bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of VEGF‐C Gene Polymorphisms and Environmental Factors on Oral Cancer Susceptibility in Taiwan
Authors: Chen Mu‐Kuan 
Published: August 2013

Objectives:Oral cancer, which is the fourth most common male cancer, is associated with environmental carcinogens in Taiwan. Vascular endothelial growth factor (VEGF)‐C, an angiogenic/lymphangiogenic factor with high expression levels in tumor tissues, plays important roles in the development of several malignancies. This study was designed to examine associations of five VEGF‐C gene polymorphisms with the susceptibility to and clinicopathological characteristics of oral squamous cell carcinoma.Methods:Five single‐nucleotide polymorphisms (SNPs) of VEGF‐C were analyzed by a real‐time polymerase chain reaction (PCR) in 470 male patients with oral cancer and 426 cancer‐free controls.Results:In this study, we found that the VEGF‐C rs7664413and rs2046463 polymorphisms were associated with oral‐cancer susceptibility but not with any clinicopathological parameters. The GGACA or GACTG haplotype of five VEGF‐C SNPs (rs3775194, rs11947611, rs1485766, rs7664413, and rs2046463) combined was also related to the risk of oral cancer. Among 611 male smokers, VEGF‐C polymorphism carriers who also chewed betel quid were found to have a 14.5‐24.2‐fold risk of having oral cancer compared to the VEGF‐C wild‐type carrier who did not chew betel quid. Among 461 male betel‐quid chewers, VEGF‐C polymorphism carriers who also smoked had a 2.7‐18.1‐fold risk of having oral cancer compared to those who carried the wild type but did not smoke.Conclusions:Our results suggest that the two SNPs of VEGF‐C (rs7664413andrs2046463) and either of two haplotypes of five SNPs combined have potential predictive significance in oral carcinogenesis. Gene‐environmental interactions among VEGF‐C polymorphisms, smoking, and betel‐quid chewing might alter one's susceptibility to oral cancer.
Personalized Cancer Care for Head and Neck Squamous Cell Carcinoma
Authors: Geltzeiler Mathew N. , Andersen Peter E. , Gross Neil D. , Cantor Emma L. , Berlow Noah , Pal Ranadip , Keller Charles 
Published: August 2013

Objectives:Tumor resistance to single‐agent chemotherapy is ubiquitous, and recurrence after initial therapy remains a therapeutic challenge. The objectives of our study are: 1) Characterize functional therapeutic targets for primary tumor cells from a recurrent head and neck squamous cell carcinoma (SCCa) patient. 2) Determine a personalized drug combination accomplished by mathematical modeling.Methods:A patient with stage IVa floor of mouth SCCa refused surgery and received cytotoxic chemoradiation in 2012. Following progression, the patient underwent radical excision at OHSU. A portion of the specimen was converted to a primary‐cell culture. Tumor cells were screened for functional therapeutic targets with a custom high‐throughput 60‐drug panel of molecularly‐targeted agents. A personalized drug combination was generated using a probabilistic Boolean algorithm which cross‐correlates drug‐screen results with known drugs targets.Results:Twelve drugs decreased tumor cell growth to less than 20% of control. Inhibitors of cyclin‐dependent kinases, proteasomes, Hsp90, vascular endothelial growth factor, and platelet‐derived growth factor receptor had the lowest IC50 values. Dinaciclib was the most potent (absolute IC50 of 4nM). The Boolean algorithm predicted 7 two‐target, synergistic combinations that should result in tumor cell death. An example is ALK inhibition simultaneously with WEE1 or PRCKD. Absolute IC50 for crizotinib (ALK inhibitor) and pelitinib (PRCKD and WEE1 inhibitor) were 1.57uM and 1.43uM, respectively.Conclusions:Molecularly‐targeted drug screening and mathematical modeling may provide a feasible mechanism for choosing combinations of targeted therapies that abrogate tumor cell resistance. Once validated, this treatment paradigm may be a powerful method for guiding therapy when a patient develops resistance to the standard‐of‐care.
Prognostic Factors in Recent Head and Neck Squamous Cell Carcinoma of Unknown Primary Site (HNSCCUP)
Authors: Kobayashi Kenya , Omura Go , Saito Yuki , Ebihara Yasuhiro , Asakage Takahiro , Yamasoba Tatsuya 
Published: August 2013

Objectives:HNSCCUP is heterogeneous and the treatment strategies remain controversial. Recently p16 overexpression may be becoming a good prognostic surrogate marker in oropharyngeal carcinoma. We investigated prognostic factors for HNSCCUP, including p16 status.Methods:Forty patients with HNSCCUP who visited our department from 1996 to 2010 were retrospectively reviewed. The nodal stage was N1, N2, and N3 in 4, 22, and 14 patients, respectively. Neck dissection alone was performed in 19 patients, neck dissection together with adjuvant irradiation in 14 patients, and chemoradiotherapy in 7 patients with unresectable nodes. We immunohistochemically assessed p16 expression in neck metastasis. As prognostic factors, we analyzed N stage, location, extracapsular spread (Ex), primary site, heavy smoking and drinking, and p16 expression.Results:The primary cancer eventually emerged in 15 patients. Eight patients were p16‐positive, among whom oropharynx was the most frequent primary site (P = 0.02). The 3‐year disease‐specific survival (DSS) and overall survival rates were 74% and 65%, respectively. For DDS, N3 (56% vs 84%), level IV V metastasis (50% vs 83%), Ex (59% vs 100%), and heavy smoking and drinking (55% vs 95%) were significant adverse prognostic factors. p16‐negative patients had a low DSS (68% vs 100%), but it was not statistically significant. In multivariate analysis, N3 and Ex had significant correlations with prognosis.Conclusions:p16 overexpression can predict the primary site in the oropharynx and may become a positive prognostic factor. N stage, Ex, location of neck metastasis, smoking and drinking status, and p16 expression should be considered in the treatment for HNSCCUP.
Safety and Quality Considerations in Transoral Surgery for Neoplastic Disease
Authors: Stoddard Timothy R. , Haughey Bruce H. , Holsinger F. Christopher , Nussenbaum Brian , Stadler Michael E. 
Published: August 2013

Objectives:1) Review the importance of quality and patient safety initiatives in surgical care, identifying the specific role that these play in transoral surgical (TOS) procedures. 2) Describe the usefulness of a surgical safety checklist designed for TOS procedures.Methods:Expert opinion, clinical consensus, and a comprehensive literature search were conducted in this project. A systematic review of the literature between 1946 and January 2013 was performed using Pubmed and Medline. Search terms included: quality, patient safety, otolaryngology, head and neck surgery, Surgical checklist, clinical care pathway, transoral laser microsurgery, transoral robotic surgery. Altogether, 200 abstracts were initially reviewed, and 51 studies were selected based on their relevance to the objectives listed above.Results:A comprehensive review of quality and patient safety initiatives in surgical care revealed that clinical care pathways and surgical safety checklists are effective tools in reducing perioperative morbidity, mortality, and cost of care. In otolaryngology‐head and neck surgery, checklists have only been described for endoscopic sinus surgery. A comprehensive, yet usable, surgical quality and safety checklist for TOS procedures was then developed by the authors based on previously successful models from the literature, as well as from expert opinion.Conclusions:Transoral surgery (TOS), including the use of lasers and/or robotics, is an increasingly used and important treatment option for the management of neoplastic diseases of the head and neck. We propose a comprehensive surgical safety checklist that addresses the unique risks and technical requirements of TOS procedures.
Association of Idiopathic Subglottic Stenosis and Body Mass Index
Authors: Lalich Ian J. , Kasperbauer Jan L. , Maldonado Fabien , Ekbom Dale C. , Edell Eric S. 
Published: August 2013

Objectives:1) Describe factors associated with development, disease control, and rate of recurrence in patients with Idiopathic Subglottic Stenosis (ISS). 2) Evaluate the relationship between Body Mass Index (BMI) and ISS.Methods:A retrospective chart review was performed for patients treated at the Mayo Clinic Rochester between 1996 and December 2012. All patients 16 years and older with a clinical diagnosis and/or treatment of ISS were reviewed. Patients with an identifiable etiology for stenosis including trauma, prior neck surgery, previous tracheostomy, multiple intubations (>6 lifetime intubations), prolonged intubation (>1 week), Wegener's Granulomatosis, or an antecedent explanation for their stenosis were excluded. Outcome measurements included symptom free interval, recurrence, and number of procedures performed.Results:Features were collected on 182 female and 4 male patients. At diagnosis, 121 (65%) patients were overweight, and 76 (41%) patients were obese. The mean BMI at first surgery was 28.7 kg/m2. Ninety‐one patients experienced at least one recurrence at a mean of 2.3 years following treatment. Mean number of recurrences, relative to follow‐up interval, for class BMI >30.0 kg/m2 was 1.6 recurrences/year compared with 1.0 recurrences/year for BMI < 30 kg/m2 (P = 0.050). Increasing incidence of the following comorbidities was significantly associated with increases in BMI: heartburn (P = 0.012), gastroesophageal reflux disease (P = 0.011), hypertension (P = <0.001), cardiac history (P = 0.045), hyperlipidemia/dyslipidemia (P = <0.001), and diabetes mellitus (P = 0.004).Conclusions:ISS patients with elevated BMI appear to have an increased risk of recurrent disease. Encouraging lifestyle change and weight reduction may assist in disease control.
Safety Concerns of the CO2 Laser in Traditional and Hand‐Held Modes in Transoral Laser Microsurgery
Authors: Coughlan Carolyn A. , Verma Sunil P. 
Published: August 2013

Objectives:Comparisons between line‐of‐sight and fiber‐optic carbon dioxide (CO2) lasers have not been previously reported in regards to interactions with commonly used products in transoral laser microsurgery. In this study we sought to address this gap.Methods:The beams of a traditional and an Omniguide fiber‐based laser were focused on commonly used materials in transoral laser microsurgery. Three laser resistant endotracheal tubes (ETTs), a standard polyvinylcholoride (PVC) ETT, and cottonoids were evaluated. The time to penetrate through the material was recorded.Results:Neither laser beam completely penetrated any of the laser resistant ETTs within 90s of contact. However, both instantaneously perforated the absorbent coating of the laser resistant tubes, immediately exposing the underlying metal tape. The traditional laser perforated the PVC endotracheal tube at 0s, and the Omniguide laser did so within 3s. The Rusch Lasertubus ETT balloon cuff was the most resistant material to both lasers. Both laser beams perforated dry cottonoids instantaneously but were unable to penetrate excessively saturated cottonoids.Conclusions:In general the time to penetrate materials was longer for a traditional CO2 laser when used at the same power. The absorbent outer coating of all ETTs was easily penetrated with the laser, revealing highly reflective metallic tape. While supersaturated cottonoids were resistant to both lasers, dry pledgets could be penetrated. Of all ETTs tested, the Rusch Lasertubus ETT appears to be the most resistant to both lasers.
Analysis of Immortalized Normal Cell Lines Used in the Characterization of Oral Cancer
Authors: Dickman Christopher T. , Towle Rebecca , Saini Rajan , Garnis Cathie 
Published: August 2013

Objectives:1) Evaluate the molecular profiles of a panel of normal and dysplastic cell lines used in modeling oral cancer initiation and progression. 2) Determine how closely they resemble microdissected tissue of the same type.Methods:Primary cell lines OKP7, OKF4; Immortalized normal cell lines OKF4/TERT‐1, OKF4/E6E7, OKF6/TERT‐1, OKF6/TERT‐2, OKF6/E6E7, OKP7/bmi1/TERT; and dysplastic cell lines DOK and POE9n/TERT were analyzed for DNA copy number variation, mRNA, and miRNA expression. These data were compared to microdisected normal and dysplastic tissue using SMRT v.2 DNA microarrays, Agilent Human Gene Expression 44K microarrays, and Exiqon LNA RT miRNA PCR panels.Results:All but one of the immortalized cell lines contained major alterations in DNA copy number. Clustering analysis showed that mRNA and miRNA expression of the immortalized normal cell lines is distinct from normal tissue and is more similar to the primary and dysplastic cell lines, regardless of the tissues from which they derived, or if and how they have been immortalized. However the expression of tumor suppressors for example p53 was significantly lower in the immortalized cells (p=0.0021), regardless of immortalization method.Conclusions:This experiment provides valuable information for those wishing to use normal or dysplastic oral cell lines. One will need to keep in mind the genomic mutations and the altered expression inherent to these lines when applying the conclusions of studies done on these cell lines.
Clinical Outcome of Negative Rigid Esophagoscopy in Patients with Suspected Foreign Body Ingestion
Authors: Ong Yew Kwang , Lim Audrey , Lim Chwee Ming 
Published: August 2013

Objectives:Identify the reasons and clinical outcome for negative rigid esophagoscopy (NRE) in patients with suspected foreign body (FB) ingestion.Methods:A retrospective chart review was performed on patients with a history of FB ingestion with negative rigid esophagoscopy over a 12‐year period. Patients with suspected FB ingestion underwent rigid esophagoscopy (RE) when they were symptomatic and/or when the radiological investigations revealed suspicious feature(s) of an FB. NRE patients were categorized as 1) passed out FB; 2) false positive indications for RE; or 3) migrated FB. Clinical outcomes were evaluated based on successful FB removal and complications following either FB ingestion or treatment related interventions.Results:89 (12.3%) out of 723 patients who underwent rigid esophagoscopy for suspected FB ingestion had NRE. 61.8% (55/89) had spontaneous FB passage without any complications; 36.0% (32/89) had a false positive indication for RE; and 2.2% (2/89) had migrated FB necessitating neck exploration with successful removal of the offending FB. Abnormal calcifications seen on radiological investigation accounts for 34.4% of these patients having false positive indications for RE, with 2 patients having thoracic exploration to rule out a migrated thoracic esophageal FB.Conclusions:The prevalence of NRE in patients with suspected FB is low (12.3%). However, 36.0% of patients had rigid esophagoscopy performed due to false positive indication, and nearly a third of these patients were primarily due to abnormal calcifications seen on the radiological investigations.
Difficult Airway Simulation for Novice Physicians: A Randomized Trial Comparing Traditional and Video‐Assisted Laryngoscopy
Authors: Ambrosio Art A. , Pfannenstiel Travis J. , Bach Kevin K. , Cornelissen Christopher , Gaconnet Cory , Brigger Matthew T. 
Published: August 2013

Objectives:Detect a difference in intubation success and total intubation times between novice physicians using either a Macintosh laryngoscope or a video‐assisted laryngoscope (Glidescope®) on a difficult airway manikin simulator.Methods:This prospective randomized trial was performed in June 2012. 40 first year residents with less than five total live intubations were recruited. Training was provided by both faculty otolaryngologists and anesthesiologists using both laryngoscope types on a manikin airway simulator in a standard intubation scenario. This was followed by randomization to use one of the aforementioned laryngoscopes in a difficult intubation scenario. The difficult airway simulation entailed oral cavity/oropharyngeal obstruction using tongue inflation, with rigid cervical spine immobilization preventing extension and elevation of the head and limiting oral cavity opening. Success was defined as a confirmed endotracheal intubation by the instructor in 120 seconds or less.Results:The Macintosh laryngoscope group (n=19) had an intubation success rate of 52.63% with a mean intubation time of 69.0 (95% CI: 52.7, 85.2) seconds. The video‐assisted group (n=21) demonstrated a significantly higher success rate of 100% (p<0.0001) and a decreased mean intubation time of 23.1 (95% CI: 18.4, 27.8) seconds (p<0.0001).Conclusions:Novice physicians with little to no prior intubation experience showed significantly higher intubation success with lower intubation times using a video assisted laryngoscope in a difficult airway manikin simulator.
Topiramate for the Management of Vestibular Migraine
Authors: Perez Angel J. , Jardine Dinchen A. , Gille Theresa M. , Conley George S. 
Published: August 2013

Objectives:Vestibular migraine (VM) is considered to be the second most‐common cause of vertigo and the most common cause of spontaneous episodic vertigo. Topiramate has been used effectively for the prevention of migraine headaches, however, there are few quality studies showing its effectiveness for the prophylaxis of VM. We seek to determine the efficacy of topiramate for the treatment of VM.Methods:Retrospective chart review over a 24‐month period (2010‐2012) of patients evaluated at a tertiary neurotology clinic. A coding query was performed to identify potential patients with a diagnosis of VM. Records were reviewed for diagnostic criteria for VM and the use of topiramate as a primary prophylactic treatment. The subjective reduction in the frequency and severity of vertigo attacks was the primary measured outcome.Results:Of 109 patients identified with a diagnosis of vestibular migraine, 30 (27.5%) met the accepted diagnostic criteria for probable vestibular migraine and 22 (20.2%) met criteria for definite vestibular migraine. Nineteen (19) of those patients were treated with topiramate, out of which 13 (68%) reported significant improvement in the frequency or severity of vertigo attacks during a 10 month average follow up. Two patients discontinued topiramate due to side effects despite efficacy. No medication adverse events occurred on these patients.Conclusions:Given its safety and efficacy in classic migraine prophylaxis, topiramate has been proposed as a treatment for VM. Data from this preliminary cohort supports its role in vestibular migraine prophylaxis. Larger, prospective studies are needed to confirm these findings.
Airway Management in Children with Limited Oral Opening
Authors: Meyers Jason A. , Yue Ruixian A. , Sidman James D. 
Published: August 2013

Objectives:1) Describe largest population reported in the literature of children with limited oral opening that does not allow for routine orotracheal intubation with direct laryngoscopy. 2) Analyze incidence and outcome of airway compromise or loss in this population. 3) Identify factors that preclude decannulation in children with limited oral opening.Methods:Retrospective chart review of children who were identified by the Children's Hospitals and Clinics of Minnesota craniofacial team over the last 15 years as having limited oral opening that did not allow for routine orotracheal intubation by direct laryngoscopy.Results:Ten children (mean age 13 years, range 7‐17 years) were identified for inclusion into the study. A total of 109 operations requiring general anesthesia (average of 10.9 per patient, range 0‐23) were performed on patients without a tracheostomy in place. Flexible fiberoptic nasal intubation was performed in 58 cases, 37 by otolaryngology (64%) and 21 by anesthesiology (36%). The remainder of airway control was by mask ventilation (33 cases), various methods of orotracheal intubation (12 cases), and unknown (6 cases). There was a total of 118 patient years without a tracheostomy tube in place (average of 11.8 years per patient). During this period there were no episodes of acute airway compromise that resulted in neurologic deficits.Conclusions:Select children with limited oral opening that does not allow for routine orotracheal intubation with direct laryngoscopy can be safely managed without a tracheostomy, even when the child requires frequent procedures under general anesthesia.
Healing Mechanisms of Human Traumatic Tympanic Membrane Perforations
Authors: Lou Zheng C. 
Published: August 2013

Objectives:Prospectively assess the healing mechanism of human traumatic tympanic membrane perforation (TMP).Methods:The spontaneous healing process of 20 patients with traumatic TMPs was photographed and analyzed.Results:Of the 20 patients with traumatic TMPS, 16 suffered dry perforations and four had wet perforations. Of the 16 dry perforations, in 13 patients, centripetal migrating epithelium was the first layer to close the perforation, followed by the fibrous layer. In 3 of 16 dry perforations, outward epithelial migration was observed on the side of perforation edge. Of the four wet perforations, granulation tissue formation of a fibrous layer was the first layer to close the perforation, after which it was covered by migrating epithelium. Additionally, within 1 week after injury, healing of dry perforations was slow, the estimated percentage not exceeding 30%, while that of wet perforations was significantly faster; the estimated percentages were 60‐95%.Conclusions:The healing mechanism of human traumatic TMPs may be related to the eardrum condition. Centripetal migrating epithelium from the proliferation center plays a crucial role in healing of dry perforations. In contrast, granulation tissue formation from the connective tissue layer plays an important role in healing of wet perforations.
Effect of Onchocerca Volvulus Chitinase on MUC5B Expression in Human Airway Epithelial Cells
Authors: Kim Young‐Dae , Bae Chang‐Hoon , Song Si‐Youn 
Published: August 2013

Objectives:Chitin is an essential structural component of the wall of fungal cells and is present in the exoskeleton of arthropods. It has been generally assumed that mammals lack the ability to produce chitinase proteins, the enzymes responsible for chitin degradation. However, recent studies have demonstrated that mammals produce chitinases and chitinase‐like proteins, and chitinase plays a potential role in human asthma and allergic inflammation. In this study, the effect and brief signaling pathway of chitinase on MUC5B expression were investigated in human airway epithelial cells.Methods:In the mucin‐producing human NCI‐H292 airway epithelial cells and the primary cultures of normal nasal epithelial cells, the effect and signaling pathway of chitinase on MUC5B expression were investigated using the reverse transcriptase‐polymerase chain reaction (RT‐PCR), real‐time PCR, enzyme immunoassay, and immunoblot analysis with several specific inhibitors and small interfering RNA (siRNA).Results:In the mucin‐producing human NCI‐H292 airway epithelial cells, chitinase increased MUC5B expression. Chitinase significantly activated the phosphorylation of p38 MAPK but not the phosphorylation of ERK1/2. SB203580 (p38 MAPK inhibitor) significantly attenuated chitinase‐induced MUC5B mRNA expression, but U0126 (ERK1/2 inhibitor) did not. Knockdown of p38 MAPK by p38 MAPK siRNA significantly blocked chitinase‐induced MUC5B expression. In the primary cultures of normal nasal epithelial cells, chitinase significantly increased MUC5B gene expression, and this was significantly attenuated after pretreatment with SB203580.Conclusions:These results suggest that chitinase induces MUC5B expression by activation of the p38 MAPK signaling pathway in human airway epithelial cells.