Review of treatment strategies after lymphadenectomy: from molecular therapeutics to immediate microsurgical lymphatic reconstruction.

OBJECTIVE: Lymphedema is a common complication of cancer treatment, such as lymphadenectomy and radiation therapy. It is a debilitating condition with pathologic tissue changes that hinder effective curative treatment and jeopardize patients' quality of life. Various attempts to prevent the development of lymphedema have been made, with improvements in the incidence of the pathology. However, it is still prevalent among survivors of cancer. In this paper, we review both molecular therapeutics and immediate surgical lymphatic reconstruction as treatment strategies after lymphadenectomy. Specifically, we discuss pro-lymphangiogenic molecules that have proved efficient in animal models of lymphedema and clinical trials, and review currently available microsurgical techniques of immediate lymphatic reconstruction. METHODS: A literature search was conducted in PubMed, Embase, Cochrane Library, and Google Scholar through May 2022. Searches were done separately for molecular therapeutics and microsurgical techniques for immediate lymphatic reconstruction. Search terms used for (1) non-surgical methods include 'lymphangiogenesis,' 'lymphedema,' 'growth factor,' and 'gene therapy.' Search terms used for (2) surgical methods include 'lymphedema,' 'lymph node excision,' 'lymphatic vessels,' 'primary prevention,' and 'microsurgery.' RESULTS: Various pro-lymphangiogenic factors with therapeutic potential include VEGF-C, VEGF-D, HGF, bFGF, PDGF, IGF, Retinoic acid, Ang-1, S1P, TLR4, and IL-8. Microsurgical lymphatic reconstruction for prevention of secondary lymphedema includes lymphovenous anastomosis, vascularized lymph node flap transfer, and lymph-interpositional flap transfer, with promising clinical outcomes. CONCLUSIONS: With growing knowledge of the lymphangiogenic pathway and lymphedema pathology and advances in microsurgical techniques to restore lymphatic channels, molecular and surgical approaches may represent a promising method for primary prevention of lymphedema.

Determining Accurate Dye Combinations for Sentinel Lymph Node Detection: A Systematic Review.

Background: Lymphatic dyes are commonly used to map the drainage path from tumor to lymphatics, which are biopsied to determine if spread has occurred. A blue dye in combination with technetium-99 is considered the gold standard for mapping, although many other dyes and dye combinations are used. Not all of these substances have the same detection efficacy. Methods: A systematic review of PubMed, SCOPUS, Web of Science, and Medline was performed. The predefined search terms were (indocyanine green OR isosulfan blue OR lymphazurin OR patent blue OR methylene blue OR fluorescein OR technetium-99) AND combination AND dye AND (sentinel lymph node biopsy OR lymphedema OR lymphatics OR lymph OR microsurgery OR cancer OR tumor OR melanoma OR carcinoma OR sarcoma). Results: The initial search returned 4267 articles. From these studies, 37 were selected as candidates that met inclusion criteria. After a full-text review, 34 studies were selected for inclusion. Eighty-nine methods of sentinel lymph node (SLN) detection were trialed using 22 unique dyes, dye combinations, or other tracers. In total, 12,157 SLNs of 12,801 SLNs were identified. Dye accuracy ranged from 100% to 69.8% detection. Five dye combinations had 100% accuracy. Dye combinations were more accurate than single dyes. Conclusions: Combining lymphatic dyes improves SLN detection results. Replacing technetium-99 with ICG may allow for increased access to SLN procedures with comparable results. The ideal SLN tracer is a low-cost molecule with a high affinity for lymphatic vessels due to size and chemical composition, visualization without specialized equipment, and no adverse effects.

Prospective, multicenter study of antimicrobial-coated, noncrosslinked, acellular porcine dermal matrix (XenMatrix™ AB Surgical Graft) for hernia repair in all centers for disease control and prevention wound classes: 24-month follow-up cohort.

Prospective, multicenter, single-arm study of antimicrobial-coated, noncrosslinked, acellular porcine dermal matrix (AC-PDM) in a cohort involving all centers for disease control and prevention wound classes in ventral/incisional midline hernia repair (VIHR). Materials and methods: Seventy-five patients (mean age 58.6±12.7 years; BMI 31.3±4.9 kg/m2) underwent ventral/incisional midline hernia repair with AC-PDM. Surgical site occurrence (SSO) was assessed in the first 45 days post-implantation. Length of stay, return to work, hernia recurrence, reoperation, quality of life, and SSO were assessed at 1, 3, 6, 12, 18, and 24 months. Results: 14.7% of patients experienced SSO requiring intervention within 45 days post-implantation, and 20.0% thereafter (>45 d post-implantation). Recurrence (5.8%), definitely device-related adverse events (4.0%), and reoperation (10.7%) were low at 24 months; all quality-of-life indicators were significantly improved compared to baseline. Conclusion: AC-PDM exhibited favourable results, including infrequent hernia recurrence and definitely device-related adverse events, with reoperation and SSO comparable to other studies, and significantly improved quality of life.

Lymphatic endothelial cell RXRα is critical for 9-cis-retinoic acid-mediated lymphangiogenesis and prevention of secondary lymphedema.

Secondary lymphedema is a debilitating disease characterized by abnormal soft tissue swelling and caused by lymphatic system dysfunction. Despite a high prevalence of secondary lymphedema after cancer treatments, current management is supportive and there are no approved therapeutic agents that can thwart disease progression. We have previously demonstrated that 9-cis-retinoic acid (9-cisRA) has the potential to be repurposed for lymphedema as it mitigates disease by promoting lymphangiogenesis at the site of lymphatic injury. Although the efficacy of 9-cisRA has been demonstrated in previous studies, the mechanism of action is not completely understood. In this study, we demonstrate that when RXRα is specifically deleted in lymphatic endothelial cells, 9-cisRA fails to induce lymphangiogenesis in vitro and prevent pathologic progression of postsurgical lymphedema in vivo. These findings demonstrate that downstream nuclear receptor RXRα plays a critical role in the therapeutic efficacy of 9-cisRA in postsurgical lymphedema.

Use of a bovine pericardial patch angioplasty for completion of a complicated end to side anastomosis of a recipient vessel in the free flap reconstruction of a radiated wound: A case report.

Soft tissue sarcomas treated by extensive surgical resection and adjuvant radiation can lead to large tissue deficits that require free flap repair. Significant radiation can further compromise vessels necessitating novel therapeutic approaches. We describe an 82-year-old man who presented with a posterior thigh sarcoma and underwent wide local tumor resection and immediate reconstruction with a microvascular free flap. Due to radiated recipient vessels, this case required bovine patch angioplasty as a conduit for end to side anastomosis. Initial resection and pathology revealed a large myxofibrosarcoma. Wide local resection and radiotherapy resulted in a large irradiated soft tissue defect of 26 x 15 x 4 cm with exposed, radiation damaged neurovascular structures, and a lack of available regional flap options. The planned free flap, a 30 x 8 cm skin island from the left latissimus dorsi muscle with end-to-side anastomosis to the popliteal artery was complicated by friability of the vessel wall and insufficient perfusion. Given the extent of resection and radiation, there were no alternative recipient vessels present within the field. A bovine pericardial patch angioplasty of 2.5 cm in length was performed to the diseased popliteal vessel and an end to side anastomosis was successfully performed between the thoracodorsal artery and the patch. Improved reperfusion of the free flap was noted immediately following anastomosis indicating completion of the anastomosis of our complicated recipient vessel. During the uncomplicated postoperative course, the flap had good perfusion with Doppler signals present, and incision sites intact at discharge from acute hospitalization. Recurrent sarcomas that have undergone extensive resection and radiotherapy pose significant reconstructive challenges. For defects that require free tissue reconstruction when there are limited options for healthy, recipient vessels, bovine pericardial patch angioplasty may act as a robust conduit for diseased vessels.

Silicone Breast Implant Surface Texture Impacts Gene Expression in Periprosthetic Fibrous Capsules.

BACKGROUND: Silicone breast implants with smooth outer shells are associated with higher rates of capsular contracture, whereas textured implants have been linked to the development of breast implant-associated anaplastic large cell lymphoma. By assessing the gene expression profile of fibrous capsules formed in response to smooth and textured implants, insight into the development of breast implant-associated abnormalities can be gained. METHODS: Miniature smooth or textured silicone implants were surgically inserted into female rats ( n = 10) and harvested for the surrounding capsules at postoperative week 6. RNA sequencing and quantitative polymerase chain reaction were performed to identify genes differentially expressed between smooth and textured capsules. For clinical correlation, the expression of candidate genes was assayed in implant capsules harvested from human patients with and without capsular contracture. RESULTS: Of 18,555 differentially expressed transcripts identified, three candidate genes were selected: matrix metalloproteinase-3 ( MMP3 ), troponin-T3 ( TNNT3 ), and neuregulin-1 ( NRG1 ). In textured capsules, relative gene expression and immunostaining of MMP3 and TNNT3 was up-regulated, whereas NRG1 was down-regulated compared to smooth capsules [mean relative fold change, 8.79 ( P = 0.0059), 4.81 ( P = 0.0056), and 0.40 ( P < 0.0001), respectively]. Immunostaining of human specimens with capsular contracture revealed similar gene expression patterns to those of animal-derived smooth capsules. CONCLUSIONS: An expression pattern of low MMP3 /low TNNT3 /high NRG1 is specifically associated with smooth implant capsules and human implant capsules with capsular contracture. The authors' clinically relevant breast implant rat model provides a strong foundation to further explore the molecular genetics of implant texture and its effect on breast implant-associated abnormalities. CLINICAL RELEVANCE STATEMENT: The authors have demonstrated that there are distinct gene expression profiles in response to smooth versus textured breast implants. Since surface texture may be linked to implant-related pathology, further molecular analysis of periprosthetic capsules may yield strategies to mitigate implant-related complications.

Tissue Expanders in Staged Calvarial Reconstruction: A Systematic Review.

Cranioplasties are common procedures in plastic surgery. The use of tissue expansion (TE) in staged cranioplasties is less common. We present two cases of cranioplasties with TE and systematically review literature describing the use of TE in staged cranioplasties and postoperative outcomes. A systematic review was performed by querying multiple databases. Eligible articles include published case series, retrospective reviews, and systematic reviews that described use of TE for staged bony cranioplasty. Data regarding study size, patient demographics, preoperative characteristics, staged procedure characteristics, and postoperative outcomes were collected. Of 755 identified publications, 26 met inclusion criteria. 85 patients underwent a staged cranioplasty with TE. Average defect size was 122 cm 2 , and 30.9% of patients received a previous reconstruction. Average expansion period was 14.2 weeks. The most common soft tissue closures were performed with skin expansion only (75.3%), free/pedicled flap (20.1%), and skin graft (4.7%). The mean postoperative follow-up time was 23.9 months. Overall infection and local complication rates were 3.53 and 9.41%, respectively. The most common complications were cerebrospinal fluid leak (7.1%), hematoma (7.1%), implant exposure (3.5%), and infection (3.5%). Factors associated with higher complication rates include the following: use of alloplastic calvarial implants and defects of congenital etiology ( p = 0.023 and 0.035, respectively). This is the first comprehensive review to describe current practices and outcomes in staged cranioplasty with TE. Adequate soft tissue coverage contributes to successful cranioplasties and TE can play a safe and effective role in selected cases.

Does plastic surgery need a rewiring? A survey and systematic review on robotic-assisted surgery.

Background: This is a paucity of data regarding plastic surgeons' opinions on robotic-assisted surgery (RAS). We developed a questionnaire aimed to survey plastic surgeons regarding training in robotics, concerns about widespread implementation, and new research directions. Methods: A survey was created using Google Forms and sent to practicing plastic surgeons and trainees. Responses regarding desired conference proceedings about robotics, robotic residency training, and perceived barriers to implementation were elicited. Survey responses were utilized to direct a systematic review on RAS in plastic surgery. Results: The survey received 184 responses (20.4%; 184/900). The majority (92.8%) of respondents were/are plastic surgery residents, with the most common fellowships being microsurgery (39.2%). Overall, 89.7% of respondents support some integration of robotics in the future of plastic surgery, particularly in pelvic/perineum reconstruction (56.4%), abdominal reconstruction (46.5%), microsurgery (43.6%), and supermicrosurgery (44.2%). Many respondents (66.1%) report never using a robot in their careers. Respondents expressed notable barriers to widespread robotic implementation, with cost (73.0%) serving as the greatest obstacle. A total of 10 studies (pelvic/perineum = 3; abdominal = 3; microsurgery = 4) were included after full-text review. Conclusions: Evidence from our survey and review supports the growing interest and utility of RAS within the plastic and reconstructive surgery (PRS) and mirrors the established trend in other surgical subspecialties. Cost analyses will prove critical to implementing RAS within PRS. With validated benefits, plastic surgery programs can begin creating dedicated curricula for RAS.

Piezo1-Regulated Mechanotransduction Controls Flow-Activated Lymphatic Expansion.

BACKGROUND: Mutations in PIEZO1 (Piezo type mechanosensitive ion channel component 1) cause human lymphatic malformations. We have previously uncovered an ORAI1 (ORAI calcium release-activated calcium modulator 1)-mediated mechanotransduction pathway that triggers lymphatic sprouting through Notch downregulation in response to fluid flow. However, the identity of its upstream mechanosensor remains unknown. This study aimed to identify and characterize the molecular sensor that translates the flow-mediated external signal to the Orai1-regulated lymphatic expansion. METHODS: Various mutant mouse models, cellular, biochemical, and molecular biology tools, and a mouse tail lymphedema model were employed to elucidate the role of Piezo1 in flow-induced lymphatic growth and regeneration. RESULTS: Piezo1 was found to be abundantly expressed in lymphatic endothelial cells. Piezo1 knockdown in cultured lymphatic endothelial cells inhibited the laminar flow-induced calcium influx and abrogated the flow-mediated regulation of the Orai1 downstream genes, such as KLF2 (Krüppel-like factor 2), DTX1 (Deltex E3 ubiquitin ligase 1), DTX3L (Deltex E3 ubiquitin ligase 3L,) and NOTCH1 (Notch receptor 1), which are involved in lymphatic sprouting. Conversely, stimulation of Piezo1 activated the Orai1-regulated mechanotransduction in the absence of fluid flow. Piezo1-mediated mechanotransduction was significantly blocked by Orai1 inhibition, establishing the epistatic relationship between Piezo1 and Orai1. Lymphatic-specific conditional Piezo1 knockout largely phenocopied sprouting defects shown in Orai1- or Klf2- knockout lymphatics during embryo development. Postnatal deletion of Piezo1 induced lymphatic regression in adults. Ectopic Dtx3L expression rescued the lymphatic defects caused by Piezo1 knockout, affirming that the Piezo1 promotes lymphatic sprouting through Notch downregulation. Consistently, transgenic Piezo1 expression or pharmacological Piezo1 activation enhanced lymphatic sprouting. Finally, we assessed a potential therapeutic value of Piezo1 activation in lymphatic regeneration and found that a Piezo1 agonist, Yoda1, effectively suppressed postsurgical lymphedema development. CONCLUSIONS: Piezo1 is an upstream mechanosensor for the lymphatic mechanotransduction pathway and regulates lymphatic growth in response to external physical stimuli. Piezo1 activation presents a novel therapeutic opportunity for preventing postsurgical lymphedema. The Piezo1-regulated lymphangiogenesis mechanism offers a molecular basis for Piezo1-associated lymphatic malformation in humans.

Prolymphangiogenic Effects of 9-cis Retinoic Acid Are Enhanced at Sites of Lymphatic Injury and Dependent on Treatment Duration in Experimental Postsurgical Lymphedema.

Background: Patients undergoing surgical treatment for solid tumors are at risk for development of secondary lymphedema due to intraoperative lymphatic vessel injury. The damaged lymphatic vessels fail to adequately regenerate and lymphatic obstruction leads to fluid and protein accumulation in the interstitial space and chronic lymphedema develops as a result. There are currently no effective pharmacological agents that reduce the risk of developing lymphedema or treat pre-existing lymphedema, and management is largely palliative. The present study investigated the efficacy of various 9-cis retinoic acid (9-cis RA) dosing strategies in reducing postsurgical lymphedema by utilizing a well-established mouse tail lymphedema model. Methods and Results: Short-duration treatment with 9-cis RA did not demonstrate a significant reduction in postoperative tail volume, nor an improvement in lymphatic clearance. However, long-term treatment with 9-cis RA resulted in decreased overall tail volume, dermal thickness, and epidermal thickness, with an associated increase in functional lymphatic clearance and lymphatic vessel density, assessed by LYVE-1 immunostaining, compared with control. These effects were seen at the site of lymphatic injury, with no significant changes observed in uninjured sites such as ear skin and the diaphragm. Conclusions: Given the reported results indicating that 9-cis RA is a potent promoter of lymphangiogenesis and improved lymphatic clearance at sites of lymphatic injury, investigation of postoperative 9-cis RA administration to patients at high risk of developing lymphedema may demonstrate positive efficacy and reduced rates of postsurgical lymphedema.

Lymphatic Tissue Bioengineering for the Treatment of Postsurgical Lymphedema.

Lymphedema is characterized by progressive and chronic tissue swelling and inflammation from local accumulation of interstitial fluid due to lymphatic injury or dysfunction. It is a debilitating condition that significantly impacts a patient's quality of life, and has limited treatment options. With better understanding of the molecular mechanisms and pathophysiology of lymphedema and advances in tissue engineering technologies, lymphatic tissue bioengineering and regeneration have emerged as a potential therapeutic option for postsurgical lymphedema. Various strategies involving stem cells, lymphangiogenic factors, bioengineered matrices and mechanical stimuli allow more precisely controlled regeneration of lymphatic tissue at the site of lymphedema without subjecting patients to complications or iatrogenic injuries associated with surgeries. This review provides an overview of current innovative approaches of lymphatic tissue bioengineering that represent a promising treatment option for postsurgical lymphedema.

Urinary Bladder Matrix Improves Irradiated Wound Healing in a Murine Model.

ABSTRACT: Radiation skin damage is associated with chronic wounds and poor healing. Existing localized treatment modalities have limited benefit. Therefore, there has been increased interest in biologically based solutions. In this study, we aimed to determine the effect of topical urinary bladder matrix (UBM) on chronic irradiated skin wounds using an established murine model. Our findings demonstrated that topical urinary bladder matrix significantly accelerated the healing of irradiated wounds on day 7 (P = 0.0216), day 14 (P = 0.0140), and day 21 (P = 0.0393). Histologically, urinary bladder matrix treatment was associated with higher-quality reorganization and reepithelialization of wounds, an increased density of myofibroblasts (P = 0.0004), and increased collagen deposition (P < 0.0001). In addition, quantitative real-time polymerase chain reaction data demonstrated decreased expression of profibrotic mediators (P = 0.0049). We conclude that urinary bladder matrix may be a useful, noninvasive, adjunctive therapy for the treatment of chronic irradiated skin wounds.

Reconstructive Surgeons as Essential Operative Consultants: Quantifying the True Value of Plastic Surgeons to an Academic Medical Center.

BACKGROUND: The revenue generated by plastic surgeons assisting other surgical services is poorly captured by hospital accounting systems, which categorize solely by attending physician of record. The financial impact of reconstructive surgery is thus systematically underestimated. The authors sought to quantify the overlooked value of plastic surgeons as consultants who facilitate complex and profitable operations. METHODS: Hospital billing data were reviewed for inpatient operations over a 3-year fiscal period (2015 to 2017). Cases in which a plastic surgeon assisted were identified. Case mix index, a measure of complexity that correlates with profit, and contribution margin, defined as revenue minus cost, were obtained for each case. RESULTS: Five hundred fifty-four cases required a reconstructive surgeon; 18,904 nonconsultation cases were identified for comparison. Average net revenue per case involving a consultation was 1.79 times greater than for control cases (p < 0.0001). Average contribution margin was 1.73 times greater (p < 0.005). The highest contribution margins stemmed from joint cases with cardiothoracic surgery and neurosurgery. Case mix index was significantly higher for consultation cases than for controls (4.5 versus 3.9; p < 0.0001). In 434 cases (78 percent), plastic surgery assisted with an integral aspect of the operation, meaning the surgery could not have been technically performed without reconstructive assistance. CONCLUSIONS: The authors' findings demonstrate that cases involving plastic surgeons have a higher profit margin than those performed by any department alone. However, this revenue is not appropriately attributed because of oversimplified financial metrics. The skill set of reconstructive surgeons is an undervalued resource for both patient care and hospital economics.

Current Understanding of Pathological Mechanisms of Lymphedema.

Significance: Lymphedema is a common disease that affects hundreds of millions of people worldwide with significant financial and social burdens. Despite increasing prevalence and associated morbidities, the mainstay treatment of lymphedema is largely palliative without an effective cure due to incomplete understanding of the disease. Recent Advances: Recent studies have described key histological and pathological processes that contribute to the progression of lymphedema, including lymphatic stasis, inflammation, adipose tissue deposition, and fibrosis. This review aims to highlight cellular and molecular mechanisms involved in each of these pathological processes. Critical Issues: Despite recent advances in the understanding of the pathophysiology of lymphedema, cellular and molecular mechanisms underlying the disease remains elusive due to its complex nature. Future Directions: Additional research is needed to gain a better insight into the cellular and molecular mechanisms underlying the pathophysiology of lymphedema, which will guide the development of therapeutic strategies that target specific pathology of the disease.

Current Advancements in Animal Models of Postsurgical Lymphedema: A Systematic Review.

Significance: Secondary lymphedema is a debilitating disease caused by lymphatic dysfunction characterized by chronic swelling, dysregulated inflammation, disfigurement, and compromised wound healing. Since there is no effective cure, animal model systems that support basic science research into the mechanisms of secondary lymphedema are critical to advancing the field. Recent Advances: Over the last decade, lymphatic research has led to the improvement of existing animal lymphedema models and the establishment of new models. Although an ideal model does not exist, it is important to consider the strengths and limitations of currently available options. In a systematic review adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we present recent developments in the field of animal lymphedema models and provide a concise comparison of ease, cost, reliability, and clinical translatability. Critical Issues: The incidence of secondary lymphedema is increasing, and there is no gold standard of treatment or cure for secondary lymphedema. Future Directions: As we iterate and create animal models that more closely characterize human lymphedema, we can achieve a deeper understanding of the pathophysiology and potentially develop effective therapeutics for patients.

From Bench to Bedside: The Role of a Multidisciplinary Approach to Treating Patients with Lymphedema.

Background: Lymphedema is a condition characterized by dysfunction of the lymphatic system resulting in chronic, progressive soft tissue edema that can negatively impact individuals' function, self-image, and quality of life. Understanding of the disease process has evolved significantly in the past two decades with advances in diagnostic modalities and surgical techniques revolutionizing prior treatment algorithms. Methods and Results: We reviewed our current approach at the University of Southern California to improving outcomes in lymphedema treatment. Given the complexity of this medical condition, patients are best served by a multidisciplinary approach. At our institution, this involves a collaborative effort between bench researchers, lymphatic therapists, medical physicians, and lymphedema surgeons. Basic science and translational research provide further understanding into the underlying mechanisms of lymphangiogenesis and the possibility for potential therapeutic interventions. Our surgical algorithms require patients to undergo a thorough diagnostic evaluation and consultation with certified lymphatic therapists prior to undergoing either physiologic or debulking operations. Patients are followed clinically following any interventions. Further community outreach and education is carried out in order to improve upon early diagnosis and symptom recognition. Conclusions: Optimizing lymphedema care requires a collaborative interplay between researchers, physicians, and therapists. Additionally, patient and provider education on early disease recognition and treatment options is an equally critical aspect of improving patient outcomes.

A Survey of Current Preferences of Plastic Surgeons Regarding the Assessment and Reduction of Preoperative Patient Anxiety.

BACKGROUND: Preoperative anxiety is a common phenomenon in plastic surgery that has been associated with numerous negative patient outcomes. Little is known about the preferences of plastic surgeons regarding management of patient preoperative anxiety OBJECTIVE: To determine the preferences of plastic surgeons regarding the assessment and reduction of adult preoperative patient anxiety in their primary practice setting. METHODS: The membership of the American Council of Academic Plastic Surgeons (ACAPS) was surveyed using an anonymous, online questionnaire from April to June of 2020. RESULTS: A total of 100 participants from a membership of 532 responded (19%). The majority of respondents (63%) did not formally assess patient anxiety but supported the use of standardized scales to measure anxiety (57%). Most plastic surgeons preferred patient education (81%), family member presence (69%), and visit from the anesthesiologist (54%) to reduce patient anxiety. Plastic surgeons also allocated the most responsibility to anesthesiologists (63%) and plastic surgeons (62%) to reduce preoperative anxiety. DISCUSSION: Most plastic surgeon members of ACAPS did not assess their patients' anxieties preoperatively but appeared willing to use anxiety scales. Plastic surgeons also supported several measures to reduce anxiety, especially patient education, family member preferences, and anesthesiologist visits. Although plastic surgeons appeared to hold multiple parties responsible to manage preoperative anxiety, they held themselves and anesthesiologists most responsible. Future studies are needed to determine whether these views cohere with those of other healthcare providers and whether these preferences change for pediatric patients. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Risk Factors for Wound Complications After Soft Tissue Sarcoma Resection.

ABSTRACT: Soft tissue sarcomas are a heterogenous group of malignant tumors that represent approximately 1% of adult malignancies. Although these tumors occur throughout the body, the majority involved the lower extremity. Management may involve amputation but more commonly often includes wide local resection by an oncologic surgeon and involvement of a plastic surgeon for reconstruction of larger and more complex defects. Postoperative wound complications are challenging for the surgeon and patient but also impact management of adjuvant chemotherapy and radiation therapy. To explore risk factors for wound complications, we reviewed our single-institution experience of lower-extremity soft tissue sarcomas from April 2009 to September 2016. We identified 127 patients for retrospective review and analysis. The proportion of patients with wound complications in the cohort was 43.3%. Most notably, compared with patients without wound complications, patients with wound complications had a higher proportion of immediate reconstruction (34.5% vs 15.3%; P = 0.05) and a marginally higher proportion who received neoadjuvant radiation (30.9% vs 16.7%; P = 0.06).

Role of stem cell therapies in treating chronic wounds: A systematic review.

BACKGROUND: The impairment of cutaneous wound healing results in chronic, non-healing wounds that are caused by altered wound environment oxygenation, tissue injury, and permissive microbial growth. Current modalities for the treatment of these wounds inadequately address the complex changes involved in chronic wound pathogenesis. Consequently, stem cell therapies have emerged as a potential therapeutic modality to promote cutaneous regeneration through trophic and paracrine activity. AIM: To investigate current literature regarding use of stem cell therapies for the clinical treatment of chronic, non-healing wounds. METHODS: PubMed, EMBASE, Cochrane Library, Web of Science, and Scopus were queried with combinations of the search terms "mesenchymal stem cells," "adult stem cells," "embryonic stem cells," "erythroid precursor cells," "stem cell therapies," and "chronic wounds" in order to find relevant articles published between the years of 2000 and 2019 to review a 20-year experience. Reference lists from the articles were reviewed to identify additional pertinent articles. Retrieved manuscripts (reviews, case reports/series, retrospective/prospective studies, and clinical trials) were evaluated by the authors for their depiction of clinical stem cell therapy use. Data were extracted from the articles using a standardized collection tool. RESULTS: A total of 43 articles describing the use of stem cell therapies for the treatment of chronic wounds were included in this review. While stem cell therapies have been explored in in vitro and in vivo applications in the past, recent efforts are geared towards assessing their clinical role. A review of the literature revealed that adipose-derived stem cells, bone marrow-derived stem cells, bone marrow-derived mononuclear cells, epidermally-derived mesenchymal stem cells, fibroblast stem cells, keratinocyte stem cells, placental mesenchymal stem cells, and umbilical cord mesenchymal stem cells have all been employed in the treatment of chronic wounds of various etiologies. Most recently, embryonic stem cells have emerged as a novel stem cell therapy with the capacity for multifaceted germ cell layer differentiation. With the capacity for self-renewal and differentiation, stem cells can enrich existing cell populations in chronic wounds in order to overcome barriers impeding the progression of wound healing. Further, stem cell therapies can be utilized to augment cell engraftment, signaling and activity, and resultant patient outcomes. CONCLUSION: Assessing observed clinical outcomes, potential for stem cell use, and relevant therapeutic challenges allows wound care stakeholders to make informed decisions regarding optimal treatment approaches for their patients' chronic wounds.

Patient Characteristics Associated with Free Nipple Graft Reduction Mammoplasty.

PURPOSE: Surgical approaches for reduction mammoplasty most commonly incorporate a parenchymal vascular pedicle. For patients with larger breasts where pedicle viability may be compromised due to excessive length, the free nipple graft (FNG) technique provides a safe alternative. Criteria for whether a patient should undergo a FNG remains controversial due to variable reports in the literature with small sample sizes and inherent surgeon-dependent bias. To address this, we sought to investigate perioperative factors associated with performing FNGs at our institution in order to better elucidate specific indications for this surgery. METHODS: A retrospective chart review was performed for 323 patients who underwent a reduction mammoplasty from August 2009 to July 2019 at Keck Hospital and LAC+USC Medical Center. Data regarding patient demographics, comorbidities, pre-operative breast characteristics, and post-operative complications were extracted. Student's t-test, Fisher's exact test, and logistic regression were performed in R. RESULTS: Of 323 patients, 15 received an FNG. Independent variables analyzed included: age, body mass index (BMI), obesity, smoking, diabetes, hypertension, surgical indication, sternal notch-to-nipple length, nipple-to-inframammary fold length, and weight of breast specimens removed. BMI, obesity, gigantomastia, and weight of specimen resected were significantly associated with use of the FNG (p < 0.001, p < 0.05, p < 0.0001, p < 0.0001, respectively). Regression analysis revealed that patients who had an average of more than 1500 g of tissue removed from each breast were 1.41 (95% CI: 1.17-1.71, p<0.001) times more likely to undergo an FNG procedure than those who had less than 1500 g of tissue removed. Demographic data and breast characteristics, such as notch-to-nipple length and nipple-to-inframammary fold length, were not significantly associated. CONCLUSION: Total weight of the breast specimens removed and BMI were significantly associated with the FNG technique. Removing more than 1500 g gof total breast tissue was also significantly correlated. These findings may guide surgeons during the decision-making process of when to use an FNG.