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.

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.

Autologous Breast Reconstruction Trends in the United States: Using the Nationwide Inpatient Sample Database.

BACKGROUND: Autologous tissue is the criterion standard in breast reconstruction, but traditionally has been used as a secondary option after implant-based options because of reduced reimbursement relative to effort and required additional technical skill. We intended to evaluate the overall frequency and trends of autologous breast reconstruction (ABR), the trends of ABR in teaching versus nonteaching hospitals and the trends of ABR in different hospital regions in the United States. METHODS: Using the Nationwide Inpatient Sample database, we examined the clinical data of patients who underwent immediate or delayed ABR from 2009 to 2016 in the United States. RESULTS: A total of 146,185 patients underwent ABR during this period. The overall rate of ABR increased 112%, from 26.6% to 56.5%. The majority of ABR were delayed reconstructions (62.3%), which increased gradually from 54.9% to 80% during the study period. The overall frequency of flaps included the deep inferior epigastric perforator (32.1%), latissimus dorsi myocutaneous (28.4%), free transvers rectus abdominus myocutaneous (15.9%), pedicled transvers rectus abdominus myocutaneous flap (14.5%), gluteal artery perforator (0.6%), superficial inferior epigastric artery (0.6%), and unspecified-ABR (7.2%). Most ABRs were performed in teaching hospitals (78.6%) versus nonteaching hospitals (21.4%). The teaching hospitals' ABR rate increased from 70.5% to 88.7%. The greatest proportion of ABRs were performed in the south (39.6%) followed by northeast (23.0%), midwest (18.9%), and west (18.5%). CONCLUSIONS: The deep inferior epigastric perforator flap has become the predominant ABR method in the United States. In addition to more delayed reconstructions being performed in recent years, ABR rates are increasing overall and shifting from pedicled flaps to free flaps.

The Future of Fat Grafting.

One of the earliest reported cases of autologous fat grafting (AFG) was by Neuber in 1893 and consisted of the transfer of small lobules of fat from the upper arm for cicatrical depression of the face. He advocated the use of smaller grafts, noting that pieces larger than the size of a bean would form cysts. In 1895, Czerny excised a lumbar lipoma and transplanted it to the chest for breast reconstruction. Since these early reports, the knowledge base around AFG has expanded exponentially, as illustrated by the other papers within this special topic. As we embark on the next phase of AFG in the clinical setting, there are several directions which are near-clinical translation. This paper discusses future directions in fat grafting that build on optimization of our current techniques as clinical indications expand, such as supplementing purified lipoaspirate and the associated regulatory burden, or deconstructing adipose tissue to selectively use adipose graft components for a variety of regenerative indications.

Surgical Decision Making in Autologous Fat Grafting: An Evidence-Based Review of Techniques to Maximize Fat Survival.

Autologous fat grafting is an important tool in plastic surgery and is widely used for a variety of applications, both aesthetic and reconstructive. Despite an ever-increasing list of indications and extensive research over many years into improving outcomes, fat grafting remains plagued by incomplete and often unpredictable graft survival. Decisions made at each stage of surgery can potentially contribute to ultimate success, including donor site selection and preparation, fat harvest, processing, and purification of lipoaspirate, recipient site preparation, and delivery of harvested fat to the recipient site. In this review, we examine the evidence for and against proposed techniques at each stage of fat grafting. Areas of consensus identified include use of larger harvesting and grafting cannulas and slow injection speeds to limit cell damage due to shearing forces, grafting techniques emphasizing dispersion of fat throughout the tissue with avoidance of graft pooling, and minimizing exposure of the lipoaspirate to the environment during processing. Safety considerations include use of blunt-tipped needles or cannulas to avoid inadvertent intravascular injection as well as awareness of cannula position and avoidance of danger zones such as the subgluteal venous plexus. We believe that using the evidence to guide surgical decision-making is the key to maximizing fat grafting success. Level of Evidence: 4.

Safety Considerations of Fat Grafting in Buttock Augmentation.

Autologous fat grafting for buttock augmentation is one of the fastest growing plastic surgery procedures, but has also received significant publicity for the relatively high mortality rate secondary to fat emboli. The literature has grown exponentially in the past 5 years on this subject, helping to clarify our knowledge and providing recommendations to minimize risks, including avoiding intramuscular injections, placing the patient in the jackknife position, and utilizing larger-bore cannulas. Since the application of these recommendations, the rate of pulmonary fat embolism has decreased from 0.097% to 0.04%, with a current mortality of 1 in 14,921, making it statistically safer than abdominoplasty. Despite the evolution in our knowledge, techniques, and outcomes, it remains of utmost importance to properly select and educate patients about the safety of fat grafting for buttock augmentation. Level of Evidence: 4.

Autologous Fat Grafting for Oncologic Patients: A Literature Review.

Autologous fat grafting (AFG) serves as an effective method to address volume defects, contour irregularities, and asymmetry in both aesthetic and reconstructive procedures. In recent years, there has been growing concern about the potential of cancer recurrence and interference with cancer surveillance in oncologic patients receiving AFG. The adipose tissue contains adipose-derived stem cells (ASCs), a specific type of mesenchymal stem cells, that facilitate secretion of numerous growth factors which in turn stimulate tissue regeneration and angiogenesis. As such, it has been theorized that ASCs may also have the potential to stimulate cancer cell proliferation and growth when used in oncologic patients. Multiple research studies have demonstrated the ability of ACSs to facilitate tumor proliferation in animal models. However, clinical research in oncologic patients has yielded contradictory findings. Although the literature pertaining to oncologic safety in head and neck, as well as sarcoma, cancer patients remains limited, studies demonstrate no increased risk of tumor recurrence in these patient populations receiving AFG. Similarly, both the efficacy and safety of AFG have been well established in breast cancer patients through numerous clinical studies. More recently, preclinical research in animal models has shown that AFG has the potential to facilitate tissue regeneration and improve joint contracture following irradiation. Ultimately, further research is needed to elucidate the safety of AFG in a variety of oncologic patients, as well as explore its use in tissue regeneration, particularly in the setting of radiotherapy. Level of Evidence: 4.

The Effect of Lipoaspirate Processing Technique on Complications in Autologous Fat Grafting for Breast Reconstruction: A Propensity Score Analysis Study.

BACKGROUND: The use of autologous fat grafting (AFG) is becoming increasingly common as an adjunct to breast reconstruction. However, there is a paucity of data comparing the varying processing devices. OBJECTIVES: The goal of this study was to compare the outcomes of 2 commercially available AFG processing devices. METHODS: A retrospective review was conducted of patients who underwent AFG with dual-filter (Puregraft) or single-filter (Revolve) processing systems between 2016 and 2019. Propensity score matching was utilized to adjust for confounding. A total of 38 breasts from the Puregraft group were matched with 38 breasts from the Revolve group. RESULTS: Matching was successful in achieving a similar distribution of baseline characteristics between the 2 groups. The mean number of AFG sessions was comparable between the 2 groups (P = 0.37) with a similar median total volume (Puregraft, 159 mL vs Revolve, 130 mL; P = 0.23). Complication rates were similar between the 2 devices (Puregraft, 26%; Revolve, 18%; P = 0.47). Patients with at least 1 complication had higher overall AFG volume (median, 200 mL vs 130 mL; P = 0.03) and number of sessions (mean, 2.4 vs 1.8, P = 0.009) compared with those without any postoperative complication. CONCLUSIONS: Overall complication rates were comparable between 2 commonly used, commercially available AFG processing systems, and therefore the choice of which to use should be based on surgeon preference. Future studies are underway to decipher whether either system offers superior graft retention, cosmetic, or patient-reported outcomes.

Review of Quantitative Imaging for Objective Assessment of Fat Grafting Outcomes in Breast Surgery.

This article presents a comprehensive review of the use of quantitative measurements based on breast images to assess fat retention, breast aesthetics, and fat necrosis after autologous fat grafting. Breast volume measured from MRI and 3-dimensional surface images is widely used as a measure of fat retention. Breast aesthetics are assessed from a combination of anthropometric (distance and contour) measurements on breast surface images. Examination of radiologic images (ultrasonography, mammography, and MRI) is utilized to assess fat necrosis. The article discusses implementation guidelines for objective outcome assessment to support robust quantification and enable investigations of fat grafting efficacy. Level of Evidence: 4.

Evaluating Unplanned Returns to the Operating Room in Head and Neck Free Flap Patients.

BACKGROUND: Head and neck oncologic surgery with reconstruction represents one of the most complex operations in otolaryngology. Unplanned return to the operating room represents an objective measure of postoperative complications. The purpose of this study was to identify reasons and risk factors for unplanned return to the operating room in patients undergoing head and neck surgery with reconstruction. METHODS: This retrospective cohort study of 467 patients undergoing head and neck surgery with free flap reconstruction used a previously-developed Head and Neck-Reconstructive Surgery-specific National Surgical Quality Improvement Program. Disease and site-specific preoperative, intraoperative, and postoperative data were gathered. Comparisons between those with and without an unexpected return to the operating room were completed with univariate and multiple logistic regression models. RESULTS: The rate of unexpected return to the operating room was 18.8% (88 patients). Most common reasons for URTOR were flap compromise (24 patients, 5.1%), postoperative infection (21 patients, 4.5%), and hematoma (20 patients, 4.3%). Two risk factors were identified by multivariate analysis: coagulopathy (ORadjusted = 2.83, 95% CI = 1.24-6.19, P = 0.010), and use of alcohol (ORadjusted = 1.9, 95% CI = 1.14-3.33, P = 0.025). CONCLUSIONS: Preexisting coagulopathy and increased alcohol consumption were associated with increased risk of unexpected return to the operating room. These findings can aid physicians in preoperative patient counseling and medical optimization and can inform more precise risk stratification of patients undergoing head and neck surgery with reconstruction. Strategies to prevent and mitigate unexpected returns to the operating room will improve patient outcomes, decrease resource utilization, and facilitate successful integration into alternative payment models.

Use of Mammographic Measurements to Predict Complications After Nipple-Sparing Mastectomy in BRCA Mutation Carriers.

BACKGROUND: There is limited data evaluating mastectomy skin flap complications of nipple-sparing mastectomy (NSM) in patients with BRCA gene mutations. The purpose of this study was to identify factors associated with post-operative complications in BRCA mutation carriers undergoing NSM. METHODS: Following institutional review board approval, we interrogated a prospectively collected institutional database for patients undergoing NSM who tested positive for BRCA1/2 mutations. Patient characteristics, preoperative details, and complications were evaluated. Digital mammogram was used to estimate the breast volume. RESULTS: From August 2009 to December 2017, 59 patients (2 males) with BRCA1/2 mutations underwent 114 NSMs. Ninety-two (80%) were risk-reduction surgeries. Thirty-two (28%) underwent single-stage reconstruction (24 autologous). The overall complication rate was 26.3% (N = 30), and 10.5% (N = 12) underwent unanticipated reoperation. 8.8% (N = 10) had full-thickness skin flap necrosis, 10.5% (N = 12) nipple necrosis, and 4.4% (N = 5) full-thickness nipple necrosis. These complications were associated with larger breast volume (799.4 cc vs. 544.1 cc, p < 0.001) and greater body mass index (27.8 vs. 24.3, p < 0.001). By univariate analysis, body mass index and breast volume greater than 675 cc were associated with significantly higher complication rate (odds ratios 1.2 and 4.5 respectively, p = 0.001). CONCLUSIONS: This study confirms that NSM in BRCA1/2 mutation carriers is associated with complications in one in four patients. Utilizing the preoperative mammograms to estimate breast size may be more helpful than breast cup size in counseling preoperatively the risks of complications.

Undergarment needs after breast cancer surgery: a key survivorship consideration.

An important aspect of breast cancer survivorship is finding comfortable undergarments that work for women's post-treatment bodies. Patients who undergo mastectomy, including both those who do and do not receive reconstruction, need bras that can accommodate new breast shape, size, and feel, as well as scarring and skin sensitivity. Our research with breast cancer patients and the literature reveal that ready-to-wear bras are inadequate for the variety of patients' needs, and many women lack support and guidance to make decisions about undergarments after cancer. This commentary describes a major quality-of-life challenge for breast cancer survivors and makes recommendations for future research. Healthcare providers need more guidance and resources to be able to help their patients prepare for this aspect of survivorship. New technologies, such as biomechanical modeling, 3D body scanning, and manufacturing techniques, should be pursued in collaboration with patients, healthcare providers, and clothing designers to ease this burden for breast cancer patients.

Validation of a CD30 Enzyme-Linked Immunosorbant Assay for the Rapid Detection of Breast Implant-Associated Anaplastic Large Cell Lymphoma.

BACKGROUND: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an uncommon type of non-Hodgkin lymphoma occurring in the fluid or capsule adjacent to textured breast implants. Diagnosis of BIA-ALCL of symptomatic patients requires demonstration of large anaplastic cells with uniform expression of CD30 protein on immunohistochemistry. OBJECTIVES: The authors investigated a novel, rapid, office-based, and economic in-situ enzyme-linked immunosorbent assay (ELISA) for screening BIA-ALCL patients. METHODS: A commercially available in-situ ELISA was standardized and validated for patients with confirmed BIA-ALCL diagnosis with clinical isolates. A panel of 9 pathologically confirmed BIA-ALCL patients was screened by serum, plasma, and periprosthetic effusion specimens and compared against serum, plasma, and nonneoplastic delayed seromas in 7 control patients. Statistical analysis demonstrated assay consistency and reliability. RESULTS: All BIA-ALCL effusions demonstrated CD30 ELISA detection at full and all serial concentrations. BIA-ALCL serum specimens and all control specimens were negative at full concentration and serial dilutions (1:100, 1:250, 1:500, and 1:1000). BIA-ALCL plasma specimens were weakly positive at full concentration and revealed no activity with serial dilution. CONCLUSIONS: This is the first study to demonstrate a viable alternative to CD30 immunohistochemistry for the screening of BIA-ALCL. Our study demonstrates 100% sensitivity in seroma fluid with no detectable CD30 in benign seroma samples. A CD30 ELISA represents a novel, low-cost screening test, which may be used to screen suspicious aspirations of delayed periprosthetic fluid collections in an office-based setting.

A Prospective Pilot Study Comparing Rate of Processing Techniques in Autologous Fat Grafting.

BACKGROUND: Autologous fat grafting (AFG) is increasing in popularity to address a variety of defects. There is interest in developing techniques to harvest, process, and inject fat to improve clinical outcomes as well as operative efficiency. OBJECTIVES: The purpose of this pilot study is to compare the rate of graft processing of two commercially available systems for graft preparation. METHODS: Twenty consecutive cases using an active filtration system (system-AF) were observed followed by 20 consecutive cases using a passive filtration system (system-PF) to compare efficiency rate. Fat processing rate was quantified in milliliters/minute. RESULTS: Forty patients underwent AFG with no differences in patient characteristics between the groups. There was 1 incidence of palpable fat necrosis per group (5%). For all patients, this was the first fat grafting procedure; 20% of patients (n = 4 per group) had additional fat grafting. Overall, the rate of adipose tissue preparation was significantly higher with system-AF compared to system-PF (19.8 mL/min vs 5.3 mL/min, P ≤ 0.001). The resulting percent of graftable fat was comparable (AF: 41% vs PF: 42%; P = 0.83). CONCLUSIONS: Time and motion studies such as this provide a means to systematically document each of the steps involved in fat grafting in a reliable fashion. The authors demonstrate a significantly higher rate of lipoaspirate processing using an active filtration system compared to a passive system. Further large-scale studies of the efficacy and cost analysis of AFG are a necessary component of determining best practices in the field.