BioMed Research International: Otolaryngology The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Microarray Analysis of Serum mRNA in Patients with Head and Neck Squamous Cell Carcinoma at Whole-Genome Scale Wed, 23 Apr 2014 12:26:03 +0000 With the increasing demand for noninvasive approaches in monitoring head and neck cancer, circulating nucleic acids have been shown to be a promising tool. We focused on the global transcriptome of serum samples of head and neck squamous cell carcinoma (HNSCC) patients in comparison with healthy individuals. We compared gene expression patterns of 36 samples. Twenty-four participants including 16 HNSCC patients (from 12 patients we obtained blood samples 1 year posttreatment) and 8 control subjects were recruited. The Illumina HumanWG-6 v3 Expression BeadChip was used to profile and identify the differences in serum mRNA transcriptomes. We found 159 genes to be significantly changed (Storey’s value ) between normal and cancer serum specimens regardless of factors including p53 and B-cell lymphoma family members (Bcl-2, Bcl-XL). In contrast, there was no difference in gene expression between samples obtained before and after surgery in cancer patients. We suggest that microarray analysis of serum cRNA in patients with HNSCC should be suitable for refinement of early stage diagnosis of disease that can be important for development of new personalized strategies in diagnosis and treatment of tumours but is not suitable for monitoring further development of disease. Markéta Čapková, Jana Šáchová, Hynek Strnad, Michal Kolář, Miluše Hroudová, Martin Chovanec, Zdeněk Čada, Martin Šteffl, Jaroslav Valach, Jan Kastner, Čestmír Vlček, Karel Smetana Jr., and Jan Plzák Copyright © 2014 Markéta Čapková et al. All rights reserved. High Level of Tregs Is a Positive Prognostic Marker in Patients with HPV-Positive Oral and Oropharyngeal Squamous Cell Carcinomas Wed, 23 Apr 2014 07:44:25 +0000 Background. Human papillomaviruses (HPVs) have been proved as one of the etiological factors of oropharyngeal squamous cell carcinoma (OPSCC). Patients with tumors of viral etiology have a lower recurrence rate and better prognosis. OPSCC is linked to an alteration in the immune system. Only a limited number of studies have correlated both the immunological parameters and HPV status with patient prognosis. The aim of this study was to determine whether HPV infection and the immunological status influence patient prognosis individually or in concurrence. Material and Methods. Sixty patients with oral and oropharyngeal carcinomas were enrolled. They were divided into HPV-positive and HPV-negative groups based on the expression of HPV 16 E6 mRNA. Basic lymphocyte subpopulations were determined in the peripheral blood by means of flow cytometry. Results. Significantly better disease-specific survival (DSS) was observed in patients with HPV-positive tumors. Nodal status, tumor grade, recurrence, and CD8+/Tregs ratio were identified as factors influencing DSS. A higher level of Tregs and a lower ratio of CD8/Tregs influenced overall survival (OS) independently of HPV status and age. Patients with HPV-positive tumors and high levels of Tregs survived significantly better than patients from the other groups. Conclusion. Better survival is associated with HPV positivity and elevated Tregs levels. Our data suggest that HPV infection and Tregs do not influence patient prognosis in concurrence. E. Lukesova, J. Boucek, E. Rotnaglova, M. Salakova, E. Koslabova, M. Grega, T. Eckschlager, B. Rihova, B. Prochazka, J. Klozar, and R. Tachezy Copyright © 2014 E. Lukesova et al. All rights reserved. Bipolar Thermofusion BiClamp 150 in Thyroidectomy: A Review of 1156 Operations Wed, 16 Apr 2014 12:59:34 +0000 Objectives. To compare the bipolar thermofusion BiClamp 150 with conventional ligature techniques for thyroid gland surgery, and report the advantages/disadvantages of both techniques. Methods. In this retrospective comparative study, all thyroid gland operations performed in the ENT Clinic Faculty Hospital Ostrava from 2006 to 2013 were included (1156 operations, 2122 lobes). Patients were categorized into two groups according to the type of vessel sealing method used, group I (BiClamp, operations) and group II (conventional ligature, operations). The number of revision surgeries due to wound hematoma was recorded as a bleeding event. Statistical analysis of the complication rate (bleeding rate, recurrent nerve palsy) and time of duration was performed. Results. The rate of revision surgery performed due to postoperative wound hematoma was significantly lower in group I (15/819, 1.83%) compared with group II (14/337, 4.15%) (). There was no statistically significant difference in the frequency of recurrent laryngeal nerve palsy between groups I and II (). The average surgery time was significantly shorter in group I (). Conclusion. Bipolar thermofusion BiClamp is an effective vessel sealing method that leads to a significant reduction in postoperative wound bleeding rates and reduces surgical time compared with conventional vessel ligature. Tomáš Pniak, Martin Formánek, Petr Matoušek, Karol Zeleník, and Pavel Komínek Copyright © 2014 Tomáš Pniak et al. All rights reserved. Minimally Invasive Video-Assisted versus Minimally Invasive Nonendoscopic Thyroidectomy Tue, 08 Apr 2014 07:23:53 +0000 Minimally invasive video-assisted thyroidectomy (MIVAT) and minimally invasive nonendoscopic thyroidectomy (MINET) represent well accepted and reproducible techniques developed with the main goal to improve cosmetic outcome, accelerate healing, and increase patient’s comfort following thyroid surgery. Between 2007 and 2011, a prospective nonrandomized study of patients undergoing minimally invasive thyroid surgery was performed to compare advantages and disadvantages of the two different techniques. There were no significant differences in the length of incision to perform surgical procedures. Mean duration of hemithyroidectomy was comparable in both groups, but it was more time consuming to perform total thyroidectomy by MIVAT. There were more patients undergoing MIVAT procedures without active drainage in the postoperative course and we also could see a trend for less pain in the same group. This was paralleled by statistically significant decreased administration of both opiates and nonopiate analgesics. We encountered two cases of recurrent laryngeal nerve palsies in the MIVAT group only. MIVAT and MINET represent safe and feasible alternative to conventional thyroid surgery in selected cases and this prospective study has shown minimal differences between these two techniques. Zdeněk Fík, Jaromír Astl, Michal Zábrodský, Petr Lukeš, Ilja Merunka, Jan Betka, and Martin Chovanec Copyright © 2014 Zdeněk Fík et al. All rights reserved. Experimental Study of Local Inner Ear Gene Therapy for Controlling Autoimmune Sensorineural Hearing Loss Mon, 07 Apr 2014 14:00:58 +0000 This study aimed to investigate the efficacy of gene therapy for treating autoimmune sensorineural hearing loss (ASHL) via local administration of a recombinant adenovirus vector containing the Fas ligand or interleukin IL-10 gene. Guinea pigs were divided into four groups, with different microinjections in the scala tympani. Group A were injected with FasL-EGFP, B with IL-10-EGFP, C with EGFP, and D with artificial perilymph. Seven days later, auditory brain-stem response (ABR) was tested, and the temporal bone was stained and observed by light microscopy. The spiral ligament and basement membrane were observed using transmission electron microscopy. FasL and IL-10 expression were examined using immunofluorescence histochemistry. Immunohistochemical analysis showed that the recombinant adenovirus vector in Groups A, B, and C can transfect the stria vascularis, the spiral ligament, the organ of Corti, the spiral ganglion, the region surrounding the small blood vessel in the modiolus, and the cochlear bone wall. Compared with those in Groups C and D, the ABR wave III mean thresholds were significantly lower and the inner ear immunoinflammatory responses in Groups A and B were significantly alleviated. Inhibition of immunoinflammatory response alleviated immunoinflammatory injury and auditory dysfunction. This technique shows potential as a novel therapy for ASHL. Chang-qiang Tan, Xia Gao, Wen-jun Cai, Xiao-yun Qian, Ling Lu, and He Huang Copyright © 2014 Chang-qiang Tan et al. All rights reserved. Biological Basis for Increased Sensitivity to Radiation Therapy in HPV-Positive Head and Neck Cancers Thu, 03 Apr 2014 08:27:35 +0000 Although development of head and neck squamous cell carcinomas (HNSCCs) is commonly linked to the consumption of tobacco and alcohol, a link between human papillomavirus (HPV) infection and a subgroup of head and neck cancers has been established. These HPV-positive tumors represent a distinct biological entity with overexpression of viral oncoproteins E6 and E7. It has been shown in several clinical studies that HPV-positive HNSCCs have a more favorable outcome and greater response to radiotherapy. The reason for improved prognosis of HPV-related HNSCC remains speculative, but it could be owned to multiple factors. One hypothesis is that HPV-positive cells are intrinsically more sensitive to standard therapies and thus respond better to treatment. Another possibility is that HPV-positive tumors uniquely express viral proteins that induce an immune response during therapy that helps clear tumors and prevents recurrence. Here, we will review current evidence for the biological basis of increased radiosensitivity in HPV-positive HNSCC. V. Bol and V. Grégoire Copyright © 2014 V. Bol and V. Grégoire. All rights reserved. Associations between GJB2, Mitochondrial 12S rRNA, SLC26A4 Mutations, and Hearing Loss among Three Ethnicities Wed, 02 Apr 2014 12:47:37 +0000 The epidemiological researches show that the mutations of GJB2, mitochondrial 12S rRNA, and SLC26A4 genes have played an important role in the hearing loss. This study aims to investigate the mutation spectrum of GJB2, mitochondrial 12S rRNA, and SLC26A4 genes of Han Chinese, Hui people, and Uyghur ethnicities in sensorineural hearing loss (SNHL) patients in northwest of China. Mutational analyses in the three genes were brought by direct sequencing and each fragment was analyzed using an ABI 3730 DNA Sequencer. The mutation frequencies for the three HL causative genes were 34.05% in Han Chinese participants, 27.47% in Hui people, and 14.44% in Uyghur participants, respectively. The prevalence of GJB2 mutations was 13.7%, 11.4%, and 11.4% in Han Chinese, Hui people, and Uyghur participants (, ), respectively. The prevalence of mtDNA 12S rRNA A1555G homozygous mutations was 6.05%, 3.27%, and 1.44% in Han Chinese, Hui people, and Uyghur participants (, ), respectively. The prevalence of SLC26A4 mutations was 14.3%, 12.8%, and 1.6% in Han Chinese, Hui people, and Uyghur participants, respectively. In summary, we find that Uyghur and Hui SNHL individuals vary significantly from Han Chinese patients in three causative HL genes' mutational spectrum, especially for Uyghur. Wan Du, Qiuju Wang, Yiming Zhu, Yanli Wang, and Yufen Guo Copyright © 2014 Wan Du et al. All rights reserved. Clinical Use of Skull Tap Vestibular Evoked Myogenic Potentials for the Diagnoses of the Cerebellopontine Angle Tumor Patients Wed, 02 Apr 2014 09:35:07 +0000 Objective. To document our experiences using a new skull tapping induced Vestibular Evoked Myogenic Potentials (tap VEMPs) technique combined with standard Auditory Vestibular Evoked Myogenic Potentials (AC VEMPs) for advanced clinical assessment of cerebellopontine angle tumor (CPAT) patients. Design and Study Sample. Three patients were selected in order to highlight observations shown in a larger patient population and to show the variability of the findings. Both tap VEMPs and AC VEMPs were acquired from the sternocleidomastoid muscle (SCM) with EMG-based biofeedback and monitoring. Results. The usefulness of VEMPs was demonstrated, indicating the presence of a tumor and contributing additional information as to the involved nerve bundles in two out of the three cases. Conclusion. Due to the sensory organ dependency and related innervations differences, acquiring both AC VEMPs and tap VEMPs is likely to increase the probability of diagnosing CPATs and provide more information on the involved vestibular nerve bundles. This study demonstrates the feasibility of the possible expansion and combination of tap VEMPs and AC VEMPs techniques into a clinical diagnostic battery for advanced assessment of CPAT patients and its contribution as a guideline for the use of tap VEMPs in general. Erdem Yavuz, Magdalena Lachowska, Katarzyna Pierchała, Krzysztof Morawski, Kazimierz Niemczyk, and Rafael E. Delgado Copyright © 2014 Erdem Yavuz et al. All rights reserved. Outcome and Prognostic Factors in T4a Oropharyngeal Carcinoma, Including the Role of HPV Infection Mon, 31 Mar 2014 16:36:37 +0000 Background. The prognosis of patients with advanced oropharyngeal carcinoma (OPSCC) is generally poor. The aim of this study is to investigate the different therapeutic approaches and identify prognostic factors associated with a worse outcome for patients treated for T4a OPSCC, in order to improve treatment selection for the individual. Methods. A retrospective study was conducted on 426 patients with T4a OPC treated between 1980 and 2010. Eleven prognostic factors including treatment modality, lymph node staging, and p16 status as a surrogate marker for human papillomavirus (HPV) infection were analyzed. Results. Univariate analysis showed a significant difference in DSS between N0 and N+ (57.1% versus 26.9%, ), primary surgical and primary nonsurgical treatment (52.7% versus 31.4%, ), and perinodal invasion (51.7% versus 19.9%, ). P16-negative patients tended towards a worse DSS than p16-positive patients (40.2% versus 64.6%, ) but responded better to primary surgery than to nonsurgical treatment (71.4% versus 34.0%, ). Multivariate analysis identified the N category as an independent prognostic factor for survival. Conclusion. The survival of p16-negative patients was worse than p16-positive patients, although they seem to respond better to primary surgery. The strongest independent prognostic factor for T4a carcinomas proved to be the presence of lymph node metastases. Georgios Psychogios, Konstantinos Mantsopoulos, Abbas Agaimy, Kathrin Brunner, Elisabeth Mangold, Johannes Zenk, and Heinrich Iro Copyright © 2014 Georgios Psychogios et al. All rights reserved. Influence of Radiofrequency Surgery on Architecture of the Palatine Tonsils Wed, 26 Mar 2014 00:00:00 +0000 Radiofrequency surgery is a widely used modern technique for submucosal volume reduction of the tonsils. So far there is very limited information on morphologic changes in the human tonsils after radiofrequency surgery. We performed histopathological study of tonsillectomy specimens after previous bipolar radiofrequency induced thermotherapy (RFITT). A total of 83 patients underwent bipolar RFITT for hypertrophy of palatine tonsils. Tonsil volume reduction was measured by 3D ultrasonography. Five patients subsequently underwent tonsillectomy. Profound histopathological examination was performed to determine the effect of RFITT on tonsillar architecture. All tonsillectomy specimens showed the intact epithelium, intact germinal centers, normal vascularization, and no evidence of increased fibrosis. No microscopic morphological changes in tonsillectomy specimens after bipolar RFITT were observed. RFITT is an effective submucosal volume reduction procedure for treatment of hypertrophic palatine tonsils with no destructive effect on microscopic tonsillar architecture and hence most probably no functional adverse effect. Jan Plzak, Pavla Macokova, Michal Zabrodsky, Jan Kastner, Petr Lastuvka, and Jaromir Astl Copyright © 2014 Jan Plzak et al. All rights reserved. Zenker's Diverticulum: Carbon Dioxide Laser Endoscopic Surgery Thu, 06 Mar 2014 13:57:38 +0000 Nowadays endoscopic diverticulotomy is the surgical approach of the first choice in treatment of Zenker's diverticulum. We report our experience with this procedure and try to sum up recent recommendations for management of surgery and postoperative care. Data of 34 patients with Zenker's diverticulum, treated by endoscopic carbon dioxide laser diverticulotomy at the Department of Otorhinolaryngology and Head and Neck Surgery, 1st Faculty of Medicine, Charles University, University Hospital Motol, Prague, Czech Republic, were prospectively stored and followed in relatively short period from May 2009 to December 2013. The average length of diverticulum was 32 mm. The average duration of surgery was 32 min. The patients were fed via feeding tube for 6.1 days and antibiotics were administered for 7 days. Mean hospitalization time was 7.4 days. We observed one transient recurrent laryngeal nerve paralysis and no other serious complications. Recurrence rate was 3%. We recommend complete transection of the diverticular septum in one procedure, systemic antibiotic treatment and exclusion of transoral intake for minimally 5 days, and contrast oesophagogram before resumption of oral intake to exclude fistula. Open diverticulectomy should be reserved for cases with inadequate endoscopic exposure and for revision surgery for multiple recurrences from endoscopic diverticulotomies. Jan Plzák, Michal Zábrodský, and Petr Lukeš Copyright © 2014 Jan Plzák et al. All rights reserved. Treatment of Laryngoceles: What Is the Progress over the Last Two Decades? Thu, 06 Mar 2014 11:24:21 +0000 Objectives. To review surgical techniques used in the treatment of laryngoceles over the last two decades and point out developments and trends. Materials and Methods. PubMed, the Cochrane Library, and the JBI Library of Systematic Reviews were searched using the term “laryngocele.” Demographic data, type of laryngocele, presence of a laryngopyocele, type of treatment and need for a tracheotomy were assessed. Results. Overall, data on 86 patients were analyzed, culled from 50 articles, of which 41 were case reports and 9 were case series. No single systematic review or meta-analysis or randomized controlled trial has been published on the topic. Altogether, 71 laryngoceles in 63 patients met the criteria for further analysis focusing on surgical treatment. An external approach was selected in 25/29 (86.2%) cases of combined laryngoceles. Microlaryngoscopic resection using a CO2 laser was performed in three cases and endoscopic robotic surgery in one case. The majority of patients with an internal laryngocele, 31/42 (73.8%), were treated using the microlaryngoscopy approach. Conclusions. Microlaryngoscopy involving the use of a CO2 laser has become the main therapeutic procedure for the treatment of internal laryngoceles during the past 20 years. An external approach still remains the main therapeutic approach for the treatment of combined laryngoceles. Karol Zelenik, Lucia Stanikova, Katarina Smatanova, Michal Cerny, and Pavel Kominek Copyright © 2014 Karol Zelenik et al. All rights reserved. Proteomic Study of HPV-Positive Head and Neck Cancers: Preliminary Results Sun, 02 Mar 2014 00:00:00 +0000 Human papillomavirus (HPV) was recently recognized as a new risk factor for head and neck squamous cell carcinoma. For oropharyngeal cancers, an HPV+ status is associated with better prognosis in a subgroup of nonsmokers and nondrinkers. However, HPV infection is also involved in the biology of head and neck carcinoma (HNC) in patients with a history of tobacco use and/or alcohol consumption. Thus, the involvement of HPV infection in HN carcinogenesis remains unclear, and further studies are needed to identify and analyze HPV-specific pathways that are involved in this process. Using a quantitative proteomics-based approach, we compared the protein expression profiles of two HPV+ HNC cell lines and one HPV− HNC cell line. We identified 155 proteins that are differentially expressed () in these three lines. Among the identified proteins, prostate stem cell antigen (PSCA) was upregulated and eukaryotic elongation factor 1 alpha (EEF1α) was downregulated in the HPV+ cell lines. Immunofluorescence and western blotting analyses confirmed these results. Moreover, PSCA and EEF1α were differentially expressed in two clinical series of 50 HPV+ and 50 HPV− oral cavity carcinomas. Thus, our study reveals for the first time that PSCA and EEF1α are associated with the HPV-status, suggesting that these proteins could be involved in HPV-associated carcinogenesis. Géraldine Descamps, Ruddy Wattiez, and Sven Saussez Copyright © 2014 Géraldine Descamps et al. All rights reserved. Early Stage Oropharyngeal Carcinomas: Comparing Quality of Life for Different Treatment Modalities Tue, 25 Feb 2014 14:10:30 +0000 Objective. To compare long-term quality of life outcomes after treating early stage oropharyngeal carcinoma either with surgery, surgery combined with radiotherapy, or surgery combined with chemoradiotherapy. Methods. Questionnaire based method: 111 eligible patients agreed to fill out a quality of life questionnaire. Results. Of the 32 scales contained in the EORTC’s combined QLQ-C30 and HN35, 11 scales show significantly better results for the surgery-only treatment group when compared to either surgery combined with radiotherapy or surgery combined with any type of adjuvant therapy. These eleven scales are role function (), social function (), nausea (), pain (), financial problems (), speech (), social eating (/<0.001), mouth opening (), sticky saliva (/<0.001), swallowing (/<0.001), and dry mouth (). Conclusion. Treatment of early stage oropharyngeal carcinoma with surgery alone has definite advantages over treatments including any form of adjuvant therapy when considering quality of life. Advantages manifest themselves especially in functional aspects of the head and neck realm; however general health aspects as well as psychosocial aspects show improvements as well. This study does not show any indication of QOL-related drawbacks of surgery-only treatment approaches. Don-Felix Ryzek, Konstantinos Mantsopoulos, Julian Künzel, Philipp Grundtner, Johannes Zenk, Heinrich Iro, and Georgios Psychogios Copyright © 2014 Don-Felix Ryzek et al. All rights reserved. The c-MYC Protooncogene Expression in Cholesteatoma Mon, 10 Feb 2014 09:56:38 +0000 Cholesteatoma is an epidermoid cyst, which is most frequently found in the middle ear. The matrix of cholesteatoma is histologically similar to the matrix of the epidermoid cyst of the skin (atheroma); their epithelium is characterized by hyperproliferation. The c-MYC protooncogene located on chromosome 8q24 encodes a transcription factor involved in the regulation of cell proliferation and differentiation. Previous studies have found aneuploidy of chromosome 8, copy number variation of c-MYC gene, and the presence of elevated level c-MYC protein in cholesteatoma. In this study we have compared the expression of c-MYC gene in samples taken from the matrix of 26 acquired cholesteatomas (15 children and 11 adults), 15 epidermoid cysts of the skin (atheromas; head and neck region) and 5 normal skin samples (retroauricular region) using RT-qPCR, providing the first precise measurement of the expression of c-MYC gene in cholesteatoma. We have found significantly elevated c-MYC gene expression in cholesteatoma compared to atheroma and to normal skin samples. There was no significant difference, however, in c-MYC gene expression between cholesteatoma samples of children and adults. The significant difference in c-MYC gene expression level in cholesteatoma compared to that of atheroma implies a more prominent hyperproliferative phenotype which may explain the clinical behavior typical of cholesteatoma. Enikő Palkó, Szilárd Póliska, Zsuzsanna Csákányi, Gábor Katona, Tamás Karosi, Frigyes Helfferich, András Penyige, and István Sziklai Copyright © 2014 Enikő Palkó et al. All rights reserved. Feasibility of Piezoelectric Endoscopic Transsphenoidal Craniotomy: A Cadaveric Study Sun, 09 Feb 2014 12:50:39 +0000 Objective. Endoscopic transsphenoidal approach has become the gold standard for surgical treatment of treating pituitary adenomas or other lesions in that area. Opening of bony skull base has been performed with burrs, chisels, and hammers or standard instruments like punches and circular top knives. The creation of primary bone flaps—as in external craniotomies—is difficult.The piezoelectric osteotomes used in the present study allows creating a bone flap for endoscopic transnasal approaches in certain areas. The aim of this study was to prove the feasibility of piezoelectric endoscopic transnasal craniotomies. Study Design. Cadaveric study. Methods. On cadaveric specimens (), a piezoelectric system with specially designed hardware for endonasal application was applied and endoscopic transsphenoidal craniotomies at the sellar floor, tuberculum sellae, and planum sphenoidale were performed up to a size of 3–5 cm2. Results. Bone flaps could be created without fracturing with the piezoosteotome and could be reimplanted. Endoscopic handling was unproblematic and time required was not exceeding standard procedures. Conclusion. In a cadaveric model, the piezoelectric endoscopic transsphenoidal craniotomy (PETC) is technically feasible. This technique allows the surgeon to create a bone flap in endoscopic transnasal approaches similar to existing standard transcranial craniotomies. Future trials will focus on skull base reconstruction using this bone flap. Peter Valentin Tomazic, Verena Gellner, Wolfgang Koele, Georg Philipp Hammer, Eva Maria Braun, Claus Gerstenberger, Georg Clarici, Etienne Holl, Hannes Braun, Heinz Stammberger, and Michael Mokry Copyright © 2014 Peter Valentin Tomazic et al. All rights reserved. A Novel Homozygous Mutation in the EC1/EC2 Interaction Domain of the Gap Junction Complex Connexon 26 Leads to Profound Hearing Impairment Thu, 16 Jan 2014 12:18:49 +0000 To date, about 165 genetic loci or genes have been identified which are associated with nonsyndromal hearing impairment. In about half the cases, genetic defects in the GJB2 gene (connexin 26) are the most common cause of inner-ear deafness. The genes GJB2 and GJB6 are localized on chromosome 13q11-12 in tandem orientation. Connexins belong to the group of “gap junction” proteins, which form connexons, each consisting of six connexin molecules. These are responsible for the exchange of ions and smaller molecules between neighboring cells. Mutational analysis in genes GJB2 and GJB6 was brought by direct sequencing of the coding exons including the intron transitions. Here we show in the participating extended family a homozygous mutation c.506G>A, (TGC>TAC) p.Cys169Tyr, in the GJB2 gene, which could be proven for the first time and led to nonsyndromal severe hearing impairment in the afflicted patients. The mutation is located in the EC1/EC2 interaction complex of the gap junction connexon 26 complex and interrupts the K+ circulation and therefore the ion homeostasis in the inner ear. The homozygous mutation p.Cys169Tyr identified here provides a novel insight into the structure-function relationship of the gap junction complex connexin/connexon 26. Ralf Birkenhäger, Nicola Prera, Antje Aschendorff, Roland Laszig, and Susan Arndt Copyright © 2014 Ralf Birkenhäger et al. All rights reserved. Oncogenic PIK3CA Mutation and Dysregulation in Human Salivary Duct Carcinoma Wed, 08 Jan 2014 15:10:42 +0000 Salivary duct carcinoma (SDC) is an aggressive malignant tumor with a high mortality, which resembles high-grade breast ductal carcinoma in morphology. The parotid gland is the most common location. Its molecular genetic characteristics remain largely unknown. We have previously reported high incidence of PIK3CA somatic mutations in head and neck squamous cell carcinoma, particularly in pharyngeal cancers. Here we examined the PIK3CA gene expression status and hotspot mutations in six cases of SDC by immunohistochemistry and genomic DNA sequencing. Immunohistochemistry showed that PIK3CA expression was elevated in all six patients with SDC. By DNA sequencing, two hotspot mutations of the PIK3CA gene, E545K (exon 9) and H1047R (exon 20), were identified in two of the six cases. Our results support that oncogenic PIK3CA is upregulated and frequently mutated in human SDC, adding evidence that PIK3CA oncogenic pathway is critical in the tumorigenesis of SDC, and may be a plausible drug target for this rare disease. Wanglong Qiu, Guo-Xia Tong, Andrew T. Turk, Lanny G. Close, Salvatore M. Caruana, and Gloria H. Su Copyright © 2014 Wanglong Qiu et al. All rights reserved. Suppression of Osteopontin Functions by Levocetirizine, a Histamine Receptor Antagonist, In Vitro Mon, 30 Dec 2013 10:19:32 +0000 Objectives. Osteopontin (OPN), a multifunctional glycoprotein secreted from a wide variety of cells after inflammatory stimulation, is well accepted to contribute to the development of allergic diseases. However, the influence of histamine H1 receptor antagonists (antihistamines) on OPN functions is not well understood. The present study was undertaken to examine the influence of antihistamines on OPN functions in vitro. Methods. Human nasal epithelial cells ( cells) were stimulated with 250 ng/mL OPN in the presence of either desloratadine (DL), fexofenadine (FEX), or levocetirizine (LCT). The levels of OPN, GM-CSF, Eotaxin, and RANTES in 24 h culture supernatants were examined by ELISA. The influence of LCT on mRNA expression and transcription factor activation in cells were also examined by real-time RT-PCR and ELISA, respectively. Key Findings. The antihistamines examined significantly suppressed the production of GM-CSF, Eotaxin, and RANTES from cells after OPN stimulation. LCT also exhibited the suppression of mRNA expression for chemokines and transcription factor, NF-κB and AP-1, activation, which were increased by the stimulation of cells with OPN. Conclusions. The suppressive activity of LCT on OPN functions on nasal epithelial cells may be responsible for the attenuating effect of the agent on allergic diseases. Toshimitsu Komatsuzaki, Isao Suzaki, Kojiro Hirano, Ken-Ichi Kanai, Kazuhito Asano, and Harumi Suzaki Copyright © 2013 Toshimitsu Komatsuzaki et al. All rights reserved. Improving Therapeutic Ratio in Head and Neck Cancer with Adjuvant and Cisplatin-Based Treatments Thu, 19 Dec 2013 15:10:46 +0000 Advanced head and neck cancers are difficult to manage despite the large treatment arsenal currently available. The multidisciplinary effort to increase disease-free survival and diminish normal tissue toxicity was rewarded with better locoregional control and sometimes fewer side effects. Nevertheless, locoregional recurrence is still one of the main reasons for treatment failure. Today, the standard of care in head and neck cancer management is represented by altered fractionation radiotherapy combined with platinum-based chemotherapy. Targeted therapies as well as chronotherapy were trialled with more or less success. The aim of the current work is to review the available techniques, which could contribute towards a higher therapeutic ratio in the treatment of advanced head and neck cancer patients. Loredana G. Marcu Copyright © 2013 Loredana G. Marcu. All rights reserved. Medium-Level Laser in Chronic Tinnitus Treatment Tue, 05 Nov 2013 15:57:27 +0000 The purpose of this study was to evaluate the effect of medium-level laser therapy in chronic tinnitus treatment. In a prospective double-blind placebo-controlled trial, either active laser (450 mW, 830 nm combined Ga-Al-As diode laser) or placebo irradiation was applied through the external acoustic meatus of the affected ear towards the cochlea. Fourty-eight patients with chronic tinnitus were studied. The main outcome was measured using the Goebel tinnitus questionnaire, visual analogue scales measuring the perceived loudness of tinnitus, the annoyance associated with tinnitus, and the degree of attention paid to tinnitus as well as psycho-acoustical matches of tinnitus pitch and loudness. The results did show only very moderate temporary improvement of tinnitus. Moreover, no statistically relevant differences between laser and placebo group could be found. We conclude that medium-level laser therapy cannot be regarded as an effective treatment of chronic tinnitus in our therapy regime considering the limited number of patients included in our study. K. Dejakum, J. Piegger, C. Plewka, A. Gunkel, W. Thumfart, S. Kudaibergenova, G. Goebel, F. Kral, and W. Freysinger Copyright © 2013 K. Dejakum et al. All rights reserved. An Investigation of Vocal Tract Characteristics for Acoustic Discrimination of Pathological Voices Thu, 31 Oct 2013 18:28:44 +0000 This paper investigates the effectiveness of measures related to vocal tract characteristics in classifying normal and pathological speech. Unlike conventional approaches that mainly focus on features related to the vocal source, vocal tract characteristics are examined to determine if interaction effects between vocal folds and the vocal tract can be used to detect pathological speech. Especially, this paper examines features related to formant frequencies to see if vocal tract characteristics are affected by the nature of the vocal fold-related pathology. To test this hypothesis, stationary fragments of vowel /aa/ produced by 223 normal subjects, 472 vocal fold polyp subjects, and 195 unilateral vocal cord paralysis subjects are analyzed. Based on the acoustic-articulatory relationships, phonation for pathological subjects is found to be associated with measures correlated with a raised tongue body or an advanced tongue root. Vocal tract-related features are also found to be statistically significant from the Kruskal-Wallis test in distinguishing normal and pathological speech. Classification results demonstrate that combining the formant measurements with vocal fold-related features results in improved performance in differentiating vocal pathologies including vocal polyps and unilateral vocal cord paralysis, which suggests that measures related to vocal tract characteristics may provide additional information in diagnosing vocal disorders. Jung-Won Lee, Hong-Goo Kang, Jeung-Yoon Choi, and Young-Ik Son Copyright © 2013 Jung-Won Lee et al. All rights reserved. Effects of Cryotherapy on the Maxillary Antrostomy Patency in a Rabbit Model of Chronic Rhinosinusitis Mon, 28 Oct 2013 14:12:28 +0000 It is acknowledged that many causes of failures in endoscopic sinus surgery are related to scarring and narrowing of the maxillary antrostomy. We assessed the effect of low-pressure spray cryotherapy in preventing the maxillary antrostomy stenosis in a chronic rhinosinusitis (CRS) rabbit model. A controlled, randomized, double-blind study was conducted on 22 New Zealand rabbits. After inducing unilateral rhinogenic CRS, a maxillary antrostomy was performed and spray cryotherapy was employed on randomly selected 12 rabbits, while saline solution was applied to the control group (). The antrostomy dimensions and the histological scores were assessed 4 weeks postoperatively. The diameter of cryotreated antrostomy was significantly larger at 4 weeks than that in the control group. At 4 weeks, the maxillary antrostomy area in the study group was significantly larger than the mean area in the control group (103.92 ± 30.39 mm2 versus 61.62 ± 28.35 mm2, ). Submucosal fibrous tissues and leukocytic infiltration in saline-treated ostia were more prominent than those in cryotreated ostia with no significant differences between the two groups regarding the histological scores. Intraoperative low-pressure spray cryotherapy increases the patency of the maxillary antrostomy at 4 weeks postoperatively with no important local side effects. Anamaria Gocea, Marian Taulescu, Veronica Trombitas, and Silviu Albu Copyright © 2013 Anamaria Gocea et al. All rights reserved. Ouabain-Induced Apoptosis in Cochlear Hair Cells and Spiral Ganglion Neurons In Vitro Tue, 22 Oct 2013 16:00:25 +0000 Ouabain is a common tool to explore the pathophysiological changes in adult mammalian cochlea in vivo. In prior studies, locally administering ouabain via round window membrane demonstrated that the ototoxic effects of ouabain in vivo varied among mammalian species. Little is known about the ototoxic effects in vitro. Thus, we prepared cochlear organotypic cultures from postnatal day-3 rats and treated these cultures with ouabain at 50, 500, and 1000 μM for different time to elucidate the ototoxic effects of ouabain in vitro and to provide insights that could explain the comparative ototoxic effects of ouabain in vivo. Degeneration of cochlear hair cells and spiral ganglion neurons was evaluated by hair-cell staining and neurofilament labeling, respectively. Annexin V staining was used to detect apoptotic cells. A quantitative RT-PCR apoptosis-focused gene array determined changes in apoptosis-related genes. The results showed that ouabain-induced damage in vitro was dose and time dependent. 500 μM ouabain and 1000 μM ouabain were destructively traumatic to both spiral ganglion neurons and cochlear hair cells in an apoptotic signal-dependent pathway. The major apoptotic pathways in ouabain-induced spiral ganglion neuron apoptosis culminated in the stimulation of the p53 pathway and triggering of apoptosis by a network of proapoptotic signaling pathways. Yong Fu, Dalian Ding, Lei Wei, Haiyan Jiang, and Richard Salvi Copyright © 2013 Yong Fu et al. All rights reserved. Microbiological Profile of Adenoid Hypertrophy Correlates to Clinical Diagnosis in Children Mon, 23 Sep 2013 08:25:48 +0000 Objective. Adenoid hypertrophy is a common condition in childhood, which may be associated with recurring acute otitis media (RAOM), otitis media with effusion (OME), and obstructive sleep apnea syndrome (OSAS). These different clinical characteristics have some clinical overlap; however, they might be explained by distinct immunologic and infectious profiles and result in various histopathologic findings of adenoid specimens. Methods. A total of 59 children with adenoid hypertrophy undergoing adenoidectomy were studied. Three series of identical adenoid specimens were processed to hematoxylin-eosin (H.E.) and Gram staining and to respiratory virus specific real-time PCR, respectively. Results. According to the clinical characteristics, patients were recruited into three groups: RAOM (), OME (), and OSAS (). Bacterial biofilms were detected in 21 cases, while at least one of the studied respiratory viruses was detected in 52 specimens. RAOM cases were significantly associated with biofilm existence (, ). In contrast, OME group was characterized by the absence of bacterial biofilm and by normal mucosa. Showing a statistically significant correlation, all OME cases were positive for human bocavirus (HBoV, ). Conclusions. Bacterial biofilms might contribute to the damage of respiratory epithelium and recurring acute infections resulting in RAOM. In OME cases persisting respiratory viruses, mainly HBoV, can cause subsequent lymphoid hyperplasia leading to ventilation disorders and impaired immunoreactivity of the middle ear cleft. Anita Szalmás, Zoltán Papp, Péter Csomor, József Kónya, István Sziklai, Zoltán Szekanecz, and Tamás Karosi Copyright © 2013 Anita Szalmás et al. All rights reserved. Polymorphisms in the Human Cytochrome P450 and Arylamine N-Acetyltransferase: Susceptibility to Head and Neck Cancers Mon, 16 Sep 2013 14:12:38 +0000 The occurrence of head and neck cancer (HNC) is associated with smoking and alcohol drinking. Tobacco smoking exposes smokers to a series of carcinogenic chemicals. Cytochrome P450 enzymes (CYP450s), such as CYP1A1, CYP1B1, and CYP2D6, usually metabolize carcinogens to their inactive derivatives, but they occasionally convert the chemicals to more potent carcinogens. In addition, via CYP450 (CYP2E1) oxidase, alcohol is metabolized to acetaldehyde, a highly toxic compound, which plays an important role in carcinogenesis. Furthermore, two N-acetyltransferase isozymes (NATs), NAT1 and NAT2, are polymorphic and catalyze both N-acetylation and O-acetylation of aromatic and heterocyclic amine carcinogens. Genetic polymorphisms are associated with a number of enzymes involved in the metabolism of carcinogens important in the induction of HNC. It has been suggested that such polymorphisms may be linked to cancer susceptibility. In this paper, we select four cytochrome P450 enzymes (CYP1A1, CYP1BA1, CYP2D6, and CYP2E1), and two N-acetyltransferase isozymes (NAT1 and NAT2) in order to summarize and analyze findings from the literature related to HNC risk by focusing on (i) the interaction between these genes and the environment, (ii) the impact of genetic defect on protein activity and/or expression, and (iii) the eventual involvement of race in such associations. Rim Khlifi, Olfa Messaoud, Ahmed Rebai, and Amel Hamza-Chaffai Copyright © 2013 Rim Khlifi et al. All rights reserved. A Model for Provision of ENT Health Care Service at Primary and Secondary Hospital Level in a Developing Country Wed, 04 Sep 2013 10:08:37 +0000 ENT problems are the most common reason for a visit to a doctor in both rural and urban communities. In many developing countries, there is a lack of ENT specialists and overburdened hospital facilities. To date, there is no comprehensive study that has evaluated the spectrum of ENT disorders in a rural community. Methods. A prospective study was done for a period of three years to profile the cases presenting to the outpatient clinic in a secondary care hospital and in the camps conducted in tribal areas in Vellore District of Tamil Nadu, India. Trained community volunteers were used to identify ENT conditions and refer patients. Results. A total of 2600 patients were evaluated and treated. Otological symptoms were the most commonly reported with allergic rhinitis being the second most commonly reported. Presbycusis was the most common disability reported in the rural community. The other symptoms presented are largely related to hygiene and nutrition. Conclusion. Using trained community workers to spread the message of safe ENT practices, rehabilitation of hearing loss through provision of hearing aids, and the evaluation and surgical management by ENT specialist helped the rural community to access the service. Lingamdenne Paul Emerson, Anand Job, and Vinod Abraham Copyright © 2013 Lingamdenne Paul Emerson et al. All rights reserved. Auditory Verbal Cues Alter the Perceived Flavor of Beverages and Ease of Swallowing: A Psychometric and Electrophysiological Analysis Tue, 27 Aug 2013 13:24:11 +0000 We investigated the possible effects of auditory verbal cues on flavor perception and swallow physiology for younger and elder participants. Apple juice, aojiru (grass) juice, and water were ingested with or without auditory verbal cues. Flavor perception and ease of swallowing were measured using a visual analog scale and swallow physiology by surface electromyography and cervical auscultation. The auditory verbal cues had significant positive effects on flavor and ease of swallowing as well as on swallow physiology. The taste score and the ease of swallowing score significantly increased when the participant’s anticipation was primed by accurate auditory verbal cues. There was no significant effect of auditory verbal cues on distaste score. Regardless of age, the maximum suprahyoid muscle activity significantly decreased when a beverage was ingested without auditory verbal cues. The interval between the onset of swallowing sounds and the peak timing point of the infrahyoid muscle activity significantly shortened when the anticipation induced by the cue was contradicted in the elderly participant group. These results suggest that auditory verbal cues can improve the perceived flavor of beverages and swallow physiology. Aya Nakamura and Satoshi Imaizumi Copyright © 2013 Aya Nakamura and Satoshi Imaizumi. All rights reserved. Inferior Flap Tympanoplasty: A Novel Technique for Anterior Perforation Closure Tue, 13 Aug 2013 09:23:00 +0000 Objective. To report a novel tympanoplasty modification for anterior tympanic membrane perforation closure. Materials and Methods. A prospective study on 13 patients who underwent inferior tympanoplasty between December 2008 and May 2011 was carried out. In our technique, an inferior rather than a posterior flap is raised and the graft is laid from the inferior direction to obtain better access to the anterior part of the tympanic membrane perforation and provide better support. Results. A total of 13 patients underwent the novel inferior tympanoplasty technique with a mean age of 33 years. Six patients had undergone tympanoplasties and/or mastoidectomies in the past, 3 in the contralateral ear. A marginal perforation was observed in 3 cases, total perforation in 2 and subtotal in 1 case. The mean preoperative pure-tone average was 40.4 dB (10 to 90 dB), compared to 26.5 dB (10 to 55 dB) postoperatively. All perforations were found to be closed but one (92.3% success rate). Conclusions. The inferior tympanoplasty technique provides a favorable outcome in terms of tympanic membrane closure and hearing improvement for anterior perforations, even in difficult and complex cases. It is based on a well-known technique and is easy to implement. Haim Gavriel and Ephraim Eviatar Copyright © 2013 Haim Gavriel and Ephraim Eviatar. All rights reserved. INF-α and Ototoxicity Thu, 25 Jul 2013 14:07:53 +0000 Introduction. INF-α is a common drug for the treatment of hepatitis B and C. Although a variety of related complications are discussed, possible ototoxic effects of this mediation are not well described. Methods and Materials. In a before-after control study, 24 patients who received INF-α for the treatment of hepatitis B and C and 30 normal controls were included. Subjective and objective ototoxicity evaluations via questionnaire, high frequency audiometry, and measuring transiently evoked otoacoustic emissions (TEOAEs) were performed one week before and one month after the prescription of the drug. Results. Subjective hearing complaint, tinnitus, and vertigo were seen in just 3 cases, which was not statistically significant (). In the frequency range of 4000 to 8000 Hz before (9.38 ± 1.0 and 10.7 ± 1.2, resp.) and after (17.9 ± 2.6 and 17.6 ± 2.6, resp.) one month of treatment, a significant difference () was detected. Progressive decreases in amplitude of the OAE during TEOAE measurement in 1, 2, and 4 frequencies among 41.66%, 18.75 %, and 43.75% were observed, respectively. The hearing loss was seen more among older and male cases significantly. Conclusion. The results showed ototoxicity of INF-α that may encourage planning hearing monitoring in patients receiving this drug. Mohammad Reza Sharifian, Shima Kamandi, Hamid Reza Sima, Mohammad Ali Zaringhalam, and Mehdi Bakhshaee Copyright © 2013 Mohammad Reza Sharifian et al. All rights reserved. Button Battery Foreign Bodies in Children: Hazards, Management, and Recommendations Thu, 11 Jul 2013 13:46:01 +0000 Objective. The demand and usage of button batteries have risen. They are frequently inadvertently placed by children in their ears or noses and occasionally are swallowed and lodged along the upper aerodigestive tract. The purpose of this work is to study the different presentations of button battery foreign bodies and present our experience in the diagnosis and management of this hazardous problem in children. Patients and Methods. This study included 13 patients. The diagnostic protocol was comprised of a thorough history, head and neck physical examination, and appropriate radiographic evaluation. The button batteries were emergently extracted under general anesthesia. Results. The average follow-up period was 4.3 months. Five patients had a nasal button battery. Four patients had an esophageal button battery. Three patients had a button battery in the stomach. One patient had a button battery impacted in the left external ear canal. Apart from a nasal septal perforation and a tympanic membrane perforation, no major complications were detected. Conclusion. Early detection is the key in the management of button battery foreign bodies. They have a distinctive appearance on radiography, and its prompt removal is mandatory, especially for batteries lodged in the esophagus. Physicians must recognize the hazardous potential and serious implications of such an accident. There is a need for more public education about this serious problem. Mohammed Hossam Thabet, Waleed Mohamed Basha, and Sherif Askar Copyright © 2013 Mohammed Hossam Thabet et al. All rights reserved. Cytogenetic Abnormality in Exfoliated Cells of Buccal Mucosa in Head and Neck Cancer Patients in the Tunisian Population: Impact of Different Exposure Sources Mon, 24 Jun 2013 15:42:29 +0000 Chromosome/DNA instability could be one of the primary causes of malignant cell transformation. The objective of the present study was to evaluate the spontaneous genetic damages in exfoliated cells of buccal mucosa of head and neck cancer (HNC) by counting micronucleus (MN) and binucleated (BN) cells frequencies. MN and BN frequencies were significantly increased in HNC patients compared with controls (5.53 ± 3.09/1000 cells, 5.63 ± 2.99/1000 cells versus 2.36 ± 2.11/1000 cells, 3.09 ± 1.82/1000 cells, ). Regarding the gender and the age, the frequencies of the MN and BN were significantly higher than those of controls (). The evaluation of the MN and BN frequencies revealed a significant increase () in the cases in relation to the control group after controlling the risk factors (tobacco smoking and chewing and occupational exposure) of HNC. Moreover, MN and BN frequencies were significantly increased in smokers and chewers compared with nonsmokers and nonchewers among patients (). MN frequency was significantly () different between patients occupationally exposed (6.99 ± 3.40/1000 cells) and nonexposed (4.70 ± 2.48/1000 cells) among HNC group. The logistic regression model illustrated that HNC was significantly associated with frequencies of MN (OR = 8.63, ) and BN (OR = 5.62, ). Our results suggest that increased chromosome/DNA instabilities may be associated with HNC. Rim Khlifi, Fatma Trabelsi-Ksibi, Amine Chakroun, Ahmed Rebai, and Amel Hamza-Chaffai Copyright © 2013 Rim Khlifi et al. All rights reserved.