Contralateral Autologous Augmentation in DIEP Flap Reconstruction: Employing CT Angiography & Volumetric Analysis for Preoperative Planning.

SUMMARY: Autologous reconstruction accounts for approximately 20% of all breast reconstruction. In cases of unilateral reconstruction, contralateral breast augmentation using autologous tissue can be performed to improve symmetry and is a viable option for patients interested in having more volume relative to their current size without the use of implants. CT scans have been used for preoperative planning for autologous reconstruction to evaluate available perforators. In this study, we report our experience using CT angiography for preoperative volumetric assessment for autologous contralateral breast augmentation in the setting of unilateral autologous breast reconstruction. Twelve patients underwent autologous augmentation during the study period. The average reconstruction flap weight was 561.2±253.6 grams, while the average augmentation flap weight was 218.0±133.7 grams. No patients experienced flap loss and we demonstrate that the predicted volumes for the augmented and reconstructed breasts were comparable to the actual respective flap volumes. Additionally, post-operative patient-reported outcome measures demonstrate high levels of satisfaction across multiple BREAST-Q subscales. This study demonstrates the utility of using CT angiography to estimate reconstructive volumes to help preoperative planning and achieve predictable postoperative breast volumes. It also supports that contralateral autologous augmentation is a good option for patients who would like to avoid implants and are interested in a small to moderate increase in size.

Management of Neuropathic Pain with Neurectomy Combined with Dermal Sensory Regenerative Peripheral Nerve Interface (DS-RPNI).

Neuropathic pain affects a large percentage of the U.S. population and leads to tremendous morbidity. Numerous nonsurgical and surgical treatments have been utilized to try and manage neuropathic pain with varying degrees of success. Recent research investigating ways to improve prosthetic control have identified new mechanisms for preventing neuromas in both motor and sensory nerves with free muscle and dermal grafts, respectively. These procedures have been used to treat chronic neuropathic pain in nonamputees, as well, in order to reduce failure rates found with traditional neurectomy procedures. Herein, we focus our attention on Dermal Sensory-Regenerative Peripheral Nerve Interfaces (DS-RPNI, free dermal grafts) which can be used to physiologically "cap" sensory nerves following neurectomy and have been shown to significantly decrease neuropathic pain.

Understanding Factors Associated with Paid Malpractice Claims in Plastic Surgery.

BACKGROUND: Few studies have investigated malpractice broadly in the field of plastic surgery. The purpose of this analysis was to characterize plastic surgery malpractice cases and examine factors influencing malpractice case outcomes, thereby identifying areas of patient safety concern. METHODS: The Candello database, which catalogs approximately 30% of all paid and unpaid malpractice claims in the United States, was used to obtain cases involving plastic surgery closed between 2009 and 2018. A total of 2674 cases were identified. A multivariable regression model was developed to analyze factors associated with a malpractice case closing with indemnity payment. RESULTS: A total of 716 claims (26.8%) resulted in an indemnity payment. The clinical severity was determined to be high in 229 cases (8.6%). Emotional trauma [ n = 558 (20.9%)] was the most frequently cited injury category. Major differences between procedure groups were not observed, with consistent severity of injury across categories. Poor surgical technique, problems with communication among providers, inadequate informed consent, and deficient documentation were significant factors predictive of malpractice cases closing with payment. Issues with technical performance resulting in a known complication and patient factors were protective against paid claims. CONCLUSIONS: The financial and clinical severity of malpractice claims in plastic surgery were relatively low overall. Multiple factors were found to be associated with a case closing with an indemnity payment. These data highlight the importance of the informed consent process and managing expectations in the clinical care of surgical patients.

Cross-Sectional Analysis of Insurance Coverage for Lymphedema Treatments in the United States.

Importance: Lymphedema is a debilitating condition that affects approximately 1 in 1000 individuals in the United States. Complete decongestive therapy is currently the standard of care, and innovative surgical techniques have demonstrated potential to further improve outcomes. Despite the growing armamentarium of treatment options, a large proportion of patients with lymphedema continue to struggle because of limited access to care. Objective: To define the current state of insurance coverage for lymphedema treatments in the United States. Design, Setting, and Participants: A cross-sectional analysis of insurance reimbursement for lymphedema treatments in 2022 was designed. The top 3 insurance companies per state based on market share and enrollment data maintained by the Kaiser Family Foundation were included. Established medical policies were gathered from insurance company websites and phone interviews, and descriptive statistics were performed. Main Outcomes and Measures: Treatments of interest included nonprogrammable pneumatic compression, programmable pneumatic compression, surgical debulking, and physiologic procedures. Primary outcomes included level of coverage and criteria for coverage. Results: This study included 67 health insurance companies representing 88.7% of the US market share. Most insurance companies offered coverage for nonprogrammable (n = 55, 82.1%) and programmable (n = 53, 79.1%) pneumatic compression. However, few insurance companies offered coverage for debulking (n = 13, 19.4%) or physiologic (n = 5, 7.5%) procedures. Geographically, the lowest rates of coverage were seen in the West, Southwest, and Southeast. Conclusions and Relevance: This study suggests that in the United States, less than 12% of individuals with health insurance, and even fewer patients without health insurance, have access to pneumatic compression and surgical treatments for lymphedema. The stark inadequacy of insurance coverage must be addressed through research and lobbying efforts to mitigate health disparities and promote health equity among patients with lymphedema.

Outcomes of breast reconstruction in patients with stage IV breast cancer.

BACKGROUND: Patients with Stage IV breast cancer are living longer but breast reconstruction in this setting remains controversial. There is limited research evaluating the benefits of breast reconstruction in this patient cohort. STUDY DESIGN: Drawing from the Mastectomy Reconstruction Outcomes Consortium (MROC) dataset, a prospective cohort study that involved 11 leading medical centers in the US and Canada, we compared patient-reported outcomes (PROs) assessed utilizing the BREAST-Q, a condition-specific, validated patient-reported outcome measure (PROM) for mastectomy reconstruction, as well as complications between a cohort of patients with Stage IV disease undergoing reconstruction and a control group of women with Stage I-III disease also receiving reconstruction. RESULTS: Among the MROC population, 26 patients with Stage IV and 2613 women with Stage I-III breast cancer underwent breast reconstruction. Preoperatively, the Stage IV cohort reported significantly lower baseline scores for satisfaction with breast (p = 0.004), psychosocial well-being (p = 0.043) and sexual well-being (p = 0.001), compared with Stage I-III women. Following breast reconstruction, Stage IV patients' mean PRO scores improved over baseline and were not significantly different from those of Stage I-III reconstruction patients. There were also no significant differences in overall/any (p = 0.782), major (p = 0.751) or minor complication (p = 0.787) rates between the two groups at two years following reconstruction. CONCLUSIONS: The findings in this study suggest that breast reconstruction offers significant quality-of-life benefits for women with advanced breast cancer with no increase in postoperative complications and thus may be a reasonable option in this clinical setting.

The Impact of Social Media on Applicants' Perceptions of Plastic Surgery Training Programs.

OBJECTIVE: Given recent COVID-19 restrictions on in-person visiting subinternships and interviews, this study sought to evaluate the program information that was most influential to future plastic surgery applicants as they researched residency programs on social media. DESIGN AND SETTING: An electronic survey targeting medical students interested in plastic surgery was deployed to assess the importance of various information sources in forming perceptions of residency programs. Applicants were invited to participate through an Instagram "Story" (where the survey was embedded) and through an electronic survey link sent via email to interested program applicants and interviewees. PARTICIPANTS AND RESULTS: There were 83 respondents, among which 92% were current medical students planning to apply to Plastic Surgery. The most utilized resources that informed program interest were: mentors (86%), peers/partners (60%), and geographic location preference (55%). Among social media content, applicants most desired posts about resident life (66%) and team bonding activities (61%). Overall, 72% of respondents agreed/strongly agreed that social media played a role in informing their interest to apply to a specific residency program. CONCLUSION: The study demonstrated that prospective plastic surgery applicants expect programs to have a social media presence, and thus, programs should invest time and thought in their social media strategy. While electronic sources are not the most important sources of information rated among applicants, social media plays an influential role in guiding interest in specific programs. To best inform applicant perspectives during the recruiting process, programs should prioritize content that gives a picture of "resident life" and team dynamics.

A Zeb1/MtCK1 metabolic axis controls osteoclast activation and skeletal remodeling.

Osteoclasts are bone-resorbing polykaryons responsible for skeletal remodeling during health and disease. Coincident with their differentiation from myeloid precursors, osteoclasts undergo extensive transcriptional and metabolic reprogramming in order to acquire the cellular machinery necessary to demineralize bone and digest its interwoven extracellular matrix. While attempting to identify new regulatory molecules critical to bone resorption, we discovered that murine and human osteoclast differentiation is accompanied by the expression of Zeb1, a zinc-finger transcriptional repressor whose role in normal development is most frequently linked to the control of epithelial-mesenchymal programs. However, following targeting, we find that Zeb1 serves as an unexpected regulator of osteoclast energy metabolism. In vivo, Zeb1-null osteoclasts assume a hyperactivated state, markedly decreasing bone density due to excessive resorptive activity. Mechanistically, Zeb1 acts in a rheostat-like fashion to modulate murine and human osteoclast activity by transcriptionally repressing an ATP-buffering enzyme, mitochondrial creatine kinase 1 (MtCK1), thereby controlling the phosphocreatine energy shuttle and mitochondrial respiration. Together, these studies identify a novel Zeb1/MtCK1 axis that exerts metabolic control over bone resorption in vitro and in vivo.

Topical captopril: a promising treatment for secondary lymphedema.

Transforming growth factor-beta 1 (TGF-ß1)-mediated tissue fibrosis is an important regulator of lymphatic dysfunction in secondary lymphedema. However, TGF-ß1 targeting can cause toxicity and autoimmune complications, limiting clinical utility. Angiotensin II (Ang II) modulates intracellular TGF-ß1 signaling, and inhibition of Ang II production using angiotensin-converting enzyme (ACE) inhibitors, such as captopril, has antifibrotic efficacy in some pathological settings. Therefore, we analyzed the expression of ACE and Ang II in clinical lymphedema biopsy specimens from patients with unilateral breast cancer-related lymphedema (BCRL) and mouse models, and found that cutaneous ACE expression is increased in lymphedematous tissues. Furthermore, topical captopril decreases fibrosis, activation of intracellular TGF-ß1 signaling pathways, inflammation, and swelling in mouse models of lymphedema. Captopril treatment also improves lymphatic function and immune cell trafficking by increasing collecting lymphatic pumping. Our results show that the renin-angiotensin system in the skin plays an important role in the regulation of fibrosis in lymphedema, and inhibition of this signaling pathway may hold merit for treating lymphedema.

A Review of Laser Therapies for the Treatment of Scarring and Vascular Anomalies.

Significance: Laser use has become part of the gold standard of treatment as an effective adjuvant in multimodal therapy for pathologic scarring caused by burns, trauma, acne, and surgery, as well as vascular anomalies. Understanding indications and applications for laser therapy is essential for physicians to improve patient outcomes. Recent Advances: Since the 1980s, the medical use of lasers has continuously evolved with improvements in technology. Novel lasers and fractionated technologies are currently being studied in the hopes to improve treatment efficacy, while reducing complications. Recent advancements include acne treatment with novel picosecond lasers, new hypertrophic scar therapies with simultaneous laser and intense pulsed light use, and novel systems such as lasers with intralesional optical fiber delivery devices. In addition, optimizing the timing of laser therapy and its use in multimodal treatments continue to advance the field of photothermolysis. Critical Issues: Selecting the correct laser for a given indication is the fundamental decision when choosing a laser balancing effective treatment with minimal complications. This article covers the principles of laser therapy, the preferred lasers used for the treatment of scarring and vascular anomalies, and discusses the current evidence behind these laser choices. Future Directions: To optimize laser therapy, larger randomized control trials and split scar studies are needed. Continued advancement through better randomized controlled studies will help to improve patient outcomes on a broader scale.

Umbilicoplasty in Abdominoplasty: Modifications for Improved Aesthetic Results.

Umbilicoplasty is a key component of any abdominoplasty as the umbilicus has been described as the central aesthetic subunit to the abdomen. Here, we describe our preferred technique for umbilicoplasty which involves a half-moon design with periumbilical defatting which in our hands produces consistent, aesthetically pleasing results.

High Frequency Spectral Ultrasound Imaging Detects Early Heterotopic Ossification in Rodents.

Heterotopic ossification (HO) is a devastating condition in which ectopic bone forms inappropriately in soft tissues following traumatic injuries and orthopedic surgeries as a result of aberrant mesenchymal progenitor cell (MPC) differentiation. HO leads to chronic pain, decreased range of motion, and an overall decrease in quality of life. While several treatments have shown promise in animal models, all must be given during early stages of formation. Methods for early determination of whether and where endochondral ossification/soft tissue mineralization (HO anlagen) develop are lacking. At-risk patients are not identified sufficiently early in the process of MPC differentiation and soft tissue endochondral ossification for potential treatments to be effective. Hence, a critical need exists to develop technologies capable of detecting HO anlagen soon after trauma, when treatments are most effective. In this study, we investigate high frequency spectral ultrasound imaging (SUSI) as a noninvasive strategy to identify HO anlagen at early time points after injury. We show that by determining quantitative parameters based on tissue organization and structure, SUSI identifies HO anlagen as early as 1-week postinjury in a mouse model of burn/tenotomy and 3 days postinjury in a rat model of blast/amputation. We analyze single cell RNA sequencing profiles of the MPCs responsible for HO formation and show that the early tissue changes detected by SUSI match chondrogenic and osteogenic gene expression in this population. SUSI identifies sites of soft tissue endochondral ossification at early stages of HO formation so that effective intervention can be targeted when and where it is needed following trauma-induced injury. Furthermore, we characterize the chondrogenic to osteogenic transition that occurs in the MPCs during HO formation and correlate gene expression to SUSI detection of the HO anlagen.

Novel Lineage-Tracing System to Identify Site-Specific Ectopic Bone Precursor Cells.

Heterotopic ossification (HO) is a form of pathological cell-fate change of mesenchymal stem/precursor cells (MSCs) that occurs following traumatic injury, limiting range of motion in extremities and causing pain. MSCs have been shown to differentiate to form bone; however, their lineage and aberrant processes after trauma are not well understood. Utilizing a well-established mouse HO model and inducible lineage-tracing mouse (Hoxa11-CreERT2;ROSA26-LSL-TdTomato), we found that Hoxa11-lineage cells represent HO progenitors specifically in the zeugopod. Bioinformatic single-cell transcriptomic and epigenomic analyses showed Hoxa11-lineage cells are regionally restricted mesenchymal cells that, after injury, gain the potential to undergo differentiation toward chondrocytes, osteoblasts, and adipocytes. This study identifies Hoxa11-lineage cells as zeugopod-specific ectopic bone progenitors and elucidates the fate specification and multipotency that mesenchymal cells acquire after injury. Furthermore, this highlights homeobox patterning genes as useful tools to trace region-specific progenitors and enable location-specific gene deletion.

The role of neutrophil extracellular traps and TLR signaling in skeletal muscle ischemia reperfusion injury.

Ischemia reperfusion (IR) injury results in devastating skeletal muscle fibrosis. Here, we recapitulate this injury with a mouse model of hindlimb IR injury which leads to skeletal muscle fibrosis. Injury resulted in extensive immune infiltration with robust neutrophil extracellular trap (NET) formation in the skeletal muscle, however, direct targeting of NETs via the peptidylarginine deiminase 4 (PAD4) mechanism was insufficient to reduce muscle fibrosis. Circulating levels of IL-10 and TNFα were significantly elevated post injury, indicating toll-like receptor (TLR) signaling may be involved in muscle injury. Administration of hydroxychloroquine (HCQ), a small molecule inhibitor of TLR7/8/9, following injury reduced NET formation, IL-10, and TNFα levels and ultimately mitigated muscle fibrosis and improved myofiber regeneration following IR injury. HCQ treatment decreased fibroadipogenic progenitor cell proliferation and partially inhibited ERK1/2 phosphorylation in the injured tissue, suggesting it may act through a combination of TLR7/8/9 and ERK signaling mechanisms. We demonstrate that treatment with FDA-approved HCQ leads to decreased muscle fibrosis and increased myofiber regeneration following IR injury, suggesting short-term HCQ treatment may be a viable treatment to prevent muscle fibrosis in ischemia reperfusion and traumatic extremity injury.

Use of the Omental Free Flap for Treatment of Chronic Anterior Skull Base Infections.

Chronic complications following anterior cranial fossa tumor extirpation, such as cerebrospinal fluid leak, meningitis, mucocele, pneumocephalus, and abscess, negatively impact patient quality of life. Robust vascularized tissue is generally required to adequately reconstruct and obliterate this complex geometric space. The aim of this study was to describe outcomes and advantages of the omental flap for these defects. Following institutional review board approval, a prospective, reconstructive database was reviewed from 2011 to 2020. Four patients with chronic anterior skull base complications treated with omental flap reconstruction were identified, with chart reviews performed. Median time from the index operation until the complication ultimately required a free omental transfer was 7.3 years. All patients underwent adjuvant radiation with the indications for surgery, including cerebral abscess, recurrent meningitis, osteomyelitis, and pneumocephalus. All free flaps survived without any need for revision. There were no donor site complications. One patient had delayed healing at an adjacent nasal wound that healed secondarily. At a median follow-up of 19.4 months, none of the patients had recurrent infections. The omental free flap has a number of properties, which make it ideally suitable for anterior skull base defects. Its malleable nature combined with the presence of multiple vascular arcades enable flexibility in flap design to contour to the crevices of 3-dimensional skull base defects. Although other free flaps are available to the plastic surgeon, the versatility and reliability of the omentum make it a first-line consideration for anterior skull base reconstruction.

Regulation of lymphatic function and injury by nitrosative stress in obese mice.

OBJECTIVE: Obesity results in lymphatic dysfunction, but the cellular mechanisms that mediate this effect remain largely unknown. Previous studies in obese mice have shown that inducible nitric oxide synthase-expressing (iNOS+) inflammatory cells accumulate around lymphatic vessels. In the current study, we therefore tested the hypothesis that increased expression of iNOS results in nitrosative stress and injury to the lymphatic endothelial cells (LECs). In addition, we tested the hypothesis that lymphatic injury, independent of obesity, can modulate glucose and lipid metabolism. METHODS: We compared the metabolic changes and lymphatic function of wild-type and iNOS knockout mice fed a normal chow or high-fat diet for 16 weeks. To corroborate our in vivo findings, we analyzed the effects of reactive nitrogen species on isolated LECs. Finally, using a genetically engineered mouse model that allows partial ablation of the lymphatic system, we studied the effects of acute lymphatic injury on glucose and lipid metabolism in lean mice. RESULTS: The mesenteric lymphatic vessels of obese wild-type animals were dilated, leaky, and surrounded by iNOS+ inflammatory cells with resulting increased accumulation of reactive nitrogen species when compared with lean wild-type or obese iNOS knockout animals. These changes in obese wild-type mice were associated with systemic glucose and lipid abnormalities, as well as decreased mesenteric LEC expression of lymphatic-specific genes, including vascular endothelial growth factor receptor 3 (VEGFR-3) and antioxidant genes as compared with lean wild-type or obese iNOS knockout animals. In vitro experiments demonstrated that isolated LECs were more sensitive to reactive nitrogen species than blood endothelial cells, and that this sensitivity was ameliorated by antioxidant therapies. Finally, using mice in which the lymphatics were specifically ablated using diphtheria toxin, we found that the interaction between metabolic abnormalities caused by obesity and lymphatic dysfunction is bidirectional. Targeted partial ablation of mesenteric lymphatic channels of lean mice resulted in increased accumulation of iNOS+ inflammatory cells and increased reactive nitrogen species. Lymphatic ablation also caused marked abnormalities in insulin sensitivity, serum glucose and insulin concentrations, expression of insulin-sensitive genes, lipid metabolism, and significantly increased systemic and mesenteric white adipose tissue (M-WAT) inflammatory responses. CONCLUSIONS: Our studies suggest that increased iNOS production in obese animals plays a key role in regulating lymphatic injury by increasing nitrosative stress. In addition, our studies suggest that obesity-induced lymphatic injury may amplify metabolic abnormalities by increasing systemic and local inflammatory responses and regulating insulin sensitivity. These findings suggest that manipulation of the lymphatic system may represent a novel means of treating metabolic abnormalities associated with obesity.

Short- and Long-Term Outcomes by Procedure Type for Nonsagittal Single-Suture Craniosynostosis.

BACKGROUND: Minimally invasive approaches for the treatment of single-suture craniosynostosis are sometimes touted as equivalent to cranial vault reconstruction. While techniques for sagittal synostosis have been reviewed previously, evidence regarding open and less invasive surgical techniques for metopic, coronal, and lambdoid synostosis has yet to be reviewed. METHODS: Systematic searches were performed using Embase.com and PubMed. Included studies reported short- or long-term outcomes, compared at least 2 standard techniques, discussed single-suture coronal, metopic, or lambdoid craniosynostosis, and enrolled at least 20 study participants. Two authors screened titles and abstracts, and also performed full text review and data extraction. Given heterogeneous outcomes, qualitative synthesis was performed after data extraction. RESULTS: The search strategy yielded 2348 articles. Of these, 313 were removed as duplicates, and 1935 were excluded during title/abstract review. After full text review of 100 articles, 19 were selected for data extraction. The heterogeneity of outcomes precluded meta-analysis and required qualitative synthesis. While short-term outcomes indicated decreased morbidity of minimally invasive techniques, only 2 articles presented long-term reoperation rates. One study reported higher reoperation rates in the less invasive technique, and the second reported no reoperations in the median follow-up period of 33 months. CONCLUSION: Studies comparing long-term outcomes between different surgical techniques for single-suture craniosynostosis remain deficient. The development of standardized outcome measures is essential, and prospective, multicenter studies are necessary to assess the long-term efficacy of these procedures.

Baseline Lymphatic Dysfunction Amplifies the Negative Effects of Lymphatic Injury.

BACKGROUND: Genetic mutations and obesity increase the risk of secondary lymphedema, suggesting that impaired lymphatic function before surgical injury may contribute to disease pathophysiology. Previous studies show that obesity not only decreases lymphatic function, but also markedly increases pathologic changes, such as swelling, fibroadipose deposition, and inflammation. However, although these reports provide circumstantial evidence supporting the hypothesis that baseline lymphatic defects amplify the effect of lymphatic injury, the mechanisms regulating this association remain unknown. METHODS: Baseline lymphatic morphology, leakiness, pumping, immune cell trafficking, and local inflammation and fibroadipose deposition were assessed in wild-type and Prox1-haploinsufficient (Prox1) mice, which have previously been shown to have abnormal vasculature without overt evidence of lymphedema. In subsequent experiments, wild-type and Prox1 mice underwent popliteal lymph node dissection to evaluate the effect of lymphatic injury. Repeated testing of all variables was conducted 4 weeks postoperatively. RESULTS: At baseline, Prox1 mice had dilated, leaky lymphatic vessels corresponding to low-grade inflammation and decreased pumping and transport function, compared with wild-type mice. Popliteal lymph node dissection resulted in evidence of lymphedema in both Prox1 and wild-type mice, but popliteal lymph node dissection-treated Prox1 mice had increased inflammation and decreased lymphatic pumping. CONCLUSIONS: Subclinical lymphatic dysfunction exacerbates the pathologic changes of lymphatic injury, an effect that is multifactorial and related to increased lymphatic leakiness, perilymphatic accumulation of inflammatory cells, and impaired pumping and transport capacity. These findings suggest that preoperative testing of lymphatic function may enable clinicians to more accurately risk-stratify patients and design targeted preventative strategies.

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.

Regulatory T Cells Mediate Local Immunosuppression in Lymphedema.

Patients who suffer from lymphedema have impaired immunity and, as a result, are at an increased risk for infections. Furthermore, previous studies have shown that lymphadenectomy impairs acquisition of adaptive immune responses and antibody production in response to foreign antigens. Although it is clear that antigen presentation in lymph nodes plays a key role in adaptive immunity, the cellular mechanisms that regulate impaired immune responses in patients with lymphedema or following lymphatic injury remain unknown. We have previously found that axillary lymph node dissection, both clinically and in a mouse model, results in a marked increase in the number of regulatory T cells in the ipsilateral limb. In this study, we focus on the role of regulatory T cells in immunosuppression and show that regulatory T-cell proliferation in tissues distal to site of lymphatic injury contributes to impaired innate and adaptive immune responses. More importantly, using Foxp3-DTR transgenic mice, we show that depletion of regulatory T cells in the setting of lymphatic injury restores these critical immune-mediated responses. These findings provide additional evidence that immune responses following lymphatic injury play a key role in mediating the pathology of lymphedema.