Faculty Bibliography

Modern sarcoma treatment has created new challenges for plastic surgeons. This study was designed to review the recent experience and practice patterns following complex sarcoma resection at a large sarcoma center. All cases from October 2013 to October 2014 involving rare nonepithelial tumors, a multidisciplinary surgical team, radiation and/or chemotherapy treatments, and plastic surgical reconstruction were included in the analysis. In addition to evaluating clinical outcomes, cases were reviewed to identify factors associated with excellent or poor patient care. Review of these cases formed the basis of the greatest healing opportunity for soft tissue (GHOST) protocol. Our patient population included seven males (64%) and four females (36%). All except one patient was exposed to radiotherapy, chemotherapy, or some combination. Diverse procedures were used for reconstruction. Early complications occurred in two patients (18%), and late complications in four patients (36%). Sarcoma resection was found to be highly morbid in our series. Patients with poor preoperative nutritional status were more likely to experience complications postoperatively. The decision to stage a reconstruction was complex and influenced by several factors. Multimodal sarcoma treatments may involve highly morbid procedures and create complex wounds. The GHOST protocol is a useful reference for plastic surgeons.

Over the past year of editorial transition at the Journal, I have spent an inordinate amount of time pondering the attributes of leadership. Mary Travis Bassett, the New York City Health Commissioner, received due acclaim during the Ebola fears last year as a leader with empathy, depth of understanding, and calm in the midst of all too frequent political posturing. "I was thinking, as a parent myself, how scared a parent must be. Information is a really good antidote to fear," she was quoted as reflecting by Josh Dawsey in the Wall Street Journal last October. (Am J Public Health. Published online ahead of print April 16, 2015: e1. doi:10.2105/AJPH.2015.302657).

Differential thermal nociception across inbred mouse strains has genetic determinants. Thermal nociception is largely attributed to the heat/capsaicin receptor TRPV1; however, the contribution of this channel to the genetics of thermal nociception has not been revealed. In this study we compared TRPV1 expression levels and electrophysiological properties in primary sensory neurons and thermal nociceptive behaviors between two (C57BL/6 and BALB/c) inbred mouse strains. Using immunofluorescence and patch-clamp physiology methods, we demonstrated that TRPV1 expression was significantly higher in isolectin B4 (IB4) -positive trigeminal sensory neurons of C57BL/6 relative to BALB/c; the expression in IB4-negative neurons was similar between the strains. Furthermore, using electrophysiological cell classification (current signature method), we showed differences between the two strains in capsaicin sensitivity in IB4-positive neuronal cell types 2 and 13, that were previously reported as skin nociceptors. Otherwise electrophysiological membrane properties of the classified cell types were similar in the two mouse strains. In publicly available nocifensive behavior data and our own behavior data from the using the two mouse strains, C57BL/6 exhibited higher sensitivity to heat stimulation than BALB/c, independent of sex and anatomical location of thermal testing (the tail, hind paw and whisker pad). The TRPV1 selective antagonist JNJ-17203212 inhibited thermal nociception in both strains; however, removing IB4-positive trigeminal sensory neurons with IB4-conjugated saporin inhibited thermal nociception on the whisker pad in C57BL/6, but not in BALB/c. These results suggest that TRPV1 expression levels in IB4-positive type 2 and 13 neurons contributed to differential thermal nociception in skin of C57BL/6 compared to BALB/c.

Introduction: Lymphedema, a common complication of cancer treatment, is characterized by inflammation, fibrosis, and adipose deposition. We previously have shown that macrophage infiltration is increased in mouse models of lymphedema. Because macrophages are regulators of lymphangiogenesis and fibrosis, this study aimed to determine the role of these cells in lymphedema using depletion experiments. Methods: Matched biopsy specimens of normal and lymphedema tissues were obtained from patients with unilateral upper extremity breast cancer-related lymphedema and macrophage accumulation was assessed using immunohistochemistry. In addition, we used a mouse tail model of lymphedema to quantify macrophage accumulation and analyze outcomes of conditional macrophage depletion. Results: Histological analysis of clinical lymphedema biopsies revealed significantly increased macrophage infiltration. Similarly, in the mouse tail model, lymphatic injury increased the number of macrophages and favored M2 differentiation. Chronic macrophage depletion using lethally irradiated wild-type mice reconstituted with CD11b-DTR mouse bone marrow did not decrease swelling, adipose deposition, or overall inflammation. Macrophage depletion after lymphedema had become established significantly increased fibrosis, accumulation of CD4+ cells, and promoted Th2 differentiation while decreasing lymphatic transport capacity and VEGF-C expression. Conclusion: Our findings suggest that macrophages home to lymphedematous tissues and differentiate into the M2 phenotype. In addition, our findings suggest that macrophages have an anti-fibrotic role in lymphedema and either directly or indirectly regulate CD4+ cell accumulation and Th2 differentiation. Finally our findings suggest that lymphedema associated macrophages are a major source of VEGF-C and that impaired macrophage responses after lymphatic injury results in decreased lymphatic function.

BACKGROUND: Acellular dermal matrix (ADM) is widely used for structural or dermal replacement purposes. Given its innate biocompatibility and its potential to vascularize, we explored the possibility of ADM to function as a small interfering RNA (siRNA) delivery system. Specifically, we sought to improve ADM vascularization by siRNA-mediated inhibition of prolyl hydroxylase domain-2 (PHD2), a cytoplasmic protein that regulates hypoxia inducible factor-1alpha, and improve neovascularization. MATERIALS AND METHODS: Fluorescently labeled siRNA was used to rehydrate thin implantable ADM. Pharmacokinetic release of siRNA was determined. Twelve millimeter sections of ADM reconstituted with PHD2 siRNA (nonsense siRNA as control) and applied to dorsal wounds of 40 FVB mice. Grafts were sewn in, bolstered, and covered with occlusive dressings. Photographs were taken at 0, 7, and 14 d. Wounds were harvested at 7 and 14 d and analyzed (messenger RNA, protein, histology, and immunohistochemistry). RESULTS: Release kinetics was first-order with 80% release by 12 h. By day 14, PHD2-containing ADM appeared viable and adherent, whereas controls appeared nonviable and nonadherent. Real-time reverse transcription-polymerase chain reaction demonstrated near-complete knockdown of PHD2, whereas vascular endothelial growth factor and FGF-2 were increased 2.3- and 4.7-fold. On enzyme-linked immunosorbent assay, vascular endothelial growth factor was increased more than fourfold and stromal cell-derived factor doubled. Histology demonstrated improved graft incorporation in treated groups. Immunohistochemical demonstrated increased vascularity measured by CD31 staining and increased new cell proliferation by denser proliferating cell nuclear antigen staining in treated versus controls. CONCLUSIONS: We concluded that ADM is an effective matrix for local delivery of siRNA. Strategies to improve the matrix and/or genetically alter the local tissue environment can be envisioned.

BACKGROUND: Although the majority of nasal alterations in rhinoplasty result from either augmentation or reduction of bone and cartilaginous substructure, modifications of influential soft-tissue provide significant contribution to the final result. The depressor septi nasi muscle is a soft-tissue structure well known to influence the final result in rhinoplasty. The objective of this study was to perform a standardized, comprehensive review of relevant data published with regard to the depressor septi nasi muscle. METHODS: A comprehensive search of the terms "depressor septi muscle" and "depressor septi nasi muscle" was performed using the PubMed, MEDLINE, and Cochrane databases. Articles were reviewed for relevancy and included if criteria were met. A secondary review was performed of all articles cited, to maximize diligence. RESULTS: Forty-three articles were identified in the initial search. Thirteen of the 43 were found to meet inclusion criteria. Secondary search revealed additional studies meeting inclusion criteria. Altogether, there were 175 cadaver specimens and 821 surgically treated patients for which data were available. Anatomical reports and nomenclature were found to vary. Surgical approach and muscle treatment diverged, with objective data showing no superior method. CONCLUSIONS: Although variation exists in anatomical reports regarding the depressor septi nasi muscle, the prevailing thought is that it originates from the maxilla and/or orbicularis oris muscle. More importantly, the muscle inserts on the medial crura and adjacent soft tissue. Disruption of this relationship provides the basis for surgical treatment of tip descent on animation.

Objectives: The aim of this study was to quantify the polymerization volumetric shrinkage of one regular and two low shrinkage bulk fill composites in class I cavities with or without an adhesive layer, using three-dimensional (3D) micro-computed tomography (muCT). Methods: Class I cavity preparations (2.5 mm depth x 4 mm length x 4 mm wide) were standardized in 36 extracted human third molars, which were randomly divided in six groups (n = 6 each) as follows: Group VIT (regular composite without bonding agent); Group SDR (low shrinkage flowable composite without bonding agent); Group TET (low shrinkage composite without bonding agent); Group VIT/P (regular composite with bonding agent); Group SDR/X (low shrinkage flowable composite with bonding agent); TET/T (low shrinkage composite with bonding agent). Each tooth was scanned via microCT at cavity preparation, immediately after cavity filling, and after light-curing. Acquired muCT data were imported into Amira software for analysis and volume values evaluated between steps from cavity preparation until light-curing. Results: Both low shrinkage composites showed a significantly less volumetric shrinkage than VIT. The use of dental adhesive significantly decreased the average volumetric contraction similarly for the three composites, by about 20%. Conclusion: Both low shrinkage composites showed less volumetric polymerization contraction than the regular composite. The use of dental adhesive decreased the total volumetric shrinkage for all evaluated composites. (c) 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2014.

Traumas, malformative or dysplastic pathologies, atrophy, osteoradionecrosis, and benign or malignant neoplasm can cause bone deficits in the mandible. Consequent mandibular defects can determine aesthetic and functional problems; therefore, being able to perform a good reconstruction is of critical importance.Several techniques have been proposed for mandibular reconstruction over the years. In this article, we present and discuss the evolution during the time of the methods of mandible reconstruction as well as pros and cons of each procedure on the basis of experience of 10 years in the maxillofacial department of the Catholic University of Sacred Heart of Rome.Free flaps represent the gold standard method of reconstruction of large mandibular defects: the fibula bone flap represents the best choice for large defects involving the arch and the mandibular ramus, whereas the deep circumflex iliac artery represents a valid alternative for mandibular defects involving the posterior region.In cases where free flap reconstructions are contraindicated, the use of regional pedicle flap combined with autologous bone grafts still represents a valid choice. Patients who are not deemed suitable for long and demanding surgery can still be treated using alloplastic materials in association with regional pedicle flap or, when adjuvant radiation therapy is needed, by simple locoregional pedicle flap. Finally, in selected cases, the bone transporting technique should be considered as a valid alternative to the more "traditional" reconstructive methods because of the extraordinary potential and its favorable cost-benefit ratio.