of 9%, nipple necrosis in 4%, infection in 12%, hematoma in 1%, seroma in 5%, explantation in 4%, and 9% experienced unplanned return to operating room. Complication rates computed in this review do not seem to vary considerably from complication rates reported in reviews on NSM in general.1,7,9,33
High-level scientific evidence concerning complications following the use of ADM in NSM and IBR is surprisingly limited in existing literature. There is nothing in the data collected for this review and meta-analysis, suggesting that the use of ADM changes the outcome of NSM and IBR. The favorable outcome is still based on the good judgment and skills of the joint efforts of breast- and plastic surgeons. On the other hand, no data suggests either that the use of ADM significantly aggravates the outcomes of ADM-based NSM and IBR.
This article is the first to provide systematically summarized data on complications specifically related to NSM and IBR with ADM. The use of ADM in NSM and IBR can be done with acceptable complication rates in carefully selected patients. The use of ADM does not seem to change the complication rates following NSM and IBR. However, the current literature regarding this subject is still limited and standardized reporting is warranted. We recommend future studies to include specific definitions when reporting complication rate. Furthermore, future studies should elaborate on demographic characteristics of the included study samples and include predictor analysis to enhance knowledge of high risk patients.
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