Search

The size and shape of the chin and mandible are fundamental to sexual dimorphism. Deficiencies in these structures distract from the male facial esthetic. When deficient, these areas of the facial skeleton can be augmented by alloplastic augmentation or skeletal rearrangement. This article discusses these alternatives with emphasis on the design and techniques of alloplastic skeletal augmentation.

Background The demand for body contouring surgery continues to rise. The inclusion of the superficial fascial system (SFS) during closure of such procedures has been shown to improve outcomes; however, currently reported wound complication rates remain high. The authors assess whether decreased quantities of SFS are associated with wound complications in these patients. Methods A retrospective study of patients undergoing body contouring surgery was performed. Preoperatively, ultrasound images were obtained of the SFS. Using Cellprofiler, the mean gray values (MGVs) of the SFS were calculated to quantify this structure. Chart review was performed to identify postoperative wound complications. Results Thirty-six patients were included: 30 abdominoplasties, 3 bilateral medial thigh lifts, and 3 bilateral brachioplasties. The overall wound complication rate was 22.5%. There were no significant differences in body mass index, age, smoking status, weight of resected specimen, or diabetes when comparing the complication and noncomplication groups. However, the MGV was significantly greater in the noncomplication group compared with the complication group (0.135 ± 0.008 vs 0.099 ± 0.005, respectively, P = 0.03). The average MGV for the entire cohort was 0.127. Patients with an MGV of greater than 0.127 had a wound complication rate of 0% compared with that of 39% for patients with an MGV of 0.127 or less (P = 0.005). Conclusions Poor quantities of SFS identified by ultrasound were associated with increased wound complications in patients undergoing body contouring surgery. Furthermore, patients with better than average SFS seem to be protected from such complications.

Background The shape of the mandible is the fundamental determinant of the appearance and sexual dimorphism of the lower one-third of the face. Utilization of computer-aided design/computer-aided manufactured (CAD/CAM) alloplastic implants provides unparalleled planning and sophistication in the correction of skeletal deficiencies, irregularities, and asymmetry. Objectives This study presented the rationale, indications, techniques, and results of the senior author’s (M.J.Y.) 15-year experience employing CAD/CAM alloplastic implants to correct deficiencies and asymmetries of the mandible. Methods A retrospective review of a prospectively maintained database was reviewed of all patients who underwent aesthetic augmentation of the mandible employing CAD/CAM alloplastic implants by the senior author. Results Over a 15-year period, 123 patients underwent mandibular augmentation utilizing CAD/CAM alloplastic implants. The majority of patients were men (76.4%) with an average age of 31 years (range, 24-63 years). All implants were bilateral. Complications included infection requiring implant removal (2.4%) and patient dissatisfaction resulting in either implant revision (4.1%) or implant removal (2.4%). Conclusions As described here, CAD/CAM alloplastic implants are an effective modality to augment aesthetic mandible contour deficiencies. Level of Evidence: 4

Background Opioids are a mainstay of pain management. To limit the use of opioids, enhanced recovery after surgery (ERAS) protocols implement multimodal approaches to treat postoperative pain. Objectives The aim of this paper was to be the first to assess the efficacy of an ERAS protocol for plastic surgery outpatients that includes ultrasound-guided, surgeon-led regional blocks. Methods A retrospective review of patients undergoing outpatient plastic surgery on an ERAS protocol was performed. These patients were compared to a well-matched group not on an ERAS protocol (pre-ERAS). Endpoints included the amounts of opioid, antinausea, and antispasmodic medication prescribed. ERAS patients were given a postoperative questionnaire to assess both pain levels (0-10) and opioid consumption. ERAS patients anticipated to have higher levels of pain received ultrasound-guided anesthetic blocks. Results There were 157 patients in the pre-ERAS group and 202 patients in the ERAS group. Patients in the pre-ERAS group were prescribed more opioid (332.3 vs 100.3 morphine milligram equivalents (MME)/patient; P < 0.001), antinausea (664 vs 16.3 mg of promethazine/patient; P < 0.001), and antispasmodic (401.3 vs 31.2 mg of cyclobenzaprine/patient; P < 0.001) medication. Patients on the ERAS protocol consumed an average total of 22.7 MME/patient postoperatively. Average pain scores in this group peaked at 5.32 on postoperative day 1 and then decreased significantly daily. Conclusions Implementation of an ERAS protocol for plastic surgery outpatients with utilization of ultrasound-guided regional anesthetic blocks is feasible and efficacious. The ability to significantly decrease prescribed opioids in this unique patient population is noteworthy. Level of Evidence: 4

Introduction Ubiquitin-like with plant homeodomain and ring finger domains 1 (UHRF1) encodes a master regulator of DNA methylation that has emerged as an epigenetic driver in human cancers. To date, no studies have evaluated UHRF1 expression in malignant pleural mesothelioma (MPM). This study was undertaken to explore the therapeutic potential of targeting UHRF1 in MPM. Methods Microarray, real-time quantitative reverse transcription–polymerase chain reaction, immunoblot, and immunohistochemistry techniques were used to evaluate UHRF1 expression in normal mesothelial cells (NMCs) cultured with or without asbestos, MPM lines, normal pleura, and primary MPM specimens. The impact of UHRF1 expression on MPM patient survival was evaluated using two independent databases. RNA-sequencing, proliferation, invasion, and colony formation assays, and murine xenograft experiments were performed to evaluate gene expression and growth of MPM cells after biochemical or pharmacologic inhibition of UHRF1 expression. Results UHRF1 expression was significantly higher in MPM lines and specimens relative to NMC and normal pleura. Asbestos induced UHRF1 expression in NMC. The overexpression of UHRF1 was associated with decreased overall survival in patients with MPM. UHRF1 knockdown reversed genomewide DNA hypomethylation, and inhibited proliferation, invasion, and clonogenicity of MPM cells, and growth of MPM xenografts. These effects were phenocopied by the repurposed chemotherapeutic agent, mithramycin. Biochemical or pharmacologic up-regulation of p53 significantly reduced UHRF1 expression in MPM cells. RNA-sequencing experiments exhibited the pleiotropic effects of UHRF1 down-regulation and identified novel, clinically relevant biomarkers of UHRF1 expression in MPM. Conclusions UHRF1 is an epigenetic driver in MPM. These findings support the efforts to target UHRF1 expression or activity for mesothelioma therapy.

Background The aim of this study was to prospectively screen patients with a positive family history of carcinoid small intestine neuroendocrine tumors (SI-NETs) to elucidate the benefits of early detection and operative intervention. Methods A single-center, prospective trial was conducted from 2008 to 2014 that evaluated patients with 2 or more blood relatives with carcinoid SI-NETs. All eligible patients were screened with urine/serum biochemistries and various imaging modalities. Operative intervention was elected in patients found to have at least 1 positive diagnostic study. Results Twenty-nine patients from 13 families had occult carcinoid SI-NETs (15 female, 14 male). Twenty-four of the 29 patients (83%) had multifocal disease found in either the distal jejunum or ileum. On average, 75.9 cm (range, 13–195) of bowel was resected in 1 segment. Three patients were found to have stage IV disease at operation. All stage I-IIIB patients who had R0 resections have remained disease-free, with a median follow-up of 35 months. Conclusion Familial carcinoid SI-NETs often are asymptomatic and can be diagnosed with aggressive screening. With early detection, there may be a window of opportunity for operative resection to change the natural history of this disease and even prove to be curative.

Although immunosuppression has been a key component to the success of solid-organ transplantation, the morbidity associated with long-term immunosuppression remains a substantial burden, particularly as recipients of transplants live longer. Indeed, malignancy is one of the most common reasons for mortality following transplantation and the most common of these cancers are cutaneous in origin. Recently, the incidence of these malignancies has been on the rise, partly due to the fact that recipients of these transplants are living longer as a result of improvements in surgical technique, immunosuppression and perioperative management. Although there have been initiatives to increase awareness of cutaneous malignancies following transplantation, such programs are not standardized and there continues to be gaps in skin cancer education and post-operative surveillance. This review provides an update on the epidemiology, risk factors, clinical management, prevention and surveillance of cutaneous malignancies.

Rationale: Whereas asbestos burden has been linked to cytogenetic alterations in malignant pleural mesotheliomas, epigenetic aberrations induced by these fibers have not been fully delineated. Objectives: The objective of this study was to establish an in vitro model to characterize early epigenetic events potentially contributing to malignant pleural mesothelioma. Methods: Normal human mesothelial cells (LP9 and LP3) were cultured with or without crocidolite asbestos fibers (1 or 2 μg/cm(2)) for up to 10 days. Messenger RNA, microRNA, and protein levels were assessed by quantitative reverse transcriptase–polymerase chain reaction and immunoblot techniques. Methylation-specific polymerase chain reaction, pyrosequencing, and quantitative chromatin immunoprecipitation techniques were used to correlate changes in gene expression with epigenetic alterations in the respective promoters. Results: Asbestos mediated time- and dose-dependent repression of Ras association domain–containing protein 1 (RASSF1A), p16 kinase 4a inhibitor (p16INK4a), and p14 alternative reading frame (p14ARF) in normal mesothelial cells; this phenomenon coincided with upregulation of DNA methyltransferase 1 (DNMT1) as well as increased expression of enhancer of zeste homolog 2 (EZH2). Upregulation of EZH2 coincided with repression of microRNA 26A and microRNA 101, which target the 3′ untranslated region of the EZH2 transcript. Silencing of RASSF1A, p16INK4a, and p14ARF coincided with recruitment of EZH2 and concomitant increases in the PRC-2–mediated repressive histone mark, histone H3 lysine 27 trimethylation (H3K27me3), and decreased levels of histone H3 lysine 27 acetylation (H3K27ac3) (histone activation mark) within the respective promoters. Asbestos induced de novo DNA methylation in the promoter of RASSF1A, but not within the INK4a/ARF locus. 5-Aza-2′-deoxycytidine (0–0.5 μM for 72 h) induced dose-dependent activation of RASSF1A (but not p16/p14) in malignant pleural mesothelioma cells; this phenomenon coincided with DNA demethylation and decreased occupancy of DNA methyltransferase 3B within the RASSF1A promoter. Conclusions: Asbestos mediates rapid inactivation of Hippo, Retinoblastoma, and p53 tumor suppressor pathways in normal human mesothelial cells via epigenetic repression of RASSF1A, p16INK4A, and p14ARF, respectively. This in vitro model may prove useful for delineating the sequence of epigenetic events contributing to malignant pleural mesothelioma, and the development of novel strategies for treatment and possible prevention of these neoplasms.

Background Chronic granulomatous disease (CGD) is a rare genetic disorder causing recurrent infections. More than one-quarter of patients develop hepatic abscesses and liver dysfunction. Recent reports suggest that disease-modifying treatment with corticosteroids is effective for these abscesses. Comparison of corticosteroid therapy to traditional invasive treatments has not been performed. Methods Records of 268 patients with CGD treated at the National Institutes of Health from 1980 to 2014 were reviewed. Patients with liver involvement and complete records were included. We recorded residual reactive oxygen intermediate (ROI) production by neutrophils, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase germline mutation status, laboratory values, imaging characteristics, time to repeat hepatic interventions, and overall survival among 3 treatment cohorts: open liver surgery (OS), percutaneous liver-directed interventional radiology therapy (IR), and high-dose corticosteroid management (CM). Results Eighty-eight of 268 patients with CGD suffered liver involvement. Twenty-six patients with a median follow-up of 15.5 years (8.5-32.9 years of follow-up) had complete records and underwent 100 standard interventions (42 IR and 58 OS). Eight patients received a treatment with high-dose corticosteroids only. There were no differences in NADPH genotype, size, or number of abscesses between patients treated with OS, IR, or CM. Time to repeat intervention was extended in OS compared with IR (18.8 vs 9.5 months, P = .04) and further increased in CM alone (median time to recurrence not met). Impaired macrophage and neutrophil function measured by ROI production correlated with shorter time to repeat intervention (r = 0.6, P = .0019). Conclusions Treatment of CGD-associated liver abscesses with corticosteroids was associated with fewer subsequent hepatic interventions and improved outcome compared to invasive treatments.

A major breakthrough in cancer immunotherapy was the discovery of immune checkpoint proteins, which function to effectively inhibit the immune system through various mechanisms. The first of such molecules shown to inhibit both T-cell proliferation and IL-2 production was cytotoxic T-lymphocyte associated protein 4 (CTLA-4). With this discovery, efforts turned to blocking this inhibitory pathway in an attempt to activate dormant T-cells directed at cancer cells. The first antibody directed against CTLA-4, ipilimumab, was quickly ushered into clinical trials and was approved by the US Food and Drug Administration (FDA) for the treatment of metastatic melanoma in 2011. Following the success of ipilimumab, other immune checkpoints were studied as possible targets for inhibition. One such interaction was that of the programmed cell death-1 (PD-1) T-cell receptor and its ligand found on many cancer cells, programmed death-ligand 1 (PD-L1). Unfortunately, the untoward effects of blocking the immune system's natural inhibitory mechanisms have manifested clinically as diarrhea, rash, and hepatitis. Nevertheless, the exciting field of immune checkpoint inhibitors offers a potential curative option for many cancer patients who previously had a more dismal prognosis. The authors aim to provide a comprehensive review of the literature and update on the use of CTLA-4, PD-1 and PD-L1 targeted therapy in the treatment of cancer and other molecules still in the early development phase.

The adoption of minimally invasive approaches to the management of esophageal disease has been slow, except for the laparoscopic management of gastroesophageal reflux disease. However, the advent of new surgical technologies - in particular, robotic-assisted surgical systems - has revolutionized esophageal surgery.The literature was systematically reviewed using the keywords "robotic," "esophageal surgery," "esophagectomy," "fundoplication," and "esophageal myotomy." The reference lists from these articles were then also analyzed.Forty-nine studies were included in our comprehensive review of robotic-assisted esophageal surgery, and they consisted of literature reviews, case reports, retrospective and prospective case series, and randomized controlled trials.Robotic-assisted esophageal surgery is a safe and effective way of treating esophageal disorders, including gastroesophageal reflux disease, achalasia, leiomyomas, and cancer. The use of robotic surgical systems has many benefits for managing disorders of the esophagus, but more studies, including randomized controlled trials, are necessary.

Background Patients presenting with locally advanced, metastatic paraganglioma with life-threatening compressive symptoms of critical anatomic structure pose a significant management challenge. Methods We present a case of a 15-year-old patient with enlarging right neck mass causing dysphagia and respiratory compromise from near complete obstruction of the oropharynx. Results Evaluation of the patient's family history led to the identification of a mutation in the succinate dehydrogenase subunit B (SDSD) gene (G725A). Laboratory and imaging workup revealed an 8.8 × 6.6 × 4.1 cm metabolically and biochemically active right neck mass, a tumor in the left para-aortic region, and multiple bony lesions consistent with widely metastatic disease. Multidisciplinary management included preoperative clinical optimization, coil embolization, and palliative resection of the neck mass. Conclusion Although the currently available treatment options for patients with advanced metastatic paraganglioma render no survival benefit, a multidisciplinary management approach aimed at relief of tumor-related symptoms and catecholamine excess should be undertaken. © 2015 Wiley Periodicals, Inc. Head Neck, 2015

Highlights • Nasopharyngeal mucosal melanoma is a rare pathology with an unclear etiology and oftentimes obscure clinical presentation. • We present a report of a lady who had a complete response to systemic treatment of metastatic melanoma of unknown origin. • Six years later, a diagnosis of primary nasopharyngeal melanoma was made after an extensive work-up for recurrent symptoms of severe right-sided epistaxis and hearing loss. • Surgical resection was performed followed by radiation therapy. The patient has since been without evidence of recurrent or metastatic disease and resolution of bleeding., Introduction Primary nasopharyngeal melanoma is an exceedingly rare pathology with unclear etiology and oftentimes obscure clinical presentation. Despite improved diagnostic capabilities, these lesions are often diagnosed at an advanced stage and associated prognosis is poor, partly due to high rates of recurrences and metastasis. Presentation of case A 74-year-old woman was diagnosed with metastatic melanoma to the liver, of unknown primary. Just prior to the time of diagnosis, she experienced several episodes of severe epistaxis which she managed conservatively. Her symptoms eventually subsided without further medical evaluation. The patient was initially treated with interleukin-2 (IL-2) for her advanced disease, but her cancer progressed. She was then enrolled in a protocol for percutaneous hepatic perfusion (PHP) with melphalan and had complete radiographic resolution of disease, yet her nosebleeds recurred and persisted despite conservative measures. Six years after her initial diagnosis, a nasopharyngoscopy demonstrated a pigmented lesion in the posterior nasopharynx. Surgical resection was performed (pathology consistent with mucosal melanoma) followed by radiation therapy. She has since had complete resolution of bleeding and shows no evidence of cancer. Discussion To our knowledge, this is the first report of a diagnosis of primary nasopharyngeal melanoma 6-years following complete remission of metastatic disease. Surgery remains the primary treatment for disease and symptom control in this setting. Conclusion Timely diagnosis of nasopharyngeal melanomas remains challenging. Thorough clinical evaluations should be performed in such patients, and attention should be paid to recurrent and persistent symptoms, such as epistaxis and hearing loss. This may allow for earlier detection of primary disease.

Tumors of the mediastinum as well as normal thymus glands in patients with myasthenia gravis have traditionally been resected using large and morbid incisions. However, robotic-assisted mediastinal resections are gaining popularity because of the many advantages that the robot provides. However, few comprehensive reviews of the literature on robotic-assisted mediastinal resections exist.A systemic review of the current medical literature was performed, excluding cases related to esophageal pathology. These studies were evaluated and their findings are reported in this comprehensive review. Approximately 48 papers met the inclusion criteria for review.Robotic-assisted surgical systems are increasingly being used in mediastinal resections. Based on the available literature, robotic-assisted thoracoscopic surgery in the mediastinum is feasible and safe. Robotic-assisted mediastinal surgery appears to be superior to open approaches of the mediastinum and is comparable with videothoracoscopic surgery when patient outcomes are considered.Increased robotic experience and more studies, including randomized controlled trials, are needed to validate the findings of the current literature.

A 61-year-old female with a past medical history significant for von Hippel–Lindau (VHL) syndrome presented with multiple bilateral pulmonary lesions found on surveillance computed tomography scan. Positron emission tomography demonstrated avidity in a lesion in the right upper lobe. After an equivocal biopsy, a lobectomy via a thoracoscopic approach was performed as this lesion was concerning for a primary lung cancer. Pathology revealed a diagnosis of pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma. To our knowledge, this is the first reported case of a pulmonary MALT lymphoma in a patient with VHL.

Surgical resection remains the treatment of choice for carotid body tumors (CBTs). Although perioperative complications such as carotid artery injury and neurological deficits occur infrequently, they can be devastating. The aim of this study was to evaluate whether clinical factors or preoperative imaging findings can accurately predict perioperative complications. Twenty CBTs were resected from 19 patients. Preoperative computed tomography (CT) and magnetic resonance imaging (MRI) of the neck were used to measure the degree of circumferential involvement of the CBT to the internal carotid artery (ICA), carotid artery narrowing, tumor length, tumor volume, and the distance from the tip of the C2 dens to the superior aspect of the CBT (dens-CBT). Operative reports and Shamblin classification (I–III) of each tumor were independently reviewed. Preoperative imaging features were compared to perioperative cranial nerve injury (CNI), rates of carotid artery injury, and major carotid artery repairs, as well as Shamblin classifications ≥II. CNI was associated with a high-lying CBT (dens-CBT = 1.8 vs. 2.9 cm, p

Background Development of effective cancer therapies may be limited by intratumoral heterogeneity, which facilitates outgrowth and organ-specific dissemination of treatment resistant clones. At present, limited information is available regarding epigenetic landscapes of pulmonary metastases. This study was undertaken to characterize epigenetic signatures of pulmonary metastases and to identify potential therapeutic targets. Methods RNA and DNA were extracted from 65 pulmonary metastases resected from 12 patients (5 with sarcoma, 7 with adrenocortical carcinoma). Quantitative reverse transcription polymerase chain reaction techniques were used to evaluate expression levels of cancer-testis (CT) genes (NY-ESO-1, MAGE-A3, MAGE-A9, MAGE-A12, GAGE1, CT-45, SSX-1, and SSX-2), tumor suppressor (TS) genes (p16 and RASSF1A), and genes encoding epigenetic modifiers (DNMT1, DNMT3A, DNMT3B, EZH2, EED, and SUZ12), aberrantly expressed in human malignant diseases. Pyrosequencing techniques were used to quantitate DNA methylation levels in LINE1, NBL2, and D4Z4 repetitive sequences and promoter methylation status of differentially regulated genes. Results of these analyses were compared with a standardized panel of normal lung tissues. Results Pulmonary metastases exhibited histologically related and patient-specific global DNA demethylation. Significant interpatient heterogeneity of gene expression was observed even among patients with similar tumor histologic features. Epigenetic signatures appeared consistent among metastases from the same patient, irrespective of the time of resection (synchronous/metachronous) or the anatomic location. EZH2, EED, and SUZ12 (core components of Polycomb repressive complex-2 [PRC-2]) were upregulated in the majority of metastases. Conclusions Pulmonary metastases exhibit patient-specific epigenetic clonality, which may be exploited for precision therapies targeting aberrant CT or TS gene expression. PRC-2 may be a shared target for epigenetic therapy of pulmonary metastases.

Lung cancer is the leading cause of cancer death among both sexes in the United States and non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Over the last several decades, there have been many advances in both surgical approaches and systemic therapies for the treatment of NSCLC, but the prognosis for advanced disease remains poor. New research, however, is exploring the use of targeted therapies for the treatment of NSCLC. The anaplastic lymphoma kinase (ALK) is involved in normal mammalian central nervous system development. A novel fusion gene involving ALK and the echinoderm microtubule-associated protein-like 4 (EML4) gene has been associated with approximately 5% of NSCLCs and is mutually exclusive of other oncogenic driver mutations. Targeted therapies against this ALK rearrangement are a relatively new treatment modality that aims to improve the prognosis of patients with late-stage disease. Two such drugs have Food and Drug Administration (FDA) approval currently: Crizotinib and Ceritinib. Many other ALK inhibitors are currently being studied in clinical trials as well. The authors aim to provide a comprehensive review of ALK inhibitors for use in NSCLC as well as the future directions and challenges to developing these targeted therapies.