Gina Farias-Eisner

Obesity impairs lymphatic fluid transport and dendritic cell migration to lymph nodes.

Introduction Obesity is a major cause of morbidity and mortality resulting in pathologic changes in virtually every organ system. Although the cardiovascular system has been a focus of intense study, the effects of obesity on the lymphatic system remain essentially unknown. The purpose of this study was to identify the pathologic consequences of diet induced obesity (DIO) on the lymphatic system. Methods Adult male wild-type or RAG C57B6-6J mice were fed a high fat (60%) or normal chow diet for 8–10 weeks followed by analysis of lymphatic transport capacity. In addition, we assessed migration of dendritic cells (DCs) to local lymph nodes, lymph node architecture, and lymph node cellular make up. Results High fat diet resulted in obesity in both wild-type and RAG mice and significantly impaired lymphatic fluid transport and lymph node uptake; interestingly, obese wild-type but not obese RAG mice had significantly impaired migration of DCs to the peripheral lymph nodes. Obesity also resulted in significant changes in the macro and microscopic anatomy of lymph nodes as reflected by a marked decrease in size of inguinal lymph nodes (3.4-fold), decreased number of lymph node lymphatics (1.6-fold), loss of follicular pattern of B cells, and dysregulation of CCL21 expression gradients. Finally, obesity resulted in a significant decrease in the number of lymph node T cells and increased number of B cells and macrophages. Conclusions Obesity has significant negative effects on lymphatic transport, DC cell migration, and lymph node architecture. Loss of T and B cell inflammatory reactions does not protect from impaired lymphatic fluid transport but preserves DC migration capacity. Future studies are needed to determine how the interplay between diet, obesity, and the lymphatic system modulate systemic complications of obesity.

Lymph Node Transplantation Results in Spontaneous Lymphatic Reconnection and Restoration of Lymphatic Flow

Background: Although lymph node transplantation has been shown to improve lymphatic function, the mechanisms regulating lymphatic vessel reconnection and functional status of lymph nodes remains poorly understood. Methods: The authors developed and used LacZ lymphatic reporter mice to examine the lineage of lymphatic vessels infiltrating transferred lymph nodes. In addition, the authors analyzed lymphatic function, expression of vascular endothelial growth factor (VEGF)-C, maintenance of T- and B-cell zone, and anatomical localization of lymphatics and high endothelial venules. Results: Reporter mice were specific and highly sensitive in identifying lymphatic vessels. Lymph node transfer was associated with rapid return of lymphatic function and clearance of technetium-99 secondary to a massive infiltration of recipient mouse lymphatics and putative connections to donor lymphatics. T- and B-cell populations in the lymph node were maintained. These changes correlated with marked increases in the expression of VEGF-C in the perinodal fat and infiltrating lymphatics. Newly formed lymphatic channels in transferred lymph nodes were in close anatomical proximity to high endothelial venules. Conclusions: Transferred lymph nodes have rapid infiltration of functional host lymphatic vessels and maintain T- and B-cell populations. This process correlates with increased endogenous expression of VEGF-C in the perinodal fat and infiltrating lymphatics. Anatomical proximity of newly formed lymphatics and high endothelial venules supports the hypothesis that lymph node transfer can improve lymphedema by exchanges with the systemic circulation.

Diminishing relative contraindications for immediate breast reconstruction.

Background: The rise in U.S. immediate breast reconstruction over the past decade may reflect greater patient awareness or expanding use in women not previously offered reconstruction. The purpose of the current study was to determine whether reconstruction in high-risk surgical and oncologic patients was a factor contributing to increased reconstruction rates, specifically using prosthetic techniques. Methods: Information from a cohort of mastectomy patients from 2001 to 2012 was extracted from an institutional database, including the presence of high-risk surgical or oncologic features (age over 60 years old, body mass index greater than 30, comorbidities, smoking, advanced disease, and prior or postmastectomy radiotherapy). Trends in reconstruction rates and method were analyzed with Poisson regression. Reconstructive success was defined as tissue expander exchange to a permanent implant or autologous techniques without vascular complications. Results: A total of 10,299 patients were included. Immediate reconstruction in high-risk patients increased from 45.0 to 70.7 of 100 mastectomies (p < 0.01). Although autologous use increased only for obese patients (p < 0.01), prosthetic techniques were greater for all high-risk features (p < 0.01). Reconstructive success was 88 percent in high-risk patients; however, the number of failures was greater, including tissue expander loss, implant explantation, and flap vascular complications. Conclusions: The proportion of high-risk patients undergoing immediate breast reconstruction—specifically using prosthetic-based techniques—increased over the study period. Increased complications may be a tradeoff for the benefits of reconstruction. These findings support diminishing relative contraindications for immediate breast reconstruction at a tertiary cancer center. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, IV.

Abstract 146: diet-induced obesity results in lymphatic dysfunction and impaired T cell function.

Suday, M arch 9, 2014 producing two dividing cells and 10% one differentiated and one proliferating cell. Here too, division outcomes were independent of neighbours or close relations. These stem-like cells generated colonies containing hundreds of cells, mostly proliferating. Combinatorial statistics using the timelapse data predicted the distribution of clone sizes in a large sample of cells (n=1462) cultured for 7days, indicating the probabilities of each type of division were balanced as in vivo. Hypersupplementation (20ng/mL) or withdrawal (0ng/mL) of EGF, or addition of R-Spondin to the culture imbalanced the generation of proliferating or differentiating cells indicating that the fate of the progenitor-like cells was subject to external regulation. Transcriptional analysis revealed a distinct pattern of gene expression in 8-cell colonies derived from stem and progenitor-like cells. Validation of these results by immunostaining revealed the proportion of cells expressing differentiation associated genes in progenitor-derived colonies in accordance with the timelapse data.

Abstract 86: Lymph Node Transplantation Generates Spontaneous Lymphatic Reconnection and Restoration of Lymphatic Flow

PurPose: Although lymph node transplantation has been shown to improve lymphatic function in patients with lymphedema, the mechanisms regulating lymphatic vessel reconnection and the functional status of lymph nodes (LNs) remains poorly understood. In this study we developed a novel reporter mouse that allowed us to determine the origin of lymphatic endothelial cells (LECs) and vessels forming functional connections with transferred LNs.

Abstract 27. The Use of Liposomal Bupivacaine in Patients Undergoing Abdominally-Based Autologous and Implant-Based Breast Reconstruction

CONCLUSION: Despite their similarities in clinical and radiographic presentation, pediatric JE phalangeal fractures are a distinct entity from SH2 fractures. Presenting with significantly more radiographic angulation and clinical instability, JE fractures more frequently required operative fixation compared to SH2 fractures. This distinction is important when determining the treatment strategy employed (operative fixation versus nonoperative management) as well as potential length and degree of immobilization/stabilization for nonoperative management to increase the success of treatment.

Intraoperative Indocyanine Green Laser Angiography in Pediatric Autologous Ear Reconstruction.

Summary: Skin flap vascularity is a critical determinant of aesthetic results in autologous ear reconstruction. In this study, we investigate the use of intraoperative laser-assisted indocyanine green angiography (ICGA) as an adjunctive measure of skin flap vascularity in pediatric autologous ear reconstruction. Twenty-one consecutive pediatric patients undergoing first-stage autologous total ear reconstruction were retrospectively evaluated. The first 10 patients were treated traditionally (non-ICGA), and the latter 11 patients were evaluated with ICGA intraoperatively after implantation of the cartilage construct and administration of suction. Relative and absolute perfusion units in the form of contour maps were generated. Statistical analyses were performed using independent sample Student t test. Statistically significant differences in exposure and infection were not found between the 2 groups. However, decreased numbers of surgical revisions were required in cases with ICGA versus without ICGA (P = 0.03), suggesting that greater certainty in skin flap perfusion correlated with a reduction in revision surgeries. In cases of exposure, we found an average lowest absolute perfusion unit of 14.3, whereas cases without exposure had an average of 26.1 (P = 0.02), thereby defining objective parameters for utilizing ICGA data in tailoring surgical decision making for this special population of patients. Defined quantitative parameters for utilizing ICGA in evaluating skin flap vascularity may be a useful adjunctive technique in pediatric autologous ear reconstruction.

Abstract: Liposomal Bupivacaine Reduces Postoperative Narcotic Use in Patients Undergoing Abdominal-Based Autologous and Implant-Based Breast Reconstruction

PurPose: Treatment of post-operative pain after breast reconstruction remains a significant challenge for plastic surgeons. Liposomal bupivacaine (LB, Exparel Pacira Pharmaceuticals, Inc., Parsippany, NJ) has been proven to effectively relieve pain in the immediate postoperative period. The purpose of our study is to explore the effects of intraoperatively delivered LB on postoperative narcotic use in women undergoing autologous and implant-based breast reconstruction.

Orthognathic Consequences of Sphincter Pharyngoplasty in Cleft Patients: A 2-Institutional Study

Background: Understanding long-term sequelae of cleft treatment is paramount in the refinement of treatment algorithms to accomplish optimized immediate and long-term outcomes. In this study, we reviewed sphincter pharyngoplasties as a method of velopharyngeal insufficiency (VPI) treatment in relationship to orthognathic surgery. Methods: Cleft lip/palate and cleft palate patients, 15 years of age and older, were reviewed for demographics, VPI surgery, revisions, and subsequent orthognathic surgery at 2 institutions. Chi-square test, Student’s t test, and logistic regression analyses were performed. Results: In 214 patients reviewed (mean age, 19.5 years), 61.7% were male, 18.2% had isolated cleft palate, 61.2% had unilateral cleft lip and palate, and 20.6% had bilateral cleft lip and palate. A total of 33.6% were diagnosed with VPI and received a sphincter pharyngoplasty (mean age, 11.9 years). When subsequent orthognathic surgery was examined, sphincter pharyngoplasty was not associated with maxillary advancement (P = 0.59) but did correlate with an increase in mandibular surgery from 2.8% to 11.1% (P = 0.02). The indications for mandibular surgery in the pharyngoplasty population were related to congenital micrognathia. When cephalometric analyses were evaluated, sphincter pharyngoplasty resulted in a decreased sella-to-nasion-to-B point angle (mean, 79.0–76.3 degrees, P = 0.02) and a higher incidence of normal to class II maxillomandibular relationships as defined by A point-to-nasion-to-B point angles >0.5 (P = 0.02). Conclusions: Sphincter pharyngoplasty decreases anterior mandibular growth and the discrepancy between maxillomandibular skeletal relationships because of the frequent predisposition of cleft patients to maxillary hypoplasia. In patients with congenital mandibular micrognathia, a small increase in mandibular surgeries may occur.

Abstract 144: cd4+ cells are key regulators of pathologic changes in lymphedema.

our oBjeCtives are: 1. Demonstrate that grafting human skin onto TCR (T-cell receptor) αβ-/-γδ-/-, RAG (recombination activating gene)1-/and RAG-2-/-γc-/mice results in scars morphologically and histologically consistent with human HSc. 2. Characterize histologic and cellular changes that occur in scars with removal of specific immune cell subsets. 3. Compare scar response over time nude and knockout mice.