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1.  Combining decellularized human adipose tissue extracellular matrix and adipose-derived stem cells for adipose tissue engineering 
Acta biomaterialia  2013;9(11):8921-8931.
Repair of soft-tissue defects resulting from lumpectomy or mastectomy has become an important rehabilitation process for breast cancer patients. This study aimed to provide an adipose tissue engineering platform for soft-tissue defect repair by combining decellularized human adipose tissue extracellular matrix (hDAM) and human adipose-derived stem cells (hASCs). To derive hDAM, incised human adipose tissues underwent a decellularization process. Effective cell removal and lipid removal were proved by immunohistochemical analysis and DNA quantification. Scanning electron microscope examination showed three-dimensional nanofibrous architecture in hDAM. hDAM composition included collagen, sulfated glycosaminoglycan, and vascular endothelial growth factor but lacked major histocompatibility complex antigen I. hASC viability and proliferation on hDAM were proven in vitro. hDAM implanted subcutaneously in Fischer rats did not cause an immunogenic response, and it underwent remodeling as indicated by host cell infiltration, neovascularization, and adipose tissue formation. Fresh fat grafts (Coleman technique) and engineered fat grafts (hDAM combined with hASCs) were implanted subcutaneously in nude rats. The implanted engineered fat grafts maintained volume at week 8, and the hASCs contributed to adipose tissue formation. In summary, the combination of hDAM and hASCs provides not only a clinically translatable platform for adipose tissue engineering but also a vehicle for elucidating fat grafting mechanisms.
doi:10.1016/j.actbio.2013.06.035
PMCID: PMC3965366  PMID: 23816649
Decellularization; Adipose tissue extracellular matrix; Adipose-derived stem cell; Fat grafting; Adipose tissue engineering
2.  The Advantages of Free Abdominal-Based Flaps Over Implants for Breast Reconstruction in Obese Patients 
Plastic and reconstructive surgery  2012;130(5):991-1000.
BACKGROUND
We hypothesized that for obese patients, abdominal-based free flap, rather than implant-based, and delayed, rather than immediate, breast reconstruction would result in fewer overall complications and reconstruction losses.
METHODS
We retrospectively analyzed consecutive implant- and abdominal-based free-flap breast reconstructions performed in obese patients between 2005 and 2010 utilizing the World Health Organization obesity classifications: class I (30.0–34.9 kg/m2), class II (35.0–39.9 kg/m2), and class III (≥40 kg/m2). Primary outcome measures included flap failures and overall complications. Logistic regression analysis identified associations between patient, defect, and reconstructive characteristics and surgical outcomes.
RESULTS
The analysis included 990 breast reconstructions (548 flaps vs. 442 implants) in 700 patients. Mean follow-up was 17 months. Age (p<0.01), smoking (p=0.02), medical illness (p=0.01), and BMI>37 (p=0.01) predicted overall complications on regression analysis. Implants demonstrated a higher failure rate (15.8%) than flaps (1.5%; p<0.001). While failure rates were similar for immediate and delayed flap reconstructions overall (1.3% vs. 1.9%; p=0.7) and among obesity classifications, there was a trend toward more implant failures in immediate rather than delayed reconstructions (16.8% vs. 5.3%; p=0.06). Differences between immediate implant versus flap reconstruction failure rates were highest among more obese patients (class II [24.7% vs. 1.3%, respectively; p<0.01] and class III [25.4% vs. 0%, respectively; p<0.01] compared to class I [11.7% vs. 1.4%, respectively; p<0.01]).
CONCLUSIONS
Obese patients, particularly patients with class II and III obesity, experience higher failure rates with implant-based breast reconstruction, particularly immediate reconstruction. Free flap techniques or delayed implant reconstruction may be warranted in this population.
doi:10.1097/PRS.0b013e318267efc5
PMCID: PMC3749735  PMID: 23096600
3.  Chest Wall Reconstruction and Advanced Disease 
Seminars in Plastic Surgery  2004;18(2):117-129.
Clinical experience supports a role for palliative procedures in patients with locally advanced or recurrent breast cancer, yet numerous challenges are entailed in both the extirpation and reconstruction of the chest wall in these cases. The defects may be profound and complicated by prior surgery, radiation therapy, or patient-related variables. The reconstructive techniques employed must neither encumber nor delay any necessary postoperative therapy and must not result in unacceptable morbidity or compromise quality of life. Our surgical approach to these cases incorporates a team of specialists from a broad spectrum of medical and surgical disciplines. Each operative plan is tailored to the specific needs and requirements of the individual patient.
doi:10.1055/s-2004-829046
PMCID: PMC2884721  PMID: 20574490
Chest wall reconstruction; advanced breast cancer
4.  Automated calculation of symmetry measure on clinical photographs 
1 ABSTRACT
Breast cancer is one of the most prevalent forms of cancer in the world. More than 250,000 American women are diagnosed with breast cancer annually. Fortunately, the survival rate is relatively high and continually increasing due to improved detection techniques and treatment methods. The quality of life of breast cancer survivors is ameliorated by minimizing adverse effects on their physical appearance. Breast reconstruction is important for restoring the survivor’s appearance. In breast reconstructive surgery, there is a need to develop technologies for quantifying surgical outcomes and understanding women’s perceptions of changes in their appearance. Methods for objectively measuring breast anatomy are needed in order to help breast cancer survivors, radiation oncologists, and surgeons quantify changes in appearance that occur with different breast reconstructive surgical options. In this study, we present an automated method for computing a variant of the normalized Breast Retraction Assessment (pBRA), a common measure of symmetry, from routine clinical photographs taken to document breast cancer treatment procedures.
doi:10.1111/j.1365-2753.2010.01477.x
PMCID: PMC2958233  PMID: 20630015
BRA; pBRA; Automated Detection; Digital Photographs; Umbilicus; Nipple Complex; Breast Cancer
5.  Quantifying the Aesthetic Outcomes of Breast Cancer Treatment: Assessment of Surgical Scars from Clinical Photographs 
Accurate assessment of the degree of scaring that results from surgical intervention for breast cancer would enable more effective pre-operative counseling. The resultant scar that accompanies an open surgical intervention may be characterized by variance in thickness, color, and contour. These factors significantly impact the overall appearance of the breast. A number of studies have addressed the mechanical and pathologic aspects of scarring. The majority of these investigations have focused on the physiologic process of scar formation and means to improve the qualities of a scar. Few studies have focused on quantifying the visual impact of scars. This manuscript critically reviews current methods used to assess scars in terms of overall satisfaction after surgery. We introduce objective, quantitative measures for assessing linear breast surgical scars using digital photography. These new measurements of breast surgical scars are based on calculations of contrast and area. We demonstrate, using the intra-class correlation coefficient (ICC), that the new measures are robust to observer variability in annotating the scar region on clinical photographs. As an example of the utility of the new measures, we use them to quantify the aesthetic differences of reconstruction following skin-sparing mastectomy vs. conventional mastectomy.
doi:10.1111/j.1365-2753.2010.01476.x
PMCID: PMC2958242  PMID: 20630016
Aesthetics; Breast Neoplasm; Esthetics; Mastectomy; Outcomes; Prostheses and Implants; Reconstructive Surgical Procedures; Surgical Flaps; Surgical Scars; Treatment Outcome; Quality of Life; Breast Conservation Therapy
6.  A Pilot Study on Using Eye Tracking to Understand Assessment of Surgical Outcomes from Clinical Photography 
Journal of Digital Imaging  2010;24(5):778-786.
Appearance changes resulting from breast cancer treatment impact the quality of life of breast cancer survivors, but current approaches to evaluating breast characteristics are very limited. It is challenging, even for experienced plastic surgeons, to describe how different aspects of breast morphology impact overall assessment of esthetics. Moreover, it is difficult to describe what they are looking for in a manner that facilitates quantification. The goal of this study is to assess the potential of using eye-tracking technology to understand how plastic surgeons assess breast morphology by recording their gaze path while they rate physical characteristics of the breasts, e.g., symmetry, based on clinical photographs. In this study, dwell time, transition frequency, dwell sequence conditional probabilities, and dwell sequence joint probabilities were analyzed across photographic poses and three observers. Dwell-time analysis showed that all three surgeons spent the majority of their time on the anterior–posterior (AP) views. Similarly, transition frequency analysis between regions showed that there were substantially more transitions between the breast regions in the AP view, relative to the number of transitions between other views. The results of both the conditional and joint probability analyses between the breast regions showed that the highest probabilities of transitions were observed between the breast regions in the AP view (APRB, APLB) followed by the oblique views and the lateral views to complete evaluation of breast surgical outcomes.
doi:10.1007/s10278-010-9338-x
PMCID: PMC3180533  PMID: 20852914
Breast neoplasm; Eye movements; Biomedical image analysis; Decision support; Evaluation research
7.  3D Symmetry Measure Invariant to Subject Pose During Image Acquisition 
In this study we evaluate the influence of subject pose during image acquisition on quantitative analysis of breast morphology. Three (3D) and two-dimensional (2D) images of the torso of 12 female subjects in two different poses; (1) hands-on-hip (HH) and (2) hands-down (HD) were obtained. In order to quantify the effect of pose, we introduce a new measure; the 3D pBRA (Percentage Breast Retraction Assessment) index, and validate its use against the 2D pBRA index. Our data suggests that the 3D pBRA index is linearly correlated with the 2D counterpart for both of the poses, and is independent of the localization of fiducial points within a tolerance limit of 7 mm. The quantitative assessment of 3D asymmetry was found to be invariant of subject pose. This study further corroborates the advantages of 3D stereophotogrammetry over 2D photography. Problems with pose that are inherent in 2D photographs are avoided and fiducial point identification is made easier by being able to panoramically rotate the 3D surface enabling views from any desired angle.
doi:10.4137/BCBCR.S7140
PMCID: PMC3140267  PMID: 21792310
three-dimensional; stereophotogrammetry; subject pose; validation; breast; symmetry; surgical planning; pBRA
8.  Assessment of Breast Aesthetics 
Plastic and reconstructive surgery  2008;121(4):186e-194e.
A good aesthetic outcome is an important endpoint of breast cancer treatment. Subjective ratings, direct physical measurements, measurements on photographs, and assessment by three-dimensional imaging are reviewed and future directions in aesthetic outcome measurements are discussed. Qualitative, subjective scales have frequently been used to assess aesthetic outcomes following breast cancer treatment. However, none of these scales has achieved widespread use because they are typically vague and have low intra- and inter- observer agreement. Anthropometry is not routinely performed because it is impractical to conduct the large studies needed to validate anthropometric measures, i.e., studies in which several observers measure the same subjects multiple times. Quantitative measures based on digital/digitized photographs have yielded acceptable results but have some limitations. Three-dimensional imaging has the potential to enable consistent, objective assessment of breast appearance, including properties, such as volume, that are not available from two-dimensional images. However, further work is needed to define 3D measures of aesthetic properties and how they should be interpreted.
doi:10.1097/01.prs.0000304593.74672.b8
PMCID: PMC3097998  PMID: 18349598
Aesthetics; Breast Neoplasm; Esthetics; Mastectomy; Outcomes; Prostheses and Implants; Reconstructive Surgical Procedures; Surgical Flaps; Treatment Outcome; Quality of Life; Breast Conservation Therapy
9.  Validation of Stereophotogrammetry of the Human Torso 
The objective of this study was to determine if measurements of breast morphology computed from three-dimensional (3D) stereophotogrammetry are equivalent to traditional anthropometric measurements obtained directly on a subject using a tape measure. 3D torso images of 23 women ranged in age from 36 to 63 who underwent or were scheduled for breast reconstruction surgery were obtained using a 3dMD torso system (3Q Technologies Inc., Atlanta, GA). Two different types (contoured and line-of-sight distances) of a total of nine distances were computed from 3D images of each participant. Each participant was photographed twice, first without fiducial points marked (referred to as unmarked image) and second with fiducial points marked prior to imaging (referred to as marked image). Stereophotogrammetry was compared to traditional direct anthropometry, in which measurements were taken with a tape measure on participants. Three statistical analyses were used to evaluate the agreement between stereophotogrammetry and direct anthropometry. Seven out of nine distances showed excellent agreement between stereophotogrammetry and direct anthropometry (both marked and unmarked images). In addition, stereophotogrammetry from the unmarked image was equivalent to that of the marked image (both line-of-sight and contoured distances). A lower level of agreement was observed for some measures because of difficulty in localizing more vaguely defined fiducial points, such as lowest visible point of breast mound, and inability of the imaging system in capturing areas obscured by the breast, such as the inframammary fold. Stereophotogrammetry from 3D images obtained from the 3dMD torso system is effective for quantifying breast morphology. Tools for surgical planning and evaluation based on stereophotogrammetry have the potential to improve breast surgery outcomes.
doi:10.4137/BCBCR.S6352
PMCID: PMC3076012  PMID: 21494398
three-dimensional; anthropometry; validation; breast; photogrammetry; stereophotogrammetry; surgical planning
10.  Analysis of Breast Contour using Rotated Catenary 
Surgical reconstruction of natural-appearing breasts is a challenging task. Currently, surgical planning is limited to the surgeon’s subjective assessment of breast morphology. Therefore, it is useful to develop objective measurements of breast contour. In this paper, a novel quantitative measure of the breast contour based on catenary theory is introduced. A catenary curve is fitted on the breast contour (lateral and inferior) and the key parameter determining the shape of the curve is extracted. The new catenary analysis was applied to pre- and post-operative clinical photographs of women who underwent tissue expander/implant (TE/Implant) reconstruction. A logistic regression model was developed to predict the probability that the observed contour is that of a TE/Implant reconstruction from the catenary parameter, patient age, and patient body mass index. It was demonstrated that the parameters contain useful information for distinguishing TE/Implant reconstructed breasts from pre-operative breasts.
PMCID: PMC3041438  PMID: 21347015
11.  A Research Agenda for Appearance Changes Due to Breast Cancer Treatment 
Breast cancer is one of the most prevalent forms of cancer in the US. It is estimated that more than 180,000 American women will be diagnosed with invasive breast cancer in 2008. Fortunately, the survival rate is relatively high and continually increasing due to improved detection techniques and treatment methods. However, maintaining quality of life is a factor often under emphasized for breast cancer survivors. Breast cancer treatments are invasive and can lead to deformation of the breast. Breast reconstruction is important for restoring the survivor’s appearance. However, more work is needed to develop technologies for quantifying surgical outcomes and understanding women’s perceptions of changes in their appearance. A method for objectively measuring breast anatomy is needed in order to help both the breast cancer survivors and their surgeons take expected changes to the survivor’s appearance into account when considering various treatment options. In the future, augmented reality tools could help surgeons reconstruct a survivor’s breasts to match her preferences as much as possible.
PMCID: PMC3085417  PMID: 21655363
breast cancer; 3D imaging of breast; computer-assisted image analysis; quality of life
12.  Coordinated prophylactic surgical management for women with hereditary breast-ovarian cancer syndrome 
BMC Cancer  2008;8:101.
Background
Women with BRCA1 or BRCA2 mutations have a substantially increased risk of breast and ovarian cancer compared with the general population. Therefore, prophylactic mastectomy (PM) and bilateral salpingo-oophorectomy (BSO) have been proposed as risk-reduction strategies for BRCA1/2 mutation carriers. We aimed to assess the feasibility of coordinated PM and BSO in hereditary breast-ovarian cancer syndrome.
Methods
High risk women for breast and ovarian cancer who underwent coordinated PM and BSO were included in this study. Clinical characteristics and surgical and oncologic outcomes were retrospectively reviewed.
Results
Twelve patients underwent coordinated PM and BSO. Ten had history of previous breast cancer. Autologous breast reconstruction was performed in ten patients. The mean age at surgery was 43 (range 34–65). Mean operating time was 9.3 hours (range 3–16) with a mean postoperative hospitalization of 5.4 days (range 4–8). Intraoperatively, there were no major surgical complications. Postoperatively, one patient developed an abdominal wound dehiscence, another reoperation for flap congestion; one had umbilical superficial epidermolysis, and one patient developed aspiration pneumonia. At a mean follow-up of 84 months, 10 of patients were cancer-free. Although no patients developed a new primary cancer, two developed a distant recurrence.
Conclusion
Coordinated PM and BSO is a feasible procedure with acceptable morbidity in selected high-risk patients that desire to undergo surgery at one operative setting.
doi:10.1186/1471-2407-8-101
PMCID: PMC2362122  PMID: 18410690
13.  A Novel Quantitative Measure of Breast Curvature Based on Catenary 
Quantitative, objective measurements of breast curvature computed from clinical photographs could be used to investigate factors that impact reconstruction and facilitate surgical planning. This paper introduces a novel quantitative measure of breast curvature based on catenary. A catenary curve is used to approximate the overall curvature of the breast contour, and the curvature measure is extracted from the catenary curve. The catenary curve was verified by comparing its length, the area enclosed by the curve, and the curvature measure from the catenary curve to those from manual tracings of the breast contour. The evaluation of the proposed analysis employed untreated and postoperative clinical photographs of women who were undergoing tissue expander/implant (TE/Implant) reconstruction. Logistic regression models were developed to distinguish between the curvature of breasts undergoing TE/Implant reconstruction and that of untreated breasts based on the curvature measure and patient variables (age and body mass index). The relationships between the curvature measures of untreated breasts and patient variables were also investigated. The catenary curve approximates breast curvature reliably. The curvature measure contains useful information for quantifying the curvature differences between breasts undergoing TE/Implant reconstruction and untreated breasts, and identifying the effect of patient variables on the breast shape.
doi:10.1109/TBME.2012.2184541
PMCID: PMC3334380  PMID: 22271826
Breast cancer; breast curvature; breast reconstruction; catenary; digital photographs

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