Impact of Mastectomy Flap Necrosis on Patient-Reported Quality-of-Life Measures After Nipple-Sparing Mastectomy: A Preliminary Analysis.

BACKGROUND: Mastectomy skin flap necrosis (SFN) is common following nipple-sparing mastectomy (NSM), but studies on its quality-of-life (QOL) impact are limited. We examined patient-reported QOL and satisfaction after NSM with/without SFN utilizing the BREAST-Q patient-reported outcome measure (PROM) survey. PATIENTS AND METHODS: Patients undergoing NSM between April 2018 and July 2021 at our institution were examined; the BREAST-Q PROM was administered preoperatively, and at 6 months and 1 year postoperatively. SFN extent/severity was documented at 2-3 weeks postoperatively; QOL and satisfaction domains were compared between patients with/without SFN. RESULTS: A total of 573 NSMs in 333 patients were included, and 135 breasts in 82 patients developed SFN (24% superficial, 56% partial thickness, 16% full thickness). Patients with SFN reported significantly lower scores in the satisfaction with breasts (p = 0.032) and psychosocial QOL domains (p = 0.009) at 6 months versus those without SFN, with scores returning to baseline at 1 year in both domains. In the "physical well-being-of-the-chest" domain, there was an overall decline in scores among all patients; however, there were no significant differences at any time point between patients with or without SFN. Sexual well-being scores declined for patients with SFN compared with those without at 6 months and also at 1 year, but this did not reach significance (p = 0.13, p = 0.2, respectively). CONCLUSIONS: Patients undergoing NSM who developed SFN reported significantly lower satisfaction and psychosocial well-being scores at 6 months, which returned to baseline by 1 year. Physical well-being of the chest significantly declines after NSM regardless of SFN. Future studies with larger sample sizes and longer follow-up are needed to determine SFN's impact on long-term QOL.

Decoding the Mastectomy SKIN Score: An Evaluation of Its Predictive Performance in Immediate Breast Reconstruction.

BACKGROUND: The skin ischemia and necrosis (SKIN) score was introduced to standardize the assessment of mastectomy skin flap necrosis (MSFN) severity and the need for reoperation. The authors evaluated the association between the SKIN score and the long-term postoperative outcomes of MSFN after mastectomy and immediate breast reconstruction. METHODS: The authors conducted a retrospective cohort study of consecutive patients who developed MSFN after mastectomy and immediate breast reconstruction from January of 2001 to January of 2021. The primary outcome was breast-related complications after MSFN. Secondary outcomes were 30-day readmission, operating room (OR) débridement, and reoperation. Study outcomes were correlated with the SKIN composite score. RESULTS: The authors identified 299 reconstructions in 273 consecutive patients with mean follow-up time of 111.8 ± 3.9 months. Most patients had a composite SKIN score of B2 (25.0%, n = 13), followed by D2 (17.3%) and C2 (15.4%). We found no significant difference in rates of OR débridement ( P = 0.347), 30-day readmission ( P = 0.167), any complication ( P = 0.492), or reoperation for a complication ( P = 0.189) based on the SKIN composite score. The composite skin score was a poor predictor of reoperation, with an area under the curve of 0.56. A subgroup analysis in patients who underwent implant-based reconstruction revealed no difference in rates of OR débridement ( P = 0.986), 30-day readmission ( P = 0.530), any complication ( P = 0.492), or reoperation for a complication ( P = 0.655) based on the SKIN composite score. CONCLUSIONS: The SKIN score was a poor predictor for postoperative MSFN outcomes and reoperation. An individualized risk-assessment tool that incorporates the anatomic appearance of the breast, imaging data, and patient-level risk factors is needed. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, IV.

Iterative qualitative approach to establishing content validation of a patient-reported outcome measure for arm lymphedema: the LYMPH-Q Upper Extremity Module.

BACKGROUND: Breast cancer-related lymphedema (BRCL) is one of the most common causes of upper extremity (UE) lymphedema in developed nations and substantially impacts health-related quality of life. To advance our understanding of the epidemiology and treatment of BRCL, rigorously developed and validated patient-reported outcome measures (PROMs) are needed. This study aimed to demonstrate the iterative content validity of a modular UE lymphedema-specific PROM called the LYMPH-Q UE module. METHODS: A multi-step iterative qualitative approach was used. Semi-structured interview data from in-depth qualitative interviews with adult women (18 years and older) with BCRL were used to develop the first set of the LYMPH-Q UE scales. The content validity of these scales was demonstrated with patient and clinician feedback. Over the course of cognitive debriefing interviews, additional concepts of lymphedema worry and impact on work were identified as missing from the LYMPH-Q UE module. Subsequently, two new qualitative studies (a focus group and in-depth concept elicitation interviews with patients) were conducted, and two new scales were developed to measure lymphedema worry and impact on work life and their content validity was demonstrated. RESULTS: Qualitative data from in-depth and cognitive interviews with 15 (age 40-74 years) and 16 (age 38-74 years) women with BRCL, respectively, and feedback from 12 clinical experts, were used to develop and demonstrate the content validity of six LYMPH-Q UE scales measuring symptoms, function, appearance, psychological, information, and arm sleeve. Additionally, data from in-depth interviews with 12 (age 35-72 years) women with UE lymphedema and four focus groups (n = 16 women; age 35-74 years) was used to develop and assess the content validity of two new LYMPH-Q UE scales measuring lymphedema worry and impact on work life. The content validity of the previously established six scales was also demonstrated in these subsequent qualitative studies. CONCLUSION: The LYMPH-Q UE is a modular PROM developed using international guidelines for PROM development and can be used in clinical practice, research, and quality improvement to enhance patient-centered shared decision-making. This study's innovative and iterative approach to content validation demonstrates that the LYMPH-Q UE is a comprehensive measure that includes important concepts relevant to patients with UE lymphedema.

TRPV4-Expressing Tissue-Resident Macrophages Regulate the Function of Collecting Lymphatic Vessels via Thromboxane A2 Receptors in Lymphatic Muscle Cells.

Rationale: TRPV4 channels are critical regulators of blood vascular function and have been shown to be dysregulated in many disease conditions in association with inflammation and tissue fibrosis. These are key features in the pathophysiology of lymphatic system diseases, including lymphedema and lipedema; however, the role of TRPV4 channels in the lymphatic system remains largely unexplored. TRPV4 channels are calcium permeable, non-selective cation channels that are activated by diverse stimuli, including shear stress, stretch, temperature, and cell metabolites, which may regulate lymphatic contractile function. Objective: To characterize the expression of TRPV4 channels in collecting lymphatic vessels and to determine the extent to which these channels regulate the contractile function of lymphatics. Methods and Results: Pressure myography on intact, isolated, and cannulated lymphatic vessels showed that pharmacological activation of TRPV4 channels with GSK1016790A (GSK101) led to contractile dysregulation. The response to GSK101 was multiphasic and included, 1) initial robust constriction that was sustained for ≥1 minute and in some instances remained for ≥4 minutes; and 2) subsequent vasodilation and partial or complete inhibition of lymphatic contractions associated with release of nitric oxide. The functional response to activation of TRPV4 channels displayed differences across lymphatics from four anatomical regions, but these differences were consistent across different species (mouse, rat, and non-human primate). Importantly, similar responses were observed following activation of TRPV4 channels in arterioles. The initial and sustained constriction was prevented with the COX inhibitor, indomethacin. We generated a controlled and spatially defined single-cell RNA sequencing (scRNAseq) dataset from intact and microdissected collecting lymphatic vessels. Our data uncovered a subset of macrophages displaying the highest expression of Trpv4 compared to other cell types within and surrounding the lymphatic vessel wall. These macrophages displayed a transcriptomic profile consistent with that of tissue-resident macrophages (TRMs), including differential expression of Lyve1 , Cd163 , Folr2 , Mrc1 , Ccl8 , Apoe , Cd209f , Cd209d , and Cd209g ; and at least half of these macrophages also expressed Timd4. This subset of macrophages also highly expressed Txa2s , which encodes the thromboxane A2 (TXA2) synthase. Inhibition of TXA2 receptors (TXA2Rs) prevented TRPV4-mediated contractile dysregulation. TXA2R activation on LMCs caused an increase in mobilization of calcium from intracellular stores through Ip3 receptors which promoted store operated calcium entry and vasoconstriction. Conclusions: Clinical studies have linked cancer-related lymphedema with an increased infiltration of macrophages. While these macrophages have known anti-inflammatory and pro-lymphangiogenic roles, as well as promote tissue repair, our results point to detrimental effects to the pumping capacity of collecting lymphatic vessels mediated by activation of TRPV4 channels in macrophages. Pharmacological targeting of TRPV4 channels in LYVE1-expressing macrophages or pharmacological targeting of TXA2Rs may offer novel therapeutic strategies to improve lymphatic pumping function and lymph transport in lymphedema.

Satisfaction with Breasts Following Autologous Reconstruction: Assessing Associated Factors and the Impact of Revisions.

BACKGROUND: Autologous breast reconstruction (ABR) may confer higher patient reported outcomes than implant breast reconstruction, but an in-depth examination of factors associated with satisfaction after ABR is lacking. We aimed to determine independent predictors of 1-year Satisfaction with Breasts after ABR and assess the importance of elective procedures on satisfaction. METHODS: A retrospective analysis of patients who underwent abdominal-based ABR between 2010 and 2021 and completed the BREAST-Q Satisfaction with Breasts module at 1-year was performed. Elective procedures comprised of breast revision and nipple areolar complex (NAC) reconstruction. RESULTS: 959 patients were included. Satisfaction with Breasts score improved from 53 (IQR: 44 to 64) preoperatively to 64 (53 to 78) at 1-year postoperatively (p<0.001). Factors significantly associated with decreased postoperative score included lower preoperative scores (ß=0.19 [95% CI: 0.08, 0.31], p=0.001), older age (ß=-0.17 [-0.34, -0.01], p=0.042), Asian race (versus White, ß=-6.7 [-12, -1.7], p=0.008), and a history of psychiatric diagnoses (ß=-3.4 [-6.2, -0.66], p=0.015). Patients who received radiation (ß=-5.6 [-9.0, -2.3], p=0.001) or had mastectomy skin flap/nipple necrosis (ß=-3.8 [-7.6, -0.06], p=0.046) also had significantly decreased scores. Satisfaction with Breasts significantly improved after breast revision procedures (54 [42 to 65] to 65 [54 to 78], p<0.001) and NAC reconstruction (58 [47 to 71] to 67 [57 to 82], p<0.001). CONCLUSION: Multiple independent patient and treatment level factors are associated with lower 1-year Satisfaction with Breasts following ABR. Elective procedures have the potential to improve satisfaction. Understanding these findings is imperative for optimizing clinical decision making and managing expectations.

Breast cancer-related lymphedema results in impaired epidermal differentiation and tight junction dysfunction.

Breast cancer-related lymphedema (BCRL) is characterized by skin changes, swelling, fibrosis, and recurrent skin infections. Clinical studies have suggested that lymphedema results in skin barrier defects; however, the underlying cellular mechanisms and the effects of bacterial contamination on skin barrier function remain unknown. In matched biopsies from patients with unilateral BCRL, we observed decreased expression of filaggrin and the tight junction protein zona occludens-1 (ZO-1) in skin affected by moderate lymphedema, or by subclinical lymphedema in which dermal backflow of lymph was identified by indocyanine green lymphography, relative to controls (areas without backflow and from the unaffected arm). In vitro stimulation of keratinocytes with lymph fluid obtained from patients undergoing lymphedema surgery led to the same changes, as well as increased expression of keratin 14, a marker of immature keratinocytes. Finally, using mouse models of lymphedema, we showed that like the clinical scenario, the expression of skin barrier proteins was decreased relative to normal skin and that colonization with S. epidermidis bacteria amplified this effect, as well as lymphedema severity. Taken together, our findings suggest that lymphatic fluid stasis contributes to skin barrier dysfunction in lymphedema.

Age Impacts Clinical and Patient Reported Outcomes following Post Mastectomy Breast Reconstruction.

BACKGROUND: While the current literature indicates that age should not be a deterring factor in postmastectomy breast reconstruction (PMBR), the true impact of increasing age on postoperative outcomes remains unknown. The purpose of this study is to understand the impact of age on complications and patient-reported outcomes (PROs) using BREAST-Q longitudinally 5-years after PMBR. METHODS: We conducted a retrospective analysis of patients who underwent autologous (ABR) or implant-based reconstruction (IBR). Age was studied as both a categorical and continuous variable. Outcome measures included complications and BREAST-Q scores at preoperative, 6-months, and 1-5 years postoperative. RESULTS: 4,730 patients were included, of which 1,536 (32.5%) underwent ABR while 3,194 (67.5%) had IBR. Older age was significantly associated with increased risk of developing mastectomy skin flap/nipple necrosis, infection, and seroma. Older age was negatively correlated with Satisfaction with Breasts (ß=-0.06 [-0.12, -0.01]; p=0.033) and positively correlated with Psychosocial Well-being (ß=0.14 [0.09, 0.20]; p<0.001). Older age was not correlated with Physical Well-being of the Chest (ß=-0.03 [-0.08, 0.02], p=0.2) and Sexual Well-being (ß=-0.04 [-0.12, 0.02]; p=0.2). Subgroup analyses of ABR and IBR patients demonstrated different complications and PRO profiles. CONCLUSIONS: Our analysis of the impact of age on surgical outcomes and PROs suggests that complication rates increase with age and older age is negatively correlated with Satisfaction with Breasts but positively correlated with Psychosocial Well-being. Overall, older patients should be informed about the potential associated risks and anticipated patient reported outcomes.

A Phase II Study Evaluating the Effect of Intensity Modulated Postmastectomy Radiation Therapy on Implant Failure Rates in Breast Cancer Patients With Immediate, 2-Stage Implant Reconstruction With an MRI Imaging Correlative Substudy.

PURPOSE: Postmastectomy radiation therapy is a mainstay in the adjuvant treatment of node-positive breast cancer, but it poses risks for women with breast reconstruction. Multibeam intensity-modulated radiation therapy improves dose conformality and homogeneity, potentially reducing complications in breast cancer patients with implant-based reconstruction. To investigate this hypothesis, we conducted a single-arm phase 2 clinical trial of breast cancer patients who underwent mastectomy/axillary dissection and prosthesis-based reconstruction. METHODS AND MATERIALS: The primary endpoint was the rate of implant failure (IF) within 24 months of permanent implant placement, which would be considered an improvement over historical controls if below 16%. IF was defined as removal leading to a flat chest wall or replacement with another reconstruction. Patients were analyzed in 2 cohorts. Cohort 1 (RT-PI) received radiation therapy to the permanent implant. Cohort 2 (RT-TE) received radiation therapy to the TE. IF rates, adverse events, and quality of life were analyzed. Follow-up/postradiation therapy assessments were compared with the baseline/preradiation therapy assessments at 3 to 10 weeks after exchange surgery. A subgroup underwent serial magnetic resonance imaging (MRI) sessions to explore the association between MRI-detected changes and capsular contracture, a known adverse effect of radiation therapy. RESULTS: Between June 2014 and March 2017, 119 women were enrolled. Cohort 1 included 45 patients, and cohort 2 had 74 patients. Among 100 evaluable participants, 25 experienced IF during the study period. IF occurred in 8/42 (19%) and 17/58 (29%) in cohorts 1 and 2, respectively. Among the IFs, the majority were due to capsular contracture (13), infection (7), exposure (3), and other reasons (2). Morphologic shape features observed in longitudinal MRI images were associated with the development of Baker grade 3 to 4 contractures. CONCLUSIONS: The rate of IF in reconstructed breast cancer patients treated with intensity-modulated radiation therapy was similar to, but not improved over, that observed with conventional, 3-dimensional-conformal methods. MRI features show promise for predicting capsular contracture but require validation in larger studies.

TCF1-LEF1 co-expression identifies a multipotent progenitor cell (TH2-MPP) across human allergic diseases.

Repetitive exposure to antigen in chronic infection and cancer drives T cell exhaustion, limiting adaptive immunity. In contrast, aberrant, sustained T cell responses can persist over decades in human allergic disease. To understand these divergent outcomes, we employed bioinformatic, immunophenotyping and functional approaches with human diseased tissues, identifying an abundant population of type 2 helper T (TH2) cells with co-expression of TCF7 and LEF1, and features of chronic activation. These cells, which we termed TH2-multipotent progenitors (TH2-MPP) could self-renew and differentiate into cytokine-producing effector cells, regulatory T (Treg) cells and follicular helper T (TFH) cells. Single-cell T-cell-receptor lineage tracing confirmed lineage relationships between TH2-MPP, TH2 effectors, Treg cells and TFH cells. TH2-MPP persisted despite in vivo IL-4 receptor blockade, while thymic stromal lymphopoietin (TSLP) drove selective expansion of progenitor cells and rendered them insensitive to glucocorticoid-induced apoptosis in vitro. Together, our data identify TH2-MPP as an aberrant T cell population with the potential to sustain type 2 inflammation and support the paradigm that chronic T cell responses can be coordinated over time by progenitor cells.

Immediate Lymphatic Reconstruction with Vascularized Omentum Lymph Node Transplant: Reducing the Risk of Both Painful Contracture and Lymphedema.

Patients undergoing extensive lymph node dissection and radiation are at high risk for not only lymphedema but also painful contracture. In a standard lymphadenectomy, immediate lymphatic reconstruction using a lymphovenous bypass is effective in reconstructing the lymphatic defect. However, a more aggressive nodal clearance leaves the patient with a large cavity and skeletonized neurovascular structures, often resulting in severe contracture, pain, cosmetic deformity, and venous stricture. Adjuvant radiotherapy to the nodal bed can lead to severe and permanent disability despite physical therapy. Typically, these patients are referred to us after the fact, where surgery will rarely restore the patient to normal function. In an effort to avoid lymphedema and contracture, we have been reconstructing both the lymphatic and soft tissue defect during lymphadenectomy, using vascularized omentum lymphatic transplant (VOLT). A total of 13 patients underwent immediate reconstruction with VOLT at the time of axillary (n = 8; 61.5%) or groin (n = 5; 38.5%) dissection. No postoperative complications were observed. The mean follow-up time was 15.1 ±â€…12.5 months. Only one lower extremity patient developed mild lymphedema (11% volume differential), with excellent scores in validated patient-reported outcomes. All patients maintained full range of motion with no pain. None of the 13 patients required a compression garment. Immediate lymphatic reconstruction with VOLT is a promising procedure for minimizing the risk of lymphedema and contracture in the highest risk patients undergoing particularly extensive lymph node dissection and radiotherapy.

Lymphatic-Dependent Modulation of the Sensitization and Elicitation Phases of Contact Hypersensitivity.

Allergic contact dermatitis is a common inflammatory skin disease comprising 2 phases. During sensitization, immune cells are activated by exposure to various allergens, whereas repeated antigen exposure induces local inflammation during elicitation. In this study, we utilized mouse models lacking lymphatics in different skin regions to characterize the role of lymphatics separately in the 2 phases, using contact hypersensitivity as a model of human allergic inflammatory skin diseases. Lymphatic-deficient mice exhibited no major difference to single antigen exposure compared to controls. However, mice lacking lymphatics in both phases displayed reduced inflammation after repeated antigen exposure. Similarly, diminished immune response was observed in mice lacking lymphatics only in sensitization, whereas the absence of lymphatics only in the elicitation phase resulted in a more pronounced inflammatory immune response. This exaggerated inflammation is driven by neutrophils impacting regulatory T cell number. Collectively, our results demonstrate that skin lymphatics play an important but distinct role in the 2 phases of contact hypersensitivity. During sensitization, lymphatics contribute to the development of the antigen-specific immunization, whereas in elicitation, they moderate the inflammatory response and leukocyte infiltration in a neutrophil-dependent manner. These findings underscore the need for novel therapeutic strategies targeting the lymphatics in the context of allergic skin diseases.

Disparity Reduction in United States Breast Reconstruction: An Analysis From 2005-2017 Using 3 Nationwide Data Sets.

BACKGROUND: Following passage of the Women's Health and Cancer Rights Act (WHCRA), a steady rise in breast reconstruction rates was reported; however, a recent update is lacking. This study aimed to evaluate longitudinal trends in breast reconstruction (BR) rates in the U.S. and relevant sociodemographic factors. METHODS: Mastectomy cases with/without BR from 2005 through 2017 were abstracted from the National Surgical Quality Improvement Program (NSQIP), Surveillance, Epidemiology, and End Results (SEER) Program, and National Cancer Database (NCDB). BR rates were examined using Poisson regression. Multivariable logistic regression analysis of NCDB data was used to identify predictors of reconstruction. Race and insurance distributions were evaluated over time. RESULTS: Of 1,554,381 mastectomy patients, 507,631 (32.7%) received BR. Annual reconstruction rates per 1000 mastectomies increased from 2005 to 2012 (NSQIP: Incidence Rate Ratio (IRR) 1.077; SEER: 1.090; NCDB: 1.092) and stabilized from 2013 to 2017. NCDB data showed that patients who were younger (≤59 years), privately insured, had fewer comorbidities, and underwent contralateral prophylactic mastectomy were more likely to undergo BR (all p<0.001). Over time, the increase in BR rates was higher among Black (252.3%) and Asian (366.4%) patients than White patients (137.3%). BR rates increased more among Medicaid (418.6%) and Medicare (302.8%) patients than privately insured (125.3%) patients. CONCLUSIONS: This analysis demonstrates stabilization in immediate BR rates over the last decade; reasons behind this stabilization are likely multifactorial. Disparities based on race and insurance type have decreased, with a more equitable distribution of BR rates.

Quality of Life After Axillary Lymph Node Dissection Among Racial and Ethnic Minority Women.

Importance: Higher lymphedema rates after axillary lymph node dissection (ALND) have been found in Black and Hispanic women; however, there is poor correlation between subjective symptoms, quality of life (QOL), and measured lymphedema. Additionally, racial and ethnic differences in QOL have been understudied. Objective: To evaluate the association of race and ethnicity with long-term QOL in patients with breast cancer treated with ALND. Design, Setting, and Participants: This cohort study enrolled women aged 18 years and older with breast cancer who underwent unilateral ALND at a tertiary cancer center between November 2016 and March 2020. Preoperatively and at 6-month intervals, arm volume was measured by perometer and QOL was assessed using the Upper Limb Lymphedema-27 (ULL-27) questionnaire, a validated tool for assessing lymphedema that evaluates how arm symptoms affect physical, psychological, and social functioning. Data were analyzed from November 2016 to October 2023. Exposures: Breast surgery and unilateral ALND in the primary setting or after sentinel lymph node biopsy. Main Outcomes and Measures: Scores in each domain of the ULL-27 were compared by race and ethnicity. Factors impacting QOL were identified using multivariable regression analyses. Results: The study included 281 women (median [IQR] age, 48 [41-58] years) with breast cancer who underwent unilateral ALND and had at least 6 months of follow-up. Of these, 30 patients (11%) self-identified as Asian individuals, 57 (20%) as Black individuals, 23 (8%) as Hispanic individuals, and 162 (58%) as White individuals; 9 individuals (3%) who did not identify as part of a particular group or who were missing race and ethnicity data were categorized as having unknown race and ethnicity. Median (IQR) follow-up was 2.97 (1.96-3.67) years. The overall 2-year lymphedema rate was 20% and was higher among Black (31%) and Hispanic (27%) women compared with Asian (15%) and White (17%) women (P = .04). Subjective arm swelling was more common among Asian (57%), Black (70%), and Hispanic (87%) women than White (44%) women (P < .001), and lower physical QOL scores were reported by racial and ethnic minority women at nearly every follow-up. For example, at 24 months, median QOL scores were 87, 79, and 80 for Asian, Black, and Hispanic women compared with 92 for White women (P = .003). On multivariable analysis, Asian race (ß = -5.7; 95% CI, -9.5 to -1.8), Hispanic ethnicity (ß = -10.0; 95% CI, -15.0 to -5.2), and having Medicaid (ß = -5.4; 95% CI, -9.2 to -1.7) or Medicare insurance (ß = -6.9; 95% CI, -10.0 to -3.4) were independently associated with worse physical QOL (all P < .001). Conclusions and Relevance: Findings of this cohort study suggest that Asian, Black, and Hispanic women experience more subjective arm swelling after unilateral ALND for breast cancer compared with White women. Black and Hispanic women had higher rates of objective lymphedema than their White counterparts. Both minority status and public medical insurance were associated with worse physical QOL. Understanding disparities in QOL after ALND is an unmet need and may enable targeted interventions to improve QOL for these patients.

Reducing Disparities: Regional Anesthesia Blocks for Mastectomy with Reconstruction Within Standardized Regional Anesthesia Pathways.

BACKGROUND: Recent data suggest disparities in receipt of regional anesthesia prior to breast reconstruction. We aimed to understand factors associated with block receipt for mastectomy with immediate tissue expander (TE) reconstruction in a high-volume ambulatory surgery practice with standardized regional anesthesia pathways. PATIENTS AND METHODS: Patients who underwent mastectomy with immediate TE reconstruction from 2017 to 2022 were included. All patients were considered eligible for and were offered preoperative nerve blocks as part of routine anesthesia care. Interpreters were used for non-English speaking patients. Patients who declined a block were compared with those who opted for the procedure. RESULTS: Of 4213 patients who underwent mastectomy with immediate TE reconstruction, 91% accepted and 9% declined a nerve block. On univariate analyses, patients with the lowest rate of block refusal were white, non-Hispanic, English speakers, patients with commercial insurance, and patients undergoing bilateral reconstruction. The rate of block refusal went down from 12 in 2017 to 6% in 2022. Multivariable logistic regression demonstrated that older age (p = 0.011), Hispanic ethnicity (versus non-Hispanic; p = 0.049), Medicaid status (versus commercial insurance; p < 0.001), unilateral surgery (versus bilateral; p = 0.045), and reconstruction in earlier study years (versus 2022; 2017, p < 0.001; 2018, p < 0.001; 2019, p = 0.001; 2020, p = 0.006) were associated with block refusal. CONCLUSIONS: An established preoperative regional anesthesia program with blocks offered to all patients undergoing mastectomy with TE reconstruction can result in decreased racial disparities. However, continued differences in age, ethnicity, and insurance status justify future efforts to enhance preoperative educational efforts that address patient hesitancies in these subpopulations.

Remote Symptom Monitoring with Clinical Alerts Following Mastectomy: Do Early Symptoms Predict 30-Day Surgical Complications.

BACKGROUND: Electronic patient-reported outcome measures (ePROMs) for real-time remote symptom monitoring facilitate early recognition of postoperative complications. We sought to determine whether remote, electronic, patient-reported symptom-monitoring with Recovery Tracker predicts 30-day readmission or reoperation in outpatient mastectomy patients. METHODS: We conducted a retrospective review of breast cancer patients who underwent outpatient (< 24-h stay) mastectomy with or without reconstruction from April 2017 to January 2022 and who received the Recovery Tracker on Days 1-10 postoperatively. Of 5,130 patients, 3,888 met the inclusion criteria (2,880 mastectomy with immediate reconstruction and 1,008 mastectomy only). We focused on symptoms concerning for surgical complications and assessed if symptoms reaching prespecified alert levels-prompting a nursing call-predicted risk of 30-day readmission or reoperation. RESULTS: Daily Recovery Tracker response rates ranged from 45% to 70%. Overall, 1,461 of 3,888 patients (38%) triggered at least one alert. Most red (urgent) alerts were triggered by pain and fever; most yellow (less urgent) alerts were triggered by wound redness and pain severity. The 30-day readmission and reoperation rates were low at 3.8% and 2.4%, respectively. There was no statistically significant association between symptom alerts and 30-day reoperation or readmission, and a clinically relevant increase in risk can be excluded (odds ratio 1.08; 95% confidence interval 0.8-1.46; p = 0.6). CONCLUSIONS: Breast cancer patients undergoing mastectomy with or without reconstruction in the ambulatory setting have a low burden of concerning symptoms, even in the first few days after surgery. Patients can be reassured that symptoms that do present resolve quickly thereafter.

Early Complications in Prepectoral Tissue Expander-Based Breast Reconstruction.

BACKGROUND: Prepectoral implant placement for postmastectomy breast reconstruction has increased in recent years. Benefits of prepectoral reconstruction may include lack of animation deformities and reduced postoperative pain, but its complication profile is currently unclear. This study aimed to examine the complication profile of prepectoral tissue expanders (TEs) to determine factors associated with TE loss. METHODS: A retrospective review was performed to identify all patients who underwent immediate prepectoral TE reconstruction from January 2018 to June 2021. The decision to use the prepectoral technique was based on mastectomy skin quality and patient comorbidities. Patient demographics, comorbidities, and operative details were evaluated. Outcomes of interest included TE loss, seroma, hematoma, infection/cellulitis, mastectomy skin flap necrosis requiring revision, and TE exposure. Logistic regression analysis was performed to identify factors associated with TE loss. RESULTS: The study identified 1225 TEs. The most frequent complications were seroma (8.7%, n = 106), infection/cellulitis (8.2%, n = 101), and TE loss (4.2%, n = 51). Factors associated with TE loss in the univariate analysis included ethnicity, history of smoking, body mass index, mastectomy weight, and neoadjuvant chemotherapy. In the multivariate regression analysis, only mastectomy weight had a positive association with TE loss (odds ratio, 1.001; p = 0.016). CONCLUSION: Prepectoral two-stage breast reconstruction can be performed safely with an acceptable early complication profile. The study data suggest that increasing mastectomy weight is the most significant factor associated with TE loss. Further research examining the quality of the soft tissue envelope and assessing patient-reported outcomes would prove beneficial.

Comparisons of Impact of Vein Grafting with Different Indications on Outcomes of Reconstruction with Free Flaps.

BACKGROUND: Prior studies have shown an increased risk of complications and flap loss with the use of vein grafts in microsurgery. We hypothesize that indication for use of a vein graft can affect flap complications and loss rates. METHODS: We performed a retrospective review of all patients at our institution from 2010 to 2020 who underwent free flap reconstruction and required use of a vein graft. Indications for vein grafting included: salvage of flap during primary operation after microvascular compromise, augmentation of flow during primary operation, lengthening of the flap pedicle during the primary operation, and salvage of the flap during a secondary salvage operation after microvascular compromise. RESULTS: A total of 79 patients met the study inclusion criteria. There were significant differences among the vein graft indication groups and the following: area of reconstruction (p = 0.002), vein graft length (p = 0.018), vessels grafted (p = 0.001), vein graft donor site (p = 0.011), and total flap loss (p = 0.047). Of the four indications for vein grafting, salvage of the flap during secondary salvage operation after microvascular compromise had the highest rate of total flap loss (26.7%). There were no significant associations between other flap complications and vein graft indications. CONCLUSION: Vein graft use in the primary reconstructive setting is efficacious, with low risk of thrombosis. Use in secondary procedures, however, is associated with higher rates of total flap loss, likely due to the thrombotic process, which was initiated prior to the use of the graft resulting in the salvage procedure and not secondary to the graft itself.

Therapy-Induced Senescence Contributes to the Efficacy of Abemaciclib in Patients with Dedifferentiated Liposarcoma.

PURPOSE: We conducted research on CDK4/6 inhibitors (CDK4/6i) simultaneously in the preclinical and clinical spaces to gain a deeper understanding of how senescence influences tumor growth in humans. PATIENTS AND METHODS: We coordinated a first-in-kind phase II clinical trial of the CDK4/6i abemaciclib for patients with progressive dedifferentiated liposarcoma (DDLS) with cellular studies interrogating the molecular basis of geroconversion. RESULTS: Thirty patients with progressing DDLS enrolled and were treated with 200 mg of abemaciclib twice daily. The median progression-free survival was 33 weeks at the time of the data lock, with 23 of 30 progression-free at 12 weeks (76.7%, two-sided 95% CI, 57.7%-90.1%). No new safety signals were identified. Concurrent preclinical work in liposarcoma cell lines identified ANGPTL4 as a necessary late regulator of geroconversion, the pathway from reversible cell-cycle exit to a stably arrested inflammation-provoking senescent cell. Using this insight, we were able to identify patients in which abemaciclib induced tumor cell senescence. Senescence correlated with increased leukocyte infiltration, primarily CD4-positive cells, within a month of therapy. However, those individuals with both senescence and increased TILs were also more likely to acquire resistance later in therapy. These suggest that combining senolytics with abemaciclib in a subset of patients may improve the duration of response. CONCLUSIONS: Abemaciclib was well tolerated and showed promising activity in DDLS. The discovery of ANGPTL4 as a late regulator of geroconversion helped to define how CDK4/6i-induced cellular senescence modulates the immune tumor microenvironment and contributes to both positive and negative clinical outcomes. See related commentary by Weiss et al., p. 649.