Evolution of chromosome-arm aberrations in breast cancer through genetic network rewiring.

The basal breast cancer subtype is enriched for triple-negative breast cancer (TNBC) and displays consistent large chromosomal deletions. Here, we characterize evolution and maintenance of chromosome 4p (chr4p) loss in basal breast cancer. Analysis of The Cancer Genome Atlas data shows recurrent deletion of chr4p in basal breast cancer. Phylogenetic analysis of a panel of 23 primary tumor/patient-derived xenograft basal breast cancers reveals early evolution of chr4p deletion. Mechanistically we show that chr4p loss is associated with enhanced proliferation. Gene function studies identify an unknown gene, C4orf19, within chr4p, which suppresses proliferation when overexpressed-a member of the PDCD10-GCKIII kinase module we name PGCKA1. Genome-wide pooled overexpression screens using a barcoded library of human open reading frames identify chromosomal regions, including chr4p, that suppress proliferation when overexpressed in a context-dependent manner, implicating network interactions. Together, these results shed light on the early emergence of complex aneuploid karyotypes involving chr4p and adaptive landscapes shaping breast cancer genomes.

Breast Implant-Related Adverse Events During Mammography: An Assessment of the Food and Drug Administration Manufacturer and User Facility Device Experience Database.

BACKGROUND: Adverse events arising in patients with breast implants during mammography reported by the Food and Drug Administration include implant rupture, pain, and impaired visualization. However, data supporting these claims were collected in 2004, and since, newer implant generations have been developed with overall rate of implantation increasing by 48%. OBJECTIVES: This article aims to determine the current incidence of implant-related adverse events arising during mammography. METHODS: We analyzed reports regarding silicone and saline breast implants published in the Food and Drug Administration Manufacturer and User Facility Device Experience database between 2008 and November 2018. Search terms included "mammogram," "mammography," "radiograph," "breast cancer screening," "breast cancer test," and "x-ray." RESULTS: Of the 20 539 implant-related adverse events available in the Manufacturer and User Facility Device Experience database, 427 were retrieved using our search strategy and 41 were related to mammography. Thirty-five of identified cases (85.4%) reported implant rupture, of which 19 (54.3%) were confirmed by a healthcare professional, 9 (25.7%) were clinically confirmed by saline implant deflation, and 7 (20.0%) were unverified reports by patients. Sixteen ruptures (45.7%) occurred with silicone implants, whereas 19 ruptures (54.3%) occurred with saline. Other adverse events included pain (29.3%), change in implant appearance (14.6%), and swelling (7.3%). CONCLUSIONS: Although implant rupture, pain, change in implant appearance, and swelling may occur, minimal implant-related adverse events arise during mammography. Given the extremely low reported risk of implant rupture, this should neither prevent patients from adhering to breast cancer screening programs nor deter patients from seeking breast implants. Patients should be aware of these reported risks and discuss screening options with their breast cancer screening team.

Nerve Blocks in Breast Plastic Surgery: Outcomes, Complications, and Comparative Efficacy.

BACKGROUND: As plastic surgeons continue to evaluate the utility of nonopioid analgesic alternatives, nerve block use in breast plastic surgery remains limited and unstandardized, with no syntheses of the available evidence to guide consensus on optimal approach. METHODS: A systematic review was performed to evaluate the role of pectoralis nerve blocks, paravertebral nerve blocks, transversus abdominus plane blocks, and intercostal nerve blocks in flap-based breast reconstruction, prosthetic-based reconstruction, and aesthetic breast plastic surgery, independently. RESULTS: Thirty-one articles reporting on a total of 2820 patients were included in the final analysis; 1500 patients (53 percent) received nerve blocks, and 1320 (47 percent) served as controls. Outcomes and complications were stratified according to procedures performed, blocks employed, techniques of administration, and anesthetic agents used. Overall, statistically significant reductions in opioid consumption were reported in 91 percent of studies evaluated, postoperative pain in 68 percent, postanesthesia care unit stay in 67 percent, postoperative nausea and vomiting in 53 percent, and duration of hospitalization in 50 percent. Nerve blocks did not significantly alter surgery and/or anesthesia time in 83 percent of studies assessed, whereas the overall, pooled complication rate was 1.6 percent. CONCLUSIONS: Transversus abdominus plane blocks provided excellent outcomes in autologous breast reconstruction, whereas both paravertebral nerve blocks and pectoralis nerve blocks demonstrated notable efficacy and versatility in an array of reconstructive and aesthetic procedures. Ultrasound guidance may minimize block-related complications, whereas the efficacy of adjunctive postoperative infusions was proven to be limited. As newer anesthetic agents and adjuvants continue to emerge, nerve blocks are set to represent essential components of the multimodal analgesic approach in breast plastic surgery.

Wound Healing: A Comprehensive Review.

Wound healing is an intricate, tightly regulated process that is critical to maintaining the barrier function of skin along with preserving all other skin functions. This process can be influenced by a variety of modifiable and nonmodifiable factors. As wound healing takes place in all parts of the human body, this review focuses on cutaneous wound healing and highlights the classical wound healing phases. Alterations in any of these phases can promote chronic wound development and may impede wound healing.

Current Advances in Hypertrophic Scar and Keloid Management.

Hypertrophic scars and keloids are caused by excessive tissue response to dermal injury due to local fibroblast proliferation and collagen overproduction. This response occurs because of pathologic wound healing due to dysregulation in the inflammatory, proliferative, and/or remodeling phase. Patients with hypertrophic scars or keloids report reduced quality of life, physical status, and psychological health. Hypertrophic scars or keloids will develop in 30 to 90% of individuals, and despite their prevalence, treatment remains a challenge. Of the treatments currently available for hypertrophic scars and keloids few have been adequately supported by studies with appropriate experimental design. Here, we aim to review the available literature to provide up-to-date information on the etiology, epidemiology, histology, pathophysiology, prevention, and management options available for the treatment of hypertrophic scars and keloids and highlight areas where further research is required.

Negative Pressure Wound Therapy: Mechanism of Action and Clinical Applications.

Negative pressure wound therapy (NPWT) promotes healing by evenly applying negative pressure on the surface of the wound. The system consists of a sponge, a semiocclusive barrier, and a fluid collection system. Its effectiveness is explained by four main mechanisms of action, including macrodeformation of the tissues, drainage of extracellular inflammatory fluids, stabilization of the environment of the wound, and microdeformation. Rarely will complications linked to NPWT occur, but special care must be taken to prevent events such as toxic shock syndrome, fistulization, bleeding, and pain. New NPWT modalities have been recently developed to make NPWT suitable for a wider variety of wounds. These include NPWT with instillation therapy (NPWTi-d), different cleansing options, and application of NPWT on primarily closed incisions. Finally, vacuum-assisted wound closure therapy has been demonstrated to be efficient for various clinical settings, such as the management of diabetic foot ulcers, pressure ulcerations, chronic wounds, and skin grafts.

Radiation-Induced Tissue Damage: Clinical Consequences and Current Treatment Options.

Radiation therapy is a valuable tool in the treatment of numerous malignancies but, in certain cases, can also causes significant acute and chronic damage to noncancerous neighboring tissues. This review focuses on the pathophysiology of radiation-induced damage and the clinical implications it has for plastic surgeons across breast reconstruction, osteoradionecrosis, radiation-induced skin cancers, and wound healing. The current understanding of treatment modalities presented here include hyperbaric oxygen therapy, autologous fat grafting and stem cells, and pharmaceutical agents.

Current Concepts in Capsular Contracture: Pathophysiology, Prevention, and Management.

Over 400,000 women in the United States alone will have breast implant surgery each year. Although capsular contracture represents the most common complication of breast implant surgery, surgeons continue to debate the precise etiology. General agreement exists concerning the inflammatory origin of capsular fibrosis, but the inciting events triggering the inflammatory cascade appear to be multifactorial, making it difficult to predict why one patient may develop capsular contracture while another will not. Accordingly, researchers have explored many different surgical, biomaterial, and medical therapies to address these multiple factors in an attempt to prevent and treat capsular contracture. In the current paper, we aim to inform the reader on the most up-to-date understanding of the pathophysiology, prevention, and treatment of capsular contracture.

Spontaneous necrosis of a single digit: watershed necrosis.

Anatomical variations in the superficial and deep palmar arches are common, but rarely lead to digital necrosis. We report the case of necrosis of the third digit caused by a 'watershed' effect in the context of atherosclerotic disease and rare congenital variations of the superficial and deep palmar arches.

Breast Implant-associated Anaplastic Large Cell Lymphoma: A Canadian Surgical Oncology Survey.

BACKGROUND: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) awareness has increased, resulting in concerns regarding the safety of implant-based reconstruction. Breast cancer patients are first seen by surgical oncologists, who are therefore potentially the first health-care professionals to encounter concerns regarding BIA-ALCL. We therefore surveyed surgical oncologists on their understanding of BIA-ALCL to better assess potential effects on plastic surgery practice. METHODS: An anonymous web-based survey consisting of 9 multiple-choice questions was sent to breast surgical oncologists that are members of the Canadian Society of Surgical Oncology (n = 135). RESULTS: Forty-two members responded (n = 42/135, 31%) and all participants were aware of BIA-ALCL. All participants reported that BIA-ALCL has not deterred them from referring patients for implant-based reconstruction. Twenty-two respondents (52%) discuss BIA-ALCL with their patients and 21% (n = 9) believe that BIA-ALCL typically follows a metastatic course. Eight respondents (19%) reported having a poor understanding of BIA-ALCL, while 14% (n = 6) were unable to identify the link to textured implants. There were no statistical differences based on case-load volume. CONCLUSIONS: Approximately half of the respondent Canadian breast surgical oncologists discuss BIA-ALCL with their patients, yet there is a knowledge gap in terms of the epidemiology and clinical-pathological course of BIA-ALCL. It is of utmost importance to ensure that the plastic surgery community aims at including surgical oncologist colleagues in educational platforms regarding BIA-ALCL to ensure collaboration and unity in an effort to offer the most accurate information to patients, and prevent misinformation that may deter patients from seeking implant-based reconstruction.

Perception of Implants among Breast Reconstruction Patients in Montreal.

BACKGROUND: In light of the recent surge of media coverage and social media influence regarding breast implants, it is essential to understand patients' concerns and misconceptions so that we can better serve them. METHODS: The authors designed a survey study for assessing the awareness and perception of patients toward breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) and breast implant illness (BII). In total, 130 patients presenting to the senior author's breast reconstruction clinic completed the survey. The survey assessed patients' knowledge on and their perception of BIA-ALCL and BII. RESULTS: "News article" and "Television" were most often selected as sources of information for BIA-ALCL (21% and 20%, respectively) and BII (20% and 25%, respectively). A total of 100 patients (77%) had previous knowledge of BIA-ALCL. Forty-seven percent (n = 47/100) responded that they were unsure of the fate of a person diagnosed with BIA-ALCL, and 25% (n = 25/100) were unaware of the association between BIA-ALCL and specific implant type. Patients who were unaware of BIA-ALCL prognosis reported being less likely to receive breast implants in the future (P = 0.012, χ2 = 19.48). Eighty-nine patients (68%) had previous knowledge of BII. A total of 60 symptoms were mentioned by patients, with "Fatigue" (12%, n = 26) being cited the most often. CONCLUSIONS: The present survey highlights the importance for plastic surgeons to frequently discuss these entities with their patients. This should be done despite the obscurity of BII, in an effort to offer the best available evidence to our patients.

Use of Decision Analysis and Economic Evaluation in Breast Reconstruction: A Systematic Review.

BACKGROUND: Decision analysis allows clinicians to compare different strategies in the context of uncertainty, through explicit and quantitative measures such as quality of life outcomes and costing data. This is especially important in breast reconstruction, where multiple strategies can be offered to patients. This systematic review aims to appraise and review the different decision analytic models used in breast reconstruction. METHODS: A search of English articles in PubMed, Ovid, and Embase databases was performed. All articles regardless of date of publishing were considered. Two reviewers independently assessed each article, based on strict inclusion criteria. RESULTS: Out of 442 articles identified, 27 fit within the inclusion criteria. These were then grouped according to aspects of breast reconstruction, with implant-based reconstruction (n = 13) being the most commonly reported. Decision analysis (n = 19) and/or economic analyses (n = 27) were employed to discuss reconstructive options. The most common outcome was cost (n = 27). The decision analysis models compared and contrasted surgical strategies, management options, and novel adjuncts. CONCLUSIONS: Decision analysis in breast reconstruction is growing exponentially.The most common model used was a simple decision tree. Models published were of high quality but could be improved with a more in-depth sensitivity analysis. It is essential for surgeons to familiarize themselves with the concept of decision analysis to better tackle complicated decisions, due to its intrinsic advantage of being able to weigh risks and benefits of multiple strategies while using probabilistic models.

The Potential Role of Corticosteroid Prophylaxis for the Prevention of Microscopic Fat Embolism Syndrome in Gluteal Augmentations.

BACKGROUND: Microscopic fat embolism syndrome (micro-FES) has been recently identified as a potentially fatal complication following gluteal augmentation utilizing autologous fat grafts; safety recommendations advocating for subcutaneous lipo-injections may be insufficient for its prevention. OBJECTIVES: The authors of this systematic review evaluated the potential role of corticosteroid prophylaxis for the prevention of micro-FES in gluteal augmentation procedures. METHODS: The authors performed a systematic search employing the National Library of Medicine (PubMed), Medline, and Embase databases. Search terms were those pertaining to studies reporting the efficacy of prophylactic corticosteroid administration on micro-FES incidence in a high-risk surrogate population. RESULTS: Thirteen articles met the inclusion criteria for review, comprising 2 studies reporting on the efficacy of a single intravenous (IV) corticosteroid dose for the prophylaxis of micro-FES, 9 studies reporting on multiple prophylactic IV doses, and 2 additional studies reporting on the efficacy of inhaled corticosteroids in this context. All studies were identified from the orthopedic literature given that none were available directly from within plastic surgery. The prophylactic efficacy of multiple IV doses of methylprednisolone, or a single larger dose, was established, whereas the efficacy of inhaled corticosteroids remains elusive. CONCLUSIONS: A single perioperative IV dose of methylprednisolone may be most appropriate for utilization by plastic surgeons; the safety and implication of this therapy on wound healing and fat graft survival are discussed. Further studies directly evaluating the efficacy of corticosteroid prophylaxis in the gluteal augmentation population are indicated. Finally, recommendations pertaining to the prevention, timely recognition, and effective management of micro-FES are discussed.

Forearm-Based Ulnar Gutter versus Hand-Based Thermoplastic Splint for Pediatric Metacarpal Neck Fractures: A Blinded, Randomized Trial.

BACKGROUND: Use of a hand-based thermoplastic splint for treatment of isolated fifth metacarpal neck fractures in pediatric patients has not previously been studied in a randomized blinded trial. METHODS: The authors conducted a blinded, 1:1 allocation, two-arm parallel group, superiority design, randomized controlled trial in patients aged 16 years or younger with isolated fifth metacarpal neck fractures. Patients were immobilized for 3 weeks in a conventional forearm-based ulnar gutter or hand-based thermoplastic splint. Primary outcome was difference in active range of motion between splint groups. Secondary outcomes included fracture union, treatment adherence, grip strength, and patient-reported pain and functional outcomes. RESULTS: Between February of 2013 and August of 2014, 40 patients were enrolled in the trial. No differences were observed in baseline characteristics between groups. Mean range of motion was significantly better in the thermoplastic splint group compared with the ulnar gutter splint group at 3 weeks (p = 0.048). All patients had full range of motion at 12 weeks. Treatment adherence was 75 percent and 59 percent for ulnar gutter and thermoplastic splint groups, respectively (p = 0.46). Among ulnar gutter splint patients, decreased grip strength (injured versus noninjured) was observed at 3 and 6 weeks, and was significantly weaker compared with thermoplastic splint patients (p = 0.01). Reported pain scores were similar between groups. Patient-reported functional outcome scores were similar between groups at each time point. No nonunions were observed at 12 weeks. CONCLUSION: In pediatric patients, hand-based thermoplastic splints resulted in improved early range of motion and grip strength, with no increased pain, nonadherence, or complications compared with conventional ulnar gutter splints. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, I.

The patient's perspective on carpal tunnel surgery related to the type of anesthesia: a prospective cohort study.

BACKGROUND: The purpose of this study was to provide prospective independently analyzed evidence on how patients feel about a carpal tunnel release (CTR) performed under local anesthesia only (no sedation or tourniquet) versus with local anesthesia, intravenous (IV) sedation, and a tourniquet. METHODS: This prospective cohort study compared 100 consecutive CTRs done with only lidocaine and epinephrine in Saint John, New Brunswick to 100 consecutive CTRs done with IV sedation in Davenport, Iowa. Patient perspectives on the anesthesia were captured in a blinded questionnaire 1 week postoperatively. RESULTS: For subsequent surgery, 93 % of wide awake patients would choose local anesthesia only and 93 % of sedated patients would choose sedation. Wide awake patients spent less time at the hospital (M = 2.6 h) than sedated patients (M = 4.0 h; p < .001). Preoperative blood work, electrocardiograms, and/or chest radiographs were done for 3 % of wide awake patients and 48 % of sedated patients (p < 0.001). Preoperative anxiety levels for wide awake patients were lower than for sedated patients (p = 0.007); postoperative anxiety was similar. There were no anesthesia complications in either group. Narcotics were used by 5 % of unsedated patients and 67 % of sedated patients (p < 0.001). Adequate pain control was reported by 89 % and 90 % of patients, respectively. CONCLUSIONS: The majority of patients from both cohorts liked whichever method of anesthesia they received and would choose it again. However, sedated patients spent more time at the hospital, required more preoperative testing, and reported greater preoperative anxiety.

Systematic review of the best evidence in intramedullary fixation for metacarpal fractures.

BACKGROUND: Intramedullary (IM) fixation has been described as a reliable method of treatment for certain fracture patterns but has not been widely adopted into practice. The purpose of this study was to evaluate the literature comparing IM fixation to other forms of treatment for metacarpal fractures. METHODS: A systematic review was performed to identify studies investigating the treatment of metacarpal fractures using IM fixation. Inclusion and exclusion criteria were predetermined. Two reviewers independently identified appropriate articles for review based on the criteria. Primary outcome measures were range of motion (ROM) (Styf et al., Rev Chir Orthop Reparatrice Appar Mot 74(Suppl 2):268-270, 2008) and complications. Secondary outcomes included loss of reduction, grip strength, Disabilities of arm, shoulder and hand (DASH) scores, radiographic measures and pain scores. RESULTS: Eight studies were eligible for review. Studies were of level II-IV evidence, and captured a total of 435 patients. The ROM post-operatively was found to be greater in the IM group in half of the studies. IM fixation trended toward higher complication rates in one study, but no differences were statistically significant. IM fixation fared similarly or superiorly to its competitor in each of the secondary outcomes. A formal meta-regression analysis was not possible given the heterogeneity of studies. CONCLUSIONS: IM fixation may have a role in the treatment of certain metacarpal fractures. No conclusive recommendations can be made based on the available studies included in this literature search. Further study of this technique and its applications using high level evidence is warranted.

Survey on current hydrotherapy use among North American burn centers.

The authors have reviewed hydrotherapy practices in North American burn centers and described the epidemiology of hydrotherapy-associated nosocomial infections. A web-based survey was distributed to the directors of all burn care facilities listed by the American Burn Association. Questions addressed aspects of practice, including the method, additives, disposable liners, decontamination practices, nosocomial pathogens, and perceptions regarding the "ideal" method of hydrotherapy. The response rate was 44%, 59 of 142 centers, or 827 of 1900 beds. Hydrotherapy is regularly used by 83% of centers. Among these centers, 10% use exclusively immersion hydrotherapy (IH), 54% use exclusively shower cart hydrotherapy (SCH), and 35% use a combination of IH and SCH. Disposable liners are used at 80% of centers. Tap water alone is used by 51% of centers, 27% add detergent, 16% chlorhexidine, and 7% povidone-iodine. The majority of centers (57%) do not routinely culture their hydrotherapy equipment, 20% culture weekly, 7% monthly, and 17% less than once per month. Directors believe that Pseudomonas aeruginosa, methicillin-sensitive Staphylococcus aureus, and methicillin-resistant S. aureus are the most common nosocomial pathogens, followed by Acinetobacter species and Candida albicans. The relative frequency of occurrence of the first three pathogens did not vary with regard to the hydrotherapy method used. Given the opportunity to redesign, 45% of burn unit directors would implement SCH only, 42% a combination of SCH and IH, 2% exclusively IH, and 11% no hydrotherapy or bedside irrigation only. The prevalence of hydrotherapy use at North American burn centers has decreased since 1990 (83% vs 95%), yet continues to be used at the majority of centers. The use of IH has also declined (55% vs 81%). The trend away from the exclusive use of IH will likely continue, because more centers incorporate showering methods.