Outcome of use of acellular-dermal matrix to augment
implant-based breast reconstruction
Matthew D. Barbera, Linda Williamsb, Elaine D.C. Andersona, Glyn T.
Neadesa, Cameron Rainec, Oliver Younga, Dhananjay Kulkarnia, Ian
Younga, J. Michael Dixona.
aEdinburgh
Breast Unit, Western General Hospital, Edinburgh, United
Kingdom EH4 2XU
bCentre for Population Health Sciences, University of Edinburgh
Medical School, Teviot Place, Edinburgh, United Kingdom EH8 9AG
cDepartment
of Plastic Surgery, St John’s Hospital, Livingston, United
Kingdom EH54 6PP
Address for correspondence – Mr Matthew D. Barber, Consultant
Breast Surgeon, Edinburgh Breast Unit, Western General Hospital,
Edinburgh, United Kingdom EH4 2XU
Tel – + 44 131 537 1629
Fax – + 44 131 537 1610
e-mail – matthew.barber@luht.scot.nhs.uk
An original article
Presented as - “232 sheets of acellular dermal matrix or how we
spent £500000 on pigskin” by Matthew D. Barber, Association of
Breast Surgery Meeting, Manchester, 21st May 2013. Abstract
published - Eur J Surg Oncol 2013; 39(5):517-518.
Abstract
Introduction
The use of acellular dermal matrix (ADM) has revolutionised the technique of
implant-based breast reconstruction. It offers the option of a one-stage
procedure and is felt to have benefits in cosmetic outcome but the medium and
long-term outcomes are unknown.
Methods
All cases where ADM was used in a breast reconstructive procedure in the
Edinburgh Breast Unit from its initial use on 7/7/2008 to 31/7/2012 were
reviewed retrospectively. Follow up was completed to 30/11/2012.
Results
147 patients received 232 sheets of ADM (156 Strattice, 73 Permacol and 3
Alloderm). 40 reconstructions were lost (17.2% or 27.2% of patients). 7 of 27
(25.9%) patients requiring adjuvant therapy had this delayed due to problems
with the reconstruction. 30 of 80 patients (37.5%) undergoing unilateral
surgery have undergone contralateral surgery. Implant loss varied significantly
with smoking (34.6% loss rate in smokers vs 13.2% in non-smokers, p=0.001),
with radiotherapy (28.1% loss rate vs 13.8% with no radiotherapy, p=0.001) and
with incision type. There was no statistically significant variation by operating
surgeon, type of ADM used, chemotherapy use, patient weight, breast weight or
nipple preservation. Patients underwent a mean of 1.54 further operations
(range 0-7).
Conclusions
While offering potential cosmetic and financial benefits, the use of ADM with
implant-based reconstructions has a significant rate of implant loss, further
surgery and potential delay in adjuvant therapy. These must be considered
when planning treatment and consenting patients.
Keywords – Breast, mastectomy, breast reconstruction, acellular dermal matrix,
surgical complications.
Introduction
Implant-based breast reconstruction has tended to be less preferred to
myocutaneous flaps because of limitations in cosmetic outcome, requirement for
tissue expansion or a two-stage procedure and the need for ongoing
maintenance. However, it offers advantages in terms of length of time taken for
surgery and recovery with less interference with muscle function. The use of
acellular dermal matrix (ADM) to augment implant-based reconstruction has in
recent years provided the opportunity for a single-stage procedure without
tissue-expansion and with suggestions of improved cosmetic outcome compared
with submuscular placement, in part due to better inframammary fold definition
[1-3]. Despite significant expense for the ADM, cost-savings have been suggested
when compared with flap reconstructions due to reductions in theatre time and
hospital stay[4]. A variety of materials have been used and include tissue
derived from human, porcine and bovine sources, processed in varying manners
to produce an acellular, non-reactive, connective tissue support to cover pole of
the breast implant. The ADM provides a framework into which the host tissue
can integrate. However, there remains very little published evidence of the
outcome of this technique. Reports of inflammatory reactions to the implanted
material and increased failure rates have raised concerns.
This paper presents the experience of the Edinburgh Breast Unit using ADM as
part of breast reconstruction between the introduction of the technique in 2008
to 2012. The study aimed to determine the loss rate of the technique and to
identify potential risk factors and implications of this.
Methods
Patients in whom ADM was used were identified from records of material
ordered with cross reference to theatre lists. All cases undertaken from the first
use of the technique on 7/7/2008 to 31/7/2012 were identified. Casenotes
were reviewed for all patients to complete follow up to 30/11/2012. Follow up
was shorter in 5 patients. One had died and 4 were discharged to distant home
breast services. Cases were performed by consultant breast and plastic surgeons
with experience in implant-based reconstruction or by more newly appointed
consultants with experience of ADM use during training. 10 surgeons performed
the primary breast and reconstructive surgery. At least initially, many cases
were performed by two consultant breast surgeons or a consultant breast
surgeon and a consultant plastic surgeon operating together. Decisions
regarding the placement of a definitive implant (as a one-stage procedure) or
tissue expander (as a one or two-stage procedure) were made by the individual
surgeon with no unit protocol. Drains were placed in all cases. These were
removed when drainage was less than 50mls/per day or at around 7 days.
Prophylactic antibiotics were given until drains were removed. No formal
assessment of cosmetic outcome was made. The recording of seroma volume
and drainage was inconsistent and is therefore not presented. The occurrence of
erythema in the first weeks following surgery was not formally reported but is
presented where it has been noted. Adjuvant treatment was judged to have been
delayed if planned treatment dates were delayed due to complications of
surgery. Axillary sampling procedures included those undergoing sentinel node
biopsy (61 patients) and those undergoing 4-node sampling (24 patients). Data
are presented as mean (range) with median in addition for categories lacking
normal distribution. Hazard ratios are presented with 95% confidence intervals.
Statistical analysis was performed using univariate and multivariate Cox
regression. Only those variables with a univariate p value of less than or equal to
0.2 were included in the model for multivariate analysis. Breast weight was not
normally distributed and was log10 transformed prior to analysis in relation to
risk of implant loss.
Results
147 patients underwent breast reconstructive surgery using ADM in 222 breasts.
Mastectomies were performed to reduce risk (97), for primary cancer (84),
ductal carcinoma in situ (29) and cancer recurrence (12). 3 patients have had
distant cancer recurrence (one died), one patient developed breast recurrence
and one an axillary recurrence. Patients had a mean age of 47.4 (range 20-75).
Patients had a mean weight of 67.8kg (43-102) and BMI of 25.3 (16-43). Breast
weight, reconstructed breast weight and change in breast weight are presented
in table 1.
71 patients underwent bilateral reconstructions using ADM and 80 unilateral
including 4 who had bilateral surgery using ADM at different times. 30 of the 80
(37.5%) patients having unilateral breast reconstruction underwent
contralateral surgery, largely to improve symmetry. 232 sheets of ADM were
used in total (156 Strattice (LifeCell, Bridgewater, NJ, USA), 73 Permacol
(Covidien, Mansfield MA, USA) and 3 Alloderm (LifeCell, Bridgewater, NJ, USA)).
In one case a sheet of Alloderm was too small to achieve implant coverage and a
sheet of Strattice was used in addition. In 9 cases patients received further
sheets of ADM during revisional surgery.
Mean follow up was 687 days (86-1583). 40 reconstructions were lost (17.2% of
sheets of ADM involving 27.2% of patients). Loss rate was 9.5% at 3 months and
15.5% at 1 year. Losses included two instances of removal of an intact
reconstruction on the contralateral side following failure on one side at the
request of the patient and another patient where intact bilateral reconstructions
were felt to be inadequate and were revised to latissimus dorsi flaps. Mean time
to loss of implant was 167 days (9-895) with a median of 73 days. 26
reconstructed breasts were recorded as having erythema over the
reconstruction in the first 4 weeks following surgery. 70 reconstructed breasts
(31.5%) had problems with wound healing. 7 of 27 (25.9%) patients had a delay
in adjuvant therapy as a result of problems with the reconstruction. Patients
underwent 227 further operations following primary surgery with ADM (mean
1.54 per patient (range 0-7)). This included 55 planned second procedures
including revision of tissue expander to implant and nipple reconstruction.
Mean time to first further operation was 249 days (0-864) with a median of 208
days. 2 patients developed haematomas requiring evacuation following primary
reconstructive surgery and a further 2 developed haematomas following
revisional surgery. A total of 312 implants/tissue expanders were used (mean
1.4/breast (range 1-4)).
Surgeons performed surgery on between 4 and 61 breasts (mean 22.9). Implant
loss rate varied from 0 to 40% between surgeons but variation was not
statistically significant (p=0.51). Analysis of various factors potentially related to
implant loss is presented in table 2. Implant loss rate varied significantly with
smoking (p=0.002), radiotherapy to the breast/chest wall (p=0.002) and incision
used (p<0.001). Loss rates were 34.6% in current smokers (hazard ratio 2.9
(1.5-5.6) versus non-smokers) and 28.1% in those who received radiotherapy.
The effect of radiotherapy was primarily in those who received radiotherapy
following reconstruction with a loss rate in these patients of 47.6% (hazard ratio
3.7 (1.7-7.6) versus those not receiving radiotherapy). There was no significant
difference between those having had radiotherapy prior to surgery and those not
receiving radiotherapy. Those with an inframammary fold incision had a loss
rate of 80%. There was no statistically significant difference in loss rate with
receipt of chemotherapy, ADM type, nipple preservation, use of fixed-volume
implant versus expander, patient weight, breast weight, immediate
reconstruction versus previous surgery (p=0.99) or indication for mastectomy
(p=0.34). While there was statistically significant variation based on type of
axillary surgery performed and loss rate for those undergoing axillary node
clearance surgery was marked at 32.3%, this did not reach statistical significance
compared with those undergoing no axillary surgery (p=0.085). Two diabetic
patients underwent surgery, one of whom lost their reconstruction.
Discussion
The National Mastectomy and Breast Reconstruction Audit reported a loss rate
of 8.9% for primary implant-based reconstructions at 3 months [5]. At the time
of this audit few reconstructions using ADM were being performed. The loss rate
in the current study of 9.5% at 3 months is not substantially different. Our
findings suggest that follow up at 3 months is too early to judge the loss rate of
an implant-based breast reconstructive technique as a significant number of
patients can have problems after this period.
Strattice was used from August 2009 and Permacol has not been used since
October 2011 and thus follow up has been longer for Permacol. However, there
is no obvious difference in outcome between the two. Most published studies of
the outcome of reconstructions using ADM originate from the United States and
relate to use of ADMs of human origin, mainly Alloderm. Use of such products
has been limited in Europe due to comparatively high cost. Numbers in these
studies is variable but often low and follow up short. Published reconstruction
loss rates vary from 0 to 13% [6-12]. A randomized trial of 70 patients
undergoing submuscular or ADM-assisted expander/implant breast
reconstruction showed no differences in the immediate post-operative period
[13]. There have been no randomized studies examining results beyond this
period. Two recent reviews of comparative studies of reconstructions with and
without ADM (covering many of the same reports) have suggested an increased
risk of failure in those in whom ADM was used with odds ratios of 2.8 and 3.0
[14, 15], although another two have shown no difference [16, 17]. Comparisons
between ADM types are limited but one recent review of two surgeons using
different materials found similar outcomes[18].
Reconstruction loss rates were substantially higher in women who smoked.
Smoking is well known to affect wound healing and has previously been
reported to substantially increase loss rates in implant-based reconstruction
[19] and ADM or mesh-assisted reconstruction [12, 20]. In the present study, exsmokers seem to lose this risk and therefore waiting several months after
stopping smoking is recommended prior to performing an implant-based
reconstruction with ADM.
Radiotherapy also affects wound healing and higher rates of reconstruction loss
are noted [21]. Rates of reconstruction loss in those undergoing ADM-based
reconstruction and receiving radiotherapy were described as “prohibitively
high” by Parks et al [7]. Radiotherapy to the chest wall is routinely given to those
with more than 3 lymph nodes involved by metastases. It is likely that axillary
clearance surgery is a marker of those with worse disease, increasing likelihood
of chest wall radiotherapy contributed to the trend towards increased loss rates
with axillary clearance surgery. The receipt of chemotherapy would similarly be
a marker of more advanced disease increasing likelihood of chest wall
radiotherapy as well as risks of neutropaenia and infection, however, in the
present study increased loss rates seen with axillary clearance surgery or
chemotherapy did not reach statistical significance. Radiotherapy given prior to
reconstruction did not appear to significantly increase loss rates in the present
study. Similar findings have been noted previously with breast reconstruction in
general [22] (however, aesthetic outcome was poorer in this study) and in those
having ADM-assisted reconstruction [23]. Increased nipple necrosis has been
reported in those with preoperative radiotherapy undergoing ADM or meshassisted reconstruction after nipple-sparing mastectomy [20].
Some surgical approaches appear to be associated with increased reconstruction
loss. Those with higher risk seem to be those where scars overly the ADM. Any
wound healing problem then has the potential to result in exposure of the ADM
which appears not to be well tolerated. The early losses in this series with
inframammary incisions are of concern but with lower and more laterally-placed
incisions it is possible to close wounds over vascularised subcutaneous tissue
and chest wall muscle rather than ADM. A recent study has shown a reduced
rate of complications with an inframammary fold approach to mastectomy with
ADM or mesh-assisted reconstruction but increased problems with periareolar
incisions [20]. When skin reduction is required necessitating an inferior
approach, an option is to leave a de-epithelialised layer of lower breast skin to
provide further coverage of the implant. We have sometimes found it difficult to
achieve implant coverage with de-epithelialised skin alone and thus often use
this approach in combination with ADM. It remains to be seen whether these
variations improve loss rates.
While there were large variations in patient and breast weight, these did not
affect loss of reconstruction in the present study. Implant-based reconstruction
failure rates have previously been reported to be substantially increased with
obesity [19]. Two large reviews of outcome after expander and ADM-augmented
implant reconstruction suggested a small but statistically significant increase in
risk of complications with body mass index with a hazard ratio of around 1.1 [20,
24].
There is a feeling that use of a tissue expander may result in less skin tension
following surgery and hence reduce wound healing problems compared with a
fixed volume implant (although this may result in the need for a two-stage
approach). However, the present study shows no difference in loss rates
between expanders and implants. While nipple preservation was not a
significant risk factor for implant loss, the replacement of the nipple as a graft
did seem to be associated with a high loss rate and is no longer performed on our
unit. There were insufficient diabetic patients in the current study to offer a
definitive judgement on risk but caution appears warranted in this group.
Implant-based breast reconstruction with ADM is associated with a high rate of
reconstruction loss, delay in adjuvant treatment for a significant number of
patients and high rates of revisional and contralateral surgery. It does offer the
possibility of a cosmetically satisfactory one-stage reconstruction but discussion
with patients should cover risks of implant loss and likelihood of further surgery
in detail. Careful consideration should be given as to whether this reconstructive
approach is suitable for women in whom there is an expectation that adjuvant
radiotherapy or chemotherapy will be recommended and it should be used with
great caution in smokers.
Conflict of interest statement
The authors have no conflict of interest regarding this study.
Funding
No funding was received for this study.
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Figure 1. Survival curve for loss of reconstruction split by smoking habit.
Current smokers had a significantly higher rate of reconstruction loss than exsmokers (p=0.017) and non-smokers (p=0.001). There was no difference in
reconstruction loss between non-smokers and ex-smokers (p=0.67).
Figure 2. Survival curve for loss of reconstruction split by use of radiotherapy.
Those receiving post-operative radiotherapy had a significantly higher rate of
reconstruction loss than those receiving no radiotherapy (p=0.001) and those
receiving radiotherapy pre-operatively (p=0.002). There was no difference in
reconstruction loss between those receiving no radiotherapy and those receiving
radiotherapy pre-operatively (p=0.976).
Table 1. Weight of breast at mastectomy, weight of implant/expander used at
reconstruction and change in breast weight for 147 patients undergoing 222
mastectomies with implant reconstruction with acellular dermal matrix.
Mean
Range
Median
Breast weight
509g
85-2360g
400g
Reconstruction weight
406g
135-765g
400g
Change in breast weight -100g
-1795-+550g
-10g
Table 2. Implant loss rate per breast based on patient and surgical
characteristics. Statistical analysis by Cox regression.
Implant loss rate
Smoking
Breast weight
Patient weight
Radiotherapy
Chemotherapy
Incision
ADM type
Nipple preservation
Axillary surgery
Implant used
Non
Current
Ex smoker <3months
Hazard for unit increase
Hazard for unit increase
No
Preoperative
Postoperative
No
Preoperative
Postoperative
Transverse
Periareolar
Wise pattern
Vertical
Inframammary fold
Strattice
Permacol
Alloderm
No
Yes
Graft
No
Node sampling
Node clearance
Implant
Expander
18/136 (13.2%)
18/52 (34.6%)
4/41 (9.8%)
Not applicable
Not applicable
24/174 (13.8%)
6/36 (16.7%)
10/21 (47.6%)
26/179 (14.5%)
8/27 (29.6%)
5/23 (21.7%)
16/139 (11.5%)
8/37 (21.6%)
7/30 (23.3%)
3/7 (42.9%)
4/5 (80%)
24/155 (15.5%)
16/73 (21.9%)
0/3
23/157 (14.6%)
12/53 (22.6%)
3/9 (33.3%)
16/98 (16.3%)
10/85 (11.8%)
11/34 (32.3%)
17/111 (15.3%)
23/118 (19.5%)
Hazard ratio (95%
confidence interval)
2.9 (1.5-5.6)
0.8 (0.5-1.2)
0.9 (0.3-2.7)
0.98 (0.95-1.01)
1.0 (0.4-2.7)
3.7 (1.7-7.6)
2.0 (0.9-4.7)
1.8 (0.7-4.3)
1.8 (0.8-4.0)
1.9 (1.6-2.3)
3.7 (2.2-6.0)
12.5 (8.5-18.3)
1.1 (0.6-2.1)
1.6 (0.8-3.1)
2.0 (1.1-3.1)
0.6 (0.3-1.4)
1.9 (0.9-4.1)
1.2 (0.6-2.2)