Marissa M. Tenenbaum

A MODEL FOR THE PHARMACOLOGICAL TREATMENT OF CROUZON SYNDROME

OBJECTIVE Crouzon syndrome is caused by mutations in fibroblast growth factor receptor 2 (FGFR2) leading to constitutive activation of receptors in the absence of ligand binding. The syndrome is characterized by premature fusion of the cranial sutures that leads to abnormal cranium shape, restricted brain growth, and increased intracranial pressure. Surgical remodeling of the cranial vault is currently used to treat affected infants. The purpose of this study was to develop a pharmacological strategy using tyrosine kinase inhibition as a novel treatment for craniosynostotic syndromes caused by constitutive FGFR activation. METHODS Characterization of cranial suture fusion in Fgfr2 mutant mice, which carry the most common Crouzon mutation, was performed using micro-computed tomographic analysis from embryogenesis through maturation. Whole calvarial cultures from wild-type and Fgfr2 mice were established and cultured for 2 weeks in the presence of dimethyl sulfoxide control or PD173074, an FGFR tyrosine kinase inhibitor. Paraffin sections were prepared to show suture morphology and calcium deposition. RESULTS In untreated Fgfr2 cultures, the coronal suture fused bilaterally with loss of overlap between the frontal bone and parietal bone. Calvaria treated with PD173074 (2 micromol/L) showed patency of the coronal suture and were without evidence of any synostosis. CONCLUSION We report the successful use of PD173074 to prevent in vitro suture fusion in a model for Crouzon syndrome. Further studies are underway to develop an in vivo treatment protocol as a novel therapeutic modality for FGFR associated craniosynostotic syndromes.

Breast Implant-Associated Infections: The Role of the National Surgical Quality Improvement Program and the Local Microbiome.

Background: The most common cause of surgical readmission after breast implant surgery remains infection. Six causative organisms are principally involved: Staphylococcus epidermidis and S. aureus, Escherichia, Pseudomonas, Propionibacterium, and Corynebacterium. The authors investigated the infection patterns and antibiotic sensitivities to characterize their local microbiome and determine ideal antibiotic selection. Methods: A retrospective review of 2285 consecutive implant-based breast procedures was performed. Included surgical procedures were immediate and delayed breast reconstruction, tissue expander exchange, and cosmetic augmentation. Patient demographics, chemotherapy and/or irradiation status, implant characteristics, explantation reason, time to infection, microbiological data, and antibiotic sensitivities were reviewed. Results: Forty-seven patients (2.1 percent) required inpatient admission for antibiotics, operative explantation, or drainage by interventional radiology. The infection rate varied depending on surgical procedure, with the highest rate seen in mastectomy and immediate tissue expander reconstruction (6.1 percent). The mean time to explantation was 41 days. Only 50 percent of infections occurred within 30 days of the indexed National Surgical Quality Improvement Program operation. The most commonly isolated organisms were coagulase-negative Staphylococcus (27 percent), methicillin-sensitive S. aureus (25 percent), methicillin-resistant S. aureus (7 percent), Pseudomonas (7 percent), and Peptostreptococcus (7 percent). All Gram-positive organisms were sensitive to vancomycin, linezolid, tetracycline, and doxycycline; all Gram-negative organisms were sensitive to gentamicin and cefepime. Conclusions: Empiric antibiotics should be vancomycin (with the possible inclusion of gentamicin) based on their broad effectiveness against the authors’ unique microbiome. Minor infections should be treated with tetracycline or doxycycline as a second-line agent. National Surgical Quality Improvement Program data are adequate for monitoring and comparing breast infections but certainly not comprehensive. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

The impact of chemotherapy and radiation therapy on the remodeling of acellular dermal matrices in staged, prosthetic breast reconstruction

Background: An acellular dermal matrix will typically incorporate, in time, with the overlying mastectomy skin flap. This remodeling process may be adversely impacted in patients who require chemotherapy and radiation, which influence neovascularization and cellular proliferation. Methods: Multiple biopsy specimens were procured from 86 women (n = 94 breasts) undergoing exchange of a tissue expander for a breast implant. These were divided by biopsy location: submuscular capsule (control) as well as superiorly, centrally, and inferiorly along the paramedian acellular dermis. Specimens were assessed for cellular infiltration, cell type, fibrous encapsulation, scaffold degradation, extracellular matrix deposition, neovascularization, mean composite remodeling score, and type I and III collagen. Patients were compared based on five oncologic treatment groups: no adjuvant therapy (untreated), neoadjuvant chemotherapy with or without radiation, and chemotherapy with or without radiation. Results: Biopsy specimens were procured 45 to 1805 days after implantation and demonstrated a significant reduction in type I collagen over time. Chemotherapy adversely impacted fibrous encapsulation (p = 0.03). Chemotherapy with or without radiation adversely impacted type I collagen (p = 0.02), cellular infiltration (p < 0.01), extracellular matrix deposition (p < 0.04), and neovascularization (p < 0.01). Radiation exacerbated the adverse impact of chemotherapy for several remodeling parameters. Neoadjuvant chemotherapy also caused a reduction in type I (p = 0.01) and III collagen (p = 0.05), extracellular matrix deposition (p = 0.03), and scaffold degradation (p = 0.02). Conclusion: Chemotherapy and radiation therapy limit acellular dermal matrix remodeling. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Resident Cosmetic Clinic: Practice Patterns, Safety, and Outcomes at an Academic Plastic Surgery Institution

BACKGROUND Comprehensive aesthetic surgery education is an integral part of plastic surgery residency training. Recently, the ACGME increased minimum requirements for aesthetic procedures in residency. To expand aesthetic education and prepare residents for independent practice, our institution has supported a resident cosmetic clinic for over 25 years. OBJECTIVES To evaluate the safety of procedures performed through a resident clinic by comparing outcomes to benchmarked national aesthetic surgery outcomes and to provide a model for resident clinics in academic plastic surgery institutions. METHODS We identified a consecutive cohort of patients who underwent procedures through our resident cosmetic clinic between 2010 and 2015. Major complications, as defined by CosmetAssure database, were recorded and compared to published aesthetic surgery complication rates from the CosmetAssure database for outcomes benchmarking. Fishers exact test was used to compare sample proportions. RESULTS Two hundred and seventy-one new patients were evaluated and 112 patients (41.3%) booked surgery for 175 different aesthetic procedures. There were 55 breast, 19 head and neck, and 101 trunk or extremity aesthetic procedures performed. The median number of preoperative and postoperative visits was 2 and 4 respectively with a mean follow-up time of 35 weeks. There were 3 major complications (2 hematomas and 1 infection requiring IV antibiotics) with an overall complication rate of 1.7% compared to 2.0% for patients in the CosmetAssure database (P = .45). CONCLUSIONS Surgical outcomes for procedures performed through a resident cosmetic clinic are comparable to national outcomes for aesthetic surgery procedures, suggesting this experience can enhance comprehensive aesthetic surgery education without compromising patient safety or quality of care. LEVEL OF EVIDENCE 4 Risk.

Histologic, Molecular, and Clinical Evaluation of Explanted Breast Prostheses, Capsules, and Acellular Dermal Matrices for Bacteria

BACKGROUND Subclinical infections, manifest as biofilms, are considered an important cause of capsular contracture. Acellular dermal matrices (ADMs) are frequently used in revision surgery to prevent recurrent capsular contractures. OBJECTIVE We sought to identify an association between capsular contracture and biofilm formation on breast prostheses, capsules, and ADMs in a tissue expander/implant (TE/I) exchange clinical paradigm. METHODS Biopsies of the prosthesis, capsule, and ADM from patients (N = 26) undergoing TE/I exchange for permanent breast implant were evaluated for subclinical infection. Capsular contracture was quantified with Baker Grade and intramammary pressure. Biofilm formation was evaluated with specialized cultures, rtPCR, bacterial taxonomy, live:dead staining, and scanning electron microscopy (SEM). Collagen distribution, capsular histology, and ADM remodeling were quantified following fluorescent and light microscopy. RESULTS Prosthetic devices were implanted from 91 to 1115 days. Intramammary pressure increased with Baker Grade. Of 26 patients evaluated, one patient had a positive culture and one patient demonstrated convincing evidence of biofilm morphology on SEM. Following PCR amplification 5 samples randomly selected for 16S rRNA gene sequencing demonstrated an abundance of suborder Micrococcineae, consistent with contamination. CONCLUSIONS Our data suggest that bacterial biofilms likely contribute to a proportion, but not all diagnosed capsular contractures. Biofilm formation does not appear to differ significantly between ADMs or capsules. While capsular contracture remains an incompletely understood but common problem in breast implant surgery, advances in imaging, diagnostic, and molecular techniques can now provide more sophisticated insights into the pathophysiology of capsular contracture. LEVEL OF EVIDENCE 4 Therapeutic.

Uneventful versus Successful Reconstruction and Outcome Pathways in Implant-Based Breast Reconstruction with Acellular Dermal Matrices.

Background: Meaningful data to help guide resource allocation for staged tissue expander/implant-based breast reconstruction are currently lacking. The authors seek to differentiate uneventful from successful reconstruction and identify common outcome pathways and factors that portend a deviation from an uneventful, two-stage, two-operation course. Methods: A retrospective analysis of expander/implant reconstructions with or without acellular dermal matrix (2003 to 2009) was performed. Related postreconstructive events (including mastectomy flap necrosis, seroma, wound dehiscence, cellulitis, explantation, hematoma, and capsular revisions) were assessed for 2 years. Uneventful reconstruction was defined as exchange to breast implant within 2 years of tissue expander placement without complications, whereas successful reconstruction was defined as exchange to breast implant within 2 years with or without complications. Factors affecting reconstructive success were analyzed, and patterns of postreconstructive events were summarized as outcome pathways. Results: Four hundred thirteen patients (295 with acellular dermal matrix and 118 without), with 602 breasts (432 with acellular dermal matrix and 170 without) underwent reconstruction. Forty-six percent of patients (48 percent with acellular dermal matrix and 40 percent without), experienced uneventful reconstruction. Reconstructive success was achieved in 337 patients (82 percent; 82.0 percent with acellular dermal matrix and 80.5 percent without), with reconstructive failure occurring in 58 patients. Multiple logistic regression analyses determined that cellulitis, seroma, and skin necrosis (OR, 15.8, 7.7, and 8.4, respectively) were highly predictive of reconstructive failure. The authors identified 10 distinct pathways experienced by tissue expander/implant patients that were characterized by specific postreconstructive events. Conclusion: The present study will facilitate discussions among patients, providers, and payers by providing a framework for understanding the myriad outcome pathways in implant-based reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Resident perceptions on pregnancy during training: 2008 to 2015

BACKGROUND Perceptions of residents regarding pregnancy during training were compared over time and across surgical, internal medicine, obstetrics/gynecology, and anesthesia specialties. METHODS A single-institution survey was distributed to female residents in 2008 and to female and male residents in 2015. Nonparametric comparisons of Likert scale response distributions were performed on the supportiveness for pregnancy of the residency program and childbearing influences of female residents in 2008 and 2015, between specialties for each survey year, and between male and female residents in 2015. RESULTS The response rates of female residents were 74.8% and 50.5% in 2008 and 2015. In 2015, program directors and division chiefs were perceived to be more supportive of resident pregnancy than in 2008. Surgical residents had lower perceptions of support compared with other specialties. Residents in programs with female leadership perceived a more supportive environment for pregnancy. CONCLUSIONS Despite persisting negative stigma, residents across specialties report more support for pregnancy.

Nonsurgical Vulvovaginal Rejuvenation With Radiofrequency and Laser Devices: A Literature Review and Comprehensive Update for Aesthetic Surgeons

Nonsurgical vulvovaginal rejuvenation (NVR) is growing in popularity as a treatment for restoration of youthful female genitalia. Numerous radiofrequency (RF) and laser devices have entered the market claiming improvement in vaginal laxity and genitourinary syndrome of menopause. There is a paucity of evidence existing concerning the effectiveness of these devices for both pre- and postmenopausal women with laxity and/or atrophy at the histologic and clinical level. Therefore, the goal of this review is to scrutinize the peer-reviewed data on NVR with RF and laser devices, identify gaps in existing literature, and propose opportunities for further investigation.

Remodeling Characteristics and Collagen Distributions of Biologic Scaffold Materials Biopsied From Postmastectomy Breast Reconstruction Sites

ObjectiveThe study purpose was to evaluate the associations between patient characteristics and the histologic remodeling scores of acellular dermal matrices (ADMs) biopsied from breast reconstruction sites in the first attempt to generate a multivariable risk prediction model of nonconstructive remodeling. It was hypothesized that host characteristics and surgical site assessments predict the degree of graft remodeling for ADMs used during breast reconstruction. MethodsThe ADMs were biopsied from the breast reconstruction sites of n = 62 patients during a subsequent breast procedure, stained with hematoxylin-eosin, and evaluated according to a semi-quantitative scoring system for remodeling characteristics (cell types, cell infiltration, extracellular matrix deposition, scaffold degradation, fibrous encapsulation, and neovascularization) and a mean composite score. Biopsies were stained with Sirius Red and Fast Green, and analyzed to determine the collagen I:III ratio. Based on univariate analyses between subject clinical characteristics and the histologic remodeling scores, cohort variables were selected for multivariable regression models using a P value of 0.20 or less. ResultsThe composite score model yielded 3 variables: pack-year history, corticosteroid use, and radiation timing (r2 pseudo = 0.81). The model for collagen I yielded 2 variables: corticosteroid use and reason for reoperation (r2 pseudo = 0.78). The model for collagen III yielded 1 variable: reason for reoperation (r2 pseudo = 0.35). ConclusionsThese preliminary results constitute the first steps in generating a risk prediction model that predicts the patients and clinical circumstances most likely to experience nonconstructive remodeling of biologic grafts used to reconstruct the breast.

Are Residents Prepared for Surgical Cases? Implications in Patient Safety and Education

OBJECTIVE In surgical education, the areas of focus and evaluation are skewed toward technical skill and operative knowledge; less emphasized is familiarity with the patients medical history. The purposes of this study were to characterize how surgical trainees prepare for cases and to determine the comprehensiveness of their preparation. DESIGN A 27-question survey was created through a web-based software program and distributed to all resident physicians and fellows in the Departments of Surgery, Neurosurgery, and Otolaryngology at our institution. Survey responses were collected anonymously and analyzed. Institutional review board exemption was obtained. SETTING This study was performed at Washington University in St. Louis, Missouri, at an institutional hospital setting. PARTICIPANTS The survey was distributed to current surgical trainees at Washington University in St. Louis in the Departments of Surgery, Neurosurgery, and Otolaryngology. Further, 130 of 169 surgical residents and fellows completed the survey. RESULTS Most respondents (96%) taught themselves case preparation. Only 57% of respondents reviewed the patients medical record before every surgery. Although most respondents (83%) felt they were prepared or very prepared from a patient-specific standpoint, only 24% felt that their handoff of a patient to on-call colleagues was comprehensive enough to include all pertinent aspects of a patients history and expected perioperative course. From a technical perspective, most residents (63%) felt they were prepared or very prepared, and this level of comfort increased with postgraduate year; 76% of respondents would not feel comfortable telling their attending they were not adequately prepared. CONCLUSIONS Although most trainees feel prepared or very prepared for cases from a patient-specific regard, only half review the patients medical record before every surgery. Furthermore, almost all trainees have taught themselves how to prepare for surgery. This represents a critical gap in residency education and an opportunity to improve patient safety and quality of care.