Citations

OBJECTIVE Malignant peripheral nerve sheath tumors (MPNSTs) of the eighth cranial nerve (CN) are exceedingly rare. To date the literature has focused on MPNSTs occurring after radiation therapy for presumed benign vestibular schwannomas (VSs), while MPNSTs arising without prior irradiation have received little attention. The objectives of the current study are to characterize the epidemiology, clinical presentation, disease course, and outcome using a large national cancer registry database and a systematic review of the English literature. Additionally, a previously unreported case is presented. METHODS The authors conducted an analysis of the Surveillance, Epidemiology, and End Results (SEER) database, a systematic review of the literature, and present a case report. Data from all patients identified in the SEER database with a diagnosis of MPNST involving the eighth CN, without a history of prior radiation, were analyzed. Additionally, all cases reported in the English literature between January 1980 and March 2015 were reviewed. Finally, 1 previously unreported case is presented. RESULTS The SEER registries identified 30 cases between 1992 and 2012. The average incidence was 0.017 per 1 million persons per year (range 0.000–0.0687 per year). The median age at diagnosis was 55 years, and 16 (53%) were women. Thirteen cases were diagnosed upon autopsy. Of the 17 cases diagnosed while alive, the median follow-up was 118 days, with 3 deaths (18%) observed. When compared with the incidence of benign VS, 1041 VSs present for every 1 MPNST arising from the eighth CN. Including a previously unreported case from the authors' center, a systematic review of the English literature yielded 24 reports. The median age at diagnosis was 44 years, 50% were women, and the median tumor size at diagnosis was 3 cm. Eleven patients (46%) reported isolated audiovestibular complaints typical for VS while 13 (54%) exhibited facial paresis or other signs of a more aggressive process. Treatment included microsurgery alone, microsurgery with adjuvant radiation, or microsurgery with chemoradiation. Sixty-one percent of patients receiving treatment experienced recurrence, 22% of which were diagnosed with drop metastases to the spine. Ultimately, 13 patients (54%) died of progressive disease at a median of 3 months following diagnosis. The ability to achieve gross-total resection was the only feature that was associated with improved disease-specific survival. CONCLUSIONS MPNSTs of the eighth CN are extremely rare and portend a poor prognosis. Nearly half of patients initially present with findings consistent with a benign VS, often making an early diagnosis challenging. In light of these data, early radiological and clinical follow-up should be considered in those who elect nonoperative treatment, particularly in patients with a short duration of symptoms or atypical presentation. These data also provide a baseline rate of malignancy that should be considered when estimating the risk of malignant transformation following stereotactic radiosurgery for VS.

This edition of the Video Supplement entitled “Microsurgery of the Third Ventricle, Pineal Region, and Tentorial Incisura” highlights approaches to accessing the third ventricle for surgical resection of a variety of pathologies. The third ventricle has critical neurovascular anatomy that must always be respected to prevent patient harm. Visualization of critical anatomy in three dimensions from a surgeon' line of sight is important when planning the optimum surgical approach. Some of the keys to safely operating in this region include thoughtful head positioning, limitation of brain retraction, and the use of trajectories which capitalize on CSF cisterns and fissures. Some of the videos included in this volume illustrate standard operations while others depict more unique and innovative approaches that take advantage of these surgical windows. We hope you enjoy the videos included in this supplement.

Limited information is available regarding use of the Frazier free water protocol (FWP) with hospitalized patients who have dysphagia and have survived a critical illness with compromised pulmonary status. This pilot study used a two-group nonequivalent comparison group design to evaluate the FWP in 15 adults admitted to a respiratory care unit (RCU) with dysphagia concerns. Inclusion criteria included recommendation for a modified diet with thickened liquids by a dysphagia therapist and ability to follow the specific free water guidelines. The 15 control participants were chosen from a retrospective chart review of consecutive RCU admissions that met the same inclusion criteria. The intervention group for whom the free water guidelines were implemented did not differ significantly from the control group in rate of development of aspiration pneumonia, χ 2 (30) = .01, p = 1.00.

AbstractBACKGROUNDFor many years, basic and clinical researchers have taken advantage of the analytical sensitivity and specificity afforded by mass spectrometry in the measurement of proteins. Clinical laboratories are now beginning to deploy these work flows as well. For assays that use proteolysis to generate peptides for protein quantification and characterization, synthetic stable isotope–labeled internal standard peptides are of central importance. No general recommendations are currently available surrounding the use of peptides in protein mass spectrometric assays.CONTENTThe Clinical Proteomic Tumor Analysis Consortium of the National Cancer Institute has collaborated with clinical laboratorians, peptide manufacturers, metrologists, representatives of the pharmaceutical industry, and other professionals to develop a consensus set of recommendations for peptide procurement, characterization, storage, and handling, as well as approaches to the interpretation of the data generated by mass spectrometric protein assays. Additionally, the importance of carefully characterized reference materials—in particular, peptide standards for the improved concordance of amino acid analysis methods across the industry—is highlighted. The alignment of practices around the use of peptides and the transparency of sample preparation protocols should allow for the harmonization of peptide and protein quantification in research and clinical care.

AbstractBackgroundTransoral robotic surgery (TORS) has been shown to be both feasible and oncologically sound for use in early T classification hypopharyngeal cancers. The purpose of this study was to present our surgical technique for performing a transoral robotic hypopharyngectomy.MethodsA 48‐year‐old man with a T2, N2a, M0 squamous cell carcinoma of the hypopharynx underwent a transoral robotic hypopharyngectomy and a left select neck dissection of levels II to IV.ResultsThe hypopharyngeal tumor was removed en bloc after circumferential cuts were made until the tumor was finally amputated from the apex of the piriform sinus. Negative margins were achieved. A left select neck dissection was performed. The patient was tolerating an oral diet and his tracheostomy tube was decannulated before discharge.ConclusionTORS offers improved manual dexterity and tumor manipulation over conventional transoral approaches to hypopharyngeal cancers. It is both a feasible and effective method for certain early‐stage hypopharyngeal cancers. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2127–E2129, 2016

AbstractPersistent opening of the mitochondrial permeability transition pore (PTP), an inner membrane channel, leads to mitochondrial dysfunction and renders the PTP a therapeutic target for a host of life‐threatening diseases. Herein, we report our effort toward identifying small‐molecule inhibitors of this target through structure–activity relationship optimization studies, which led to the identification of several potent analogues around the N‐phenylbenzamide compound series identified by high‐throughput screening. In particular, compound 4 (3‐(benzyloxy)‐5‐chloro‐N‐(4‐(piperidin‐1‐ylmethyl)phenyl)benzamide) displayed noteworthy inhibitory activity in the mitochondrial swelling assay (EC50=280 nm), poor‐to‐very‐good physicochemical as well as in vitro pharmacokinetic properties, and conferred very high calcium retention capacity to mitochondria. From the data, we believe compound 4 in this series represents a promising lead for the development of PTP inhibitors of pharmacological relevance.