Indocyanine Green-Based Fluorescence Imaging to Guide Local Tissue Rearrangement of a Complex Morel-Lavallee Lesion About a Hip: A Technical Trick.

VIDEO AVAILABLE AT: https://ota.org/education/ota-online-resources/video-library-procedures-techniques/icg-based-fluorescence-imaging.

Virtual Surgical Subinternships: Course Objectives and a Proposed Curriculum.

BACKGROUND: Due to the recent COVID-19 pandemic, patient care and medical education have faced many significant changes. The Association of American Medical Colleges and the American Council of Academic Plastic Surgery officially recommended halting all student rotations and interviews for the year. This change has unfortunately fallen squarely at the onset of a vital season for education and recruitment of plastic surgery subinterns. This article presents a curriculum for a single institution's virtual surgical subinternship to help inspire ideas and inspiration for programs developing their own virtual subinternships. METHODS: The goals for the virtual surgical subinternship are focused on student preparation for residency and remain similar to those outlined by the core competencies for in-person rotations. The first virtual subinternship in plastic surgery modeled after the curriculum presented was offered as a 2-week course starting May of 2020. RESULTS: The components of the curriculum include a self-study syllabus, virtual case reviews, virtual suture laboratory, educational teleconferences, participation in research, and mentorship meetings. The 2-week course has approximately 25 hours of conferences and teaching, involving direct interaction with residents and faculty, and approximately 15 hours of self-directed learning. CONCLUSIONS: To the authors' knowledge, this was the first virtual subinternship offered for rising fourth-year medical students. They strongly encourage other residency training programs to offer similar virtual learning opportunities for medical students, particularly for those without access to a home plastic surgery training program. The curriculum presented in this article is simply to provide ideas, inspiration, and a potential framework for programs wishing to create similar virtual learning opportunities.

Subpectoral Implant Repositioning With Partial Capsule Preservation: Treating the Long-Term Complications of Subglandular Breast Augmentation.

BACKGROUND: Patients with long-term complications associated with subglandular breast augmentation are being seen in increasing numbers in the Southern California community. Late deformities include a characteristic "slide-down" deformity as well as capsular contracture, implant wrinkling, and nipple-areola complex enlargement. Repositioning the implant to a subpectoral pocket is a recognized revisionary technique to treat this problem; however, technical details of how this is accomplished are lacking in the literature. OBJECTIVES: To review our technique for treating long-term complications associated with subglandular implants using subpectoral repositioning with partial capsule preservation and mastopexy, without the need for an acellular dermal matrix (ADM) or mesh. METHODS: A retrospective review of all patients undergoing subpectoral repositioning over the course of 6 years was performed. Patient data and long-term outcomes were assessed. A technique is presented utilizing a partial capsulectomy that preserves a portion of the capsule as an ADM/mesh equivalent, ensuring adequate implant coverage and preventing window shading of the pectoralis major muscle. RESULTS: Twenty-four patients with subglandular implants and slide-down deformity as well as other associated complications including capsular contracture, implant wrinkling, and enlarged areolas underwent revision surgery with a subpectoral site change. Often, patients presented many years after their initial augmentation (mean 18 years, range 4-38 years). The average patient follow-up was 3.1 years (range 1.0-6.8 years). Two patients required minor revisions with local anesthetic, while another 2 revisions required general anesthesia. CONCLUSIONS: Long-term deformities associated with subglandular breast augmentation can reliably be corrected by subpectoral repositioning, mastopexy, and utilization of residual breast capsule in the place of an ADM or mesh.

Rectovaginal Fistula Repair 1 Year Later: Lessons Learned.

INTRODUCTION: Rectovaginal (RV) fistulas are notoriously difficult to treat. Various methods for repair exist, and refinements in techniques can lead to "successful" outcomes. Review of the literature demonstrates that outcomes studies are scarce and mostly limited to comments on closure rate. We have experienced "success" in our own series with 100% closure rate, regardless of fistula etiology and comorbidities (radiation, inflammation, etc). However, long-term outcomes, including various complications and quality of life changes, have previously been underreported. METHODS: Critical analysis of various outcomes after fistula repair in 14 patients was performed. Patients were surveyed and interviewed with regard to problems before and after fistula repair to obtain objective data focusing on their experience and outcomes. Conclusions are based on physician assessment and patient surveys 1 year after fistula repair and at least 6 months after ostomy reversal and are discussed within the context of data from the literature. RESULTS: Overall satisfaction rate after repairs was high. All patients would undergo attempt at repair again regardless of complications or functional changes (not present before repair). After repair, sexual dyspareunia affected 5 patients (36%); however, most abstained from sexual activity when their RV fistula became apparent. No patient admitted to dyspareunia before the development of their RV fistula. Anal sphincter and defecation function, as well as stool continence, were judged by surgeons and patients uniformly as adequate. However, 3 patients (21%) complained of intermittent problems with urination. A new/different type of pain affected 2 of 4 patients with Crohn disease. One of these patients subsequently developed a new postsphincteric RV fistula. Another patient noted new intermittent vaginal discharge after ostomy reversal, and magnetic resonance imaging suggested a residual fistula, which was not seen on follow-up sigmoidoscopy and "Blue Dye Test." CONCLUSIONS: We previously reported on algorithms for repair and refinements in techniques for "successful" repair of RV fistulas with zero recurrence rate. Long-term follow-up indicates, however, that although the overall satisfaction rate after surgery is high, true "success," defined as permanent fistula closure, is not necessarily problem free. Long-term morbidity and the management of other unique sequelae and problems are underreported.

Long-Term Outcomes in Complex Abdominal Wall Reconstruction Repaired With Absorbable Biologic Polymer Scaffold (Poly-4-Hydroxybutyrate).

Introduction: After promising early outcomes in the use of absorbable biologic mesh for complex abdominal wall reconstruction, significant criticism has been raised over the longevity of these repairs after its 2-year resorption profile. Methods: This is the long-term (5-year) follow-up analysis of our initial experience with the absorbable polymer scaffold poly-4-hydroxybutyrate (P4HB) mesh compared with a consecutive contiguous group treated with porcine cadaveric mesh for complex abdominal wall reconstructions. Our clinical analysis was performed using Stata 14.2 and Excel 16.16.23. Results: After a 5-year follow-up period, the P4HB group (n = 31) experienced lower rates of reherniation (12.9% vs 38.1%; P = 0.017) compared with the porcine cadaveric mesh group (n = 42). The median interval in months to recurrent herniation was similar between groups (24.3 vs 20.8; P = 0.700). Multivariate logistic regression analysis on long-term outcomes identified smoking (P = 0.004), African American race (P = 0.004), and the use of cadaveric grafts (P = 0.003) as risks for complication while smoking (P = 0.034) and the use of cadaveric grafts (P = 0.014) were identified as risks for recurrence. The long-term cost analysis showed that P4HB had a $10,595 per case costs savings over porcine cadaveric mesh. Conclusions: Our study identified the superior outcomes in clinical performance and a value-based benefit of absorbable biologic P4HB scaffold persisted after the 2-year resorption timeframe. Data analysis also confirmed the use of porcine cadaveric grafts independently contributed to the incidence of complications and recurrences.

Refining Approaches to Surgical Repair of Rectovaginal Fistulas.

INTRODUCTION: Rectovaginal fistulas are notorious for both their morbidity and their difficulty to treat effectively. A variety of methods for repair has been described; however, there is no consensus on the ideal repair. A better understanding of the anatomical relationship of fistulas to the anal sphincter and detrusor muscles is one of the components necessary to develop an effective treatment plan for repair and preservation of sphincter mechanics. METHODS: A review of the literature was conducted to determine the types of methods typically used by reconstructive surgeons for repair of rectovaginal fistulas. A critical clinical analysis of our series of 10 patients was performed to determine optimal strategies for and pitfalls of repair in the context of recent reports in hopes of refining surgical techniques. RESULTS: Detailed anatomical understanding of the relationship of fistulas to the surrounding sphincter muscles is described. Etiology of the fistula and its anatomical relationship to the surrounding sphincter complex is used to help develop an algorithm for repair. Suprasphincteric fistulas will necessitate a laparotomy for repair, intersphincteric fistulas will often require muscle interposition with recreation of the vaginal and rectal walls, and low/transphincteric fistulas will require local flaps mostly for coverage and repair of the sphincter muscles. CONCLUSIONS: Complex rectovaginal fistulas are both debilitating for the patient and extremely difficult to manage. Plastic surgeons are often involved in such cases only after previous attempts at repair have failed. The success of surgery in treating these patients with rectovaginal fistulas depends on a variety of factors. Unfortunately, the available literature describing these repairs lacks uniform guidance regarding approach to repair. Herein, we attempt to detail the possible anatomical variations of fistulas in relationship to the sphincter muscles to begin the discussion necessary for the development of an algorithm for repair that considers preservation of sphincter mechanism function.

The K-Wire Fixation Technique for Endoscopic Brow Lift: A Long-Term Follow-Up.

BACKGROUND: Many techniques have been presented for fixation during endoscopic brow lift, but no singular technique has become dominant. OBJECTIVES: The authors described a technique for fixation for endoscopic brow lift that is inexpensive, easy to use, and versatile and has minimal morbidity. METHODS: The charts of 284 patients who underwent the K-wire fixation technique between December 1996 and September 2018 were reviewed. This technique employs a transcutaneous K-wire to hold the brow in position until tissue adhesion creates a lasting elevation of the brow. RESULTS: A total of 284 patients underwent K-wire fixation for endoscopic brow lifting. Two patients had hematomas and 5 patients (1.8%) required a second unilateral brow lift procedure. Long-term elevation of the brow was maintained in all patients. CONCLUSIONS: K-wire fixation for endoscopic brow lift is a simple, safe, and effective technique for fixation during endoscopic brow lifting that provides long-term aesthetic results.

Treatment of Nasal Aging and Possible Long-term Nasal Enhancement with Fat Using Injectable Tissue Replacement.

This article addresses nasal aging using a minimally invasive procedure with an algorithm that includes the diagnosis of a patient's nose within the context of the individual's facial anatomy. Pyriform augmentation for the elevation of tip projection and columellar strutting with injectable fat are, to our knowledge, applied for the first time as important steps in minimally invasive rhinoplasties. This procedure offers patients with more subtle nasal changes with aging or other causes to be treated with potentially long-lasting improvements, which can be easily retreated. New techniques using injectable liquid cartilage grafts are being explored.

Hemostatic agent use in thyroid surgery: a meta-analysis.

BACKGROUND: The use of hemostatic agents in thyroid surgery has been widely reported in the literature. The aim of this study is to assess the safety and efficacy of hemostatic agents in comparison to conventional techniques for hemostasis by meta-analysis of the current literature. METHODS: Articles were identified from PubMed and EMBASE using the following keyword searches: "hemostatic agent and thyroid surgery" and "hemostatic agent and thyroidectomy". Outcomes included total operative time, estimated blood loss, length of hospital stay, and intraoperative and postoperative complications. Data were extracted following review of appropriate studies by two independent authors and outcome differences were calculated using analysis of variance and the Bonferroni method. RESULTS: Thirty-four publications were identified and 10 studies met our inclusion criteria, totaling 941 patients, 519 (55.1%) of which received a hemostatic agent during thyroid surgery. Of these patients who had hemostatic agents, 369 (71%) received a hemostatic gel and 150 (29%) received an oxidized cellulose patch. Outcome measures in each of these groups were compared with the patients receiving only conventional methods of hemostasis. The risk of hematoma formation in the hemostatic gel group was comparable to conventional hemostatic methods (95% CI: 0.33, 2.59). This was also true when comparing conventional hemostasis to the patch (95% CI: 0.64, 15.24). No difference in the risk for seroma formation was found between the conventional and hemostatic gel groups (95% CI: 0.26, 3.95). Drain output was significantly less in the gel group 40.75±35.6 mL compared to 66.26±31.2 mL in the conventional group (95% CI: -23.422, -7.460). Patients who received hemostatic agents had shorter hospital stays when compared to the conventional group (95% CI: -1.057, -0.203). CONCLUSIONS: Our meta-analysis suggests that the use of a hemostatic agent in thyroid surgery yields minimal advantages for the management of perioperative bleeding risk.

Safety of same-day thyroidectomy: meta-analysis and systematic review.

BACKGROUND: Performance of thyroid surgery as a same day surgery procedure has been a controversial topic. This study aimed to compare the safety and efficacy of outpatient thyroid surgery with inpatient thyroid surgery by meta-analysis of current literature. METHODS: Articles were identified from the following keyword searches: outpatient thyroidectomy/thyroid surgery, same day thyroidectomy/thyroid surgery. Outcomes included perioperative complications including recurrent laryngeal nerve (RLN) injury, hypocalcemia, and readmissions. Data were extracted following review of appropriate studies by authors and random effects models were used. RESULTS: 34 potentially relevant publications were identified and 14 studies fulfilled the predetermined inclusion criteria, totaling 10,478 patients, 4,565 of whom were discharged the same day following thyroid surgery. There was no difference in malignancy rate between the two groups (95% CI, 0.84-2.31; P=0.196). Inpatient group were 2.23 times (95% CI, 1.36-3.36; P=0.001) more likely to develop transient RLN injury and 2.32 times (95% CI, 1.06-5.06; P=0.034) more likely to have documented transient hypocalcemia compared to outpatients. Inpatient groups were 2.10 times (95% CI, 1.33-3.33; P=0.002) more likely to have documented other complications. The two groups also had similar readmission rates (95% CI, 0.71-1.41; P=1.000). CONCLUSIONS: Our meta-analysis suggests that discharging selective patients the same day after a thyroid surgery is as safe, feasible, and efficacious as admitting them for observation. Admitting patients after thyroid surgery is associated with higher reported risk of complications.

Amnion Membrane in Diabetic Foot Wounds: A Meta-analysis.

BACKGROUND: Amniotic membrane is tissue obtained from human placenta rich in cytokines, growth factors, and stem cells that possess the ability to inhibit infection, improve healing, and stimulate regeneration. METHODS: A meta-analysis was performed examining randomized controlled trials comparing amniotic tissue products with standard of care in nonhealing diabetic foot ulcers including PubMed, Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews. RESULTS: A search of 3 databases identified 596 potentially relevant articles. Application of selection criteria led to the selection of 5 randomized controlled trials. The 5 selected randomized controlled trials represented a total of 311 patients. The pooled relative risk of healing with amniotic products compared with control was 2.7496 (2.05725-3.66524, P < 0.001). CONCLUSIONS: The current meta-analysis indicates that the treatment of diabetic foot ulcers with amniotic membrane improves healing rates in diabetic foot ulcers. Further studies are needed to determine whether these products also decrease the incidence of subsequent complications, such as amputation or death, in diabetic patients.

Ethnic and economic disparities effect on management of hyperparathyroidism.

BACKGROUND: Successful parathyroidectomy requires advanced surgeon experience. We aim to examine population characteristics at risk of being managed by low-volume surgeons. METHODS: A cross-sectional study was performed utilizing the Nationwide Inpatient Sample database, 2004 to 2009. The study population included adult inpatients who underwent parathyroidectomy for primary hyperparathyroidism. RESULTS: A total of 3,503 discharge records were included. Men, Hispanics, and those with Medicaid/Medicare health coverage were more likely to be managed by low-volume surgeons (P < .05 each). Low-volume surgeons were more likely to operate in rural (odds ratio [OR], 3.99; 95% confidence interval [CI], 1.95 to 8.16; P < .001) or nonteaching hospitals (OR, 2.15; 95% CI, 1.42 to 3.27; P < .001). Southern region of the United States had a high prevalence of low-volume surgeons compared with other regions (Southern: 51.3%, Northeast: 24.3%, Midwest: 25.6%, and West: 27.6%, P < .001). Operations by the low-volume surgeons associated with a higher risk of postoperative complications (OR, 1.81; 95% CI, 1.11 to 2.97) and a hospital stay more than 2 days (OR, 7.12; 95% CI, 3.75 to 13.45; P < .001). CONCLUSIONS: Certain populations are at risk of management by low-volume surgeons based on their demographic and economic characteristics.

A National Perspective of the Risk, Presentation, and Outcomes of Pediatric Thyroid Cancer.

IMPORTANCE: Thyroid cancer is the most common endocrine malignant neoplasm in children and adolescents. Despite a more advanced presentation of thyroid cancer, younger patients tend to have a more favorable prognosis and a lower mortality rate than adults with thyroid cancer. OBJECTIVE: To examine the presentation and outcomes of thyroid cancer in pediatric patients. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional weighted analysis was performed using data from the Nationwide Inpatient Sample from January 1, 2003, to December 31, 2010. Patient data were derived from a sample of 20% of community hospitals in the United States. Six hundred forty-four children and adolescents (age, <18 years; hereinafter referred to as children) with thyroid cancer were compared with 43 536 adults (age, ≥18 years) with thyroid cancer. Data were analyzed from December 7, 2014, to November 19, 2015. EXPOSURES: Thyroid cancer and thyroidectomy. MAIN OUTCOMES AND MEASURES: Presentation and management characteristics of thyroid cancer and thyroidectomy outcomes in relation to surgeon volume and specialty. RESULTS: A total of 644 cases of pediatric thyroid cancer were included (female, 77.3%; mean [SEM] age, 13.8 [0.2] years), corresponding to a weighted sample of 32 563. Compared with adults with thyroid cancer, children were more likely to present with cervical lymph node involvement (31.5% vs 14.7%; odds ratio [OR], 2.29; 95% CI, 1.76-2.97; P < .001) and lung metastases (5.7% vs 2.2%; OR, 2.79; 95% CI, 1.82-4.28; P < .001), whereas bone metastases were more frequent in adults (0.3% vs 1.1%; OR, 0.23; 95% CI, 0.06-0.90; P = .04). Children were more likely to be treated by a low-volume surgeon (26.9% vs 16.0%; OR, 2.09; 95% CI, 1.26-3.48; P = .005) or a pediatric surgeon (14.5% vs 9.6%; OR, 1.66; 95% CI, 1.04-2.67; P = .04) and in a low-volume hospital (20.5% vs 15.2%; OR, 2.97; 95% CI, 1.60-5.54; P < .001) or a teaching hospital (81.7% vs 63.1%; OR, 3.61; 95% CI, 2.33-5.60; P < .001). Compared with those treated by low-volume surgeons, children treated by high-volume surgeons were less likely to experience postoperative complications (14.3% vs 35.9%; OR, 0.16; 95% CI, 0.05-0.51; P = .002) or a hospital stay of more than 1 day (49.8% vs 67.9%; OR, 0.36; 95% CI, 0.15-0.90; P = .03). Management by pediatric surgeons did not significantly alter the risk for postoperative complications compared with other specialties (21.3% vs 18.5%; OR, 1.71; 95% CI, 0.64-4.53, P = .28). Management of thyroid cancer in children was significantly more costly (>$10 067.08/case) compared with adults (P = .04). CONCLUSIONS AND RELEVANCE: Compared with thyroid cancer in adults, pediatric thyroid cancer is more likely to present as advanced disease and to be managed by low-volume or pediatric surgeons. In addition, within the United States, surgeon volume appears to be more crucial in determining thyroidectomy outcomes than the surgeon's field of specialization.

Is vascular flow a predictor of malignant thyroid nodules? A meta-analysis.

BACKGROUND: Several reports have proposed that increased vascular flow on color Doppler sonography may be associated with malignancy in thyroid nodules. Others have described no correlation between the presence of flow and risk of malignancy. The purpose of this study was to determine whether the vascularity of a thyroid nodule can aid in the prediction of malignancy by performing a meta-analysis of the current literature. METHODS: Independent reviewers conducted a systematic review of publications from PubMed, EMBASE, and the Cochrane Database of Systematic Review using the following keyword searches: "vascular thyroid nodule", and "vascular malignant thyroid nodule". Outcomes included vascular flow pattern, nodule size, calcifications, echogenicity, margins, and shape. Data were extracted following review of appropriate studies, and outcome differences were calculated using analysis of variance and the Bonferroni method. RESULTS: Eighty-nine publications were identified and 14 prospective studies met inclusion criteria totaling 4,154 thyroid nodules, 1,419 (34%) of which were malignant. Thirty-three percent of malignant thyroid nodules had no vascular flow, while 17% had peripheral and 50% had internal vascular flow. There was no significant difference in vascular flow (95% CI: -14.329, 4.257), or peripheral vascular flow rate between malignant and benign thyroid nodules (95% CI: -29.254, 4.313). Also, there was no significant difference in internal vascularity between malignant and benign thyroid nodules (95% CI: -72.067, 2.824). CONCLUSIONS: It appears that utilization of vascular flow on color Doppler sonography may not accurately predict malignancy in thyroid nodules. Further studies are warranted to investigate the predictive role of increased vascularity in diagnosing suspicious thyroid nodules.

Pre-Operative Antisepsis Protocol Compliance and the Effect on Bacterial Load Reduction.

BACKGROUND: Adequate skin preparation is essential to preventing surgical site infection. Many products are available, each with specific manufacturers' directions. This lack of standardization may lead to incorrect use of the agents and affect the bacterial load reduction. We hypothesize that a lack of adherence to utilization protocols for surgical skin antiseptics affects bacterial load reduction. METHODS: Thirty subjects who routinely perform surgical skin preparation were recruited from four hospitals. Participants completed a questionnaire of both demographics and familiarity with two of the most common skin prep formulas: Chlorhexidine gluconate-isopropyl alcohol (CHG-IPA) and povidone-iodine (PVI) scrub and paint. Randomly selecting one formula, subjects performed skin preparation for ankle surgery on a healthy standardized patient. This was repeated using the second formula on the opposite ankle. Performance was recorded and reviewed by two independent evaluators using standardized dichotomous checklists created against the manufacturer's recommended application. Swabs of the patients' first interweb space and medial malleolus were obtained before, 1 min after, and 30 min after prep, and plated on Luria Bertani agar. Bacterial loads were measured in colony forming units (CFUs) for each anatomical site. Data was analyzed using a univariate linear regression. RESULTS: Subjects had an average of 12.7 ± 2.2 y operating room experience and 8.8 ± 1.5 y of skin prep experience. Despite this, no participant performed 100% of the manufacturers' steps correctly. All essential formula-specific steps were performed 90% of the time for CHG-IPA and 33.3% for PVI (p = 0.0001). No correlation was found between experience or familiarity and number of correct steps for either formula. Average reduction in CFUs was not different between CHG-IPA and PVI at 30 min for all anatomical sites (75.2 ± 5.4% vs. 73.7 ± 4.5%, p = 0.7662). Bacterial reductions at 30 min following skin prep were not substantially correlated with operator experience, protocol compliance, or total prep time for either formula. CONCLUSION: This study demonstrates existing problems with infection prevention as those tasked with pre-operative skin preparation do so with tremendous incongruence according to manufacturer guidelines. No effect on bacterial load was identified, however with a larger sample size this may be noted. Standardization of the prep solutions as well as simplification and education of the correct techniques may enhance protocol compliance.

Association of Surgeon Volume With Outcomes and Cost Savings Following Thyroidectomy: A National Forecast.

IMPORTANCE: Incidence of thyroidectomies is continuing to increase. Identifying factors associated with favorable outcomes can lead to cost savings. OBJECTIVE: To assess the association of surgeon volume with clinical outcomes and costs of thyroidectomy. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional analysis performed in October of 2014 of adult (≥ 18 years) inpatients in US community hospitals using the Nationwide Inpatient Sample for the years 2003 through 2009. EXPOSURES: Thyroidectomy. MAIN OUTCOMES AND MEASURES: Complications, length of stay, and cost following thyroidectomy in relation to surgeon volume. Surgeon volumes were stratified into low (1-3 thyroidectomies per year), intermediate (4-29 thyroidectomies per year), and high (≥ 30 thyroidectomies per year). RESULTS: A total of 77,863 patients were included. Procedures performed by low-volume surgeons were associated with a higher risk of postoperative complications compared with high-volume surgeons (15.8% vs 7.7%; OR, 1.55 [95% CI, 1.19-2.03]; P = .001). Mean (SD) hospital cost was significantly associated with surgeon volume (high volume, $6662.69 [$409.31]; intermediate volume, $6912.41 [$137.20]; low volume, $10,396.21 [$345.17]; P < .001). During the study period, if all operations performed by low-volume surgeons had been selectively referred to intermediate- or high-volume surgeons, savings of 11.2% or 12.2%, respectively, would have been incurred. On the basis of the cost growth rate, greater savings are forecasted for high-volume surgeons. With a conservative assumption of 150,000 thyroidectomies per year in the United States, referral of all patients to intermediate- or high-volume surgeons would produce savings of $2.08 billion or $3.11 billion, respectively, over a span of 14 years. CONCLUSIONS AND RELEVANCE: A surgeon's expertise (measured by surgical volume of procedures per year) is associated with favorable clinical as well as financial outcomes. Our model estimates that considerable cost savings are attainable if higher-volume surgeons perform thyroid procedures in the United States.

Melatonin suppression of aerobic glycolysis (Warburg effect), survival signalling and metastasis in human leiomyosarcoma.

Leiomyosarcoma (LMS) represents a highly malignant, rare soft tissue sarcoma with high rates of morbidity and mortality. Previously, we demonstrated that tissue-isolated human LMS xenografts perfused in situ are highly sensitive to the direct anticancer effects of physiological nocturnal blood levels of melatonin which inhibited tumour cell proliferative activity, linoleic acid (LA) uptake and metabolism to 13-hydroxyoctadecadienoic acid (13-HODE). Here, we show the effects of low pharmacological blood concentrations of melatonin following oral ingestion of a melatonin supplement by healthy adult human female subjects on tumour proliferative activity, aerobic glycolysis (Warburg effect) and LA metabolic signalling in tissue-isolated LMS xenografts perfused in situ with this blood. Melatonin markedly suppressed aerobic glycolysis and induced a complete inhibition of tumour LA uptake, 13-HODE release, as well as significant reductions in tumour cAMP levels, DNA content and [(3) H]-thymidine incorporation into DNA. Furthermore, melatonin completely suppressed the phospho-activation of ERK 1/2, AKT, GSK3ß and NF-kB (p65). The addition of S20928, a nonselective melatonin antagonist, reversed these melatonin inhibitory effects. Moreover, in in vitro cell culture studies, physiological concentrations of melatonin repressed cell proliferation and cell invasion. These results demonstrate that nocturnal melatonin directly inhibited tumour growth and invasion of human LMS via suppression of the Warburg effect, LA uptake and other related signalling mechanisms. An understanding of these novel signalling pathway(s) and their association with aerobic glycolysis and LA metabolism in human LMS may lead to new circadian-based therapies for the prevention and treatment of LMS and potentially other mesenchymally derived solid tumours.