The lymphatic system maintains fluid homeostasis and orchestrates immune cell trafficking throughout tissues. While extensively studied in cancer and lymphedema, its role in nonlymphoid organs, particularly the kidney, remains an emerging area of investigation. Previous research established molecular connections among NF-κB, VEGFR-3, and PROX-1 in regulating lymphatic growth during inflammation, and studies using global knockout mice revealed that the NF-κB1 subunit (p50) influences lymphatic vessel density. However, the role of RelA - a key component of the canonical NF-κB heterodimer - in regulating lymphatic growth and kidney function following acute kidney injury (AKI) remains unexplored. Using an inducible, predominantly lymphatic endothelial cell-specific RelA-knockout mouse model, we demonstrated that RelA expression in VEGFR-3+ cells is essential for VEGFR-3-driven lymphangiogenesis following AKI. Knockout mice exhibited substantially worse kidney function, altered histological features, impaired VEGFR-3-dependent lymphangiogenesis, and dysregulated immune cell trafficking compared with WT mice. Compensatory upregulation of PROX-1 and podoplanin occurred despite decreased VEGFR-3 and LYVE-1 total protein expression, suggesting complex regulatory mechanisms. Our findings suggest that RelA is a critical sensor for inflammation and regulator of protective lymphangiogenesis following kidney injury and provide insights into potential therapeutic targets for improved kidney injury outcomes.

Background:The purpose of this study was to assess the utility of the BREAST-Q in identifying patients with persistent postmastectomy pain (PPMP) and to determine predictors of pain among a large reconstructive cohort. Methods:We retrospectively reviewed BREAST-Q physical well-being of the chest (PWBC) scores for patients who underwent breast reconstruction from 2010-2023. PPMP was defined by an International Classification of Diseases diagnosis of pain 3 months to 2 years after mastectomy. Linear regression modeled the association between PWBC score and PPMP, and separately modeled associations with demographic and clinical covariates. Multivariable linear mixed-effects regression was used to analyze PWBC scores over time. Results:A total of 6988 patients (implant N = 5466; autologous N = 1522) had at least 1 PWBC score preoperatively or 1-5 years postoperatively. PPMP (3.2% of patients) was associated with a lower PWBC score (β = -14, P < 0.001). Factors associated with greater odds of PPMP were marital status, number of psychiatric diagnoses, chemotherapy, and radiation. At 1-2 years postoperatively, factors associated with a lower PWBC score included Asian race, Hispanic ethnicity, radiation, and axillary lymph node dissection. Autologous reconstruction demonstrated more favorable long-term PWBC scores compared with implant-based reconstruction. Conclusions:PPMP was associated with worse PWBC scores. Radiation was the only common predictor of both PPMP and PWBC scores. This correlation, along with differences in predictors, suggests that the BREAST-Q captures some, but not all, elements of postmastectomy pain. Additional validated measures are needed to measure chronic postoperative pain in the breast cancer population.

Impaired lymphatic function causes cholesterol to accumulate in tissues, driving swelling known as lymphoedema. Lipid clearance could be an effective therapeutic strategy. Impaired lymphatic function causes cholesterol to accumulate in tissues, driving swelling known as lymphoedema. Lipid clearance could be an effective therapeutic strategy.

Breast lymphedema (BLE) is an underrecognized sequela of breast cancer treatment that can lead to chronic swelling, pain, and recurrent infections. While lymphovenous anastomosis (LVA) is well established for the management of extremity lymphedema, its application to BLE has rarely been described. Here, we discuss a case of LVA for refractory BLE following delayed autologous reconstruction. A 49-year-old woman developed severe left-sided BLE after deep inferior epigastric artery perforator flap reconstruction. The clinical course was complicated by nine episodes of cellulitis requiring hospital admission for intravenous treatment despite compliance with prophylactic antibiotics and compression therapy. The patient underwent indocyanine green (ICG)-guided supermicrosurgical LVA within the reconstructed breast. Immediate postoperative decongestion was observed, and substantial reductions in breast pain and improvements in symmetry were reported 1 month postoperatively. At 10 months postoperatively, the patient maintained durable reductions in swelling and infection frequency. Our experience showed that LVA may be safely and effectively performed in the reconstructed breast and may represent a viable physiologic option for patients with refractory BLE unresponsive to conservative therapy.

BACKGROUND:Federal price transparency regulations require disclosure of negotiated commercial prices, but whether these policies improve affordability for reconstructive surgery remains uncertain. We evaluated post-regulation changes in negotiated prices, price convergence, price variation, and overall inflation-adjusted price levels. STUDY DESIGN:Retrospective longitudinal observational study of nationwide hospital price transparency data (December 2021-June 2024). Facility rates for 125 reconstructive surgery CPT codes were linked across 403 hospitals, 51 core-based statistical areas, and four national commercial insurers, yielding 496,868 observations and 16,028 negotiated rate groups. Annualized real rate change (ARRC) was modeled using linear mixed-effects regression with hospitals nested within geographic markets, adjusting for initial within-market price percentile, service category, payer, and market structure. RESULTS:Prices converged in 677 of 886 local markets (76.4%), with the gap between high- and low-priced hospitals narrowing by 13.4 percentage points annually. Overall inflation-adjusted negotiated prices remained stable (ARRC intercept -0.012; p=0.289). Price dispersion showed no robust directional change. Greater convergence was observed among initially higher-priced hospitals, with significant variation by payer and service category but not market structure. Hospital-level heterogeneity explained substantially more variance than measured covariates (conditional R² 0.577; marginal R² 0.132; hospital ICC 0.326). Convergence remained consistent across multiple sensitivity analyses. CONCLUSIONS:Following implementation of price transparency regulations, negotiated prices for reconstructive surgery services converged between high- and low-priced hospitals without meaningful changes in overall inflation-adjusted price levels or price variation. These findings suggest that transparency alone is unlikely to improve affordability and should be complemented by additional policy strategies targeting healthcare costs.

Abdominally based free flap breast reconstruction offers excellent long-term outcomes, but donor-site morbidity remains a concern. Lower back pain is a prevalent musculoskeletal condition that may impair core stability and abdominal donor-site recovery after surgery. This study evaluated the association between a preexisting diagnosis of lower back pain and long-term physical well-being of the abdomen after surgery.We conducted a retrospective study of patients who underwent abdominally based free flap breast reconstruction between 2017 and 2024. Patients were categorized by the presence or absence of a preexisting diagnosis of lower back pain. The primary outcome was physical well-being of the abdomen, assessed using the BREAST-Q. Multivariable linear mixed-effects models evaluated the association between lower back pain and abdominal well-being.A total of 2,594 patients were included. Donor-site complications occurred in 15% of patients, including wound dehiscence (9.1%), surgical site infection (4.3%), palpable bulge (2.4%), seroma (2.2%), and hematoma (0.5%). Patients with preexisting lower back pain (n = 298, 11.5%) had significantly lower abdominal well-being scores compared with those without at 1 year (62 vs. 69; p < 0.001) and 5 years (65 vs. 76; p = 0.014). On multivariable analysis, lower back pain was independently associated with worse abdominal well-being (β = -5, 95% confidence interval [CI]: -8.9 to -0.97; p = 0.015), exceeding the minimal clinically important difference of ≥4.Preexisting lower back pain is associated with significantly worse long-term abdominal well-being after breast reconstruction. Future studies should investigate targeted interventions such as pre- and postoperative core rehabilitation protocols to improve outcomes in these high-risk patients.

Importance:Hospital global budgets gained attention as a strategy to constrain costs and improve outcomes. The Maryland all-payer model (APM), initiated in 2014 as a global budget revenue model, is an example of full-risk payment reform; yet frontline surgeon perspectives on the implementation and impact of this APM have not been evaluated. Objective:To examine surgeon experiences working under Maryland's APM. Design, Setting, and Participants:This qualitative study used a convergent mixed-methods design to assess survey responses of surgeon experiences and semistructured interviews between June 15 and November 25, 2024. Maryland surgeons were recruited via purposive and snowball sampling for surveys from academic and community surgical practices. A nested sample of respondents was selected for qualitative interviews using maximum variation sampling. Main Outcomes and Measures:The primary outcome was surgeon-reported experiences with Maryland's APM. Surveys and interview guides were designed using the Consolidated Framework for Implementation Research (CFIR) to assess awareness, communication, institutional engagement, changes in practice, and perceived effects on care delivery associated with the APM. Survey responses were summarized, and interview data were thematically analyzed and integrated using CFIR-guided joint displays. Results:Among 121 identified surgeons, 103 responded to the survey (67 [65.0%] male; practicing a mean [SD] of 16.4 [12.7] years), and 88 (85.4%) reported awareness of the APM. Of these 88 surgeons, a minority (35 [38.8%]) recalled information being distributed by their institution, and 41 (46.6%) reported receiving information from peers. Whereas 52 surgeons (59.1%) agreed that complex care had become more centralized, fewer believed that the model improved referral management (15 [17.0%] strongly agreed or agreed) or reduced preventable hospital use (16 [18.2%] strongly agreed or agreed). Most surgeons stated that the model changed the way they practiced at least slightly (56 [63.6%]). In qualitative interviews (n = 25), surgeons described surface-level understanding of the model and limited institutional communication, relying on peer discussions to interpret its implications. Many surgeons expressed confusion about performance expectations and frustration with the lack of feedback on quality metrics. They also noted that financial incentives shifted complex care to tertiary centers, contributing to resource strain. Conclusions and Relevance:In this mixed-methods study of surgeons' experiences, surgeons reported high awareness of Maryland's APM, but integrated findings revealed limited operational understanding, inconsistent institutional communication, and indirect effects on practice. Implementing alternative payment models may require more deliberate engagement of clinician stakeholders, clearer communication strategies, and alignment of clinical incentives.

BACKGROUND:The work relative value unit (wRVU) system influences Medicare reimbursement by quantifying procedural complexity and physician effort. There are known disparities in wRVU and reimbursement per hour between implant and autologous breast reconstruction, however studies analyzing temporal changes in this relationship are limited. This study evaluates 13-year trends in wRVU/hour, reimbursement/hour, and complexity measures between implant-based and free flap breast reconstruction. We hypothesize that implant-based reconstruction maintains higher wRVUs and reimbursement per hour, but valuation for free flap reconstruction has improved. METHODS:A retrospective study was conducted using the NSQIP database (2009-2021) to analyze operative times and complication rates for unilateral breast reconstruction procedures: implant-based (CPT 19340, 19342, 19357) and free flap (CPT 19364). Annual wRVU and Medicare reimbursement were sourced from the CMS. Temporal trends in wRVU/hour and reimbursement/hour were analyzed and compound annual growth rates were calculated. RESULTS:Among 27,106 cases, implant-based reconstruction had significantly shorter median operative times (1.4 hours) and higher median wRVUs per hour (11.94) compared to free flap reconstruction (6.77 hours, 6.29 wRVUs/hour; p < 0.001). Over time, immediate reconstruction CPT 19357 demonstrated increasing operative times alongside declining wRVUs/hour and reimbursement/hour (p<0.01). In contrast, immediate and delayed CPT 19364 showed a significant increase in reimbursement/hour, largely driven by decreased operative time (p<0.01). CONCLUSIONS:Although wRVU and reimbursement per hour has increased for free flap reconstruction and declined for immediate tissue expander reconstruction, free flap breast reconstruction remains undervalued. This disparity in valuation may disincentivize microsurgical reconstruction, affecting institutional support and patient access.

Electronic patient-reported outcomes (ePROs) are used postoperatively to detect complications through real-time symptom monitoring. This study examines whether alerts triggered through the “Recovery Tracker” (RT), an ePRO system, predict 30-day re-admission or re-operation after lumpectomy. We retrospectively reviewed breast cancer patients who underwent lumpectomy at a single institution between August 2018 and May 2024. Patients who completed RT surveys on postoperative days 1–5 were included. Symptom alerts categorized as red (urgent) and yellow (less urgent) were analyzed using generalized additive and univariable logistic regression models. Among 8723 included patients, 2552 (29

Breast cancer-related lymphedema (BCRL) is a common and debilitating sequela of axillary lymph node dissection (ALND). Although machine learning (ML)-based prediction models have been proposed, few focus exclusively on patients undergoing ALND, and direct comparisons with traditional statistical models remain limited. This study aimed to develop accurate and clinically feasible prediction models for BCRL using supervised ML and multivariable logistic regression. Demographic and clinical data were prospectively collected from women undergoing unilateral ALND for breast cancer at Memorial Sloan Kettering Cancer Center between 2016 and 2024. Supervised ML and multivariable logistic regression models to predict BCRL were trained and internally validated. Model performance was evaluated using area under the receiver operator characteristic curve (AUC), accuracy, sensitivity, specificity, and Brier score. Shapley additive explanations were used for model interpretability. A total of 474 eligible patients were included. BCRL developed in 113 (23.8

BACKGROUND:Secondary lymphedema is a common complication of cancer treatment and epidermal changes are recognised as histological hallmarks of secondary lymphedema; however, the role of keratinocytes in the pathophysiology of this disease remains unclear. METHODS:Hyperkeratosis, up-regulation of protease-activated receptor 2 (PAR2) and Th2-inducing cytokines were assessed in biopsy specimens from patients with unilateral breast cancer-related lymphedema (BCRL) and in a mouse model of lymphedema. PAR2 inhibition using global PAR2 knockout, keratinocyte-specific PAR2 KO and bone marrow chimera models, or keratinocyte proliferation inhibition using a topical formulation of Teriflunomide (TF), was analysed in mouse models of lymphedema. We also assessed the direct effects of patient-derived lymphedema lymph fluid (LF) on keratinocyte activation in vitro. RESULTS:Hyperkeratosis, expression of Th2-inducing cytokines and PAR2 were significantly increased in BCRL patient biopsies and mouse models. Keratinocytes play a primary role in the lymphedema development by producing T helper 2 (Th2)-inducing cytokines. Specifically, keratinocyte proliferation and PAR2 expression are early responses following lymphatic injury and regulate the expression of Th2-inducing cytokines, the migration of Langerhans cells and the infiltration of Th2-differentiated T cells into the skin. Deficiency of PAR2 or topical inhibition of thymic stromal lymphopoietin rescues secondary lymphedema by reducing Th2 inflammation. Inhibition of PAR2 activation with a small-molecule inhibitor, or the proliferation of the inhibitor TF, prevents activation of keratinocytes stimulated with lymphedema fluid. Finally, topical TF is highly effective in reducing swelling, fibrosis and inflammation and the overall pathology of lymphedema. CONCLUSIONS:Our findings suggest that lymphedema is a chronic inflammatory skin disease, and topically targeting keratinocyte inhibition may be a clinically effective therapy for this condition. KEY POINTS:Activated keratinocytes play a key role in the pathophysiology of secondary lymphedema through PAR2 by producing Th2-inducing cytokines that modulate skin inflammatory responses.

OBJECTIVE:This study prospectively compared lymphedema rates with perometer, tape measure, and bioimpedance spectroscopy (L-Dex) in patients with breast cancer undergoing axillary lymph node dissection (ALND). BACKGROUND:Perometer, tape measure, and L-Dex are all used for diagnosing lymphedema, although lymphedema rates may vary between these techniques. METHODS:From November 2016 to March 2020, patients who underwent ALND had arm measurements performed preoperatively and biannually with perometer, tape measure, and L-Dex. A lymphedema diagnosis was made if arm volume increased by ≥10% by perometer or tape measure, or if L-Dex increased ≥6.5 units from baseline. We assessed concordance between the different measurement techniques using scatter plots, Pearson correlations, and Cohen's Kappa statistic. RESULTS:We included 281 patients who underwent ALND and had at least one follow-up (median, 2.3 years; >1100 follow-up measurements). Two-year lymphedema rates were 21.9% with perometer, 34.6% with tape measure, and 67.5% with L-Dex. Evaluating all timepoints, we found moderate correlation between perometer and tape measure (R=0.67, P<0.001), perometer and L-Dex (R=0.66, P<0.001) and tape measure and L-Dex (R=0.57, P<0.001). Diagnostic agreement was weak between perometer and L-Dex (k=0.29, P<0.001), and tape measure and L-Dex (k=0.28, P<0.001); and moderate between perometer and tape measure (k=0.51, P<0.001). CONCLUSION:In our prospective ALND cohort, perometer, tape measure, and L-Dex demonstrated moderate correlation between measurements, and weak-to-moderate diagnostic agreement. Lymphedema rates varied between measurement techniques, with the highest rates observed with L-Dex, raising concern for overdiagnosis.

Secondary lymphedema (LE) can ensue after disruption of lymphatic vasculature, which may be caused by infection, surgery, or cancer treatment. Omics technologies can move the field beyond an anatomic description of lymphatic stasis by defining inflammatory, fibrotic, metabolic, lymphatic vascular, and genetic susceptibility programs that shape disease onset and progression. This review summarizes studies that use transcriptomic, proteomic, metabolomic, lipidomic, and emerging genomic or computational approaches in secondary LE. We synthesize how these datasets have identified candidate biomarkers, cell populations, signaling pathways, and therapeutic targets; highlight limitations of current platforms, samples, and bioinformatic pipelines; and propose future multi-omics strategies for diagnosis, risk stratification, and treatment development of secondary LE.

The skin, the largest organ of the human body, performs essential physiological functions including barrier protection, thermal regulation, and mechano-sensation. Despite its structural consistency, it exhibits marked regional heterogeneity, particularly under pathological conditions. Our recent investigations have revealed that in secondary lymphedema, the affected skin undergoes distinct pathomorphological changes, including hyperkeratosis, spongiosis, and altered keratinocyte polarity within the epidermis. These findings have prompted deeper studies into the molecular and epigenetic mechanisms contributing to the irreversible progression of this disease. This protocol describes a detailed, reproducible method for isolating and culturing primary keratinocytes from both full-thickness and split-thickness skin grafts obtained from lymphedematous regions. The workflow comprises tissue processing, enzymatic dissociation, selective enrichment of keratinocytes, and optimized culture conditions for downstream molecular analyses. Validation of isolated keratinocytes is performed using Western blotting, flow cytometry, and immunofluorescence histology. This approach preserves native phenotypic traits and epigenetic signatures in patient-derived keratinocytes, thereby enhancing the translational relevance of in vitro studies investigating the pathophysiology of secondary lymphedema.

BACKGROUND:Black race is associated with worse outcomes following implant and autologous breast reconstruction. Although oncoplastic surgery is increasingly used to optimize aesthetic and oncologic outcomes, it remains unclear whether similar racial disparities exist in this setting. This study evaluates the impact of race on surgical and patient-reported outcomes following oncoplastic breast surgery. METHODS:We conducted a retrospective review of patients who underwent oncoplastic procedures using reduction mammoplasty or mastopexy techniques between January 2017 and December 2024. Primary outcomes included postoperative complications. Secondary outcomes included patient-reported outcomes measured by the BREAST-Q. Demographic and clinical variables were compared between Black and White patients. Multivariable logistic regression was used to identify factors independently associated with complications. RESULTS:Among 518 patients, 18.5% identified as Black and 81.5% as White. Black patients had a higher burden of preoperative risk factors, including elevated BMI, higher ASA class, diabetes, hypertension, advanced cancer stage, and neoadjuvant chemotherapy. However, overall complication rates did not differ significantly between groups. Elevated BMI was independently associated with increased complication risk, whereas race showed no significant association. BREAST-Q scores were similar between cohorts at all time points except at 1 year; Black patients reported significantly lower scores (p=0.046). CONCLUSION:Oncoplastic surgery in Black patients is associated with complication rates and patient-reported outcomes comparable to those observed in White patients. These findings suggest that oncoplastic surgery may be a viable treatment option for Black patients. However, further prospective, multi-center studies with larger, racially diverse cohorts and longer follow-up are needed to validate these results.

Keratinocytes, once viewed as inert epidermal scaffolds, are now recognized as active participants in the cutaneous immunity. They orchestrate local immune responses by releasing cytokines, chemokines, and alarmins that shape innate and adaptive inflammation. Dysregulated keratinocyte-immune interactions underline chronic inflammatory skin disorders, such as atopic dermatitis, psoriasis, and cutaneous lupus erythematosus. More recently, keratinocytes have been identified as key contributors to secondary lymphedema, a chronic inflammatory and fibrotic condition historically attributed to lymphatic dysfunction. This review revises our understanding of keratinocytes as immunomodulatory cells, while focusing primarily on their emerging role in the pathogenesis of secondary lymphedema. We highlight and appraise recent evidence that lymphatic stasis reprograms keratinocyte differentiation, induces type 2 helper T cells-skewed inflammatory responses, and perpetuates chronic inflammation and fibrosis. Understanding this keratinocyte-immune-lymphatic axis may unveil novel therapeutic targets beyond traditional lymphangiogenic approaches.

Cellulitis is a complication for patients with breast cancer-related lymphedema (BCRL). This study evaluates the prevalence, clinical presentation, bacterial epidemiology, and treatment outcomes of cellulitis in BCRL, with a goal of identifying factors associated with recurrence.Microbiological Epidemiology of ​ Cellulitis in BCRLBlood cultures were obtained in 61% (255/418) of episodes​,12.9% (33/255) returned positive​Streptococcus agalactiae (8/33) was the most common bacteria isolated from positive culturesTreatment Overview and Antibiotic Effectiveness in BCRL CellulitisEffectiveness of Initial Antibiotic Regimen​: 87.6%Effectiveness of Antibiotic Prophylaxis (n 29): 58.6% This was a retrospective analysis of cellulitis events between December 2000 -November 2024 in a cohort of 2,920 BCRL patients at Memorial Sloan Kettering Cancer Center. Data on demographics, symptoms, laboratory findings, microbiological cultures, and antibiotic regimens were analyzed. Univariate and multivariable Cox Proportional Hazard models were applied.Table 1:Patient Demographics and Other ​Characteristics (N = 231)Table 2:Multivariable Cox proportional hazards regression model assessing risk factors for recurrent cellulitis in patients with breast cancer-related lymphedema A total of 418 cellulitis episodes were documented among 231 BCRL patients, with a cellulitis prevalence of 7.9% (231/2,920) and a recurrence rate of 39.0% (90/231). The median number of cellulitis episodes per patient was 1 (IQR: 1, 2), with a median follow-up duration of 85.5 months (IQR: 42.8, 137.6). Patients with recurrent cellulitis (≥2 episodes) had a shorter median time from lymphedema onset to first cellulitis episode compared to non-recurrent cases (4.9 months vs. 13.9 months, p=0.014) and were more likely to present with a WBC count >11 K/mcL (29.0% vs. 10.5%; p< 0.001). Blood cultures were obtained in 255 episodes (61.7%), with positive results in 33 cases (12.9%). Streptococcus agalactiae was the most common pathogen (8/33; 24.2%). Empiric antibiotic therapy was effective without modification in 87.4% of episodes. The most common first-line antibiotics were cephalosporin-based agents targeting gram-positive bacteria, excluding MRSA (59.5%), followed by agents with MRSA coverage (26.2%). Among those receiving prophylactic antibiotics, 58.6% (17/29) had no recurrent infections. Multivariable analysis showed that radiation, node dissection and time from lymphedema to infection #1 were independently associated with risk of recurrence of infection. Our findings suggest that radiation, node dissection, and time from lymphedema diagnosis to first cellulitis episode were significantly associated with risk of recurrent cellulitis. All Authors: No reported disclosures

BACKGROUND:Artificial intelligence (AI)-enabled clinical decision support systems (CDSS) demonstrate performance comparable or superior to human experts in certain tasks. However, their integration into surgical practice faces a significant implementation gap, alongside ethical, privacy, and legal concerns. Clear governance frameworks are needed to guide their responsible adoption in surgery, to prevent inconsistent application, care quality variation, and exacerbation of algorithmic bias. Here, we establish a systematic, evidence-based, and consensus-driven framework to guide the ethical, effective, and sustainable adoption of AI-enabled CDSS in surgery. STUDY DESIGN:A systematic literature review was conducted of PubMed, Cochrane Library, Medline, and Embase databases until 2024 to identify key governance themes. The themes informed the generation of candidate items, which were then refined through a multiround expert panel consensus process using a modified Delphi approach to produce the final framework. RESULTS:Thematic analysis of 80 full-text articles meeting inclusion criteria identified 4 overarching themes for AI governance: (1) technical prerequisites and model design; (2) clinical implementation and human factors; (3) ethics, safety, and trustworthiness; and (4) bias, fairness, and equity. Panel consensus evaluation resulted in the development of a 19-item framework. CONCLUSIONS:The consensus-driven framework presented here provides foundational guidance essential for navigating the complexities of implementing AI-enabled CDSS safely and ethically in surgery. Addressing the considerations outlined across these 4 core themes can facilitate the responsible adoption of AI, accelerating the transition toward an advanced, data-driven surgical practice while mitigating potential risks.