Exercise training improves obesity-related lymphatic dysfunction.

KEY POINTS: Obesity results in perilymphatic inflammation and lymphatic dysfunction. Lymphatic dysfunction in obesity is characterized by decreased lymphatic vessel density, decreased collecting lymphatic vessel pumping frequency, decreased lymphatic trafficking of immune cells, increased lymphatic vessel leakiness and changes in the gene expression patterns of lymphatic endothelial cells. Aerobic exercise, independent of weight loss, decreases perilymphatic inflammatory cell accumulation, improves lymphatic function and reverses pathological changes in gene expression in lymphatic endothelial cells. ABSTRACT: Although previous studies have shown that obesity markedly decreases lymphatic function, the cellular mechanisms that regulate this response remain unknown. In addition, it is unclear whether the pathological effects of obesity on the lymphatic system are reversible with behavioural modifications. The purpose of this study, therefore, was to analyse lymphatic vascular changes in obese mice and to determine whether these pathological effects are reversible with aerobic exercise. We randomized obese mice to either aerobic exercise (treadmill running for 30 min per day, 5 days a week, for 6 weeks) or a sedentary group that was not exercised and analysed lymphatic function using a variety of outcomes. We found that sedentary obese mice had markedly decreased collecting lymphatic vessel pumping capacity, decreased lymphatic vessel density, decreased lymphatic migration of immune cells, increased lymphatic vessel leakiness and decreased expression of lymphatic specific markers compared with lean mice (all P < 0.01). Aerobic exercise did not cause weight loss but markedly improved lymphatic function compared with sedentary obese mice. Exercise had a significant anti-inflammatory effect, resulting in decreased perilymphatic accumulation of inflammatory cells and inducible nitric oxide synthase expression. In addition, exercise normalized isolated lymphatic endothelial cell gene expression of lymphatic specific genes, including VEGFR-3 and Prox1. Taken together, our findings suggest that obesity impairs lymphatic function via multiple mechanisms and that these pathological changes can be reversed, in part, with aerobic exercise, independent of weight loss. In addition, our study shows that obesity-induced lymphatic endothelial cell gene expression changes are reversible with behavioural modifications.

Robotics in Microsurgery and Supermicrosurgery.

Microsurgery has changed the ability to perform highly precise and technical surgeries through the utilization of high-powered microscopes and specialized instruments to manipulate and repair anatomical structures as small as a few millimeters. Since the first human trials of robotic-assisted microsurgery in 2006, the expansion of microsurgery to supermicrosurgery (luminal diameter less than 1 mm) has enabled successful repair of previously inaccessible structures. Surgical robotic systems can offer two distinct operative advantages: (1) minimal access surgery-by entering body cavities through ports, flap harvest can be redesigned to affect a minimally invasive approach for flaps such as the rectus abdominis muscle, the latissimus flap, and the deep inferior epigastric perforator flap; and (2) precision-by eliminating physiologic tremor, improving ergonomics, increasing accessibility to difficult spaces, and providing motion scaling, precision is significantly enhanced. Robotic-assisted microsurgery is a promising application of robotics for the plastic surgeon and has played an important role in flap harvest, head and neck reconstruction, nerve reconstruction, gender-affirming surgery, and lymphatic reconstruction-all the while minimizing surgical morbidity. This article aims to review the history, technology, and application of microsurgery and supermicrosurgery in plastic surgery.

Robotic-Assisted Nipple Sparing Mastectomy.

Minimally invasive approaches to breast surgery have evolved from endoscopic techniques to recent developments in robotic-assisted mastectomies. Initial studies on robotic-assisted nipple-sparing mastectomy (RNSM) have shown improved patient satisfaction and aesthetic outcomes with similar complication rates and oncological outcomes in selected patients. This chapter reviews techniques used and available data on complications and clinical outcomes for RNSM. Currently, RNSM is an investigational technique in the United States and should be performed in clinical trials with U.S. Food & Drug Administration approval to rigorously evaluate the safety and effectiveness of this approach.

Robotic Surgery and Hospital Reimbursement.

The field of plastic surgery remains at the forefront of technological and surgical innovation. However, the promising applications of robotics in plastic surgery must be thoughtfully balanced with hospital finances and reimbursements. Robotic systems have been studied extensively across multiple surgical disciplines and across diverse health care systems. The results show that there may be equal or better patient outcomes than alternatives. In an era where fiscal responsibility in health care is a top priority, thoughtful budgeting and spending must be considered and revisited frequently to attain sustainable organizational models that ensure appropriate use of robotic technology.

Robotics in Implant-Based and Autologous Breast Reconstruction.

Autologous and implant-based breast reconstruction continues to evolve as new technology and mastectomy techniques become available. Robotic-assisted breast reconstruction represents a growing field within plastic surgery, with the potential to improve aesthetic and functional outcomes, as well as patient satisfaction. This article provides a review of indications, techniques, and outcome data supporting the use of robotic assistance in both implant-based and autologous breast reconstruction from surgeons around the world.

Surgical and Patient-Reported Outcomes of 694 Two-Stage Prepectoral versus Subpectoral Breast Reconstructions.

BACKGROUND: Opinion regarding the optimal plane for prosthetic device placement in breast reconstruction patients has evolved. The purpose of this study was to assess the differences in complication rates and patient satisfaction between patients who underwent prepectoral and subpectoral implant-based breast reconstruction (IBR). METHODS: The authors conducted a retrospective cohort study of patients who underwent two-stage IBR at their institution from 2018 to 2019. Surgical and patient-reported outcomes were compared between patients who received a prepectoral versus a subpectoral tissue expander. RESULTS: A total of 694 reconstructions in 481 patients were identified (83% prepectoral, 17% subpectoral). The mean body mass index was higher in the prepectoral group (27 versus 25 kg/m 2 , P = 0.001), whereas postoperative radiotherapy was more common in the subpectoral group (26% versus 14%, P = 0.001). The overall complication rate was very similar, with 29.3% in the prepectoral and 28.9% in the subpectoral group ( P = 0.887). Rates of individual complications were also similar between the two groups. A multiple-frailty model showed that device location was not associated with overall complications, infection, major complications, or device explantation. Mean scores for Satisfaction with the Breast, Psychosocial Well-Being, and Sexual Well-Being were similar between the two groups. Median time to permanent implant exchange was significantly longer in the subpectoral group (200 versus 150 days, P < 0.001). CONCLUSION: Prepectoral breast reconstruction results in similar surgical outcomes and patient satisfaction compared with subpectoral IBR. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

When Benign Becomes Cancer: Malignant Degeneration of Chronic Inflammation.

Chronic inflammation, long implicated in the genesis of malignancy, is now understood to underlie an estimated 25% of all cancers. The most pertinent malignancies, to the plastic surgeon, associated with the degeneration of chronic inflammation include Marjolin's ulcer, breast implant-associated large cell lymphoma, radiation-induced sarcoma, and Kaposi's sarcoma. The cellular and genetic damage incurred by a prolonged inflammatory reaction is controlled by an increasingly understood cytokinetic system. Advances in understanding the chronic inflammatory cascade have yielded new therapeutics and therapeutic targets.

Comparison of Skin Substitutes for Acute and Chronic Wound Management.

Chronic and acute wounds, such as diabetic foot ulcers and burns, respectively, can be difficult to treat, especially when autologous skin transplantations are unavailable. Skin substitutes can be used as a treatment alternative by providing the structural elements and growth factors necessary for reepithelialization and revascularization from a nonautologous source. As of 2020, there are 76 commercially available skin substitute products; this article provides a review of the relevant literature related to the major categories of skin substitutes available.

Copy number and gene expression differences between African American and Caucasian American prostate cancer.

BACKGROUND: The goal of our study was to investigate the molecular underpinnings associated with the relatively aggressive clinical behavior of prostate cancer (PCa) in African American (AA) compared to Caucasian American (CA) patients using a genome-wide approach. METHODS: AA and CA patients treated with radical prostatectomy (RP) were frequency matched for age at RP, Gleason grade, and tumor stage. Array-CGH (BAC SpectralChip2600) was used to identify genomic regions with significantly different DNA copy number between the groups. Gene expression profiling of the same set of tumors was also evaluated using Affymetrix HG-U133 Plus 2.0 arrays. Concordance between copy number alteration and gene expression was examined. A second aCGH analysis was performed in a larger validation cohort using an oligo-based platform (Agilent 244K). RESULTS: BAC-based array identified 27 chromosomal regions with significantly different copy number changes between the AA and CA tumors in the first cohort (Fisher's exact test, P < 0.05). Copy number alterations in these 27 regions were also significantly associated with gene expression changes. aCGH performed in a larger, independent cohort of AA and CA tumors validated 4 of the 27 (15%) most significantly altered regions from the initial analysis (3q26, 5p15-p14, 14q32, and 16p11). Functional annotation of overlapping genes within the 4 validated regions of AA/CA DNA copy number changes revealed significant enrichment of genes related to immune response. CONCLUSIONS: Our data reveal molecular alterations at the level of gene expression and DNA copy number that are specific to African American and Caucasian prostate cancer and may be related to underlying differences in immune response.

Assessing the clinical utility of measuring Insulin-like Growth Factor Binding Proteins in tissues and sera of melanoma patients.

BACKGROUND: Different Insulin-like Growth Factor Binding Proteins (IGFBPs) have been investigated as potential biomarkers in several types of tumors. In this study, we examined both IGFBP-3 and -4 levels in tissues and sera of melanoma patients representing different stages of melanoma progression. METHODS: The study cohort consisted of 132 melanoma patients (primary, n = 72; metastatic, n = 60; 64 Male, 68 Female; Median Age = 56) prospectively enrolled in the New York University School of Medicine Interdisciplinary Melanoma Cooperative Group (NYU IMCG) between August 2002 and December 2006. We assessed tumor-expression and circulating sera levels of IGFBP-3 and -4 using immunohistochemistry and ELISA assays. Correlations with clinicopathologic parameters were examined using Wilcoxon rank-sum tests and Spearman-rank correlation coefficients. RESULTS: Median IGFBP-4 tumor expression was significantly greater in primary versus metastatic patients (70% versus 10%, p = 0.01) A trend for greater median IGFBP-3 sera concentration was observed in metastatic versus primary patients (4.9 microg/ml vs. 3.4 microg/ml, respectively, p = 0.09). However, sera levels fell within a normal range for IGFBP-3. Neither IGFBP-3 nor -4 correlated with survival in this subset of patients. CONCLUSION: Decreased IGFBP-4 tumor expression might be a step in the progression from primary to metastatic melanoma. Our data lend support to a recently-described novel tumor suppressor role of secreting IGFBPs in melanoma. However, data do not support the clinical utility of measuring levels of IGFBP-3 and -4 in sera of melanoma patients.

Modified Nipple Flap with Free Areolar Graft for Component Nipple-Areola Complex Construction: Outcomes with a Novel Technique for Chest Wall Reconstruction in Transgender Men.

BACKGROUND: A primary goal in chest wall reconstruction ("top surgery") for trans men is achieving a symmetric, aesthetically pleasing position of the reconstructed male nipple-areola complex. METHODS: The senior author's (A.H.) technique for component nipple-areola complex creation in chest wall reconstruction for trans men with a modified skate flap and free areolar graft, in conjunction with double-incision mastectomy, is described. A retrospective analysis of 50 consecutive patients who underwent primary, bilateral chest wall reconstruction with this technique was undertaken for the period of March of 2015 to October of 2016. RESULTS: The average patient age was 30.64 years, and the average body mass index was 28.54 kg/m. Eighty-two percent of the sample received preoperative testosterone therapy, and average operative time was 2 hours 59 minutes. Average overall mastectomy specimen weight was 627.80 g, average length of hospital stay was 0.96 days, and average follow-up duration was 19.02 months. Complications occurred in five patients (10 percent), including seroma (4 percent), cellulitis (2 percent), hematoma (2 percent), and suture granuloma (2 percent). Only five patients (10 percent) underwent postoperative revision to adjust nipple-areola complex size, projection, or symmetry. Twenty-eight patients (56 percent) underwent secondary revisions, including scar revisions (56 percent), liposuction (12 percent), and fat grafting (2 percent). CONCLUSION: The use of a modified nipple flap and free areola graft in transgender chest wall reconstruction for trans men allows for flexible, component construction of the male nipple-areola complex in a safe and effective manner. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

CD4+ T cells are activated in regional lymph nodes and migrate to skin to initiate lymphedema.

T cell-mediated responses have been implicated in the development of fibrosis, impaired lymphangiogenesis, and lymphatic dysfunction in secondary lymphedema. Here we show that CD4+ T cells are necessary for lymphedema pathogenesis by utilizing adoptive transfer techniques in CD4 knockout mice that have undergone tail skin and lymphatic excision or popliteal lymph node dissection. We also demonstrate that T cell activation following lymphatic injury occurs in regional skin-draining lymph nodes after interaction with antigen-presenting cells such as dendritic cells. CD4+ T cell activation is associated with differentiation into a mixed T helper type 1 and 2 phenotype, as well as upregulation of adhesion molecules and chemokines that promote migration to the skin. Most importantly, we find that blocking T cell release from lymph nodes using a sphingosine-1-phosphate receptor modulator prevents lymphedema, suggesting that this approach may have clinical utility.