Bioprosthetic Mesh to Expand the Lower Pole in Tissue Expander Reconstruction: A Blinded, Prospective, Randomized, Controlled Trial
Phase: NA
Conditions: Breast Cancer
Sponsor: M.D. Anderson Cancer Center

 
 
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Full Title: Bioprosthetic Mesh to Expand the Lower Pole in Tissue Expander 
Reconstruction:  A Blinded, Prospective, Randomized, Controlled Trial 
 
1.0 Background 
 
For years, plastic surgeons have struggled with two opposing goals in tissue expander 
breast reconstruction:  protecting the implant from exposure under a thin mastectomy 
skin flap; and, creating an esthetically appealing breast with a full lower pole.  For many 
surgeons, these two goals seemed mutually exclusive.  Protecting the implant meant 
placing it completely underneath the pectoralis major and serratus muscle, forcing the 
implant into an unnaturally high position.  On the other hand, releasing the pectoralis 
major muscle allows the implant to sit within the mastectomy skin flap, but exposes the 
lower pole of the implant to a purely subcutaneous plane. 
 
In recent years, there has been a proliferation of bioprosthetic mesh products.  Some of 
these products found their way into breast reconstruction
1,2,3,4.  Plastic surgeons began 
using bioprosthetic mesh as a sling to allow the pectoralis major muscle to be released 
and then reconnected to the inframammary fold.  This hammock effect protects the 
implant from the subcutaneous plane, takes tension off of the precarious mastectomy 
flap skin, and allows better control of the inframammary fold and lateral border of the 
breast.  The additional thickness of the bioprosthetic mesh also helps to even out the 
thickness of the tissue overlying the implant, which is skin and muscle above and skin 
and mesh below
6,7,8. 
 
As experience with reconstruction using bioprosthetic mesh has grown, increasing 
evidence suggest that mesh products may be associated with increased complication 
rates, particularly seroma and infection, potentially effecting not only the reconstruction, 
but the course of cancer treatment by delaying chemotherapy or interfering with 
radiation protocols
5,9,11.  Because the mesh products consist of extracellular matrices 
that are created from different source materials (human, pig, cow), and are processed 
differently, it is logical to conclude that complication profiles, and possibly esthetic 
outcome, differ from product to product. 
 
2.0 Objectives 
 
Primary objective: 
 
1. To determine the overall complication rate for each arm and compare the 
complication rate for the group of patients using different types of mesh. 
 
Secondary objectives: 
 
1. To determine whether esthetic outcomes differs based on the type of mesh used. 
 
 

 
 
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3.0 Patient Eligibility 
 
 
All patients seen at the MD Anderson main campus (MDACC) and/or one of the MD 
Anderson regional care centers (MDACC) for immediate breast cancer reconstruction 
with tissue expanders will be eligible for the study. 
 
Inclusion Criteria 
 
Patients undergoing immediate tissue expander reconstruction following 
mastectomy by any of the surgeon co-investigators are eligible for the study. 
Patients 18 years of age or older are eligible for the study. 
Patients undergoing skin-sparing mastectomy utilizing bioprosthetic mesh are 
eligible for the study.   
Patients who have not undergone autologous tissue breast reconstruction and 
intend to undergo implant only breast reconstruction. 
Patients who intend to remain under the MDACC surgeon's care until completion of 
the reconstruction. 
 
Exclusion Criteria 
 
Patients with prior radiation to the breast/chest wall of the ipsilateral breast. 
Patients who cannot be effectively reconstructed without the use of bioprosthetic 
mesh. 
Patients who are current smokers. 
Patients requiring additional intraoperative skin resections of greater than 1 cm 
beyond the skin edge as a result of mastectomy flap devascularization. 
Patients who have a history of breast tissue expander or implant placement. 
 
4.0 Risks and Benefits 
 
 
Potential risks of each of the two arms of the study include bleeding, infection, implant 
exposure, implant malposition, seroma, delayed wound healing, mastectomy flap 
necrosis, and capsular contracture.  This study may involve unpredictable risks to the 
participants. 
 
There may be no benefits to participants in the study. 
 
5.0 Study Design 
 
This is a prospective, randomized-to-procedure, controlled, blinded-to-esthetic evaluator 
trial.  Information recorded and evaluated will include: 

 
 
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Population Variables -  
age 
body mass index (BMI) 
breast size 
past medical history 
smoking history 
tumor size and location 
mastectomy surgeon 
mastectomy method 
 
Operative Variables - 
plastic/reconstructive surgeon 
tissue expander 
tissue expander type 
quality of skin 
additional skin resection 
intraoperative fill volume 
method of lower pole expansion 
drains 
 
Postoperative Variables - 
duration of drains 
chemotherapy 
radiation 
number of post-op visits 
time to first expansion 
number of expansions 
final fill volume 
time to exchange 
type and volume of implant placed 
contralateral procedures performed 
nipple (yes/no) 
 
Outcome - 
infection 
seroma 
implant malposition 
capsular contracture 
hematoma 
histologic incorporation 
esthetic evaluation (photos, blinded evaluators) 
 
6.0 Operative Technique 
 

 
 
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Intervention Arm: 
 
After the mastectomy is performed, the pectoralis major muscle is elevated off the chest 
wall with electrocautery.  After elevation superiorly and medially, the pectoralis major 
muscle is disinserted from the chest wall along its inferior border to the 3 or 9 o’clock 
position medially. 
 
The skin envelope is evaluated.  If the inframammary fold has been violated, sutures 
are used to secure it into its appropriate anatomic location.  This is also done with the 
lateral breast skin. 
 
Bioprosthetic mesh is then sewn into the inframammary fold and lateral chest wall.  If 
Surgimend is used, then the 10 x 15 cm piece of fenestrated material is sewn to the 
fold, curved side along the fold, using a suture.  If Alloderm (acellular dermal matrix) is 
used, a 6 x 12 cm piece or 6 x 16 cm piece is trimmed into a semicircle and sewn into 
the inframammary fold. The smooth side is placed against the implant. 
 
The tissue expanders are then placed in the subpectoral/subbioprosthetic pocket.  A 
drain is placed along the inferior border between the bioprosthetic mesh and the tissue 
expander.  The superior border of the bioprosthetic mesh is closed to the inferior border 
of the pectoralis major muscle with a suture.  An additional drain is placed in the 
subcutaneous pocket.  Saline solution is then injected into the tissue expander to an 
appropriate fill volume. 
 
Skin closure is performed. 
 
7.0 Statistical Considerations 
 
Primary endpoint 
 
The study is designed to evaluate the overall complication rate post-tissue expander 
reconstruction surgery using different types of mesh.  Patients who are eligible for the 
study will be equally randomized to the following arms:  1) Alloderm; 2) Surgimend.  The 
primary endpoint, overall complication after tissue expander implant is defined as any of 
the following complications:  seroma; infection; implant malposition; capsular 
contracture; and, hematoma. 
 
Sample Size 
 
Patients who are seen at MDACC for immediate breast reconstructive surgery after 
mastectomy will be enrolled to the study and equally randomized to the two arms when 
the tissue expander is implanted:  1) Alloderm; 2) Surgimend.  The randomization will 
be stratified by surgeon in order to avoid confounding between surgeon and surgical 
method.  A total of 398 patients will be enrolled with 199 patients for each arm.  The 
information on overall complication observed after tissue expander implant and before 

 
 
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the permanent implant will be collected.  The rate of overall complication for the patients 
using Alloderm mesh (arm 1) will be compared to the patients using Surgimend mesh 
(arm 2).  With 199 patients in each arm the study will have 80% power to detect the 
difference in complication rate between 10% in the Alloderm mesh group and 20% in 
the Surgimend mesh group with a two-sided type I error rate of 0.05 (calculated by 
nQuery Advisor 7.0).  The secondary objective is esthetic evaluation.  The main 
question for the esthetic evaluation is whether the overall shape of the reconstructed 
breast is good.  Evaluators who are blinded to the arm assignment information will 
grade the patients using a 5-point Likert scale (strongly disagree, disagree, somewhat 
agree, agree, strongly agree).  Their scores will be averaged for each patient. 
 
Analysis Plans 
 
Patient information including age, BMI, smoking history, tumor size and location, breast 
size, mastectomy method, mastectomy surgeon, plastic reconstruction surgeon, quality 
of skin, tissue expander type, intraoperative fill volume, method of lower pole expansion, 
chemotherapy, and radiation therapy will be summarized.  Outcome variables which 
include complications and scores for esthetic evaluation will be studied.  Summary 
statistics including mean, standard deviation, median, and range will be provided for 
continuous variables (such as age and BMI) while frequency counts and percentages 
will be provided for categorical variables (such as smoking history and tissue expander 
type).  The overall complication rate for each arm will be calculated along with the 95% 
confidence intervals.  Fisher’s exact test or the Chi-square test will be used to evaluate 
the association between two categorical variables.  Cochran-Mantel-Haenszel test will 
be used to access the association between treatment and outcomes by adjusting the 
stratification of surgeon’s experience (<= 3 years and >3 years). Logistical regression 
model will be used to assess the effect of patient variables on overall complication.  For 
each question of the esthetic evaluation, an average score will be calculated for each 
patient based on the scores from all evaluators.  Summary statistics for the scores 
including mean, standard deviation, median, and range will be calculated.  The scores 
will be compared between the two mesh arms using Wilcoxon rank sum test. 
 
8.0 Data Collection 
 
All population variables will be collected after enrollment in the study and prior to 
surgery.  After the initial surgery, during which operative variables will be documented 
by the surgical team, patient data will be collected in clinic.  At the postoperative week 1 
visit, the patient will be assessed by the surgical team for incisional complications and 
mastectomy flap necrosis.  At the postoperative week 2 visit, expansion will begin, 
absent complications preventing expansion.  The patient will return to clinic for 
additional expansion, as determined by the a member of the surgical team, until the 
desired volume is reached.  During each of these visits, the patient will be assessed for 
seroma and infection.  After expansion, the patient will return in approximately 3 months 
for a preoperative visit, followed shortly by tissue expander exchange for a permanent 
implant.  One to twelve months following implant exchange, 5 photographs 

 
 
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(standardized photographic views) will be taken and used for aesthetic evaluation (see 
Appendix D).  Unique study numbers will be assigned to the photographs. 
 
Population variables: 
age 
BMI 
breast size 
past medical history 
smoking history 
tumor size and location 
mastectomy surgeon 
mastectomy method 
 
Operative Variables – These will collected from the operative note or at the time of 
surgery: 
plastic/reconstructive surgeon 
tissue expander 
expander type 
quality of skin 
additional skin resection 
intraoperative fill volume 
method of lower pole expansion 
drains 
 
Postoperative Variables – These will be recorded at clinic visits or retrospectively from 
clinic notes: 
duration of drains 
chemotherapy 
radiation therapy (out of study) 
number of post-op visits 
time to first expansion 
number of expansions 
final fill volume 
time to exchange 
type and volume of implant placed 
contralateral procedures performed 
nipple (yes/no) 
 
9.0 Outcome 
 
The primary endpoint, overall complication after tissue expander implant is defined as 
any of the following complications: seroma, cellulitis, abscess, red breast syndrome, 
implant malposition, capsular contracture, and hematoma.  These will be defined as 
follows: 
 

 
 
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Seroma:  Any suspected fluid collection that is either radiologically confirmed by 
ultrasound or clinically confirmed by drainage, or both. 
 
Cellulitis:  Any redness of the breast that resolves with antibiotics, or requires surgical 
removal of implant, but does not contain a purulent fluid collection. 
 
Abscess:  Any purulent fluid collection confirmed during surgical removal of implant. 
 
Red breast syndrome:  Any prolonged redness of the breast, without other symptoms of 
infection, which does not resolve with antibiotics, and does not go on to require removal 
of the implant. 
 
Malposition:  Any surgeon perceived, postoperative movement of the expander outside 
of the surgically created pocket. 
 
Capsular Contracture:   Any postoperative capsule formation, classified according to the 
Baker classification, as follows: Baker 1: normal beast; Baker 2: palpable, minimally firm 
capsule; Baker 3: visible, easily palpated, moderately firm capsule; Baker 4: painful, 
hard and breast distorted. 
 
Hematoma:  Any postoperative collection of blood requiring surgical drainage. 
 
Secondary endpoints are related to esthetic evaluation of postoperative, standardized 
five (5) view clinical photos. 
 
Esthetic Evaluation 
 
The esthetic evaluation will be based on five standardized photographic views: frontal; 
right lateral; left lateral; right three-quarter: and, left three-quarter.  Photographs will be 
taken against a blue background, standard in all clinic rooms, at a distance of five feet 
from the patient. 
 
Evaluators will include three attending plastic surgeons who are not taking care of any 
patients in the study, three plastic surgery fellows, and three physician assistants.  Their 
scores will be averaged for each statement.  Unilaterals and bilaterals will be judged 
separately. 
 
Questionnaires will evaluate the breast esthetics based on a 1 to 5 scale (strongly 
disagree, disagree, somewhat agree, agree, strongly agree) of the following statements: 
 
1. The overall shape of the reconstructed breast is good. 
2. The overall symmetry with the other breast is good. 
3. The upper pole transition is natural in appearance. 
4. The lower pole has adequate fullness and ptosis. 
5. The inframammary fold is in the appropriate position. 
6. The lateral border of the breast has good contour. 

 
 
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7. The medial border of the breast has good contour. 
8. The breast mound is in the appropriate position. 
9. The breast surface contour is generally smooth. 
10. There is minimal visible rippling of the implant. 
 
 
10.0 Number of Patients 
 
Approximately 398 patients will be enrolled in this study. 
 
11.0 Criteria for Removal from the Study 
 
 
Patients will be removed from the study if they change their mind about participation for 
any reason. 
 
12.0 Reporting Requirements 
 
 
Institutional guidelines for reporting of adverse events will be followed. 
 
13.0 Data Confidentiality Plans 
 
The confidentiality of the subjects will be preserved at all times.  In no way will any 
individual subject be identifiable upon discussion or presentation of the data.  HIPAA 
identifiers will be collected but will be replaced by unique study numbers in the 
analytical file.  The data will be stored in a password-protected computer with firewall 
protection.  Data will only be known to the PI and research staff.  Study records will be 
destroyed within five (5) years after study publication. 
 
14.0 References 
 
1. Breuing KH, Warren SM. Immediate bilateral breast reconstruction with implants 
and inferolateral AlloDerm slings. Ann Plast Surg, 55(3):232-9, 2005. 
2. Gamboa-Bobadilla GM. Implant breast reconstruction using acellular dermal 
matrix. Ann Plast Surg, 56(1):22-5, 2006. 
3. Topol BM, Dalton EF, Ponn T, et al. Immediate single-stage breast 
reconstruction using implants and human accelular dermal tissue matrix with 
adjustment of the lower pole of the breast to reduce unwanted lift. Ann Plast 
Surg, 61(5):494-9, 2008. 
4. Maxwell GP, Gabriel A. Possible future development of implants and breast 
augmentation. Clin Plast  Surg, 36(1)167-72, 2009. 
5. Becker S, Saint-Cyr M, Wong C, et al. AlloDerm versus DermaMatrix in 
immediate expander-based breast reconstruction: a preliminary comparison of 

 
 
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complication profiles and material compliance. Plast Reconstr Surg, 123(1):1-6, 
2009. 
6. Stump A, Holton LH 3rd, Connor J, et al. The use of acellular dermal matrix to 
prevent capsule formation around implants in a primate model. Plast Reconstr 
Surg, 124(1):82-91, 2009. 
7. Namnoum JD. Expander/implant reconstruction with AlloDerm: recent 
experience. Plast Reconstr Surg, 124(2):387-94, 2009. 
8. Grabov-Nardini G, Haik J, Regev E, et al. AlloDerm sling for correction of 
synmastia after immediate, tissue expander, breast reconstruction in thin women. 
Eplasty, 9:e54. 
9. Chun YS, Verma K, Rosen H, et al. Implant-based breast reconstruction using 
acellular derma matrix and the risk of postoperative complications. Plast 
Reconstr Surg, 125(2):429-36, 2010. 
10. Chen WF, Barounis D, Kalimuthu R. A novel cost-saving approach to the use of 
acellular dermal matrix (AlloDerm) in postmastectomy breast and nipple 
reconstructions. Plast Reconstr Surg, 125(2)479-81, 2010. 
11. Lanier ST, Wang ED, Chen JJ, et al. The effect of acellular dermal matrix use on 
complication rates in tissue expander/implant breast reconstruction. Ann Plast 
Surg, 64(5):674-8, 2010.