Faculty Bibliography

AIMS: Recent studies have demonstrated that augmentation of lymphangiogenesis and tissue engineering hold promise as a treatment for lymphedema. The purpose of this study was to determine whether adipose-derived stem cells (ASCs) can be used in lymphatic tissue-engineering by altering the balance between pro- and anti-lymphangiogenic cytokines. MATERIALS & METHODS: ASCs were harvested and cultured in media with or without recombinant VEGF-C for 48 h. ASCs were then implanted in mice using Matrigel plugs. Additional groups of animals were implanted with ASCs transfected with a dominant-negative TGF-beta1 receptor-II adenovirus with or without VEGF-C stimulation, since TGF-beta1 has been shown to have potent antilymphangiogenic effects. Lymphangiogenesis, lymphatic differentiation and cellular proliferation were assessed. RESULTS: Stimulation of ASCs with VEGF-C in vitro significantly increased expression of VEGF-A, VEGF-C and Prox-1. ASCs stimulated with VEGF-C prior to implantation induced a significant (threefold increase) lymphangiogenic response as compared with control groups (unstimulated ASCs or empty Matrigel plugs; p < 0.01). This effect was significantly potentiated when TGF-beta1 signaling was inhibited using the dominant-negative TGF-beta1 receptor-II virus (4.5-fold increase; p < 0.01). Stimulation of ASCs with VEGF-C resulted in a marked increase in the number of donor ASCs (twofold; p < 0.01) and increased the number of proliferating cells (sevenfold; p < 0.01) surrounding the Matrigel. ASCs stimulated with VEGF-C expressed podoplanin, a lymphangiogenic cell marker, whereas unstimulated cells did not. CONCLUSION: Short-term stimulation of ASCs with VEGF-C results in increased expression of VEGF-A, VEGF-C and Prox-1 in vitro and is associated with a marked increase lymphangiogenic response after in vivo implantation. This lymphangiogenic response is significantly potentiated by blocking TGF-beta1 function. Furthermore, stimulation of ASCs with VEGF-C markedly increases cellular proliferation and cellular survival after in vivo implantation and stimulated cells express podoplanin, a lymphangiogenic cell marker.

Nanostructures on implant surfaces have been shown to enhance osseointegration; however, commonly used evaluation techniques are probably not sufficiently sensitive to fully determine the effects of this process. This study aimed to observe the osseointegration properties of nanostructured calcium phosphate (CaP)-coated implants, by using a combination of three-dimensional imaging and conventional histology. Titanium implants were coated with stable CaP nanoparticles using an immersion technique followed by heat treatment. Uncoated implants were used as the control. After topographical and chemical characterizations, implants were inserted into the rabbit femur. After 2 and 4weeks, the samples were retrieved for micro-computed tomography and histomorphometric evaluation. Scanning electron microscopy evaluation indicated that the implant surface was modified at the nanoscale by CaP to obtain surface textured with rod-shaped structures. Relative to the control, the bone-to-implant contact for the CaP-coated implant was significantly higher at 4weeks after the implant surgery. Further, corresponding 3-D images showed active bone formation surrounding the implant. 3-D quantification and 2-D histology demonstrated statistical correlation; moreover, 3-D quantification indicated a statistical decrease in bone density in the non-coated control implant group between 2 and 4weeks after the surgery. The application of 3-D evaluation further clarified the temporal characteristics and biological reaction of implants in bone.

PURPOSE: We present a strategy to survey proteolytic processes that occur in human cancer microenvironments. EXPERIMENTAL DESIGN: In situ microdialysis during oral cancer surgery was combined with mass spectrometry-based proteomics to analyze interstitial fluid surrounding tumors and anatomically matched normal sites. Protease activity-based (18)O-profiling was utilized to reveal peptides that were processed by co-collected proteases ex vivo. RESULTS: We demonstrated for the first time the use of microdialysis in humans to collect interstitial fluid from cancer microenvironments. Proteomic profiling identified proteases and inhibitors in the microdialysis samples. A subset of peptides displayed characteristic (18)O-isotope patterns that indicated processing by endogenous proteases. CONCLUSIONS AND CLINICAL RELEVANCE: The presented approach provides unprecedented views of in vivo targets of proteases without disrupting the cancer or surrounding tissue. The methodology can be broadly adapted to other physiological conditions in which proteolytic mediators are involved (e.g. arthritic joints, inflamed muscle, other types of cancer) and where a comparison of normal and pathological tissue is sought.

INTRODUCTION: : A cervicofacial flap remains the principal method to close defects of the posterior cheek. Schrudde described a variant of this technique, termed the angle-rotation flap, which allowed primary closure of the donor site. This flap has been elevated in the deep plane for the more medial defects. We extend this technique for upper lip reconstruction. METHODS: : Two cases were reviewed that underwent upper lip reconstruction with the deep-plane Schrudde flap. RESULTS: : Two cases are presented to describe the use of the deep-plane angle-rotation flap. The first patient sustained a burn to his upper lip and the second patient had a partially grafted defect following a Mohs excision. DISCUSSION: : In patients with insignificant nasolabial folds, the deep-plane Schrudde flap is a good option to reconstruct perioral defects. The utilization of the deep plane improves the blood supply and allows improved contour for reconstruction of deeper defects

BACKGROUND: Vascularized composite tissue allotransplantation has demonstrated clinical success with standard immunosuppression in hand and upper extremity transplantation. The authors developed a fibular vascularized composite tissue allotransplantation model in nonhuman primates to investigate healing and rejection patterns of bone and associated tissues. METHODS: Five fibular vascularized composite tissue allotransplantations were performed between mismatched cynomolgus macaques (Macaca fascicularis). Vascularized fibular segments with associated muscle and skin were transplanted to recipient forearm radius defects. Recipients were treated with either tacrolimus monotherapy or tacrolimus plus co-stimulatory blockade with a novel anti-CD28 antibody. Animals were followed for 6 months with serial radiographs, blood sample collection, and biopsies. At the study endpoint, angiographic, biomechanical, histologic, and immunologic assays were performed. RESULTS: All animals survived to the experimental endpoint of 180 days. Rapid or immediate skin loss was evident secondary to vascular compromise (n = 3) or rejection (n = 1) in four animals. Despite loss of nonbony segments and the development of transplant arteriopathy consistent with chronic rejection in two animals, serial radiologic imaging and histology demonstrated bone healing and donor-recipient bony union by 10 weeks in all animals. Histology confirmed the presence of viable cortical and marrow elements. Biomechanical analysis supported donor-recipient bony union. Short-tandem repeated genotypic analysis revealed that donor marrow had been completely replaced by recipient marrow. CONCLUSIONS: In contrast to successes in extremity vascularized composite tissue allotransplantation, the authors' nonhuman primate fibular vascularized composite tissue allotransplantation model showed early skin loss, replacement of donor bone marrow, and chronic rejection. Donor-recipient bone union did occur and supports the potential for reconstruction of bony continuity defects using isolated vascularized bone allotransplants.

This case study will describe the journey of a patient admitted to an urban, tertiary medical center for bariatric surgery and the unexpected challenges encountered by the clinical staff in caring for him. Despite having awell-established bariatric surgical program, it took only one patient who deviated from the "norm" to cause thestaff to reexamine the way that bariatric patients are cared for in the facility, particularly with regard to their mobility and safe patient handling needs. The lessons learned from this experience and the patient’s own perspective have enabled a more informed approach to how bariatric patients are cared for throughout the hospital and led to an adjustment of protocols in this area of practice

Many women have a dwindled ptotic breast. The surgical solution for these two concurring problems has two separate procedures: augmentation and mastopexy. Combining these two procedure into one surgery is considered unpredictable and avoided by many physicians. This study presents a revised mastopexy-augmentation technique found to be safer and more simple, enabling these two procedures to be performed together. A retrospective review of 60 patients who underwent surgery by a single surgeon is presented. The presented method has yielded a relatively low reoperation rate of 10% and a high satisfaction rate.

PURPOSE: Problems in management of oral cancers or precancers include identification of patients at risk for metastasis, tumor recurrence, and second primary tumors or risk for progression of precancers (dysplasia) to cancer. Thus, the objective of this study was to clarify the role of genomic aberrations in oral cancer progression and metastasis. EXPERIMENTAL DESIGN: The spectrum of copy number alterations in oral dysplasia and squamous cell carcinomas (SCC) was determined by array comparative genomic hybridization. Associations with clinical characteristics were studied and results confirmed in an independent cohort. RESULTS: The presence of one or more of the chromosomal aberrations +3q24-qter, -8pter-p23.1, +8q12-q24.2, and +20 distinguishes a major subgroup (70%-80% of lesions, termed 3q8pq20 subtype) from the remainder (20%-30% of lesions, non-3q8pq20). The 3q8pq20 subtype is associated with chromosomal instability and differential methylation in the most chromosomally unstable tumors. The two subtypes differ significantly in clinical outcome with risk for cervical (neck) lymph node metastasis almost exclusively associated with the 3q8pq20 subtype in two independent oral SCC cohorts. CONCLUSIONS: Two subtypes of oral lesions indicative of at least two pathways for oral cancer development were distinguished that differ in chromosomal instability and risk for metastasis, suggesting that +3q,-8p, +8q, and +20 constitute a biomarker with clinical utility for identifying patients at risk for metastasis. Moreover, although increased numbers of genomic alterations can be harbingers of progression to cancer, dysplastic lesions lacking copy number changes cannot be considered benign as they are potential precursors to non-3q8pq20 locally invasive, yet not metastatic oral SCC.

BACKGROUND: This study is a thorough literature review of the clinical presentation and evaluation of developmental facial paralysis, with a systematic description of the various stigmata and associated anomalies. It is hoped that this approach will facilitate the differentiation of developmental facial paralysis from other causes of facial paralysis present at birth. METHODS: Forty-two cases of developmental facial paralysis were identified in a retrospective clinical review (1980 to 2010); 34 were children (80.95 percent; age, 8+/-6 years) and eight were adults (19.05 percent; age, 27+/-12 years). Thirty-one patients had simple developmental paralysis, and two patients had developmental unilateral lower lip palsy. There were nine patients with associated anomalies or craniofacial syndromes. Five of these patients had multiple cranial nerve deficits. RESULTS: Analysis of the various stigmata revealed significant correlation between the presence of developmental facial paralysis and amblyopia, hypoplastic facial nerve on imaging or surgical exploration, lower alar atresia, and skin changes (i.e., acne), but not the ear abnormalities. CONCLUSIONS: Early targeted screening and diagnosis, with prompt specialized treatment, improves the physical and emotional development of children with developmental facial paralysis and reduces the prevalence of amblyopia and other sequelae of the condition, thus facilitating reintegration among their peers. Given the dramatic presentation of this condition, accurate and reliable guidelines are necessary to facilitate early diagnosis, initiate appropriate therapy, and provide support and counseling to the family.