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Department/Unit:Otolaryngology

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Impact of Adjuvant Radiotherapy for Malignant Salivary Gland Tumors

Safdieh, Joseph; Givi, Babak; Osborn, Virginia; Lederman, Ariel; Schwartz, David; Schreiber, David
Objective Using the National Cancer Database (NCDB), we investigated the characteristics, outcomes, and benefits of adjuvant therapy for patients diagnosed with malignant salivary gland tumors between 2004 and 2012. Study Design Retrospective analysis. Setting NCDB. Subject and Methods The cases of patients diagnosed with a nonmetastatic major salivary gland tumor who underwent resection between 2004 and 2012 were abstracted from the NCDB. Patients were further included if they had pT1-4NX-1M0 high-grade disease or pT3-4NX-0M0 or pT1-4N1M0 low-grade disease. Patients were identified as having no postoperative radiation therapy or having received postoperative radiation therapy to a dose of 5000 and 7000 cGy to the head and neck region or the parotid region, and their characteristics and outcomes were compared. Results During the study period, 4068 patients met the inclusion criteria for this analysis, of which 2728 (67.1%) received postoperative radiation and 1340 (32.9%) did not. With a median follow-up of 49.1 months, there was a significant improvement in overall survival associated with those receiving postoperative radiation (5 years, 56% vs 50.6%). On multivariable analysis, radiation utilization (hazard ratio, 0.78; 95% CI, 0.71-0.86; P < 0.001) and female sex (hazard ratio, 0.88) were associated with improved survival. When the analysis was limited to patients
PMID: 28675085
ISSN: 1097-6817
CID: 2617242

Enhancing Intervention for Residual Rhotic Errors Via App-Delivered Biofeedback: A Case Study

Byun, Tara McAllister; Campbell, Heather; Carey, Helen; Liang, Wendy; Park, Tae Hong; Svirsky, Mario
Purpose: Recent research suggests that visual-acoustic biofeedback can be an effective treatment for residual speech errors, but adoption remains limited due to barriers including high cost and lack of familiarity with the technology. This case study reports results from the first participant to complete a course of visual-acoustic biofeedback using a not-for-profit iOS app, Speech Therapist's App for /r/ Treatment. Method: App-based biofeedback treatment for rhotic misarticulation was provided in weekly 30-min sessions for 20 weeks. Within-treatment progress was documented using clinician perceptual ratings and acoustic measures. Generalization gains were assessed using acoustic measures of word probes elicited during baseline, treatment, and maintenance sessions. Results: Both clinician ratings and acoustic measures indicated that the participant significantly improved her rhotic production accuracy in trials elicited during treatment sessions. However, these gains did not transfer to generalization probes. Conclusions: This study provides a proof-of-concept demonstration that app-based biofeedback is a viable alternative to costlier dedicated systems. Generalization of gains to contexts without biofeedback remains a challenge that requires further study. App-delivered biofeedback could enable clinician-research partnerships that would strengthen the evidence base while providing enhanced treatment for children with residual rhotic errors. Supplemental Material: https://doi.org/10.23641/asha.5116318.
PMCID:5544407
PMID: 28655050
ISSN: 1558-9102
CID: 2613622

The 50 Most Cited Articles in Facial Plastic Surgery

Chang, Michael T; Schwam, Zachary G; Schutt, Christopher A; Kamen, Emily M; Paskhover, Boris
Bibliometric analysis is a common method to determine the most influential articles in medical specialties, as it is an objective measure of peer recognition of scientific work. This study is the first bibliometric analysis of the literature in facial plastic surgery, to determine the most cited papers in the field. Bibliometric analysis was performed using the Science Citation Index from the Institute for Scientific Information, accessed through the Web of Science. Filter terms relevant to the field of facial plastic surgery were used to identify the 50 most cited journal articles between 1900 and 2016. The median number of citations was 150 (range 116-1091). The articles spanned a wide range of topics in the field, with the most common topics being free flap reconstruction (n = 10), nasal surgery (n = 9), and rhytidectomy (n = 6). The majority of these articles (n = 29) presented findings supported by level IV or V evidence. This analysis provides an overview of the most cited articles in facial plastic surgery, many of which introduced some of the most fundamental principles and techniques in the field. These landmark articles represent important educational points that should be reviewed by all clinicians and trainees in this field. Level of Evidence III 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 .
PMID: 28634701
ISSN: 1432-5241
CID: 2604322

Stem Cell-Mediated Paracrine Signaling Alters Fibroplasia in Human Vocal Fold Fibroblasts in Vitro

Hiwatashi, Nao; Bing, Renjie; Kraja, Iv; Branski, Ryan C
OBJECTIVES: Interactions between mesenchymal stem cells (MSCs) and native vocal fold fibroblasts (VFFs) have not been described in spite of promising preliminary data regarding the effects of MSCs on vocal fold repair in vivo. The current study employed a conditioned media (CM) model to investigate the paracrine effects of bone marrow-derived mesenchymal stem cells (BMSCs) on VFFs. METHODS: Human VFFs were treated with transforming growth factor-beta1 (TGF-beta1; 10 ng/mL), CM from human BMSCs following 48 hours of TGF-beta1 stimulation, or CM+TGF-beta1. Proliferation, immunocytochemistry for alpha smooth muscle actin (alphaSMA), migration, and collagen gel contraction were quantified as well as transcription of components of the TGF-beta signaling pathway. RESULTS: Transforming growth factor-beta1 accelerated proliferation and induced alphaSMA in VFFs; these effects were suppressed with CM ( P = .009, P < .001, respectively). The CM+TGF-beta1 condition increased cell migration ( P = .02) and decreased gel contraction; CM+TGF-beta1 also inhibited TGF-beta signaling via significant upregulation of NR4A1 as well as downregulation of S MAD3 and TGF-beta1 relative to TGF-beta1 stimulation in the absence of CM ( P = .002, P < .001, and P = .005, respectively). CONCLUSIONS: Conditioned media affected many profibrotic cell activities in TGF-beta1-stimulated VFFs, likely related to altered TGF-beta signaling. These data provide preliminary insight regarding the antifibrotic effects of MSCs and further support their progression to clinical utility.
PMID: 28635301
ISSN: 1943-572x
CID: 2604342

Microsurgically assisted inguinal hernia repair and simultaneous male fertility procedures: Rationale, technique and outcomes

Schulster, Michael L; Cohn, Matthew R; Najari, Bobby B; Goldstein, Marc
PURPOSE: Inguinal herniorrhaphy is the most common general surgical procedure. It is associated with frequent complications such as recurrence (1.9% with mesh), post-operative hematoma (4.5%), reduced sensation (0 - 42.8%), chronic post-operative pain (5.1%), vasal injury (0.1 - 0.53%) and infection (3 - 6%)1-5. Drawing on our experience utilizing the operating microscope for varicocelectomy, vasectomy reversal and repair of iatrogenic vasal obstruction from hernia repair, we employed it for inguinal hernia repair. This paper describes the rationale, technique and outcomes of microsurgically assisted inguinal hernia repair. MATERIALS AND METHODS: 291 microsurgically assisted inguinal hernia repairs were performed on 253 men by the same urologist (MG). Simultaneous microsurgical varicocelectomy or other testicular procedures were performed in 83% of cases. All were open repairs through an inguinal incision with the vas deferens, ilioinguinal nerve, genital branch of the genitofemoral nerve and spermatic vasculature identified and preserved. Median follow up was 8.6 months, and outcomes were assessed through examination, pain reporting and pathology reports. RESULTS: Chronic postoperative pain, sensory loss, infection, hematoma, vasal injury and recurrence were assessed. The incidence of hematoma was 0.85%. No hernia recurrences, chronic postoperative pain, sensory loss, infection or vasal injury was reported. CONCLUSIONS: Using an operating microscope, complications of inguinal hernia repair such as vasal obstruction, testicular atrophy, recurrence, infection, hematoma, chronic postoperative pain and loss of sensation are minimized. Microsurgically assisted hernia repair is a promising technique, especially when employed by a urologist performing simultaneous microsurgical varicocelectomy or procedures involving spermatic cord structures or testis.
PMID: 28642060
ISSN: 1527-3792
CID: 2604462

Positron-emission tomography enhancement after vocal fold injection medialization

Grant, Nazaneen; Wong, Richard J; Kraus, Dennis H; Schoder, Heiko; Branski, Ryan C
The potential for the misinterpretation of positron-emission tomography (PET) scans in the context of a possible malignancy has been confirmed in a case report showing increased 18F-fluorodeoxyglucose (FDG) uptake after unilateral vocal fold augmentation medialization. We sought to expand these findings by investigating FDG uptake in a larger cohort of patients via a retrospective chart review. We examined the records of 15 adults-8 men and 7 women-who had undergone vocal fold augmentation for unilateral vocal fold paralysis and at least one subsequent PET scan. The differences in PET standard uptake value (SUV) between the injected and noninjected vocal folds were assessed via the Wilcoxon signed-rank test. A Spearman rank correlation coefficient was then used to estimate the relationship between differences in PET uptake and the length of time between the injection and the follow-up PET scan. The mean SUV of the injected vocal folds was 3.70, and the mean in the noninjected folds was 2.97. The difference did not achieve statistical significance (p = 0.34). In addition, the rank correlation coefficient with regard to the association between the difference in PET uptake and the duration between injection and PET was -0.24, suggesting an inverse relationship. However, the correlation coefficient did not differ significantly from zero (p = 0.34). We conclude that PET uptake after vocal fold augmentation medialization is variable and that it can increase substantially. This information should be considered in the context of the diagnostic accuracy of malignancy on PET.
PMID: 28636732
ISSN: 1942-7522
CID: 2603932

The Sensory Striatum Is Permanently Impaired by Transient Developmental Deprivation

Mowery, Todd M; Penikis, Kristina B; Young, Stephen K; Ferrer, Christopher E; Kotak, Vibhakar C; Sanes, Dan H
Corticostriatal circuits play a fundamental role in regulating many behaviors, and their dysfunction is associated with many neurological disorders. In contrast, sensory disorders, like hearing loss (HL), are commonly linked with processing deficits at or below the level of the auditory cortex (ACx). However, HL can be accompanied by non-sensory deficits, such as learning delays, suggesting the involvement of regions downstream of ACx. Here, we show that transient developmental HL differentially affected the ACx and its downstream target, the sensory striatum. Following HL, both juvenile ACx layer 5 and striatal neurons displayed an excitatory-inhibitory imbalance and lower firing rates. After hearing was restored, adult ACx neurons recovered balanced excitatory-inhibitory synaptic gain and control-like firing rates, but striatal neuron synapses and firing properties did not recover. Thus, a brief period of abnormal cortical activity may induce cellular impairments that persist into adulthood and contribute to neurological disorders that are striatal in origin.
PMCID:5577933
PMID: 28636935
ISSN: 2211-1247
CID: 2603962

Endothelium-Independent Primitive Myxoid Vascularization Creates Invertebrate-Like Channels to Maintain Blood Supply in Optic Gliomas

Snuderl, Matija; Zhang, Guoan; Wu, Pamela; Jennings, Tara S; Shroff, Seema; Ortenzi, Valerio; Jain, Rajan; Cohen, Benjamin; Reidy, Jason J; Dushay, Mitchell S; Wisoff, Jeffrey H; Harter, David H; Karajannis, Matthias A; Fenyo, David; Neubert, Thomas A; Zagzag, David
Optic gliomas are brain tumors characterized by slow growth, progressive loss of vision, and limited therapeutic options. Optic gliomas contain various amounts of myxoid matrix, which can represent most of the tumor mass. We sought to investigate biological function and protein structure of the myxoid matrix in optic gliomas to identify novel therapeutic targets. We reviewed histological features and clinical imaging properties, analyzed vasculature by immunohistochemistry and electron microscopy, and performed liquid chromatography-mass spectrometry on optic gliomas, which varied in the amount of myxoid matrix. We found that although subtypes of optic gliomas are indistinguishable on imaging, the microvascular network of pilomyxoid astrocytoma, a subtype of optic glioma with abundant myxoid matrix, is characterized by the presence of endothelium-free channels in the myxoid matrix. These tumors show normal perfusion by clinical imaging and lack histological evidence of hemorrhage organization or thrombosis. The myxoid matrix is composed predominantly of the proteoglycan versican and its linking protein, a vertebrate hyaluronan and proteoglycan link protein 1. We propose that pediatric optic gliomas can maintain blood supply without endothelial cells by using invertebrate-like channels, which we termed primitive myxoid vascularization. Enzymatic targeting of the proteoglycan versican/hyaluronan and proteoglycan link protein 1 rich myxoid matrix, which is in direct contact with circulating blood, can provide novel therapeutic avenues for optic gliomas of childhood.
PMCID:5530906
PMID: 28606795
ISSN: 1525-2191
CID: 2595022

Five-year outcomes of an oropharynx-directed treatment approach for unknown primary of the head and neck

Hu, Kenneth Shung; Mourad, Waleed Fouad; Gamez, Mauricio E; Lin, Wilson; Jacobson, Adam Saul; Persky, Mark Stephen; Urken, Mark L; Culliney, Bruce E; Li, Zujun; Tran, Theresa Nguyen; Schantz, Stimson Pryor; Chadha, Juskaran; Harrison, Louis Benjamin
PURPOSE: Squamous cell carcinoma of unknown primary (SCCHNUP) is commonly treated with comprehensive radiation to the laryngopharynx and bilateral necks. In 1998, we established a departmental policy to treat SCCHNUP with radiation directed to the oropharynx and bilateral neck. METHODS: From 1998-2011, 60 patients were treated - N1: 18%, N2: 75% and N3: 7%. 82% underwent neck dissection. 55% received IMRT and 62% underwent concurrent chemoradiotherapy. RESULTS: At median follow-up of 54months, 5 patients failed regionally and 4 emerged with a primary (tongue base, hypopharynx and thoracic esophagus). Five-year rates of regional control, primary emergence, distant metastasis, disease-free survival and overall survival were 90%, 10%, 20%, 72% and 79%, respectively. The 5year rate of primary emergence in a non-oropharynx site was 3%. CONCLUSION: This is the first demonstration that an oropharynx-directed approach yields low rates of primary emergence in SCCHNUP with excellent oncologic outcomes.
PMID: 28622886
ISSN: 1879-0593
CID: 2595272

Curcumin and metformin mediated chemoprevention of oral cancer is associated with inhibition of cancer stem cells

Siddappa, Gangotri; Kulsum, Safeena; Ravindra, Doddathimmasandra Ramanjanappa; Kumar, Vinay V; Raju, Nalini; Raghavan, Nisheena; Sudheendra, Holalugunda Vittalamurthy; Sharma, Anupam; Sunny, Sumsum P; Jacob, Tina; Kuruvilla, Binu T; Benny, Merina; Antony, Benny; Seshadri, Mukund; Lakshminarayan, Padma; Hicks, Wesley Jr; Suresh, Amritha; Kuriakose, Moni A
Effective chemoprevention is critical for improving outcomes of oral cancer. As single agents, curcumin and metformin, are reported to exhibit chemopreventive properties, in vitro as well as in patients with oral cancer. In this study, the chemopreventive efficacy of this drug combination was tested in a 4NQO (4-nitro-quinoline-oxide) induced, mice oral carcinogenesis model. Molecular analysis revealed a cancer stem cell (CSC)-driven, oral carcinogenic progression in this model, wherein a progressive increase in the expression of CSC-specific markers (CD44 and CD133) was observed from 8th to 25th week, at transcript (40 to 100 fold) and protein levels (p
PMID: 28618017
ISSN: 1098-2744
CID: 2594302