Review of Outcomes in Prepectoral Prosthetic Breast Reconstruction with and without Surgical Mesh Assistance.

BACKGROUND: In the past decade, surgeons have increasingly advocated for a return to prepectoral breast reconstruction with claims that surgical mesh (including acellular dermal matrix) can reduce complication rates. However, numerous surgical and implant advancements have occurred in the decades since the initial prepectoral studies, and it is unclear whether mesh is solely responsible for the touted benefits. METHODS: The authors conducted a systematic review of all English language articles reporting original data for prepectoral implant-based breast reconstruction. Articles presenting duplicate data were excluded. Complications were recorded and calculated on a per-breast basis and separated as mesh-assisted, no-mesh prior to 2006, and no-mesh after 2006 (date of first silicone gel-filled breast implant approval). Capsular contracture comparisons were adjusted for duration of follow-up. RESULTS: A total of 58 articles were included encompassing 3120 patients from 1966 to 2019. The majority of the included studies were retrospective case series. Reported complication outcomes were variable, with no significant difference between groups in hematoma, infection, or explantation rates. Capsular contracture rates were higher in historical no-mesh cohorts, whereas seroma rates were higher in contemporary no-mesh cohorts. CONCLUSIONS: Limited data exist to understand the benefits of surgical mesh devices in prepectoral breast reconstruction. Level I studies with an appropriate control group are needed to better understand the specific role of mesh for these procedures. Existing data are inconclusive but suggest that prepectoral breast reconstruction can be safely performed without surgical mesh.

Overview of Host Defense Peptides and Their Applications for Plastic and Reconstructive Surgeons.

BACKGROUND: Host defense peptides are a family of endogenous short peptides that are found in all living beings and play a critical role in innate immunity against infection. METHODS: A nonsystematic review of host defense peptides was conducted with specific interest in properties and applications relevant to plastic and reconstructive surgery. RESULTS: In addition to their direct antimicrobial actions against pathogens, including multidrug-resistant bacteria, they also demonstrate important functions in immunomodulation, tumor cell lysis, and tissue regeneration. These properties have made them a topic of clinical interest for plastic surgeons because of their potential applications as novel antibiotics, wound healing medications, and cancer therapies. The rising clinical interest has led to a robust body of literature describing host defense peptides in great depth and breadth. Numerous mechanisms have been observed to explain their diverse functions, which rely on specific structural characteristics. However, these peptides remain mostly experimental, with limited translation to clinical practice because of numerous failures to achieve acceptable results in human trials. CONCLUSIONS: Despite the broad ranging potential of these peptides for use in the field of plastic and reconstructive surgery, they are rarely discussed in the literature or at scientific meetings. In this review, the authors provide a summary of the background, structure, function, bacterial resistance, and clinical applications of host defense peptides with the goal of stimulating host defense peptide-based innovation within the field of plastic and reconstructive surgery.

Systematic Review of the Impact of Acellular Dermal Matrix on Aesthetics and Patient Satisfaction in Tissue Expander-to-Implant Breast Reconstructions.

BACKGROUND: Acellular dermal matrix is used in most postmastectomy implant-based breast reconstructions in the United States. It is believed to be safe, despite a slightly increased complication rate. Although never established in a unifying study, the primary advantage of acellular dermal matrix is believed to be an enhanced aesthetic result, thus justifying the added expense. The purpose of this study was to assess the aesthetic benefits of acellular dermal matrix in expander-to-implant breast reconstruction. METHODS: A systematic review adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology was performed including all original studies examining aesthetic outcomes of expander-to-implant breast reconstructions with acellular dermal matrix compared to muscular coverage. Direct-to-implant and prepectoral studies were excluded from the evaluation. The results were aggregated and reported as a summary. RESULTS: Among 883 studies identified, 49 full-text articles were reviewed and nine articles ultimately met inclusion criteria. All nine studies were not randomized. Of these, three articles (1448 total patients) evaluated reconstruction aesthetic outcomes by patient satisfaction, whereas six articles evaluated the aesthetic outcomes by external observer (504 total patients). None of the articles evaluating patient satisfaction reported a difference between acellular dermal matrix and muscular reconstruction. Five of the six articles using objective outcomes demonstrated significant improvement in aesthetic outcome in the acellular dermal matrix group. CONCLUSIONS: Although little evidence exists evaluating the aesthetic benefits of acellular dermal matrix for expander-to-implant breast reconstruction, the data suggest that objective observers consider acellular dermal matrix-assisted expander-to-implant breast reconstructions aesthetically superior to reconstruction with only muscular coverage, but patients appear to be equally satisfied with both reconstructive options.

Feasibility and Efficacy of Decision Aids to Improve Decision Making for Postmastectomy Breast Reconstruction: A Systematic Review and Meta-analysis.

BACKGROUND: The decision-making process for women considering breast reconstruction following mastectomy is complex. Research suggests that fewer than half of women undergoing mastectomy have adequate knowledge and make treatment decisions that are concordant with their underlying values. This systematic review assesses the feasibility and efficacy of preoperative decision aids (DAs) to improve the patient decision-making process for breast reconstruction. METHODS: A systematic review was performed using PubMed, Ovid MEDLINE, EMBASE, CINAHL, and Cochrane Databases published prior to January 4, 2018. Studies that assessed the impact of a DA on patient decision making for breast reconstruction were identified. The effect of preoperative DAs on decisional conflict in randomized controlled trials (RCTs) was measured with inverse variance-weighted mean differences (mean difference [MD] ± 95% confidence interval [CI]). RESULTS: Among 1299 unique articles identified, 1197 were excluded after reviewing titles and abstracts against selection criteria. Among the 17 studies included in this review, 11 assessed the efficacy of DAs for breast reconstruction and 6 additional studies described the development and usability of these DAs. Studies suggest that DAs reduce patient-reported decisional conflict (MD, -4.55 [95% CI, -8.65 to -0.45], P = 0.03 in the fixed-effects model and MD, -4.70 [95% CI, -10.75 to 1.34], P = 0.13 in the random-effects model). Preoperative DAs also improved patient satisfaction with information and perceived involvement in the decision-making process. CONCLUSIONS: The existing literature suggests that DAs reduce decisional conflict, improve self-reported satisfaction with information, and improve perceived involvement in the decision-making process for women considering breast reconstruction.

Hospital Variations in Clinical Complications and Patient-reported Outcomes at 2 Years After Immediate Breast Reconstruction.

OBJECTIVE: Our objectives were to investigate case-mix adjusted hospital variations in 2-year clinical and patient-reported outcomes following immediate breast reconstruction. BACKGROUND: Over the past few decades, variations in medical practice have been viewed as opportunities to promote best practices and high-value care. METHODS: The Mastectomy Reconstruction Outcomes Consortium Study is an National Cancer Institute-funded longitudinal, prospective cohort study assessing clinical and patient-reported outcomes of immediate breast reconstruction after mastectomy at 11 leading medical centers. Case-mix adjusted comparisons were performed using generalized linear mixed-effects models to assess variation across the centers in any complication, major complications, satisfaction with outcome, and satisfaction with breast. RESULTS: Among 2252 women in the analytic cohort, 1605 (71.3%) underwent implant-based and 647 (28.7%) underwent autologous breast reconstruction. There were significant differences in the sociodemographic and clinical characteristics, and distribution of procedure types at the different Mastectomy Reconstruction Outcomes Consortium Study centers. After case-mix adjustments, hospital variations in the rates of any and major postoperative complications were observed. Medical center odds ratios for major complication ranged from 0.58 to 2.13, compared with the average major complication rate across centers. There were also meaningful differences in satisfaction with outcome (from the lowest to highest of -2.79-2.62) and in satisfaction with breast (-2.82-2.07) compared with the average values. CONCLUSIONS: Two-year postoperative complications varied widely between hospitals following post-mastectomy breast reconstruction. These variations represent an important opportunity to improve care through dissemination of best practices and highlight the limitations of extrapolating single-institution level data and the ongoing challenges of studying hospital-based outcomes for this patient population.

Evolving Trends in Textured Implant Use for Cosmetic Augmentation in the United States.

BACKGROUND: Breast implants have evolved for decades. In 2011, the U.S. Food and Drug Administration identified an association between textured breast implants and breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). The purpose of this study was to identify the trends of textured implant use since that time. METHODS: Maintenance of Certification tracer data were queried between 2011 and 2015 for cosmetic breast augmentation cases submitted by American Board of Plastic Surgery diplomates. A nested random effects logistic regression analysis was used to identify associations between variables. RESULTS: Eleven thousand seven hundred sixteen breast augmentations were performed by 880 unique surgeons. The overall proportion of cases using textured implants increased steadily from 2.3 percent in 2011 to 13.0 percent in 2015 (p < 0.001). The proportion of surgeons whose cases included both textured and smooth implants increased (from 6.2 percent to 24.3 percent), as did those using only textured implants (from 0.4 percent to 4.4 percent) (p < 0.001). Significance remained after controlling for form-stable implants, suggesting an alternative motivation for use of textured implants. Subglandular cases (20.5 percent) were more likely to use a textured implant than submuscular (8.4 percent) or dual-plane (7.8 percent) (p < 0.001) cases. CONCLUSIONS: Maintenance of Certification tracer data represent a random sampling of American Board of Plastic Surgery-certified plastic surgeons spanning the gamut of practice settings. Despite ongoing education regarding the association of BIA-ALCL with textured implants, American Board of Plastic Surgery diplomates have trended toward increased use of textured implants for cosmetic breast augmentation since 2011. This finding does not appear to be driven by the introduction of anatomical implants during the study period.

Latissimus Dorsi Flap Breast Reconstruction-A Nationwide Inpatient Sample Review.

INTRODUCTION: The latissimus dorsi (LD) myocutaneous flap has been a long term standard for breast reconstruction. The variable indications for the LD flap have not been statistically examined because of the relative infrequency of its use by any single surgeon or institution. METHODS: The Nationwide Inpatient Sample data set was queried for all patient encounters involving a LD myocutaneous flap procedure. The study population was further restricted to female patients with a history of breast cancer or previous mastectomy. Demographics, Charlson Comorbidity Index scores, previous radiation history, and additional simultaneous procedures were extracted. Analysis was performed using nonparametric correlation coefficients and linear regression models. RESULTS: In total, 2304 LD breast reconstruction hospitalizations were identified between 2008 and 2010. Average patient age was 52.1 years, average hospital length of stay (LOS) was 2.8 days, bilateral latissimus reconstruction was performed in 252 (10.9%) patients, and 1414 patients (61.4%) were delayed reconstruction. Previous irradiation was present in 389 (16.9%) patients and was correlated with delayed reconstruction (P < 0.001).Younger age was associated with bilateral latissimus reconstructions (P < 0.05), contralateral free flap reconstruction (P < 0.0001), and combination with implants or tissue expanders (both P < 0.0001).After adjustment for age and Charlson Comorbidity Index, increased LOS was observed in patients undergoing contralateral free flap reconstruction (+1.29 days, P < 0.05) and immediate reconstruction (mastectomy, +0.39 days unilateral, P < 0.05; +0.64 days, bilateral, P < 0.001). The use of tissue expanders and implants were found to decrease hospital LOS (bilateral implant, -0.65 days, P < 0.001; bilateral expander, -0.72 days, P < 0.001), likely from confounding comorbidities. Charlson Comorbidity Index was strongly related to LOS (+0.08 days per point, P < 0.005), whereas age was not statistically significant when considered with comorbidity. CONCLUSIONS: The LD is most commonly used for delayed or salvage breast reconstruction, with particular utility in irradiated patients. Younger patients tend to undergo more involved LD variants with bilateral reconstructions and expanders or implants. After adjusting for comorbidity, age and the use of bilateral latissimus flaps with implants or expanders have no adverse impact on LOS.

Revenue Generation and Plastic Surgery Training Programs: 1-Year Evaluation of a Plastic Surgery Consultation Service.

BACKGROUND: In academic institutions, residents make substantial contributions to clinical productivity. However, billing cannot be generated unless there is direct attending physician supervision of these services. The purpose of this study was to quantify clinical services provided by residents at a large academic medical center. METHODS: The authors performed a review of all consultations to the plastic surgery service between January 1 and December 31, 2014. Documentation was reviewed and hypothetical billing for services was generated using American Medical Association Current Procedural Terminology and evaluation and management codes. RESULTS: A total of 2367 consultations were reviewed during the 1-year study period. Residents provided services under indirect supervision for the majority of consultations [n = 1940 (81.9 percent)]. If these services had been billed, evaluation and management would have resulted in 6970 physician work relative value units. More than half of the encounters (52.0 percent) involved at least one procedure, resulting in an additional 3316 work relative value units from 1339 Current Procedural Terminology codes. Using a conservative estimate (2014 Medicare reimbursement rates), charges from these services would total $368,496. CONCLUSIONS: The plastic surgery consultation service is a potential source of uncaptured revenue for training programs using indirect supervision of residents. Greater than 10,000 work relative value units could have been generated from resident clinical services, which is considerably more than the national average productivity of a full-time, academic plastic surgeon. Capturing a portion of this revenue stream could improve the fiscal balance of training programs and improve the cost-effective use of resident productivity.

Unnecessary Emergency Transfers for Evaluation by a Plastic Surgeon: A Burden to Patients and the Health Care System.

BACKGROUND: Plastic surgeons are frequently consulted for hand and facial injuries, and patients are often transferred to trauma centers for evaluation of these problems. The authors sought to identify the frequency and impact of "unnecessary" transfers for emergency evaluation by a plastic surgeon at a Level I trauma center. METHODS: The authors reviewed more than 32,000 consecutive emergency department encounters at their institution between April of 2009 and April of 2013 and found 1181 patients transferred for evaluation by plastic surgery. Using a retrospective chart review, necessity of transfer was determined based on the intervention performed at the authors' institution and the availability of resources at the transferring site. RESULTS: Of all the patients referred for "emergency" evaluation, 860 (74.1 percent) were unnecessary. Transfers for hand-related issues were more likely to be coded as unnecessary compared with referrals for facial trauma and infection (76 percent versus 66 percent; p < 0.001). The average time from referral to discharge from the emergency department was 412 minutes. The expense for these unnecessary transfers exceeded $4.6 million. CONCLUSIONS: This is the first intervention-based study evaluating the impact of unnecessary transfer for evaluation of hand and facial emergencies. Using a framework based on objective outcomes, the authors found that fewer than one-third of patients required emergent transfer for evaluation by a plastic surgeon, and almost half did not receive an intervention following transfer. Based on patient time and financial expenses for these unnecessary evaluations, improvements could be made in both quality and cost of care by limiting inappropriate emergency department referrals.

Promoting medical student research productivity: the student perspective.

One-third of medical students complete medical school without significant exposure to research. This gap in their medical education is significant: research not only exposes medical students to scientific methodology and academic writing, but also encourages them to multi-task, communicate, and critically analyze the scientific literature - valuable skills that will serve them well in their future medical careers. We report herein the proceedings from a student-led symposium that aimed to promote student involvement in research at the Alpert Medical School of Brown University by providing practical information on how to successfully complete a research project.

Factors influencing fellowship selection, career trajectory, and academic productivity among plastic surgeons.

BACKGROUND: Several factors influence the career trajectory of graduating plastic surgeons, and the authors' study sought to capture characteristics of plastic surgery trainees as they relate to outcomes, including fellowship selection, career choice, and academic productivity. METHODS: Anonymous online survey data were obtained from members of the American Society of Plastic Surgeons. Correlative analysis was performed implementing the Pearson chi-square test, the Mann-Whitney test, and the Kendall tau-b correlation to determine significant correlations defined by values of p < 0.05. RESULTS: Of 4543 survey invitations sent, a total of 624 plastic surgeons (13.7 percent) completed the study. Greater numbers of publications on entering residency (p < 0.05) and on graduating from residency (p < 0.0001), stronger perceived mentorship during residency (p < 0.01), graduating from an integrated program (p < 0.01), and fellowship training (p < 0.001) were all correlated with a future career in academia. In addition, fellowship training and number of publications during and before residency were correlated with eventual academic productivity (p < 0.05). Lastly, individual tendency to prioritize economics (p < 0.01) or geographic location (p < 0.05) was associated with eventual private practice, whereas prioritization of research (p < 0.01) and culture of training institute (p < 0.001) predicted academic careers. CONCLUSIONS: Graduating plastic surgery residents from integrated programs, with greater numbers of publications, stronger mentor relationships, and fellowship training were more likely to become academic surgeons. Among this academic cohort, fellowship training and greater numbers of publications before and during residency were significantly correlated with increased academic productivity as an attending surgeon.

Clinically meaningful tumor reduction rates vary by prechemotherapy MRI phenotype and tumor subtype in the I-SPY 1 TRIAL (CALGB 150007/150012; ACRIN 6657).

PURPOSE: This study was designed to determine (1) rates of clinically meaningful tumor reduction in breast tumor size following neoadjuvant chemotherapy (NAC), (2) which receptor subtypes and MRI phenotypes are associated with clinically meaningful tumor reduction, and (3) whether MRI phenotype impacts concordance between pathologic and MRI size. METHODS: We analyzed data from the I-SPY TRIAL, a multicenter, prospective NAC trial. Reduction in tumor size from >4 to ≤4 cm was considered clinically meaningful, as crossing this threshold was considered a reasonable cutoff for potential breast conservation therapy (BCT). MRI phenotypes were scored between one (well-defined) and five (diffuse) on pre-NAC MRIs. RESULTS: Of 174 patients with tumors >4 cm, 141 (81%) had clinically meaningful tumor reduction. Response to therapy varied by MRI phenotype (p = 0.003), with well-defined phenotypes more likely than diffuse phenotypes to have clinically meaningful tumor shrinkage (91 vs. 72%, p = 0.037). Her2+ and triple-negative (Tneg) tumors had the highest rate of clinically meaningful tumor reduction (p = 0.005). The concordance between tumor diameter on MRI and surgical pathology was highest for Her2+ and Tneg tumors, especially among tumors with solid imaging phenotypes (p = 0.004). DISCUSSION: NAC allows most patients with large breast tumors to have clinically meaningful tumor reduction, meaning response that would impact ability to undergo BCT. However, response varies by imaging and tumor subtypes. Concordance between tumor size on MRI and surgical pathology was higher in well-defined tumors, especially those with a Tneg subtype, and lower in HR+ diffuse tumors.

Elevated levels of proliferating and recently migrated tumor-associated macrophages confer increased aggressiveness and worse outcomes in breast cancer.

PURPOSE: Macrophages play a major role in inflammatory processes and have been associated with poor prognosis in a variety of cancers, including breast cancer. Previously, we investigated the relationship of a subset of tumor-associated macrophages (PCNA(+) TAMs) with clinicopathologic characteristics of breast cancer. We reported that high PCNA(+) TAM counts were associated with hormone receptor (HR)-negative, high-grade tumors and early recurrence. To further understand the significance of elevated PCNA(+) TAMs and the functionality of TAMs, we examined the expression of S100A8/S100A9 with the antibody Mac387. The heterodimeric S100A8/S100A9 complex plays a role in inflammation and is increased in several cancer types. METHODS: We performed immunohistochemistry using the Mac387 antibody on 367 invasive human breast cancer cases. Results were compared to previous PCNA(+) TAM counts and were correlated with patient outcomes adjusting for HR status and histologic grade. RESULTS: Like PCNA(+) TAMs, high Mac387 counts were associated with HR negativity, high tumor grade, younger age, and decreased recurrence-free survival. Mac387, however, appears to identify both a subset of macrophages and a subset of tumor cells. The concordance between Mac387 and PCNA(+) TAM counts was low and cases that had both high Mac387 and high PCNA(+) TAMs counts had a stronger association with early recurrence. CONCLUSIONS: The presence of high numbers of PCNA(+) TAMs and Mac387-positive cells in breast cancers with poor outcomes may implicate a subset of TAMs in breast cancer pathogenesis, and may ultimately serve to develop potential cellular targets for therapeutic interventions.

Genome-wide functional profiling reveals genes required for tolerance to benzene metabolites in yeast.

Benzene is a ubiquitous environmental contaminant and is widely used in industry. Exposure to benzene causes a number of serious health problems, including blood disorders and leukemia. Benzene undergoes complex metabolism in humans, making mechanistic determination of benzene toxicity difficult. We used a functional genomics approach to identify the genes that modulate the cellular toxicity of three of the phenolic metabolites of benzene, hydroquinone (HQ), catechol (CAT) and 1,2,4-benzenetriol (BT), in the model eukaryote Saccharomyces cerevisiae. Benzene metabolites generate oxidative and cytoskeletal stress, and tolerance requires correct regulation of iron homeostasis and the vacuolar ATPase. We have identified a conserved bZIP transcription factor, Yap3p, as important for a HQ-specific response pathway, as well as two genes that encode putative NAD(P)H:quinone oxidoreductases, PST2 and YCP4. Many of the yeast genes identified have human orthologs that may modulate human benzene toxicity in a similar manner and could play a role in benzene exposure-related disease.

Biologic markers determine both the risk and the timing of recurrence in breast cancer.

Breast cancer has a long natural history. Established and emerging biologic markers address overall risk but not necessarily timing of recurrence. 346 adjuvant naïve breast cancer cases from Guy's Hospital with 23 years minimum follow-up and archival blocks were recut and reassessed for hormone-receptors (HR), HER2-receptor and grade. Disease-specific survival (DSS) was analyzed by recursive partitioning. To validate insights from this analysis, gene-signatures (proliferative and HR-negative) were evaluated for their ability to predict early versus late metastatic risk in 683 node-negative, adjuvant naïve breast cancers annotated with expression microarray data. Risk partitioning showed that adjuvant naïve node-negative outcome risk was primarily partitioned by tumor receptor status and grade but not tumor size. HR-positive and HER2-negative (HRpos) risk was partitioned by tumor grade; low grade cases have very low early risk but a 20% fall-off in DSS 10 or more years after diagnosis. Higher grade HRpos cases have risk over >20 years. Triple-negative (Tneg) and HER2-positive (HER2pos) cases DSS events occurred primarily within the first 5 years. Among node-positive cases, only low grade conferred late risk, suggesting that proliferative gene signatures that identify proliferation would be important for predicting early but not late recurrence. Using pooled data from four publicly available data sets for node-negative tumors annotated with gene expression and outcome data, we evaluated four prognostic gene signatures: two proliferation-based and two immune function-based. Tumor proliferative capacity predicted early but not late metastatic risk for HRpos cases. The immune function or HRneg specific signatures predicted only early metastatic risk in Tneg and HER2pos cases. Breast cancer prognostic signatures need to inform both risk and timing of metastatic events and may best be applied within subsets. Current signatures predict for outcome risk within 5 years of diagnosis. Predictors of late risk for HR positive disease are needed.