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Objective: To compare short-term and long-term outcomes after transcanal endoscope-assisted with microscope-assisted ossiculoplasty using the Fisch titanium total prosthesis (FTTP). Study Design: Retrospective chart review. Setting: Tertiary referral center. Patients Pediatric ( 0.05). Three months postoperative endoscopic air conduction PTA0.5-2kHz was 37.6 ± 17.4 dB (14.5 dB improvement) and 44.6 ± 19.9 dB (7.6 dB improvement) in the microscopic group (p > 0.05). Three months postoperative endoscopic PTA0.5-2kHz ABG was 26.8 ± 16.6 dB and 28.4 ± 14.7 dB in the microscopic group (p > 0.05). Latest follow-up endoscopic air conduction PTA0.5-2kHz audiogram (mean follow-up, 20.6 ± 10.4 mo) was 36.1 ± 18.2 dB (16.0 dB improvement) and 40.1 ± 16.8 dB (12.1 dB improvement) in the microscopic group (mean follow-up, 19.9 ± 10.3 mo)(p > 0.05). For endoscopic air conduction PTA0.5-2kHz, between the 3 months and latest follow-up audiogram, 25.0% showed improvement, 50.0% remained stable, and 25.0% deteriorated. In the microscopic group, 26.7% improved, 46.6% remained stable, and 26.7% deteriorated (p > 0.05). Conclusion: Our study shows that hearing results with the Fisch titanium total prosthesis are in line with literature. Endoscope-assisted total ossiculoplasty proves to be a suitable technique with comparable results to the microscopic approach.

To this day, there is no cure for recurrent respiratory papillomatosis (RRP). Multiple surgical procedures are performed to achieve symptom relief and prevention of airway obstruction. A promising drug for RRP is the vascular endothelial growth factor (VEGF) binding antibody bevacizumab. This chemotherapeutic agent has an angiogenesis-inhibiting effect which inhibits tumor growth. The objective of this review was to investigate the efficacy of bevacizumab as treatment option for RRP, and to explore the difference of its effects between intralesional and systemic treatment.A systematic search was conducted in Cochrane, PubMed, and Embase. Articles were included if bevacizumab treatment was given intralesionally and/or systemically. The methodological quality of the studies was assessed using the CAse REport (CARE) guidelines.Of 585 unique articles screened by title and abstract, 15 studies were included, yielding a total of 64 patients. In 95% of the patients treated with systemic bevacizumab, the post-bevacizumab surgical interval was considerably prolonged. More than half of them did not need any surgical intervention during mean follow-up of 21.6 months. Treatment with intralesional bevacizumab showed a lower efficacy: in 62% of the patients, the post-bevacizumab surgical interval (mean, 1.8 months follow-up) was extended when compared to the interval before the treatment.Systemically and intralesionally administered bevacizumab are effective treatment options for severe RRP. A systemic administration might be the treatment of first choice. Further prospective research with long term follow-up is advocated to elucidate this important topic.

The majority of sexually active individuals becomes infected with human papillomavirus (HPV) at least once in their lifetime. Pathways for HPV transmission vary across different mucosal sites per individual. They include autoinoculation within one host, direct transmission between individuals (including perinatal transmission and transmission during sexual activity), and indirect transmission through contact with hands. The authors aim to clarify the prevalence and route of transmission per anatomic site, inter- and intra-individually, using a narrative review of the literature. In conclusion, transmission of HPV to the oral cavity and oropharynx is hypothesised to occur mainly through sexual contact. Transmission of particles through saliva has not been proven and daily living activities are not a documented source of HPV infection. Oropharyngeal HPV related cancer survivors and their partners do not show increased risk of infection during sexual intercourse. Transmission of HPV to the oral cavity (autoinoculation with fingers or transmission through saliva in deep kissing) is probably of limited importance.

Introduction: The novel Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2, may need intensive care unit (ICU) admission in up to 12% of all positive cases for massive interstitial pneumonia, with possible long-term endotracheal intubation for mechanical ventilation and subsequent tracheostomy. The most common airway-related complications of such ICU maneuvers are laryngotracheal granulomas, webs, stenosis, malacia and, less commonly, tracheal necrosis with tracheo-esophageal or tracheo-arterial fistulae. Materials and methods: This paper gathers the opinions of experts of the Laryngotracheal Stenosis Committee of the European Laryngological Society, with the aim of alerting the medical community about the possible rise in number of COVID-19-related laryngotracheal stenosis (LTS), and the aspiration of paving the way to a more rationale concentration of these cases within referral specialist airway centers. Results: A range of prevention strategies, diagnostic work-up, and therapeutic approaches are reported and framed within the COVID-19 pandemic context. Conclusions: One of the most important roles of otolaryngologists when encountering airway-related signs and symptoms in patients with previous ICU hospitalization for COVID-19 is to maintain a high level of suspicion for LTS development, and share it with colleagues and other health care professionals. Such a condition requires specific expertise and should be comprehensively managed in tertiary referral centers.

Purpose To quantify changes in the perceived epithelial border with narrow band imaging (NBI) and white light imaging (WLI) during cholesteatoma surgery and to objectify possible benefits of NBI in otology. Methods Perioperative digital endoscopic images were captured during combined approach tympanoplasty at our tertiary referral center using WLI and NBI (415 nm and 540 nm wavelengths). Sixteen otologic surgeon defined the epithelial borders within 16 identical WLI and NBI photos. Pixels of these selections were calculated to analyze the quantitative difference between WLI and NBI. A questionnaire also analyzed the qualitative differences. Results Sixteen otologic surgeons participated in the study. Stratified per photo, only two photos yielded a significant difference: less pixels were selected with NBI than WLI. A Bland–Altman plot showed no systemic error. Stratified per otologist, four participants selected significantly more pixels with WLI than with NBI. Overall, no significant difference between selected pixels was found. Sub-analyses of surgeons with more than 5 years of experience yielded no additional findings. Despite these results, 60% believed NBI could be advantageous in defining epithelial borders, of which 83% believed NBI could reduce the risk of residual disease. Conclusion There was no objective difference in the identification of epithelial borders with NBI compared to WLI in cholesteatoma surgery. Therefore, we do not expect the use of NBI to evidently decrease the risk of residual cholesteatoma. However, subjective assessment does suggest a possible benefit of lighting techniques in otology. Level of evidence 3.

Objectives: The primary goal was to study the diagnostic potential of narrow-band imaging (NBI), and the secondary goal was to evaluate the most common mistakes when using and interpreting NBI.Design: Retrospective study.Setting: University Medical Center Groningen, tertiary referral hospital, the Netherlands.Participants: Three hundred and seventy patients who underwent rigid endoscopy of the upper aerodigestive tract. Two observers assessed all lesions. Twelve observers assessed a selection of 100 lesions. All observers were provided with both white light imaging and NBI.Main outcome measures: Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy and reasons for insufficient photograph quality.Results: When using NBI, the sensitivity, specificity, PPV, NPV and accuracy for detecting invasive carcinoma, carcinoma in situ or high-grade dysplasia were 92%, 68%, 61%, 94% and 77%, respectively. In multiple-observer analysis, values were 76%, 58%, 53%, 83% and 65% with the evaluation strictly based on type V patterns of Ni's classification, vs 83%, 68%, 64%, 85% and 74% when evaluation was also based on lesion-specific clinical characteristics. Lesions that caused misinterpretations were leukoplakia, papillomas and mucosal lesions after irradiation. In total, 185 photographs were assessed to be of suboptimal quality due to blurring (36%), bleeding (6%), insufficient zooming (15%) and/or insufficient lighting (17%).Conclusion: NBI is a relatively reliable screening method for detecting malignancy. Evaluation based on Ni's classification alone is not sufficient. To optimise NBI photograph quality, we recommend sufficient zooming and prevention of bleeding, blurring and inadequate lighting.

Proper training and assessment of skill in flexible pharyngo-laryngoscopy are central in the education of otorhinolaryngologists. To facilitate an evidence-based approach to curriculum development in this field, a structured analysis of what constitutes flexible pharyngo-laryngoscopy is necessary. Our aim was to develop an assessment tool based on this analysis. We conducted an international Delphi study involving experts from twelve countries in five continents. Utilizing reiterative assessment, the panel defined the procedure and reached consensus (defined as 80% agreement) on the phrasing of an assessment tool. FIFTY PANELISTS COMPLETED THE DELPHI PROCESS. THE MEDIAN AGE OF THE PANELISTS WAS 44 YEARS (RANGE 33-64 YEARS). MEDIAN EXPERIENCE IN OTORHINOLARYNGOLOGY WAS 15 YEARS (RANGE 6-35 YEARS). TWENTY-FIVE WERE SPECIALIZED IN LARYNGOLOGY, 16 WERE HEAD AND NECK SURGEONS, AND NINE WERE GENERAL OTORHINOLARYNGOLOGISTS. AN ASSESSMENT TOOL WAS CREATED CONSISTING OF TWELVE DISTINCT ITEMS.: Conclusion The gathering of validity evidence for assessment of core procedural skills within Otorhinolaryngology is central to the development of a competence-based education. The use of an international Delphi panel allows for the creation of an assessment tool which is widely applicable and valid. This work allows for an informed approach to technical skills training for flexible pharyngo-laryngoscopy and as further validity evidence is gathered allows for a valid assessment of clinical performance within this important skillset

OBJECTIVES/HYPOTHESIS: Recurrent respiratory papillomatosis (RRP) is a disease with a high disease burden. Few studies have assessed quality of life (QoL) of RRP patients. This study compares QoL of these patients with controls. Associations between QoL and sociodemographic and illness-related factors are examined, as is uptake of psychosocial care and speech therapy. STUDY DESIGN: Prospective cross-sectional questionnaire research. METHODS: Ninety-one RRP patients (response = 67%) from two university hospitals in the Netherlands and Finland completed the following patient reported outcome measures: (HADS), 15-dimensional health-related quality-of-life scale (15D), Voice Handicap Index (VHI) and the RAND 36-item health-related quality-of-life survey instrument (RAND-36) assessing health-related QoL and voice handicap, and they provided sociodemographic, illness-related, and allied healthcare use. Descriptive analyses, χ(2) tests, t tests, analysis of variance tests, and Pearson correlations were computed to describe the study population and to examine differences between groups. RESULTS: RRP patients had significantly higher mean scores on depression, health-related QoL (15D) and on voice problems (VHI), and significantly lower mean scores on anxiety than controls. Dutch patients had more pain and a decreased general health perception (RAND-36) than controls. Dutch patients and older patients were more depressed, women were more anxious, older patients had lower health-related QoL, and smoking was significantly associated with voice handicap. Patients who had received psychosocial care had significantly higher HADS-depression mean scores than patients who did not receive psychosocial care. CONCLUSIONS: Having RRP has significant effect on voice-related QoL and depression, but has no negative effect on anxiety and health-related QoL. Risk factors for decreased functioning are different than previously hypothesized by many authors. Prevention should be aimed at these risk factors. LEVEL OF EVIDENCE: 4. Laryngoscope, 2016.

Since 2015, the European Laryngological Society (ELS) has organized on a yearly basis the European Laryngological Live Surgery Broadcast. The goal of this paper is to demonstrate the increasing worldwide audience. The number of individual computers logged in, number of estimated audience, and number of countries with an active audience were calculated and compared to the numbers in 2015. In 2018, 19 live interventions were performed in three parallel sessions. The surgeons worked in 10 departments in 8 different countries. The number of individual computers logged in increased from 1000 in 2015 to 16000 in 2018. The estimated audience increased from 3000 to 32000 visitors. The number of countries with an active audience increased from 52 to 91. The amount of computers logged in is increasing year by year. The audience was presenting despite inconvenient broadcasting times, highlighting the educational importance. The teaching aspect remains visible on videos of this year’s and previous year’s interventions. They can be seen on website http://els.livesurgery.net/home.php . The organization of the European Laryngological Live Surgery Broadcast concurs to the idea that live broadcast of laryngologic surgery is feasible and attractive. Therefore, the ELS is going to continue to organize additional European Laryngological Live Surgery Broadcasts in the future.

OBJECTIVES/HYPOTHESIS: Antireflux therapy is incorporated in many treatment protocols for recurrent respiratory papillomatosis (RRP) because gastroesophageal reflux (GERD) is thought to worsen the disease course of RRP. It is unclear if GERD really aggravates the disease course. The aims of this systematic review were to 1) evaluate incidence of GERD among RRP patients and 2) report if GERD changes the clinical course or tissue properties of RRP. STUDY DESIGN: A search was conducted in PubMed, Embase, and Google Scholar, following the methods of Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. METHODS: Articles with original data, published after January 1, 1990, on RRP with GERD as a determinant were eligible. There was no language restriction. Data on study design, study population, statistics, outcomes (incidence and influence of GERD), and risk of bias were collected and evaluated following PRISMA protocols. RESULTS: Of 1,277 articles, 19 were selected. Gastroesophageal reflux was objectified in 25% to 100% of RRP patients. Subjective GERD was present in 0% to 70% of patients. There is no proof that GERD aggravated the clinical course or tissue properties of RRP, as measured by the number of surgeries, severity scoring systems, or dysplasia. One study did find a higher chance of web formation in patients with anterior or posterior glottic papillomas who did not receive antireflux therapy, but these results should be interpreted with care due to the study's quality. CONCLUSION: There is insufficient proof that GERD does or does not aggravate the clinical course or tissue properties of RRP. Laryngoscope, 2016.

Objectives/Hypothesis: Visualization by endoscopy is essential in the diagnosis of upper aerodigestive tract lesions. Recent studies showed that narrow band imaging (NBI) increases the diagnostic potential of conventional white light imaging (WLI) by highlighting the superficial vessels. The objective of this study was to evaluate whether the use of NBI would influence inter- and intraobserver agreement while making diagnostic decisions using rigid endoscopy of the upper aerodigestive tract. Study Design: Retrospective study. Methods: One hundred routinely collected pictures of laryngeal, hypopharyngeal, and oropharyngeal lesions were used. Rigid endoscopies and patient data collection were performed according to standard protocol. Twelve observers, grouped in different levels of experience, assessed all lesions twice with a 2 to 4 week interval. Fleiss and Cohen's kappa (kappa) values were calculated to assess inter- and intraobserver agreement. Results: Overall interobserver agreement increased from kappa = 0.34 to kappa = 0.40 by adding NBI to WLI (WLI and WLI + NBI, respectively). In experienced observers, an improvement from kappa = 0.39 to kappa = 0.43 was observed; in less-experienced observers an improvement from kappa = 0.30 to kappa = 0.37 was observed. Overall intraobserver agreement increased from moderate (kappa = 0.54) to substantial (kappa = 0.63) with addition of NBI. lntraobserver agreement for less -experienced observers improved remarkably when WLI was combined with NBI (kappa = 0.51 vs. kappa = 0.67). Conclusions: Addition of NBI during rigid endoscopies of the upper aerodigestive tract led to improvement of both inter- and intraobserver agreement.

Objective: Laryngomalacia is the most common cause of dyspnea and stridor in newborn infants. Laryngomalacia is a dynamic change of the upper airway based on abnormally pliable supraglottic structures, which causes upper airway obstruction. In the past, different classification systems have been introduced. Until now no classification system is widely accepted and applied. Our goal is to provide a simple and complete classification system based on systematic literature search and our experiences. Study Design: Retrospective cohort study with literature review. Methods: All patients with laryngomalacia under the age of 5 at time of diagnosis were included. Photo and video documentation was used to confirm diagnosis and characteristics of dynamic airway change. Outcome was compared with available classification systems in literature. Results: Eighty-five patients were included. In contrast to other classification systems, only three typical different dynamic changes have been identified in our series. Two existing classification systems covered 100% of our findings, but there was an unnecessary overlap between different types in most of the systems. Based on our finding, we propose a new a classification system for laryngomalacia, which is purely based on dynamic airway changes. Conclusion: The groningen laryngomalacia classification is a new, simplified classification system with three types, based on purely dynamic laryngeal changes, tested in a tertiary referral center: Type 1: inward collapse of arytenoids cartilages, Type 2: medial displacement of aryepiglottic folds, and Type 3: posterocaudal displacement of epiglottis against the posterior pharyngeal wall. (C) 2015 Wiley Periodicals, Inc.

Human papillomavirus (HPV) infections are well known causes of anogenital cancers. Recent studies show that HPV also plays a role in oropharyngeal cancer (OPC). A review on the role of HPV vaccination in the prevention of head and neck squamous cell carcinoma (HNSCC) with special emphasis on OPC was conducted and available vaccines and vaccination strategies in HNSCC and OPC are discussed. Prophylactic vaccination is known to be effective for prevention of anogenital HPV infection and precursor lesions in the cervix and anus. While the value of vaccination for prevention of OPC and possibly as an adjuvant treatment is still an open question, evidence to date supports the possibility that HPV vaccination may prove to be effective in reducing the incidence of this malignancy. (C) 2015 Elsevier Ltd. All rights reserved.

Objectives/HypothesisTo evaluate the short-term voice outcomes of vocal fold augmentation using fat compared to calcium hydroxylapatite product Radiesse Voice (Merz Aesthetics). Study DesignRetrospective study design. MethodsSixty-six consecutive patients with vocal fold insufficiency were recruited, including the final 33 patients treated with fat and all 33 patients treated with calcium hydroxylapatite product. Before April 2011, fat augmentation was the standard treatment; from April 2011, only calcium hydroxylapatite product was used. For all subjects, videolaryngostroboscopic evaluation, s/z ratios, and voice handicap index (VHI) were analyzed. MethodsTreatment outcomes were evaluated 3 months after the augmentation. Two patients augmented with fat (both after 6 months), versus four augmented with calcium hydroxylapatite product (mean after 7 months), needed reintervention. Mean VHI decreased from 18 points in the fat augmentation group compared to 17 points in the calcium hydroxylapatite group. Mean s/z ratio changed -0.33 in the fat augmentation group compared to -0.46 in the calcium hydroxylapatite group. ConclusionThis retrospective cohort demonstrates that there are no short-term differences in VHI outcome or number of reinterventions for augmentation with fat compared to calcium hydroxylapatite product Radiesse Voice (Merz Aesthetics). Level of EvidenceLevel 4. Laryngoscope, 125:1161-1165, 2015

Background. Recurrent respiratory papillomatosis (RRP) is mainly associated with human papillomavirus (HPV) 6 or HPV11. The purpose of this study was to compare clinical outcome, aggressiveness, and treatment response between HPV6- and HPV11-associated RRP. Methods. A retrospective cohort of 55 patients with RRP (1974-2012) was used. Surgical interventions (n = 814) were analyzed, and complications scored. HPV6/11-specific polymerase chain reaction (PCR) was performed on RRP biopsies. Results. Seventy-six percent of patients (42 of 55) were infected with HPV6 and 24% (13 of 55) with HPV11. The HPV11 group had anatomically more widespread disease. The expected number of surgical interventions was higher in the younger age ( Conclusion. Anatomically, HPV11-associated RRP behaves more aggressively. Younger patients with HPV11 and older patients with HPV6 experience a worse clinical course of RRP. (C) 2014 Wiley Periodicals, Inc.

Management of adult laryngotracheal stenosis is complex and several treatment options are known. The present study focuses on finding the right balance between minimally invasive surgery and laryngotracheal resection by reviewing a single institution's experiences. Retrospective analysis was performed of all adult and adolescent patients with laryngotracheal stenosis who underwent treatment in a tertiary referral center, between 1990 and 2012. Age, gender, etiology, treatment, recurrence, pre- and post-operative peak flow (PF), and pre- and post-treatment subjective complain scores (SCS) were registered. 87 patients with 267 interventions were analyzed. There were 238 dilatation tracheoscopies, 22 open surgeries and various other endoscopic procedures registered. Idiopathic stenoses required the most dilatation tracheoscopies, while post-tracheotomy stenoses required the least. Patients in the post-intubation and post-tracheotomy groups were significantly more often treated with open surgery compared to those in the granulomatosis with polyangiitis (GPA) and idiopathic groups. The gain in PF flow after dilatation tracheoscopy was significantly higher in the idiopathic group compared to the other groups. The median SCS of dyspnoea decreased in the whole population, while other SCS did not change remarkably. Repeated endoscopic procedures are recommended in patients with severe systemic disease which do not allow open surgery or when other comorbidities contraindicate open surgery. Open surgery very often offers the definitive solution in the treatment of laryngotracheal stenosis and cannot be avoided when the laryngeal or the tracheal framework is damaged. Patients' personal preferences have to be considered in the pre-operative assessment process.

Voice disorders can have major impact on quality of life. Problems caused by these disorders can be experienced in different domains. The Voice Handicap Index (VHI) is a well-known voice-related quality of life instrument to measure physical, emotional and functional complaints. VHI change after treatment in seven separate benign laryngeal disorders was studied. In addition, correlation between the three domains was examined. VHI forms were completed before and 3 months after treatment. In a 5-year-period, 143 patients with seven specific diagnoses were retrospectively included. VHI improved for six diagnoses polyp (p

Background The purpose of this study was to evaluate in vitro cytotoxicity and antifibrotic effects of mitomycin C on normal and scarred human vocal fold fibroblasts.

Recurrent respiratory papillomatosis (RRP) is a disease with a high disease burden. Few studies have assessed quality of life (QoL) of RRP patients. This study compares QoL of these patients with controls. Associations between QoL and sociodemographic and illness-related factors are examined, as is uptake of psychosocial care and speech therapy.Prospective cross-sectional questionnaire research.Ninety-one RRP patients (response = 67%) from two university hospitals in the Netherlands and Finland completed the following patient reported outcome measures: (HADS), 15-dimensional health-related quality-of-life scale (15D), Voice Handicap Index (VHI) and the RAND 36-item health-related quality-of-life survey instrument (RAND-36) assessing health-related QoL and voice handicap, and they provided sociodemographic, illness-related, and allied healthcare use. Descriptive analyses, χRRP patients had significantly higher mean scores on depression, health-related QoL (15D) and on voice problems (VHI), and significantly lower mean scores on anxiety than controls. Dutch patients had more pain and a decreased general health perception (RAND-36) than controls. Dutch patients and older patients were more depressed, women were more anxious, older patients had lower health-related QoL, and smoking was significantly associated with voice handicap. Patients who had received psychosocial care had significantly higher HADS-depression mean scores than patients who did not receive psychosocial care.Having RRP has significant effect on voice-related QoL and depression, but has no negative effect on anxiety and health-related QoL. Risk factors for decreased functioning are different than previously hypothesized by many authors. Prevention should be aimed at these risk factors.4. Laryngoscope, 127:1826-1831, 2017.

Antireflux therapy is incorporated in many treatment protocols for recurrent respiratory papillomatosis (RRP) because gastroesophageal reflux (GERD) is thought to worsen the disease course of RRP. It is unclear if GERD really aggravates the disease course. The aims of this systematic review were to 1) evaluate incidence of GERD among RRP patients and 2) report if GERD changes the clinical course or tissue properties of RRP.A search was conducted in PubMed, Embase, and Google Scholar, following the methods of Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines.Articles with original data, published after January 1, 1990, on RRP with GERD as a determinant were eligible. There was no language restriction. Data on study design, study population, statistics, outcomes (incidence and influence of GERD), and risk of bias were collected and evaluated following PRISMA protocols.Of 1,277 articles, 19 were selected. Gastroesophageal reflux was objectified in 25% to 100% of RRP patients. Subjective GERD was present in 0% to 70% of patients. There is no proof that GERD aggravated the clinical course or tissue properties of RRP, as measured by the number of surgeries, severity scoring systems, or dysplasia. One study did find a higher chance of web formation in patients with anterior or posterior glottic papillomas who did not receive antireflux therapy, but these results should be interpreted with care due to the study's quality.There is insufficient proof that GERD does or does not aggravate the clinical course or tissue properties of RRP. Laryngoscope, 126:2330-2339, 2016.

Sclerostin is an inhibitor of bone formation expressed by osteocytes. We hypothesized that sclerostin is expressed by cells of the same origin and also embedded within mineralized matrices. In this study, we analyzed (a) sclerostin expression using immunohistochemistry, (b) whether the genomic defect in individuals with van Buchem disease (VBD) was associated with the absence of sclerostin expression, and (c) whether this was associated with hypercementosis. Sclerostin was expressed by cementocytes in mouse and human teeth and by mineralized hypertrophic chondrocytes in the human growth plate. In individuals with VBD, sclerostin expression was absent or strongly decreased in osteocytes and cementocytes. This was associated with increased bone formation, but no overt changes in cementum thickness. In conclusion, sclerostin is expressed by all 3 terminally differentiated cell types embedded within mineralized matrices: osteocytes, cementocytes, and hypertrophic chondrocytes.

Recurrent respiratory papillomatosis (RRP) is a chronic and difficult to treat disease of the larynx. In 1998, the first article was published that described the use of the antiviral substance cidofovir to treat this disease. Although the results are promising, there remains some concern about the potential carcinogenicity of cidofovir. There is a demand for a qualitative review of the side-effects of this medicine. In this review, the side-effects of cidofovir are investigated. Special attention was given to the potential carcinogenicity of cidofovir. For this review a search is performed in PubMed and EMBASE for relevant articles in which the use of intralesional cidofovir for patients with RRP is described. Eventually, 31 articles could be included for this review. In these articles a total of 188 patients with RRP were described who underwent therapy with intralesional cidofovir. Five of these patients have developed dysplasia of the larynx during the treatment with cidofovir. This is a percentage of 2.7. This percentage is concurrent with the incidence of spontaneous malignant degeneration of RRP (2–3%). Based on this review, it can be concluded that the use of intralesional cidofovir does not increase the risk of laryngeal dysplasia. Apart from the articles that describe the intralesional administration of cidofovir, some articles have been published in which the use of intravenous cidofovir is described as a therapy for RRP. Therefore, a summary is given on the side-effects of intralesional cidofovir as well as a summary on the reported side-effects of the intravenous administration of cidofovir. Based on the outcomes of this review, recommendations are given for a safe use of cidofovir for treatment of recurrent respiratory papillomatosis in the future.

Congenital unilateral deafness is a rare disorder. The prevalence rates are unknown. The prevalence of children with severe to profound hearing losses that are congenital (or acquired before the development of speech and language) is 0.5 to 3 per 1,000 live births. Evidently, congenital unilateral deafness must have a lower prevalence. The purpose of this research was to present a new disorder, hereditary congenital unilateral deafness. A pedigree is presented in which both male and female members display symptoms of congenital unilateral deafness. Two affected persons and a normal-hearing member of the family have vestibular abnormalities without dysequilibrium. The inheritance pattern of this new syndrome is not clear. We hypothesize that the disorder might be new. A family like this has never before been presented in the medical literature.

Van Buchem disease is an autosomal recessive skeletal dysplasia characterised by generalised bone overgrowth, predominantly in the skull and mandible. Clinical complications including facial nerve palsy, optic atrophy, and impaired hearing occur in most patients. These features are very similar to those of sclerosteosis and the two conditions are only differentiated by the hand malformations and the tall stature appearing in sclerosteosis. Using an extended Dutch inbred van Buchem family and two inbred sclerosteosis families, we mapped both disease genes to the same region on chromosome 17q12-q21, supporting the hypothesis that van Buchem disease and sclerosteosis are caused by mutations in the same gene. In a previous study, we positionally cloned a novel gene, called SOST, from the linkage interval and identified three different, homozygous mutations in the SOST gene in sclerosteosis patients leading to loss of function of the underlying protein. The present study focuses on the identification of a 52 kb deletion in all patients from the van Buchem family. The deletion, which results from a homologous recombination between Alu sequences, starts approximately 35 kb downstream of the SOST gene. Since no evidence was found for the presence of a gene within the deleted region, we hypothesise that the presence of the deletion leads to a down regulation of the transcription of the SOST gene by a cis regulatory action or a position effect.

Laryngomalacia is the most common cause of dyspnea and stridor in newborn infants. Laryngomalacia is a dynamic change of the upper airway based on abnormally pliable supraglottic structures, which causes upper airway obstruction. In the past, different classification systems have been introduced. Until now no classification system is widely accepted and applied. Our goal is to provide a simple and complete classification system based on systematic literature search and our experiences.Retrospective cohort study with literature review.All patients with laryngomalacia under the age of 5 at time of diagnosis were included. Photo and video documentation was used to confirm diagnosis and characteristics of dynamic airway change. Outcome was compared with available classification systems in literature.Eighty-five patients were included. In contrast to other classification systems, only three typical different dynamic changes have been identified in our series. Two existing classification systems covered 100% of our findings, but there was an unnecessary overlap between different types in most of the systems. Based on our finding, we propose a new a classification system for laryngomalacia, which is purely based on dynamic airway changes.The groningen laryngomalacia classification is a new, simplified classification system with three types, based on purely dynamic laryngeal changes, tested in a tertiary referral center: Type 1: inward collapse of arytenoids cartilages, Type 2: medial displacement of aryepiglottic folds, and Type 3: posterocaudal displacement of epiglottis against the posterior pharyngeal wall.

To evaluate the short-term voice outcomes of vocal fold augmentation using fat compared to calcium hydroxylapatite product Radiesse Voice (Merz Aesthetics).Retrospective study design.Sixty-six consecutive patients with vocal fold insufficiency were recruited, including the final 33 patients treated with fat and all 33 patients treated with calcium hydroxylapatite product. Before April 2011, fat augmentation was the standard treatment; from April 2011, only calcium hydroxylapatite product was used. For all subjects, videolaryngostroboscopic evaluation, s/z ratios, and voice handicap index (VHI) were analyzed.Treatment outcomes were evaluated 3 months after the augmentation. Two patients augmented with fat (both after 6 months), versus four augmented with calcium hydroxylapatite product (mean after 7 months), needed reintervention. Mean VHI decreased from 18 points in the fat augmentation group compared to 17 points in the calcium hydroxylapatite group. Mean s/z ratio changed -0.33 in the fat augmentation group compared to -0.46 in the calcium hydroxylapatite group.This retrospective cohort demonstrates that there are no short-term differences in VHI outcome or number of reinterventions for augmentation with fat compared to calcium hydroxylapatite product Radiesse Voice (Merz Aesthetics).Level 4.

Recurrent respiratory papillomatosis (RRP) is mainly associated with human papillomavirus (HPV)6 or HPV11. The purpose of this study was to compare clinical outcome, aggressiveness, and treatment response between HPV6- and HPV11-associated RRP.A retrospective cohort of 55 patients with RRP (1974-2012) was used. Surgical interventions (n = 814) were analyzed, and complications scored. HPV6/11-specific polymerase chain reaction (PCR) was performed on RRP biopsies.Seventy-six percent of patients (42 of 55) were infected with HPV6 and 24% (13 of 55) with HPV11. The HPV11 group had anatomically more widespread disease. The expected number of surgical interventions was higher in the younger age (22.4 years) HPV11 group, and the older age (22.4 years) HPV6 group. Regardless of HPV type, earlier age of onset of RRP resulted in a higher number of surgical interventions.Anatomically, HPV11-associated RRP behaves more aggressively. Younger patients with HPV11 and older patients with HPV6 experience a worse clinical course of RRP.

Texto completo. Acesso restrito. p. 1661–1669 Submitted by Santiago Fabio (fabio.ssantiago@hotmail.com) on 2013-07-31T18:06:01Z No. of bitstreams: 1 111111111a.pdf: 683501 bytes, checksum: 978acc94ebde8e6074df25c384a75ff8 (MD5) Approved for entry into archive by Rodrigo Meirelles (rodrigomei@ufba.br) on 2013-11-01T11:57:18Z (GMT) No. of bitstreams: 1 111111111a.pdf: 683501 bytes, checksum: 978acc94ebde8e6074df25c384a75ff8 (MD5) Made available in DSpace on 2013-11-01T11:57:18Z (GMT). No. of bitstreams: 1 111111111a.pdf: 683501 bytes, checksum: 978acc94ebde8e6074df25c384a75ff8 (MD5) Previous issue date: 1999 Sclerosteosis is an uncommon, autosomal recessive, progressive, sclerosing, bone dysplasia characterized by generalized osteosclerosis and hyperostosis of the skeleton, affecting mainly the skull and mandible. In most patients this causes facial paralysis and hearing loss. Other features are gigantism and hand abnormalities. In the present study, linkage analysis in two consanguineous families with sclerosteosis resulted in the assignment of the sclerosteosis gene to chromosome 17q12-q21. This region was analyzed because of the recent assignment to this chromosomal region of the gene causing van Buchem disease, a rare autosomal recessive condition with a hyperostosis similar to sclerosteosis. Because of the clinical similarities between sclerosteosis and van Buchem disease, it has previously been suggested that both conditions might be caused by mutations in the same gene. Our study now provides genetic evidence for this hypothesis. Salvador

Haemorrhage, throat pain and otalgia are common complications following tonsillectomy. Haemorrhage is rarely life-threatening but in this paper we describe a fulminant secondary haemorrhage due to an aberrant external carotid artery in an eight-year-old boy. Acute surgical intervention with ligation of the external carotid artery was needed to control the bleeding.

Intralesional use of cidofovir (Vistide(A (R))) has been one of the mainstays of adjuvant therapy in patients with recurrent respiratory papillomatosis (RRP) since 1998. In 2011, a communication provided by the producer of cidofovir addressed very serious side effects concerning its off-label use. As this was a general warning, it was inconclusive whether this would account for its use in RRP. The aim of this study is to determine whether nephrotoxic, neutropenic, or oncogenic side effects have occurred after intralesional use of cidofovir in patients with RRP. Update of recent developments in RRP, a multicentre questionnaire and a multicentre retrospective chart review. Sixteen hospitals from eleven countries worldwide submitted records of 635 RRP patients, of whom 275 were treated with cidofovir. RRP patients received a median of three intralesional injections (interquartile range 2-6). There were no statistical differences in occurrence of neutropenia or renal dysfunction before and after cidofovir. There was no statistical difference in occurrence of upper airway and tracheal malignancies between the cidofovir and the non-cidofovir group. In this retrospective patient chart review, no clinical evidence was found for more long-term nephrotoxicity, neutropenia or laryngeal malignancies after the administration of intralesional cidofovir in RRP patients.

Placement of enosseous implants in the temporal bone may overcome the apparent disadvantages of skin adhesives and skinpockets for the fixation of auricular prostheses. The surgical procedure for placement of implants in the temporal bone and the results obtained in eight patients wearing implant-supported auricular prostheses are described. From the results of this study, it is obvious that osseointegrated implants have great advantages compared with skin adhesives and skinpockets to rehabilitate patients suffering from auricular defects. The major achievement of implant-supported auricular prostheses is the patients' increased comfort and confidence wearing these types of prostheses.

Background Antilaminin-332 mucous membrane pemphigoid (anti-LN-332 MMP) is a chronic subepidermal blistering disease characterized by IgG anti-epidermal basement membrane zone (BMZ) autoantibodies against laminin-332 (LN-332). Patients with anti-LN-332 MMP have an increased relative risk of malignancy. Laboratory techniques that are difficult to obtain are needed for diagnosis of anti-LN-332 MMP.Objectives To incorporate direct immunofluorescence (DIF) serration pattern analysis of IgG depositions in the diagnostic criteria of anti-LN-332 MMP.Methods Patients who met our revised inclusion criteria for anti-LN-332 MMP were selected from our biobank over the period 1997-2009. Inclusion criteria were clinical symptoms, DIF serration pattern analysis, indirect immunofluorescence (IIF) on salt-split skin, and antigen-specificity analysis of the serum including immunoblotting and/or immunoprecipitation and/or enzyme-linked immunosorbent assay (ELISA) against native LN-332.Results Ten patients met the inclusion criteria. A malignancy was found in two patients (20%). In all patients in whom it was performed (n = 9), DIF showed linear IgG deposition along the BMZ in an n-serrated pattern. Nine sera reacted by salt-split skin analysis and bound to the dermal side of the split skin. ELISA against native LN-332 was positive in 78% of the tested sera.Conclusions Anti-LN-332 MMP can clinically resemble other forms of pemphigoid. Although state-of-the-art laboratory diagnostics are necessary for definite diagnosis, the combination of simple DIF serration pattern and IIF salt-split skin analysis will exclude other forms of MMP and epidermolysis bullosa acquisita from the differential diagnosis. Because of the increased risk for malignancy patients should be thoroughly oncologically screened.

Although the association and clinical significance of human papillomavirus (HPV) infections with a subset of head and neck cancers, particularly for oropharyngeal carcinoma, has recently been well documented, the involvement of HPV in laryngeal cancer has been inadequately evaluated. Herein we review the currently known associations of HPV infections in diseases of the larynx and their potential for oncogenicity. Using several methods of detection, HPV DNA has been detected in benign (papillomatosis), indolent (verrucous carcinoma), and malignant (squamous cell carcinoma) lesions of the larynx. Consistent with the known oncogenic risk of HPV infections, common HPV types associated with laryngeal papillomatosis include low-risk HPV types 6 and 11, with high-risk HPV types 16 and 18 more commonly present in neoplastic lesions (verrucous carcinoma and squamous cell carcinoma). Although a broad range of prevalence has been noted in individual studies, approximately 25% of laryngeal squamous cell carcinomas harbor HPV infections on meta-analysis, with common involvement of high-risk HPV types 16 (highest frequency) and 18. Preliminary results suggest that these high-risk HPV infections seem to be biologically relevant in laryngeal carcinogenesis, manifested as having viral DNA integration in the cancer cell genome and increased expression of the p16 protein. Despite this knowledge, the clinical significance of these infections and the implications on disease prevention and treatment are unclear and require further investigation. (C) 2010 Wiley Periodicals, Inc. Head Neck 33: 581-586, 2011

Detailed preoperative laryngostroboscopic examination is a prerequisite for phonosurgical correction of organic dysphonia. Although suspension microlaryngoscopic surgery has proved its value in the past, it excludes functional control during the removal of vocal fold swellings. Using an indirect microlaryngostroboscopic surgical technique with topical anesthesia, functional control can be achieved during surgery. This enables the removal of vocal fold swellings with a high degree of precision. Postoperative voice evaluation was performed in 31 patients after suspension microlaryngoscopic or indirect microlaryngostroboscopic surgery. The results showed that indirect microlaryngostroboscopic surgery is at least as good as, and in some respects even better than, suspension microlaryngostroboscopic surgery. Large vocal fold swellings, extensive Reinke's edema, and submucosal swellings are considered less suitable for indirect microlaryngostroboscopic surgery, because such lesions require bimanual instrumentation.

Objectives: We describe our experience with the Groningen Dilatation Tracheoscope (Karl Storz GmbH & Co, Tuttlingen, Germany) in treating benign subglottic and tracheal stenosis. Methods: We performed a retrospective survey from a medical record analysis of 26 patients with different origins of benign, grade II (Myer-Cotton) subglottic or tracheal stenosis. All patients underwent dilatation tracheoscopy for a total of 64 times (average, 2.46 operations per patient). Five patients had to undergo subsequent operations. Patient data (sex, age at intervention, underlying and other systemic diseases) and operation data (course, intraoperative and postoperative adverse events) were recorded. Analysis of the measured preoperative and postoperative peak flow values was performed. Results: The average predilatation and postdilatation peak flow values were 225 L/min and 331 L/min, respectively Eighty percent of the patients (21 of 26) were successfully treated with 1 or more dilatation tracheoscopy interventions without supplementary treatment for the stenosis. There is only 1 tracheal cannula–dependent patient in the examined population, making the overall success rate of our treatment 96%. No major intraoperative or postoperative complications were recorded. Conclusions: Dilatation tracheoscopy is a simple, relatively safe, and effective method in the treatment of benign subglottic or tracheal stenosis of various origins. The intervention is minimally invasive and is easily repeatable in case of restenosis.

Evidence based medicine has not quite reached the field of pre- and post-operative speech therapy. Spontaneous healing of the vocal folds after surgery using standardized microphonosurgical techniques is the key to voice restoration. Pre- and post-operative speech therapy should be tailored to the nature of the vocal fold pathology. Precise, truely objective measures of the quality of speech are warranted. Better definitions of and precise goals for speech therapy are desirable.

Laryngeal surgery in children is different from laryngeal surgery in adults and optimally requires a specialized team or staff dedicated to the treatment of children. The anesthesiological approach is related to the age of the patient and is of decisive importance. Maturation of the vocal folds is a delicate process, and superficial and intermediate layers are well defined with a mature vocal ligament by age 16. Congenital or acquired cysts are mostly supraglottic retention cysts. Neonates who have been intubated for a long time can have difficulties with detubation due to intubation granulomas. Congenital laryngeal webs and laryngeal atresia cause stridor. However, smaller webs cause hoarseness and breathiness. Subglottic hemangiomas progressively obstruct the airway within the first few months of life. In rare cases, stridor is due to congenital laryngeal paralysis, which may be unilateral or bilateral. It can worsen during infancy but may be well tolerated even when bilateral. Juvenile onset of recurrent laryngeal papillomas is rare but may be suspected in conjunction with progressive dysphonia. Papillomatosis is exceptional before the age of 1 year. Sulcus glottidis in children seems to be a congenital lesion that deteriorates with increasing age. Vocal abuse is frequent in children. The important question is whether the voice problem is the child’s problem. Gastroesophageal reflux (GER) may cause roughness. The precise pathogenetic role of laryngopharyngeal reflux has not yet been established. The preoperative assessment in patients presenting with stridor is important. Progressive stridor in infants, degree of suprasternal retraction, and failure to thrive are elements that lead to the decision for performing endoscopy under general anesthesia. Some give antacids at least for as long as stridor is not controlled and/or appropriate surgical treatment has not been performed.

Contains fulltext : 79985.pdf (Publisher’s version ) (Closed access) Chromosome analysis in two young patients with multiple congenital anomalies revealed a de novo interstitial deletion of 8q that has not been reported before. The deletions were overlapping by 8.35 Mb (8q24.21q24.23). The clinical features shared by our patients were coloboma, VSD, digital abnormalities, congenital dislocation of a hip, feeding problems, psychomotor delay and convulsions. The deletion included the region for Langer-Giedion syndrome (TRPS1 and EXT1) in the girl only. However, she is too young to present features of this syndrome, apart from dysmorphic features like a bulbous nose and notched alae nasi. Several genes are present in the commonly deleted region, including genes with unknown function, and genes for which haploinsufficiency is known to have no phenotypic effect in mice (Wnt1). A gene that might play a role in the convulsions of our patients is KCNQ3.