Safety and factors affecting same-day discharge following mastectomy and immediate alloplastic reconstruction.

BACKGROUND AND OBJECTIVES: Patients undergoing breast reconstruction following mastectomy are often admitted overnight. In 2020, our institution implemented a protocol change to discharge clinically stable patients immediately. In this study, we examine the safety of same-day discharge following mastectomy and reconstruction. METHODS: Our retrospective study included female adults undergoing mastectomy and immediate alloplastic reconstruction from August 2019 to January 2020, before implementation of the same-day discharge protocol, and from March 2020 to September 2021, after the protocol implementation. Independent t-test and chi-square analysis was conducted to examine statistical differences. RESULTS: Two hundred and eighty-five patients were included. Forty-two patients underwent reconstruction before the protocol change (Group 1) and 243 patients underwent reconstruction after the protocol change (Group 2). Group 2 had a greater percentage of prepectoral implant placement. There was no difference in demographics, complications, readmission, or reoperation. Within Group 2, 157 patients were discharged the same day (Group 2a) and 88 patients required overnight admission (Group 2b). Group 2b had higher body mass index, higher percentage of bilateral mastectomy, and larger mastectomy weights. Despite no differences in complications, Group 2b exhibited higher rates of requiring intravenous antibiotics and reoperation. CONCLUSIONS: Patients may be safely discharged the same day following mastectomy and alloplastic reconstruction without an increase in complications.

Autologous Skin Grafts, versus Tissue-engineered Skin Constructs: A Systematic Review and Meta-analysis.

For over 100 years, autologous skin grafts have remained the gold standard for the reconstruction of wounds but are limited in availability. Acellular tissue-engineered skin constructs (acellular TCs) and cellular tissue-engineered skin constructs (cellular TCs) may address these limitations. This systematic review and meta-analysis compare outcomes between them. Methods: A systematic review was conducted using PRISMA guidelines, querying MEDLINE, Embase, Web of Science, and Cochrane to assess graft incorporation, failure, and wound healing. Case reports/series, reviews, in vitro/in vivo work, non-English articles or articles without full text were excluded. Results: Sixty-six articles encompassing 4076 patients were included. No significant differences were found between graft failure rates (P = 0.07) and mean difference of percent reepithelialization (p = 0.92) when split-thickness skin grafts were applied alone versus co-grafted with acellular TCs. Similar mean Vancouver Scar Scale was found for these two groups (p = 0.09). Twenty-one studies used at least one cellular TC. Weighted averages from pooled results did not reveal statistically significant differences in mean reepithelialization or failure rates for epidermal cellular TCs compared with split-thickness skin grafts (p = 0.55). Conclusions: This systematic review is the first to illustrate comparable functional and wound healing outcomes between split-thickness skin grafts alone and those co-grafted with acellular TCs. The use of cellular TCs seems promising from preliminary findings. However, these results are limited in clinical applicability due to the heterogeneity of study data, and further level 1 evidence is required to determine the safety and efficacy of these constructs.

Reconstructive Trends After Tissue-Expander Loss in Breast Reconstruction.

PURPOSE: Tissue-expander breast reconstruction (TEBR) is a common method of reconstruction after mastectomy but may result in complications that may necessitate removal. Although complications in TEBR have been well studied, there is a paucity of data regarding outcomes after tissue-expander loss. In this study, we examine the eventual reconstructive pathways and associated factors of patients who required tissue-expander removal after infection. METHODS: This retrospective study examines patients undergoing breast reconstruction at a single institution. Patients included underwent mastectomy, immediate TEBR, and subsequent tissue-expander loss. Patients who underwent autologous reconstruction after mastectomy or had successful TEBR were excluded. Patients were followed for an average of 7 years, with a minimum of 2 years and a maximum of 13 years. RESULTS: A total of 674 TEBR patients were initially screened, of which 60 patients (8.9%) required tissue-expander removal because of infection or skin necrosis. Thirty-one of these patients (group 1) did not complete reconstruction after initial tissue-expander loss, whereas the remaining 29 patients (group 2) underwent either TEBR or autologous reconstruction after tissue-expander loss. Group 1 had a significantly higher mean body mass index than group 2 (32.61 ± 8.88 vs 28.69 ± 5.84; P = 0.049) and also lived further away from our institution than group 2 (P = 0.052), which trended toward significance. There were otherwise no significant differences in demographics between the 2 groups.Among the 29 patients in group 2, 18 patients underwent a second TEBR (group 2a), and 11 patients underwent autologous reconstruction (group 2b). Patients in group 2b had a significantly greater mean number of complication related admissions (1.11 ± 0.323 vs 1.55 ± 0.688; P = 0.029) and also had higher occurrence of postmastectomy radiation therapy (16.7% vs 45.5%; P = 0.092), although this was not significant. There were otherwise no differences between the 2 groups. CONCLUSION: Our data demonstrate the trends in breast reconstruction decision making after initial tissue-expander loss. This study elucidates the factors associated with patients who undergo different reconstructive options. Further work is needed to delineate the specific reasons between the decision to pursue different reconstructive pathways among a larger cohort of patients.

Clinical Outcomes After Hematoma Development: A Study of 627 Tissue Expander Breast Reconstructions.

BACKGROUND: Hematomas after tissue expander immediate breast reconstruction (TE-IBR) pose a significant challenge during the recovery period. In this study, we aim to evaluate whether hematoma formation leads to subsequent complications and how management can impact final reconstructive goals. METHODS: A single-institution retrospective review of TE-IBRs from 2001 to 2018 was performed using an established breast reconstruction database. Demographics, medications, comorbidities, and complications were identified. Implant loss was defined as removal of the tissue expander/implant without immediate reimplantation during that operation. Hematoma size, management, transfusion requirement, reoperations, and final outcome were recorded. Reconstructive failure was defined as an implant loss that was not replaced with another implant or required secondary autologous reconstruction. RESULTS: Six hundred twenty-seven TE-IBR patients were analyzed. Postoperative hematoma (group 1) occurred in 4.1% (n = 26) of TE-IBRs and did not develop in 95.9% (group 2: n = 601). Group 2 had a higher mean body mass index (24.5 vs 27.3 kg/m, P = 0.018); however, there were no significant differences in smoking status, preoperative/postoperative radiation/chemotherapy, or other comorbidities. Group 1 was found to have increased rates of implant loss (15.4% vs 3.7%, P = 0.0033) and reconstructive failure (11.5% vs 2.8%, P = 0.0133) compared with group 2.Eighteen hematomas (69.2%) underwent surgical intervention (group 1a) compared with 30.8% (n = 8) that were clinically managed (group 1b). Group 1a had statistically significant lower rates of subsequent complications (22.2% vs 62.5%, P = 0.046) and reoperations (5.6% vs 27.5%, P = 0.037) than did group 1b, respectively.Lastly, 23.1% (n = 6) of patients who developed a hematoma were on home antithrombotics (group 1c) compared with 76.9% (n = 20) of patients with no antithrombotics (group 1d). There were statistically significant differences in transfusion rates (50% vs 0%, P = 0.001) between groups 1c and 1d, respectively. Differences in hematoma volume (330 vs 169.3 mL, P = 0.078) and reconstructive failure (33.3% vs 5%, P = 0.057) approached significance between both groups. CONCLUSIONS: Hematoma after TE-IBR should be monitored closely, as it may play a role in jeopardizing reconstruction success. Patients on home antithrombotic medication may be at increased risk of larger-volume hematomas and reconstruction failure. Plastic surgeons should consider aggressive surgical evacuation of postoperative TE-IBR hematomas to reduce subsequent complications and reoperations, thus optimizing reconstructive outcomes.

Do Postoperative Prophylactic Antibiotics Reduce Highly Virulent Infections?: An Analysis of 660 Tissue Expander Breast Reconstructions.

BACKGROUND: Many surgeons are reluctant to discontinue prophylactic antibiotics after 24 hours in tissue expander breast reconstruction (TEBR) because of fear of increased risk of surgical site infection (SSI). Currently, there is no consensus regarding antibiotic prophylaxis duration in TEBR. In addition, there remains a lack of research investigating microorganisms involved in SSI across various perioperative antibiotic protocols. The purpose of this study was to examine how 2 different prophylactic antibiotic regimens impacted the bacterial profiles of SSI and rate of implant loss after TEBR. METHODS: A single-institution retrospective review of immediate TEBRs between 2001 and 2018 was performed. Surgical site infections requiring hospitalization before stage 2 were included. Highly virulent organisms were defined as ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species). Implant loss was defined as removal of tissue expander without immediate replacement. RESULTS: Of 660 TEBRs, 85 (12.9%) developed an SSI requiring hospitalization before stage 2. Fifty-six (65.9%) received less than 24 hours of perioperative intravenous antibiotics and oral antibiotics after discharge (group 1), and 29 (34.1%) received less than 24 hours of intravenous antibiotics only (group 2). There was no significant difference in demographics, preoperative chemotherapy/radiation, acellular dermal matrix usage, or treatment of SSI between groups. In group 1, 64% (n = 36) developed culture positive SSIs, compared with 83% (n = 24) in group 2 (P = 0.076). Staphylococcus aureus was the most common bacteria in both groups. Group 2 demonstrated a significantly increased incidence of gram-positive organisms (46.4% vs 72.4%, P = 0.022) and S. aureus (21.4% vs 55.2%, P = 0.002). However, there was no significant difference in overall highly virulent (P = 0.168), gram-negative (P = 0.416), or total isolated organisms (P = 0.192). Implant loss between groups 1 and 2 (62.5% vs 62.1%, P = 0.969) respectively, was nearly identical. CONCLUSIONS: Our study demonstrates that, despite differences in bacterial profiles between 2 antibiotic protocols, prolonged postoperative antibiotic use did not protect against overall highly virulent infections or implant loss. Antibiotic stewardship guidelines against the overuse of prolonged prophylactic regimens should be considered. Further analysis regarding timing of SSIs and antibiotic treatment is warranted.

Efficacy of Fibrin Sealants in Preventing Seroma Formation in Reduction Mammaplasty: A Single Surgeon's Experience.

BACKGROUND: Fibrin sealant is a controversial method for reducing seroma formation. It is comprised of human proclotting factors, fibrinogen and thrombin. Fibrin sealants have been extensively studied for their efficacy in reducing the rates of seroma by sealing the dead space; however, in most studies, the sealants are used with surgical drains. According to the U.S. Food and Drug Administration, fibrin sealant carries the risk of life-threatening thromboembolic complications, gas emboli, and transmission of infectious agents. Despite these concerns, many plastic surgeons use such products in ambulatory surgeries even though its effect on seroma formation has yet to be elucidated. The aim of our study is to determine the efficacy of fibrin sealants in seroma prevention in reduction mammoplasty with and without surgical drains. METHODS: A retrospective chart review was performed of all bilateral reduction mammaplasty by a single-surgeon from 2014 to 2018. Patients had at least 90 days postoperative follow-up. Exclusion criteria consisted of patients younger than 18 years, had prior breast surgery, or had an incidental cancer diagnosis in breast reduction tissue specimen. RESULTS: On analysis, 159 patients met inclusion criteria and were categorized into group 1, with fibrin sealant (n = 101) and group 2, no fibrin sealant (n = 58). There were no statistical differences in patient demographics. There was no significant difference in the incidence of seroma between group 1 and group 2 (21% vs 19%, P = 0.782). Group 1 incidence of seroma was further analyzed by sealant type: Tisseal, Floseal, and Evicel (12% vs 27% vs 23%, P = 0.436). In group 1, the use of sealant alone was more likely to result in seroma formation when compared with the combination of sealant and surgical drains (25% vs 8%, P = 0.069). CONCLUSIONS: There is no difference in rate of seroma formation with the use of fibrin sealants in reduction mammaplasty. The use of fibrin sealants without surgical drains may increase the rate of seromas. Plastic surgeons could consider weighing the risk versus benefits in using fibrin sealants with or without drains in ambulatory surgeries.

Histone modifiers: Dynamic regulators of the cutaneous transcriptome.

By regulating the accessibility of the genome, epigenetic regulators such as histone proteins and the chromatin-modifying enzymes that act upon them control gene expression. Proper regulation of this "histone code" allows for the precise control of transcriptional networks that are essential for establishing and maintaining cell fate and identity, disruption of which may drive carcinogenesis. How these dynamic epigenetic regulators contribute to both skin homeostasis and disease is only beginning to be understood. Here we provide an update of the current understanding of histone modifiers in the skin. Indeed, as one of the most innovative and rapidly expanding areas in all of medicine, it is clear that epigenome-targeting therapies hold great promise for the treatment of dermatological diseases in the coming years.

BAP1: case report and insight into a novel tumor suppressor.

BACKGROUND: BRCA1-Associated-Protein 1 (BAP1) is a dynamic tumor suppressor which, when mutated, has been associated with an increased risk of uveal melanoma, cutaneous melanoma, mesothelioma, and several other cancers. Germline BAP1 mutations have been extensively studied, where they have been found to cause hereditary cancer susceptibility. However, their sporadic counterparts, tumors that display a loss of BAP1 expression due to somatically arising mutations in the BAP1 gene, remain a poorly described entity. CASE PRESENTATION: Here we present the case of a 49-year-old female who presented with an asymptomatic dome-shaped pink papule on the dorsal foot which was found on biopsy to be deficient in the BAP1 tumor suppressor. While the patient's family history did not suggest the presence of a familial cancer syndrome, germline genetic testing was performed and was negative. The patient underwent surgical excision of this sporadically appearing "BAPoma" by Mohs surgery. CONCLUSIONS: Given the relatively banal clinical appearance of these dome-shaped neoplasms, sporadic BAPomas may often be overlooked by clinicians and dermatologists. In addition to providing a representative case, here we also provide a synopsis of the current understanding of these neoplasms, both in terms of the histopathological features, as well as the molecular mechanisms underlying BAP1 function and its ability to prevent tumorigenesis.

Cytoplasmic chromatin triggers inflammation in senescence and cancer.

Chromatin is traditionally viewed as a nuclear entity that regulates gene expression and silencing. However, we recently discovered the presence of cytoplasmic chromatin fragments that pinch off from intact nuclei of primary cells during senescence, a form of terminal cell-cycle arrest associated with pro-inflammatory responses. The functional significance of chromatin in the cytoplasm is unclear. Here we show that cytoplasmic chromatin activates the innate immunity cytosolic DNA-sensing cGAS-STING (cyclic GMP-AMP synthase linked to stimulator of interferon genes) pathway, leading both to short-term inflammation to restrain activated oncogenes and to chronic inflammation that associates with tissue destruction and cancer. The cytoplasmic chromatin-cGAS-STING pathway promotes the senescence-associated secretory phenotype in primary human cells and in mice. Mice deficient in STING show impaired immuno-surveillance of oncogenic RAS and reduced tissue inflammation upon ionizing radiation. Furthermore, this pathway is activated in cancer cells, and correlates with pro-inflammatory gene expression in human cancers. Overall, our findings indicate that genomic DNA serves as a reservoir to initiate a pro-inflammatory pathway in the cytoplasm in senescence and cancer. Targeting the cytoplasmic chromatin-mediated pathway may hold promise in treating inflammation-related disorders.

Inhibition of Age-Related Therapy Resistance in Melanoma by Rosiglitazone-Mediated Induction of Klotho.

Purpose: Aging is a poor prognostic factor for melanoma. We have shown that melanoma cells in an aged microenvironment are more resistant to targeted therapy than identical cells in a young microenvironment. This is dependent on age-related secreted factors. Klotho is an age-related protein whose serum levels decrease dramatically by age 40. Most studies on klotho in cancer have focused on the expression of klotho in the tumor cell. We have shown that exogenous klotho inhibits internalization and signaling of Wnt5A, which drives melanoma metastasis and resistance to targeted therapy. We investigate here whether increasing klotho in the aged microenvironment could be an effective strategy for the treatment of melanoma.Experimental Design: PPARγ increases klotho levels and is increased by glitazones. Using rosiglitazone, we queried the effects of rosiglitazone on Klotho/Wnt5A cross-talk, in vitro and in vivo, and the implications of that for targeted therapy in young versus aged animals.Results: We show that rosiglitazone increases klotho and decreases Wnt5A in tumor cells, reducing the burden of both BRAF inhibitor-sensitive and BRAF inhibitor-resistant tumors in aged, but not young mice. However, when used in combination with PLX4720, tumor burden was reduced in both young and aged mice, even in resistant tumors.Conclusions: Using glitazones as adjuvant therapy for melanoma may provide a new treatment strategy for older melanoma patients who have developed resistance to vemurafenib. As klotho has been shown to play a role in other cancers too, our results may have wide relevance for multiple tumor types. Clin Cancer Res; 23(12); 3181-90. ©2017 AACR.

The Senescence-Associated Secretory Phenotype: Critical Effector in Skin Cancer and Aging.

Cellular senescence, a state of stable cell cycle arrest in response to cellular stress, is an indispensable mechanism to counter tumorigenesis by halting the proliferation of damaged cells. However, through the secretion of an array of diverse cytokines, chemokines, growth factors, and proteases known as the senescence-associated secretory phenotype (SASP), senescent cells can paradoxically promote carcinogenesis. Consistent with this, removal of senescent cells delays the onset of cancer and prolongs lifespan in vivo, potentially in part through SASP reduction. In this review, we consider the evidence for the SASP and "SASP-like" inflammation in driving skin carcinogenesis, emphasizing how further understanding of both the roles and mechanisms of SASP expression may offer new targets for skin cancer prevention and therapy.