Howard T. Wang

Aesthetic outcomes in breast conservation therapy.

BACKGROUND Since the National Surgical Adjuvant Breast and Bowel Project B06 (NSABP-B06) trial demonstrated equivalent survival outcomes between patients with breast cancer undergoing modified radical mastectomy versus lumpectomy and radiation, an increasing number of patients are seeking breast conservation therapy. Traditionally, only patients who have undergone total mastectomy have been referred for reconstruction. OBJECTIVE The purpose of the study was to determine the number of dissatisfied patients treated with breast conservation therapy who have suboptimal cosmesis and should be referred for reconstruction. METHODS After obtaining approval from the Institutional Review Board and patient consent, patients identified as more than 1 year posttreatment from breast conservation therapy (1999-2004) were interviewed and photographed. Data were gathered by use of a questionnaire that included patient aesthetic score, patient satisfaction, and change in body image. Photographs were shown to a surgical oncologist, a general surgeon, and a plastic surgeon for a physician aesthetic score. RESULTS Thirteen of 46 patients (28.3%) were dissatisfied with their cosmetic result. Women who were dissatisfied with their cosmetic result were more likely to have a negative change in their body image when compared with patients who were satisfied with their cosmetic result (46.2 % vs 6.1%, P = .02). Additionally, dissatisfied patients were more likely to rate their cosmetic result as poor (15.4 % vs 0%, P = .007) and were more likely to consider reconstruction (46.2% vs 9.1%, P = .01) when compared with satisfied patients. Risk factors to predict dissatisfaction in our patient population included age younger than 52 years and the resection of tumor from the upper inner quadrant. CONCLUSIONS Twenty-eight percent of patients in this study were dissatisfied with their cosmetic result. Furthermore, a large portion of these patients would consider reconstruction if it were offered. Although this study only identified a few broad risk factors for suboptimal cosmetic outcome, it confirms our hypothesis that many patients who have undergone breast conservation therapy should be referred for plastic surgery consultation.

Growth Factors Regulation of Rabbit Sodium-Dependent Neutral Amino Acid Transporter ATB0 and Oligopeptide Transporter 1 mRNAs Expression after Enterectomy

BACKGROUND Sucessful intestinal adaptation after massive enterectomy is dependent on increased efficiency of nutrient transport. However, midgut resection (MGR) in rabbits induces an initial decrease in sodium-dependent brush border neutral amino acid transport, whereas parenteral epidermal growth factor (EGF) and growth hormone (GH) reverse this downregulation. We investigated intestinal amino acid transporter B0 (ATB0) and oligopeptide transporter 1 (PEPT 1) mRNA expression after resection and in response to EGF and/or GH. METHODS Rabbits underwent anesthesia alone (control) or proximal, midgut, and distal resections. Full-thickness intestine was harvested from all groups on postoperative day (POD) 7, and on POD 14 from control and MGR rabbits. A second group of MGR rabbits received EGF and/or GH for 7 days, beginning 7 days after resection. ATB0 and PEPT 1 mRNA levels were determined by Northern blot analysis. RESULTS In control animals, ileal ATB0 mRNA abundance was three times higher than jejunal mRNA, whereas PEPT 1 mRNA expression was similar. By 7 and 14 days after MGR, jejunal ATB0 mRNA abundance was decreased by 50% vs control jejunum. A 50% decrease in jejunal PEPT 1 message was delayed until 14 days after MGR. Treatment with EGF plus GH did not alter ATB0 mRNA expression but doubled PEPT 1 mRNA in the jejunum. CONCLUSION The site of resection, time postresection, and growth factors treatment differentially influence ATB0 and PEPT 1 mRNA expression. Enhanced sodium-dependent brush border neutral amino acid transport with GH plus EGF administration is independent of increased ATB0 mRNA expression in rabbit small intestine after enterectomy.

Breast Reduction Trend among Plastic Surgeons: A National Survey

Background: A number of breast reduction techniques have been developed over the years, but debate over which technique is better for patients continues to grow. The authors’ goal was to survey members of the American Society of Plastic Surgeons to identify their preferences and practices and report their opinion regarding issues related to the various breast reduction techniques. Methods: In the fall of 2006, a one-page anonymous survey was sent to 5112 plastic surgeons who were members of the American Society of Plastic Surgeons. A follow-up survey was sent 2 weeks after the first mailing as a friendly reminder. The questionnaires were then collected over a 6-week period. Results: Of the 5112 plastic surgeons surveyed, 2665 (52 percent) responded to the survey. The majority of the respondents (69 percent) use the inferior pedicle breast reduction technique. Ninety-two percent of the respondents use intraoperative deep venous thrombosis prophylaxis. Sixty-one percent of respondents performed over 75 percent of their cases on an outpatient basis and 97 percent of respondents use general anesthesia. Ninety-three percent of the respondents use preoperative antibiotics. Over 70 percent of the respondents do not think breast reduction should be a cosmetic procedure. Conclusions: In conclusion, the inferior pedicle technique has traditionally been the procedure of choice and remains so today. However, there has been an increase in the use of the newer techniques. Plastic surgeons are becoming more cognizant of the risk of deep venous thrombosis among their patients. The majority of breast reductions are now performed as outpatient procedures.

Combined bone allograft and adipose-derived stem cell autograft in a rabbit model.

Currently available options for the repair of bony defects have substantial limitations. Much work has looked to the possibility of engineering bone using stem cells. These tissue-engineering efforts have focused on calvarial defect models, which have the advantages of minimal load-bearing and a large surface area. This study aims to solve the somewhat more challenging problem of repairing segmental bony defects such as those of the mandible and long bones. Four groups of decellularized bone tubes with cortical perforations were implanted subcutaneously in a rabbit model: empty bone tubes, bone tubes containing fibrin glue alone, bone tubes containing fibrin glue and freshly isolated autologous adipose-derived stem cells (ASCs), and bone tubes containing fibrin glue and predifferentiated autologous ASCs. Results showed a foreign body response characterized by fibrous capsule formation with minimal angiogenesis and no evidence of osteoblastic activity. Substantial changes are needed if this model is to become viable.

The use of visible light spectroscopy to measure tissue oxygenation in free flap reconstruction

The loss of a free flap is a feared complication for both the surgeon and the patient. Early recognition of vascular compromise has been shown to provide the best chance for flap salvage. The ideal monitoring technique for perioperative free flap ischemia would be noninvasive, continuous, and reliable. Visible light spectroscopy (VLS) was evaluated as a new method for predicting ischemia in microvascular cutaneous soft tissue free flaps. In an Institutional Review Board-approved prospective trial, 12 patients were monitored after free flap reconstructions. The tissue hemoglobin oxygen saturation (StO (2)) and total hemoglobin concentration (THB) of 12 flaps were continuously monitored using VLS for 72 hours postoperatively. Out of these 12 flaps 11 were transplanted successfully and 1 flap loss occurred. The StO (2 )was 48.99% and the THB was 46.74% for the 12 flaps. There was no significant difference in these values among the flaps. For the single flap loss, the device accurately reflected the ischemic drop in StO (2) indicating drastic tissue ischemia at 6 hours postoperatively before the disappearance of implantable Doppler signals or clinical signs of flap compromise. VLS, a continuous, noninvasive, and localized method to monitor oxygenation, appeared to predict early ischemic complications after free flap reconstruction.

Regulation of adipose oestrogen output by mechanical stress

Adipose stromal cells are the primary source of local oestrogens in adipose tissue, aberrant production of which promotes oestrogen receptor-positive breast cancer. Here we show that extracellular matrix compliance and cell contractility are two opposing determinants for oestrogen output of adipose stromal cells. Using synthetic extracellular matrix and elastomeric micropost arrays with tunable rigidity, we find that increasing matrix compliance induces transcription of aromatase, a rate-limiting enzyme in oestrogen biosynthesis. This mechanical cue is transduced sequentially by discoidin domain receptor 1, c-Jun N-terminal kinase 1, and phosphorylated JunB, which binds to and activates two breast cancer-associated aromatase promoters. In contrast, elevated cell contractility due to actin stress fibre formation dampens aromatase transcription. Mechanically stimulated stromal oestrogen production enhances oestrogen-dependent transcription in oestrogen receptor-positive tumour cells and promotes their growth. This novel mechanotransduction pathway underlies communications between extracellular matrix, stromal hormone output, and cancer cell growth within the same microenvironment.

An experimental design to study adipocyte stem cells for reconstruction of calvarial defects

Autogenous osteogenic differentiated rat adipose stromal cells (ASCs) were used to repopulate cadaveric processed bone in a critical calvarial defect model to improve bone healing as compared with the standard treatment of cadaveric bone implantation alone. Forty-two skeletally mature Sprague-Dawley rats were randomized to 5 groups including bone graft only, bone/osteogenic differentiated ASCs, fibrin glue/osteogenic differentiated ASCs, and bone/fibrin glue/osteogenic differentiated ASCs; 2 animal calvarias were left empty. Adipose stromal cells were isolated from the inguinal fat pad of rats and differentiated into osteogenic cells, verified using von Kossa and alkaline phosphatase staining, and osteocalcin immunohistochemistry. These cells were added to sterilized, 8-mm cadaveric bone graft disks and placed back into calvarial defect for 6 weeks. The rat calvarias then underwent bone density analysis and histology. Intact cells were observed in the bone graft of the bone/osteogenic differentiated ASC group only. Islands of bone were seen in the bone-graft-only group, the bone/osteogenic differentiated ASC group, and the bone/fibrin/osteogenic differentiated ASC group. The bone-graft-only group and bone/osteogenic differentiated ASC group were similar in bone mineral density (1397 ± 184.5 vs 1365 ± 160.4). The bone/fibrin/osteogenic differentiated ASC group density was less than the bone and bone/osteogenic differentiated ASC groups at 835.2 ± 319.5 (P < 0.001). Allograft bone scaffolds with autogenous osteogenic differentiated ASCs showed cellularity within the bone grafts and had larger bone islands. The presence of osteogenic differentiated ASCs did not increase overall bone density compared with bone graft only.

In vitro osteogenic differentiation of adipose stem cells after lentiviral transduction with green fluorescent protein.

Background: Adipose-derived stem cells (ASCs) have the potential to differentiate into osteogenic cells that can be seeded into scaffolds for tissue engineering for use in craniofacial bone defects. Green fluorescent protein (GFP) has been widely used as a lineage marker for mammalian cells. The use of fluorescent proteins enables cells to be tracked during manipulation such as osteogenic differentiation within three-dimensional scaffolds. The purpose of this study was to examine whether ASCs introduced with GFP-encoding lentivirus vector exhibit adequate GFP fluorescence and whether the expression of GFP interfered with osteogenic differentiation of ASCs in both monolayer and three-dimensional scaffolds in vitro. Methods: Primary ASCs were harvested from the inguinal fat pad of Sprague Dawley rats. Isolated ASCs were cultured and infected with a lentiviral vector encoding GFP and plated into both monolayers and three-dimensional scaffolds in vitro. The cells were then placed in osteogenic medium. Osteogenic differentiation of the GFP-ASCs was assessed using alizarin red S, alkaline phosphate staining, and immunohistochemistry staining of osteocalcin with quantification of alizarin red S and osteocalcin staining. Results: The efficacy of infection of ASCs with a lentiviral vector encoding GFP was high. Cell-cultured GFP-ASCs remained fluorescent over the 8 weeks of the study period. The GFP-ASCs were successfully induced into osteogenic cells both in monolayers and three-dimensional scaffolds. Whereas the quanitification of alizarin red S revealed no difference between osteoinduced ASCs with or without GFP, the quantification of osteocalcin revealed increased staining in the GFP group. Conclusions: Transduction of isolated ASCs using a lentiviral vector encoding GFP is an effective method for tracing osteoinduced ASCs in vitro. Quantification data showed no decrease in staining of the osteoinduced ASCs.

Anterolateral thigh flap technique in hand and upper extremity reconstruction.

The anterolateral thigh flap is an extremely versatile flap first described in 1984. The flap is based on either a septocutaneous or musculocutaneous perforator of the descending branch of the lateral circumflex femoral system. It can be designed as a skin and subcutaneous flap, fasciocutaneous, or musculocutaneous flap. Furthermore, it can be harvested as a sensate flap by taking the lateral cutaneous nerve of the thigh. Technique for harvesting the flap is described in detail. Complications include flap failure and donor site morbidity. Due to its versatility, the anterolateral thigh flap is particularly useful for upper extremity reconstruction.

Effect of Endothelial Differentiated Adipose-Derived Stem Cells on Vascularity and Osteogenesis in Poly (D, L-Lactide) Scaffolds In Vivo

Abstract Prevascularization of engineered bony constructs can potentially improve in vivo viability. However, the effect of endothelial cells on osteogenesis is unknown when placed in poly(D,L-lactide) (PLA) scaffolds alone. Adipose-derived stem cells (ASCs) have the ability to differentiate into both osteoblasts and endothelial cells by culture in specific media. We hypothesized that ASC-derived endothelial cells would improve vascularity with minimal contribution to bone formation when placed in scaffold alone. ASCs were successfully differentiated into endothelial cells (ASC-Endo) and osteoblasts (ASC-Osteo) using media supplemented with vascular endothelial growth factor and bone morphogenic protein 2, respectively. Tissue-engineered constructs were created with PLA matrices containing no cells (control), undifferentiated ASCs (ASCs), osteogenic-differentiated ASCs (ASC-Osteo), or endothelial differentiated ASCs (ASC-Endo), and these constructs were evaluated in critical-size Lewis rat calvarial defect model (n = 34). Eight weeks after implantation, the bone volume and microvessel population of bony constructs were evaluated by micro–computed tomography analysis and histologic staining. Bone volumes for ASCs and ASC-Osteo constructs, 0.7 and 0.91 mm3, respectively, were statistically greater than that for ASC-Endo, 0.28 mm3 (P < 0.05). There was no statistical difference between the PLA control (0.5 mm3) and ASC-Endo (0.28 mm3) constructs in bone formation. The percent area of microvessels within constructs was highest in the ASC-Endo group, although it did not reach statistical significance (0.065). Prevascularization of PLA scaffold with ASC-Endo cells will not increase bone formation by itself but may be used as a cell source for improving vascularization and potentially improving existing osteoblast function.