Differential Secretomes of Processed Adipose Grafts, the Stromal Vascular Fraction, and Adipose-Derived Stem Cells.

There are multiple methods to prepare lipoaspirate for autologous fat transfer; however, graft retention remains unpredictable. The purpose of this study was to compare the cellular and protein composition of adipose grafts and the stromal vascular fraction (SVF) resulting from three common techniques to prepare adipose grafts. Adipose grafts were harvested from healthy donors and processed via three techniques: centrifugation (C), a single-filter (SF) device, and a double-filtration (DF) system. Part of each graft was analyzed or further processed to isolate the SVF. Cell viability, surface markers, cytokine, and growth factors were compared between the graft and SVF as well as adipose-derived stem cells (ASCs). Overall, we found variations across the three processing techniques and among the graft components (ASCs, SVF, and fat). Cell viability within the grafts was similar (94.6%, 92.3%, and 93.6%; P = 0.93). The trend was a greater percentage of ASCs from SF versus DF or centrifugation (6.95%, 4.63%, and 1.93%, respectively, P = 0.06). Adipogenic markers (adiponectin and leptin) were similar among all three grafts (P = 0.45). Markers of tissue remodeling were greatest in the SVF compared with fat and ASCs, regardless of processing technique. There was higher relative expression of MMP-9 (2×), Extracellular matrix metalloproteinase inducer (EMMPRIN) (2.5×), endoglin (5×), and IL-8 (1.5×) in the SVF (P < 0.005). Our study identified differences in cytokine expression in adipose grafts and the SVF, particularly in cytokines important in inflammation and wound healing. These secretomes may impact graft retention and fat necrosis and have the potential implications in cell-assisted lipotransfer. There were no significant differences between the final products of any of the processing techniques.

Risk Factors for Upper Extremity Impairment after Mastectomy: A Single Institution Retrospective Review.

Background: Patients with breast cancer treated with mastectomy are more likely to develop upper extremity dysfunction compared with those treated with breast-conserving therapy. This study aimed to identify cancer and treatment characteristics that may be risk factors for development of upper extremity dysfunction in patients treated with mastectomy. Methods: The authors performed a retrospective chart review of patients at the University of Chicago who were treated with a unilateral or bilateral mastectomy from 2010 to 2020 and developed upper extremity dysfunction based on International Classification of Disease-10 codes. Patients were analyzed by side of body (left or right). Patient demographics and treatment characteristics were extracted from the electronic medical record. Results: In total, 259 patients met criteria and were included in our study. A total of 396 upper extremities were recorded as experiencing dysfunction and were analyzed. Mean age was 60 years (range = 28-96), and mean body mass index was 28.4 (SD = 7.5). An estimated 54% of patients underwent breast reconstruction. After multivariable analysis, chronic upper extremity pain was found to be associated with ipsilateral radiotherapy (P < 0.001) and ipsilateral in situ cancer (0.041). Limited range of motion was found to be associated with ipsilateral invasive cancer (P = 0.01), any ipsilateral mastectomy surgery (P < 0.001), and ipsilateral radiotherapy (P = 0.03). Musculoskeletal dysfunction was found to be associated with no ipsilateral modified radical mastectomy (P = 0.033). No oncological or treatment characteristics were found to be associated with decreased strength or adhesive capsulitis. Furthermore, breast reconstruction (implant or autologous tissue based) was not associated with upper extremity dysfunction. Conclusion: Breast cancer characteristics and treatment modalities may predispose patients treated with mastectomy to developing types of upper extremity dysfunction.

Personalizing Locoregional Therapy in Patients With Breast Cancer in 2024: Tailoring Axillary Surgery, Escalating Lymphatic Surgery, and Implementing Evidence-Based Hypofractionated Radiotherapy.

The management of axillary lymph nodes in breast cancer is continually evolving. Recent data now support omitting axillary lymph node dissection (ALND) in most patients with metastases in up to two sentinel lymph nodes (SLNs) during upfront surgery and those with residual isolated tumor cells after neoadjuvant chemotherapy (NACT). In the upfront surgery setting, ALND is still indicated, however, in patients with clinically node-positive breast cancer or more than two positive SLNs and, after NACT, in case of residual micrometastases and macrometastases. Omission of the sentinel lymph node biopsy (SLNB) can be considered in many postmenopausal patients with small luminal breast cancer, particularly when axillary ultrasound is negative. Several randomized controlled trials (RCTs) are currently aiming at eliminating the remaining indications for ALND and also establishing omission of SLNB in a broader patient population. The movement to deescalate axillary staging is in part because of the association between ALND and lymphedema, which is swelling of an extremity because of lymphatic damage and obstructed lymphatic drainage. To reduce the risk of developing this condition, patients undergoing ALND can undergo reverse mapping of the axilla and immediate reconstruction or bypass of the lymphatics from the involved extremity. Decongestion and compression are the foundation of conservative treatment for established lymphedema, while lymphovenous bypass and lymph node transfer are surgical procedures to address the physiologic dysfunction. Radiotherapy is an essential component of breast locoregional therapy: more than three decades of radiation research has optimized treatment according to patient's risk of local recurrence while substantially reducing the number of treatment visits. High-quality RCTs have shown the efficacy and safety of hypofractionation-more than 2Gy radiation dose per treatment (fraction)-significantly reducing the burden of radiotherapy treatment for many patients with breast cancer. In 2024, guidelines recommend no more than 15-16 fractions for whole-breast and nodal radiotherapy, with some recommending five fractions for whole-breast radiotherapy. In addition, simultaneous integrated boost (SIB) has been shown to be noninferior to sequential boost with regards to ipsilateral breast tumor recurrence with similar or reduced long-term side effects, also reducing overall treatment length. Further RCTs are underway investigating other indications for five fractions, including SIB and regional node irradiation, such that, in future, it may be possible for the majority of breast radiotherapy patients to be treated with a 1-week course. This manuscript serves to outline the latest updates on axillary surgical staging, lymphatic surgery, and evidence-based radiotherapy in the treatment of breast cancer.

Oncoplastic Techniques and Tricks to Have in Your Toolbox.

SUMMARY: Oncoplastic breast reconstruction seeks to address partial mastectomy defects in the setting of breast-conserving surgery to achieve superior aesthetic outcomes with comparable oncologic safety compared with traditional breast conservation surgery. As such, oncoplastic breast-conserving surgery has grown in popularity in recent years. Several techniques have been used to displace the volume with the remaining breast tissue or replace it with local soft-tissue options, with decision-making guided by patient and tumor characteristics, additional treatment requirements, patient preference, and available tissue resources. The purpose of this review is to provide an overview of considerations in oncoplastic breast reconstruction with a focus on techniques and tips to achieve optimal outcomes.

Deconstructing Fat to Reverse Radiation Induced Soft Tissue Fibrosis.

Adipose tissue is composed of a collection of cells with valuable structural and regenerative function. Taken as an autologous graft, these cells can be used to address soft tissue defects and irregularities, while also providing a reparative effect on the surrounding tissues. Adipose-derived stem or stromal cells are primarily responsible for this regenerative effect through direct differentiation into native cells and via secretion of numerous growth factors and cytokines that stimulate angiogenesis and disrupt pro-inflammatory pathways. Separating adipose tissue into its component parts, i.e., cells, scaffolds and proteins, has provided new regenerative therapies for skin and soft tissue pathology, including that resulting from radiation. Recent studies in both animal models and clinical trials have demonstrated the ability of autologous fat grafting to reverse radiation induced skin fibrosis. An improved understanding of the complex pathologic mechanism of RIF has allowed researchers to harness the specific function of the ASCs to engineer enriched fat graft constructs to improve the therapeutic effect of AFG.

A spatially resolved single-cell genomic atlas of the adult human breast.

The adult human breast is comprised of an intricate network of epithelial ducts and lobules that are embedded in connective and adipose tissue1-3. Although most previous studies have focused on the breast epithelial system4-6, many of the non-epithelial cell types remain understudied. Here we constructed the comprehensive Human Breast Cell Atlas (HBCA) at single-cell and spatial resolution. Our single-cell transcriptomics study profiled 714,331 cells from 126 women, and 117,346 nuclei from 20 women, identifying 12 major cell types and 58 biological cell states. These data reveal abundant perivascular, endothelial and immune cell populations, and highly diverse luminal epithelial cell states. Spatial mapping using four different technologies revealed an unexpectedly rich ecosystem of tissue-resident immune cells, as well as distinct molecular differences between ductal and lobular regions. Collectively, these data provide a reference of the adult normal breast tissue for studying mammary biology and diseases such as breast cancer.

Analysis of Breast Aesthetic Revision Procedures after Unilateral Abdominal-based Free-flap Breast Reconstruction: A Single-center Experience with 1251 Patients.

Although autologous free-flap breast reconstruction is the most durable means of reconstruction, it is unclear how many additional operations are needed to optimize the aesthetic outcome of the reconstructed breast. The present study aimed to determine the average number of elective breast revision procedures performed for aesthetic reasons in patients undergoing unilateral autologous breast reconstruction and to analyze variables associated with undergoing additional procedures. Methods: A retrospective review of all unilateral abdominal-based free-flap breast reconstructions performed from 2000 to 2014 was undertaken at a tertiary academic center. Results: Overall, 1251 patients were included in the analysis. The average number of breast revision procedures was 1.1 ± 0.9, and 903 patients (72.2%) underwent at least one revision procedure. Multiple logistic regression analysis demonstrated that younger age, higher body mass index, and prior oncologic surgery on the reconstructed breast were factors associated with increased likelihood of undergoing a revision procedure. The probability of undergoing at least one revision increased by 4% with every 1-unit (kg/m2) increase in a patient's body mass index. Multiple Poisson regression modeling demonstrated that younger age, prior oncologic surgery on the reconstructed breast, and bipedicle flap reconstruction were significant factors associated with undergoing a greater number of revision procedures. Conclusions: Most patients who undergo unilateral autologous breast reconstruction require at least one additional operation to optimize their breast aesthetic results. Young age and obesity increase the likelihood of undergoing additional operations. These findings can aid reconstructive microsurgeons in counseling patients and establishing patient expectations prior to their undergoing microvascular breast reconstruction.

Objective Analysis of Breast Symmetry in Female Patients Undergoing Breast Reconstruction After Total Mastectomy.

Background: Satisfaction with the breast aesthetic outcome is an expectation of breast reconstruction surgery, which is an integral part of cancer treatment for many patients. We evaluated postreconstruction breast symmetry in 82 female patients using distance and volume measurements. Objectives: Clinical factors, such as reconstruction type (implant-based and autologous reconstruction), laterality, timing of reconstruction (immediate, delayed, and sequential), radiation therapy (RT), and demographic factors (age, BMI, race, and ethnicity), were evaluated as predictors of postoperative symmetry. Matched preoperative and postoperative measurements for a subset of 46 patients were used to assess correlation between preoperative and postoperative symmetry. Methods: We used standardized differences between the left and right breasts for the sternal notch to lowest visible point distance and breast volume as metrics for breast, positional symmetry, and volume symmetry, respectively. We performed statistical tests to compare symmetry between subgroups of patients based on reconstruction type, laterality, timing, RT, and demographics. Results: Overall, reconstruction type, reconstruction timing, and RT were observed to be factors significantly associated with postoperative symmetry, with implant reconstructions and immediate reconstruction procedures, and no RT showing better postoperative breast volume symmetry. Subgroup analyses, for both reconstruction type and laterality, showed superior volume symmetry for the bilateral implant reconstructions. No correlation was observed between preoperative and postoperative breast symmetry. Demographic factors were not significant predictors of postreconstruction symmetry. Conclusions: This comprehensive analysis examines multiple clinical factors in a single study and will help both patients and surgeons make informed decisions about reconstruction options at their disposal.

Textbook outcomes in DIEP flap breast reconstruction: a Delphi study to establish consensus.

PURPOSE: Composite measures, like textbook outcomes, may be superior to individual metrics when assessing hospital performance and quality of care. This study utilized a Delphi process to define a textbook outcome in DIEP flap breast reconstruction. METHODS: A two-round Delphi survey defined: (1) A textbook outcome, (2) Exclusion criteria for a study population, and (3) Respondent opinion regarding textbook outcomes. An a priori threshold of ≥ 70% agreement among respondents established consensus among the tested statements. RESULTS: Out of 85 invitees, 48 responded in the first round and 41 in the second. A textbook outcome was defined as one that meets the following within 90 days: (1) No intraoperative complications, (2) Operative duration ≤ 12 h for bilateral and ≤ 10 h for unilateral/stacked reconstruction, (3) No post-surgical complications requiring re-operation, (4) No surgical site infection requiring IV antibiotics, (5) No readmission, (6) No mortality, (7) No systemic complications, and (8) Length of stay < 5 days. Exclusion criteria for medical and surgical characteristics (e.g., BMI > 40, HgbA1c > 7) and case-volume cut-offs for providers (≥ 21) and institutions (≥ 44) were defined. Most agreed that textbook outcomes should be defined for complex plastic surgery procedures (75%) and utilized to gauge hospital performance for microsurgical breast reconstruction (77%). CONCLUSION: This Delphi study identified (1) Key elements of a textbook outcome for DIEP flap breast reconstruction, (2) Exclusion criteria for future studies, and (3) Characterized surgeon opinions regarding the utility of textbook outcomes in serving as quality metric for breast reconstruction care.

Impact of implant-based breast reconstruction on bra fit.

Comfortable and well-fitting bras are necessary for good quality of life but hard to find for women who undergo reconstruction after breast cancer treatment. This study aimed to provide data to inform bra designs for breast cancer survivors. We measured anatomical distances used in bra design on 3D clinical photographs of patients who underwent unilateral and bilateral implant-based reconstruction to quantify changes after reconstruction relative to the measured values before the person underwent surgery. We performed additional assessments of symmetry before surgery and after reconstruction, and we used regression analyses to identify associations between the measurements and patient characteristics, such as BMI. Overall, almost all measurements changed significantly in implant-based reconstructed breasts relative to native breasts. We highlight several aspects of ergonomic bra design that will be impacted by the changes in anatomical distances. Practitioner summary: Implant-based breast reconstruction surgery changes the breast so that off-the-rack bras are inadequate. This study provides designers with measurement data from women who underwent implant-based reconstruction to inform bra designs for this population. The key factor designers need to account for is the semi-spherical shape of the reconstructed breast.

Breast Decisions: Recommender System for Appearance Counseling about Breast Reconstruction.

Appearance counseling is an important component of the consent process for breast reconstruction. The purpose of appearance counseling is to help the patient form realistic expectations of what she might look like after breast reconstruction. In this article, we introduce a recommender system, "BreastDecisions," for appearance counseling that suggests photographs of previous patients that are tailored to a specific patient to help her form realistic expectations of her own reconstruction. Methods: We present user specifications and algorithm parameters needed to incorporate the recommender system into the appearance counseling workflow. We demonstrate the system for a common counseling scenario using a knowledgebase of previous breast reconstruction patients. The medical appropriateness of the recommended photographs for use in appearance counseling was evaluated by experts using a four-point rating system. Results: The recommender system presents photographs that are medically appropriate for counseling a specific patient, depicts typical outcomes, and adapts to a variety of clinical workflows. For each of 33 patients taken as examples of breast reconstruction patients, we used the system to identify photographs for appearance counseling. The baseline average medical appropriateness of the recommended photographs was between mostly appropriate (some explanation needed) and medically appropriate (minimal explanation needed). We demonstrate filtering and ranking steps to reduce the number of recommended photographs and increase the average medical appropriateness. Conclusions: Our recommender system automatically suggests photographs of previous breast reconstruction patients for use in counseling a patient about appearance outcomes. The system is patient-specific and customizable to a particular surgeon's practice.

A Prospective, Randomized Comparison of Clinical Outcomes with Different Processing Techniques in Autologous Fat Grafting.

BACKGROUND: Autologous fat grafting is a useful tool in breast reconstruction. The authors have previously demonstrated a difference in the rate of processing adipose grafts in a randomized time and motion clinical trial. The purpose of this study was to compare clinical outcomes in commonly used grafting systems. METHODS: Three methods to prepare adipose grafts were compared: a passive washing filtration system (Puregraft system), an active washing filtration system (Revolve system), and centrifugation (Coleman technique). Postoperative complications, rates of fat necrosis, revision procedures, and additional imaging were recorded. RESULTS: Forty-six patients were included in the prospective, randomized study (15 active filtration, 15 passive filtration, and 16 centrifugation). Their mean age was 54 years and mean body mass index was 28.6 kg/m 2 . The mean length of follow-up was 16.9 ± 4 months. The overall complication rate was 12.1 percent. The probability of fat necrosis was no different between the groups (active filtration, 15 percent versus passive filtration, 14.3 percent] versus centrifugation, 8 percent; p = 0.72). Fat necrosis was highest in patients with breast conservation before grafting (60 percent; p = 0.011). There was no significant difference in contour irregularity (active filtration, 40 percent versus passive filtration, 38 percent versus centrifugation, 36 percent; p = 0.96) or additional grafting (active filtration, 40 percent versus passive filtration, 24 percent versus centrifugation, 32 percent; p = 0.34). CONCLUSIONS: This is the first prospective, randomized study to compare clinical outcomes of adipose graft preparation. There was no significant difference in early complications, fat necrosis, or rates of additional grafting among the study groups. There was significantly higher risk of fat necrosis in patients with previous breast conservation treatment regardless of processing technique. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Does a Latissimus Dorsi Flap Improve Surgical Outcomes of Implant-based Breast Reconstruction following Infected Device Explantation?

Background: The goal of this study was to assess whether adding a latissimus dorsi (LD) flap to a secondary implant-based reconstruction (IBR) improves outcomes following explantation of the primary device due to infection. Methods: We conducted a retrospective study of patients who underwent a second IBR with or without the addition of an LD flap during 2006-2019, following explantation due to infection. Surgical outcomes were collected and compared between reconstruction types. Results: A total of 6093 IBRs were identified during the study period. Of these, 109 underwent a second attempt at breast reconstruction with IBR alone (n = 86, 79%) or IBR/LD (n = 23, 21%) following explantation of an infected device. Rates of secondary device explantation due to a complication were similar between the two groups (26% in the IBR/LD group and 21% in the IBR group; P = 0.60). Among the patients who underwent prior radiotherapy, the IBR/LD group had lower rates of any complication (38% versus 56%; P = 0.43), infection (25% versus 44%; P = 0.39), and reconstruction failure (25% versus 44%; P = 0.39); however, differences were not statistically significant. Conclusion: Following a failed primary breast reconstruction due to infection, it may be appropriate to offer a secondary reconstruction. For patients with a history of radiotherapy, combining an LD flap with IBR may provide benefits over IBR alone. Although not statistically different, this outcome may have clinical significance, considering the magnitude of the effect, and may result in decreased complication rates and a higher chance of reconstructive success.

What Does "Dr. Google" Show Patients Searching for Breast Reconstruction Outcomes Photographs?

Many women with breast cancer search the internet for photographs of their potential reconstruction outcomes, but little is known about the quality, variety, and relevance of images patients are viewing. Methods: Breast reconstruction outcome photographs identified by a Google Images search were assessed based on the American Society of Plastic Surgeons/Plastic Surgery Foundation photographic guidelines. Information such as source metadata, breast reconstruction procedure information, and subject demographics was collected from the photographs. Additional analyses were conducted to assess whether nipple reconstruction or tattooing occurred and was disclosed, whether a symmetry procedure was performed and disclosed, and whether donor site scarring is visible in abdominal flap photographs. Results: We acquired and analyzed 114 photograph sets. Although a variety of images were readily available, the majority of photograph sets did not follow photographic guidelines or provide sufficient information. Most photograph sets (60%) indicated symmetry procedures when a symmetry procedure was evident, but only 40% of photograph sets disclosed a nipple procedure when a nipple procedure was evident. Only 40% of abdominal flap photographs showed donor site scarring. Subject demographics were largely missing: 50% of photograph sets included subject age, 3% included race or ethnicity, and 12% included weight or BMI. Conclusions: Although breast reconstruction outcome photographs shown by "Dr. Google" represent a variety of reconstruction types, they typically lack information that a patient needs to assess self-applicability. Patients may benefit from discussion with their healthcare team about the strengths and limitations of breast reconstruction outcome photographs available on the internet.

Long-term Quality of Life in Patients With Breast Cancer After Breast Conservation vs Mastectomy and Reconstruction.

Importance: Treatment options for early breast cancer include breast-conserving surgery with radiation therapy (RT) or mastectomy and breast reconstruction without RT. Despite marked differences in these treatment strategies, little is known with regard to their association with long-term quality of life (QOL). Objective: To evaluate the association of treatment with breast-conserving surgery with RT vs mastectomy and reconstruction without RT with long-term QOL. Design, Setting, and Participants: This comparative effectiveness research study used data from the Texas Cancer Registry for women diagnosed with stage 0-II breast cancer and treated with breast-conserving surgery or mastectomy and reconstruction between 2006 and 2008. The study sample was mailed a survey between March 2017 and April 2018. Data were analyzed from August 1, 2018 to October 15, 2021. Exposures: Breast-conserving surgery with RT or mastectomy and reconstruction without RT. Main Outcomes and Measures: The primary outcome was satisfaction with breasts, measured with the BREAST-Q patient-reported outcome measure. Secondary outcomes included BREAST-Q physical well-being, psychosocial well-being, and sexual well-being; health utility, measured using the EuroQol Health-Related Quality of Life 5-Dimension, 3-Level questionnaire; and local therapy decisional regret. Multivariable linear regression models with weights for treatment, age, and race and ethnicity tested associations of the exposure with outcomes. Results: Of 647 patients who responded to the survey (40.0%; 356 had undergone breast-conserving surgery, and 291 had undergone mastectomy and reconstruction), 551 (85.2%) confirmed treatment with breast-conserving surgery with RT (n = 315) or mastectomy and reconstruction without RT (n = 236). Among the 647 respondents, the median age was 53 years (range, 23-85 years) and the median time from diagnosis to survey was 10.3 years (range, 8.4-12.5 years). Multivariable analysis showed no significant difference between breast-conserving surgery with RT (referent) and mastectomy and reconstruction without RT in satisfaction with breasts (effect size, 2.71; 95% CI, -2.45 to 7.88; P = .30) or physical well-being (effect size, -1.80; 95% CI, -5.65 to 2.05; P = .36). In contrast, psychosocial well-being (effect size, -8.61; 95% CI, -13.26 to -3.95; P < .001) and sexual well-being (effect size, -10.68; 95% CI, -16.60 to -4.76; P < .001) were significantly worse with mastectomy and reconstruction without RT. Health utility (effect size, -0.003; 95% CI, -0.03 to 0.03; P = .83) and decisional regret (effect size, 1.32; 95% CI, -3.77 to 6.40; P = .61) did not differ by treatment group. Conclusions and Relevance: The findings support equivalence of breast-conserving surgery with RT and mastectomy and reconstruction without RT with regard to breast satisfaction and physical well-being. However, breast-conserving surgery with RT was associated with clinically meaningful improvements in psychosocial and sexual well-being. These findings may help inform preference-sensitive decision-making for women with early-stage breast cancer.

Soft-Tissue Considerations in Shoulder Surgery in the Patient With Lymphedema.

Lymphedema is a chronic, progressive, and often debilitating condition that results in swelling of the affected tissue. Secondary lymphedema is most commonly recognized by unilateral swelling of the ipsilateral extremity after the treatment of cancer. It is estimated that nearly 1.45 million women suffer from breast cancer-related lymphedema in the United States. The number of patients suffering from upper extremity lymphedema is expected to increase because multimodal treatment of breast cancer increases the long-term survival after diagnosis. Because this population ages, the likelihood of encountering a patient with concurrent lymphedema and shoulder pathology requiring orthopaedic intervention is likely to rise. A patient with an already edematous arm and/or impaired drainage of that arm is likely to have different and more complex intraoperative and postoperative courses than patients with normal lymphatic drainage. Although a lymphedematous arm should not preclude surgical intervention, there are considerations when approaching shoulder surgery in the setting of upper extremity lymphedema that may help mitigate complications and aid the patient in their orthopaedic recovery.