Epigenetic aberrations of gene expression in a rat model of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is mostly triggered by environmental and life-style factors and may involve epigenetic aberrations. However, a comprehensive documentation of the link between the dysregulated epigenome, transcriptome, and liver carcinogenesis is lacking. In the present study, Fischer-344 rats were fed a choline-deficient (CDAA, cancer group) or choline-sufficient (CSAA, healthy group) L-amino acid-defined diet. At the end of 52 weeks, transcriptomic alterations in livers of rats with HCC tumours and healthy livers were investigated by RNA sequencing. DNA methylation and gene expression were assessed by pyrosequencing and quantitative reverse-transcription PCR (qRT-PCR), respectively. We discovered 1,848 genes that were significantly differentially expressed in livers of rats with HCC tumours (CDAA) as compared with healthy livers (CSAA). Upregulated genes in the CDAA group were associated with cancer-related functions, whereas macronutrient metabolic processes were enriched by downregulated genes. Changes of highest magnitude were detected in numerous upregulated genes that govern key oncogenic signalling pathways, including Notch, Wnt, Hedgehog, and extracellular matrix degradation. We further detected perturbations in DNA methylating and demethylating enzymes, which was reflected in decreased global DNA methylation and increased global DNA hydroxymethylation. Four selected upregulated candidates, Mmp12, Jag1, Wnt4, and Smo, demonstrated promoter hypomethylation with the most profound decrease in Mmp12. MMP12 was also strongly overexpressed and hypomethylated in human HCC HepG2 cells as compared with primary hepatocytes, which coincided with binding of Ten-eleven translocation 1 (TET1). Our findings provide comprehensive evidence for gene expression changes and dysregulated epigenome in HCC pathogenesis, potentially revealing novel targets for HCC prevention/treatment.

Metabolomics-Based Discovery of Molecular Signatures for Triple Negative Breast Cancer in Asian Female Population.

Triple negative breast cancer (TNBC) is a devastating cancer disease characterized by its poor prognosis, distinct metastatic patterns, and aggressive biological behavior. Research indicates that the prevalence and presentation of TNBC varies among races, with Asian TNBC patients more commonly presenting with large invasive tumors, high node positivity, and high histologic grade. In this work, we applied ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS)-based metabolomics to discover metabolic signatures in Asian female TNBC patients. Serum samples from 31 TNBC patients and 31 healthy controls (CN) were involved in this study. A total of 2860 metabolic features were detected in the serum samples. Among them, 77 metabolites, whose levels were significantly different between TNBC with CN, were confirmed. Using multivariate statistical analysis, literature mining, metabolic network and pathway analysis, we performed an in-depth study of the metabolic alterations in the Asian TNBC population. In addition, we discovered a panel of metabolic signatures that are highly correlated with the 5-year survival rate of the TNBC patients. This metabolomic study provides a better understanding of the metabolic details of TNBC in the Asian population.

Nasal Analysis: Considerations for Ethnic Variation.

As the United States continues to be more ethnically and racially diverse, it is important for the rhinoplasty surgeon to have an appreciation and understanding of nasal variations that exist to plan for and execute ethnically congruent results. The nasal analysis is a critical component of the patient evaluation, which has been used as a tool by surgeons to identify deviations from anatomical norms or canons. In this article, the authors describe common nasal anatomical variations that exist between ethnic groups as a guide for nasal analysis. Understanding these variations will facilitate and help define important cultural aesthetics, which can be used to plan for rhinoplasties in a diverse patient population.

Subcutaneous Migration: A Dynamic Anatomical Study of Gluteal Fat Grafting.

BACKGROUND: Recent anatomical studies have demonstrated that fat placed subjacent to the fascia of the gluteus maximus muscle can migrate deep through the muscle into the submuscular space, possibly causing tears in the gluteal veins, leading to fat embolisms. The purpose of this study was to define and to study subcutaneous migration and to determine whether fat placed in the subcutaneous space under a variety of pressures and fascial integrity scenarios can indeed migrate into the deep submuscular space. METHODS: Four hemibuttocks from two cadavers were used. Proxy fat was inserted using syringes with various fascia scenarios (1: fascia intact; 2: cannula perforations; 3: 6mm fascia defects) or using expansion vibration lipofilling (4: fascia intact). Subcutaneous pressures were recorded. After injections, anatomical dissections were performed to evaluate the migration of the proxy fat for each of the scenarios. RESULTS: Scenario 1: pressure reached approximately 125 to 150 mmHg and then plateaued and all the proxy fat remained in the subcutaneous space. Scenario 2: pressure reached a 199-mmHg plateau and no proxy fat spread deeper into the muscle or beneath it. Scenario 3: pressure gradually rose to 50 mmHg then fell again and the submuscular space contained a significant amount of proxy fat. Scenario 4: pressure rose to a maximum of 30 mmHg and all of the proxy fat remained in the subcutaneous space. CONCLUSIONS: The gluteus maximus fascia is a stout wall that sets up the dangerous condition of deep intramuscular migration with subfascial injections and the protective condition of subcutaneous migration with suprafascial injections. These persuasive findings are profound enough to propose a new standard of care: no subfascial or intramuscular injection should be performed, and all injections should be performed exclusively into the subcutaneous tissue.

Clinical Implications of Gluteal Fat Graft Migration: A Dynamic Anatomical Study.

BACKGROUND: The intraoperative mortality and overall complication rate for gluteal augmentation with fat transplantation is unacceptably high. The current controversy among experts regarding safety is whether fat should be placed within the gluteus muscle or limited to only the subcutaneous space. The purpose of the present study was to test the hypothesis that under certain pressures, fat injected within the gluteal muscle can actually migrate out of the muscle and into a deeper plane containing critical neurovascular structures, by means of the process of deep intramuscular migration. METHODS: A total of eight human cadaver dissections were performed. Four hemibuttocks were selected for intramuscular fat injection. The patterns of subfascial fat migration were evaluated in three of these hemibuttocks by direct visual inspection and in one hemibuttock by endoscopic evaluation. Four other hemibuttocks were selected for subcutaneous or suprafascial fat injection. RESULTS: Proxy fat was found to migrate through the muscle and into the deep submuscular space with each intramuscular injection. With subcutaneous injection, no proxy fat was found during dissection in the intramuscular septae or submuscular space. CONCLUSIONS: The intramuscular insertion of fat, which up to this point has been considered reasonable to perform in the superficial muscle and even recommended in the literature, is now deemed to be an inexact and risky surgical technique. This technique, because of the migratory nature of injected fat, should be avoided from further use in fat transplantation to the gluteal region.

Gluteal Ligamentous Anatomy and Its Implication in Safe Buttock Augmentation.

BACKGROUND: The number of buttock augmentations with fat transfer is steadily increasing, but a number of fatalities caused as a direct result of gluteal fat grafting have been reported. The technical details relating to cannula size, injection angle or trajectory, and plane of injection are critical for avoiding morbidity and mortality. However, the ligamentous anatomy has not been thoroughly explored, particularly how the ligaments are encountered in the clinical setting of fat transfer by means of cannulas. METHODS: The gluteal regions of five fresh cadavers were dissected, for a total of 10 hemidissections. All pertinent cutaneous ligaments in the region were identified. In addition, cannulas were used to simulate typical variations in injection planes. RESULTS: The osseocutaneous and fasciocutaneous ligaments of the buttocks were identified. CONCLUSIONS: The authors describe important ligamentous structures consistently found in the region in cadaveric dissections and discuss the implications while safely performing gluteal augmentation. The anatomical features, boundaries, and soft-tissue attachment points may play a role in cannula-directed fat injection misguidance. The ligaments, when not released, can lead to undesired deep injection and therefore fat lobule migration into the venous system. The density, danger zones, and soft-tissue attachments must be clarified further as we continue to offer our patients improved buttock contour with a higher safety profile.

Refinements in Upper Blepharoplasty: The Five-Step Technique.

Periorbital tissues are a keystone in facial beauty and a representation of youth. The aesthetically pleasing and youthful upper eyelids are full, with a defined tarsal upper lid crease and with smooth, taut pretarsal and preseptal skin. The upper blepharoplasty is a critical component of any facial rejuvenation procedure. This five-step procedure provides key steps in the correction of upper lid age-related changes and provides a reliable and reproducible method of achieving excellent results. Furthermore, the addition of fractionated fat restores volume and youthfulness of the upper lid, and also improves the skin quality of the upper lid.

Gluteal Augmentation and Contouring with Autologous Fat Transfer: Part I.

Gluteal augmentation with autologous fat transfer is an increasingly popular procedure that has the ability to transform a patient's entire body silhouette and gluteal appearance. Proper patient selection, preoperative evaluation, and planning are critical to the success of the procedure. Using the preoperative planning, surgical technique, and postoperative care described, the procedure can be performed safely with powerful and consistent results and avoidance of complications associated with gluteal fat transfer.

Staying Safe during Gluteal Fat Transplantation.

Gluteal augmentation with fat transplantation is increasing in demand but has been associated with a concerning number of fatality reports. Despite these reports, various surgeons have safely performed gluteal fat transplantation on a large number of patients with no reported mortality. The important aspects of safely performing gluteal fat transplantation are reviewed. Proper patient selection, favorable instrumentation, patient positioning, proper technique, and knowledge of anatomy are critical to improving the safety of this procedure. Adherence to these key principles should allow a reduction in mortality from this procedure, which would safely allow its continued offering in the setting of increasingly high demand.

Implications of Facial Asymmetry in Rhinoplasty.

Many rhinoplasty patients present with a chief complaint of nasal deviation and are unaware of any inherent facial asymmetries; however, recognizing and discussing the interrelation between the deviated nose and facial asymmetry is an important consideration in surgical planning. The objective of this study was to evaluate whether a surgeon's subjective assessment of facial analysis in the setting of nasal deviation correlates with objective anthropometric measurements. In addition, this study sought to further quantify the frequency of facial asymmetry associated with nasal deviation to highlight important anatomical trends for the rhinoplasty surgeon. Finally, this study presents the senior author's (R.J.R.) method of addressing a deviated nose on an asymmetric face. In this study, the authors demonstrated that nasal deviation is closely related to facial asymmetry. Furthermore, the authors demonstrated that objective facial analysis closely correlates to anthropometric facial measurements. In addition, the wide side of the face correlates to the short side of the face and the nose tends to deviate away from the wide side of the face. During surgical correction of the deviated nose in the setting of facial asymmetry, the surgeon's goal should be to obtain nasal symmetry and center the nose on a line between the mid glabella and the mid Cupid's bow. This may reduce the perception of a facial asymmetry, leading to increased patient satisfaction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, IV.

Review of 3-dimensional Facial Anatomy: Injecting Fillers and Neuromodulators.

To achieve consistent results utilizing facial injectables, practitioners must understand the pertinent anatomy of the forehead, temple, cheek, nose, and perioral areas. A detailed understanding of facial blood vessels, nerves, and musculature is essential for safe and effective placement of fillers and neuromodulators.

Technical Refinements in Autologous Hand Rejuvenation.

The aging hand is characterized by skin changes and soft-tissue deflation, which leads to rhytides, dermal atrophy, and distinct anatomical structures. Soft-tissue deflation and prominent hand anatomy can be corrected with volume augmentation using dermal fillers or lipofilling. Fat transfer volumizes the hand with prolonged durability and efficacy, autologous tissue replacement, and possible dermal regeneration. The senior author's (R.J.R.) technique for hand rejuvenation is described, which uses minimal access and blunt dissection to effectively augment the soft-tissue compartments of the hand. This approach addresses the prominent aged anatomy of the hand, providing excellent contour and aesthetic outcomes.

Trans-scaphoid Trans-lunotriquetral Perilunate Dislocation in a Patient with a Carpal Coalition.

SUMMARY: Congenital carpal coalitions are rare conditions that arise from a failure or an incomplete cavitation of a common cartilaginous precursor of the carpal bones between the fourth and eighth week of intrauterine life. The incidence of coalitions has been estimated to occur in about 0.1% of the population and up to 1.6% in people of African descent. This study reports a case of trans-scaphoid trans-lunotriquetral perilunate dislocation with a lunotriquetral coalition and successful management with closed reduction, percutaneous fixation, and a thumb spica cast.

Research productivity and gender disparities: a look at academic plastic surgery.

OBJECTIVES: The h-index has utility in examining the contributions of faculty members by quantifying both the amount and the quality of research output and as such is a metric in approximating academic productivity. The objectives of this study were (1) to evaluate the relationship between h-index and academic rank in plastic surgery and (2) to describe the current gender representation in academic plastic surgery to assess whether there are any gender disparities in academic productivity. DESIGN: The h-index was used to evaluate the research contributions of plastic surgeons from academic departments in the United States. RESULTS: There were 426 (84%) men and 79 (16%) women in our sample. Those in higher academic ranks had higher h-index scores (p < 0.0005). There was a significant difference in overall mean h-index by gender, where the mean scores were 9.0 and 6.0 for men and women, respectively (p = 0.0005). When analyzed by academic rank, there was a significant difference in academic productivity between men and women in assistant and associate professor positions (6.4 vs 5.1, respectively; p = 0.04). CONCLUSIONS: The h-index is able to objectively and reliably quantify academic productivity in plastic surgery. We found that h-indices increased with higher academic rank, and men had overall higher scores than their female colleagues. Adoption of this metric as an adjunct to other objective and subjective measures by promotions committees may provide a more reliable measure of research relevance and academic productivity in academic plastic surgery.

Reconstructive algorithm and classification system for transoral oropharyngeal defects.

BACKGROUND: Transoral techniques for oropharyngeal tumors, such as transoral robotic surgery (TORS) and transoral laser microsurgery, require new reconstructive considerations. METHODS: Defects from 92 patients undergoing TORS were classified into 4 classes. A reconstruction algorithm was followed. Perioperative outcomes and complications were assessed. Forty-seven patients completed the MD Anderson Dysphagia Inventory (MDADI) swallowing questionnaire and a modified Velopharyngeal Insufficiency Quality of Life (VPIQL) questionnaire postoperatively. RESULTS: The most common reconstructions involved velopharyngoplasties with local flaps (39%), local flaps alone (25%), or secondary healing (20%). More advanced defects (class III and IV defects) required regional and free flaps more often. No significant differences were found in MDADI scores or VPIQL scores among the 4 defect classes. Only adjuvant radiotherapy was a predictor of poor swallowing (p = .02). CONCLUSION: The classification system for transoral oropharyngeal defects maps defects into 4 classes and guides the reconstructive thought process.

Transoral robotic surgery for the management of oropharyngeal minor salivary gland tumors.

BACKGROUND: In this study we report our preliminary experience with the use of transoral robotic surgery (TORS) for the management of minor salivary gland malignancies of the oropharynx and outcomes. METHODS: This was a retrospective review of 10 patients followed over a 5-year period at a single tertiary academic medical center. Patient, tumor, clinicopathologic, functional, and oncologic outcomes were collected and analyzed. RESULTS: All cancers treated were either T1 (40%) or T2 (60%). Negative margins were achieved in all patients. Four patients received adjuvant radiation therapy (40%). No patients experienced surgical complications and all had excellent functional outcomes. Mean follow-up was 24 months (range, 2-60 months) with locoregional and distant control achieved in 8 patients (80%) and 9 patients (90%), respectively. CONCLUSIONS: Minor salivary malignancies of the oropharynx are a surgical disease. Short-term follow-up data demonstrate feasibility, low morbidity, good functional, and oncologic results for TORS management of these malignancies.