The Efficiency of (videolaryngo) stroboscopy in Detecting T1a Glottic Carcinoma and Its Preliminary Stages.

OBJECTIVE: The efficiency of laryngovideostroboscopy (LVS) in detecting premalignancies of the vocal fold and early glottic cancer was determined in a prospective monocentric study. In addition, the recovery rate of the mucosal membrane on the vocal fold after surgical intervention was determined by LVS. METHODS: We included 159 patients with a leukoplakia of the vocal folds and 50 healthy controls. Clinicopathological data and LVS characteristics (amplitude, mucosal wave, nonvibratory segment, glottic closure, phase symmetry, periodicity) at the lesion site were obtained and compared with the histopathological results. LVS parameters were recorded before cordectomy and in a 12-month follow-up interval. Patients who had prior laryngosurgery, radiotherapy, or laryngeal scarring were excluded. RESULTS: Absent or greatly reduced mucosal waves were found in all patients with an invasive carcinoma, in 94% with a severe intraepithelial neoplasia (SIN III), in 38% with a moderate squamous intraepithelial neoplasia (SIN II), in 32% with a mild squamous intraepithelial neoplasia (SIN I), and in 23% with a hyperkeratosis without dysplasia. The sensitivity and specificity of LVS in predicting an invasive carcinoma based on the absence or reduction of mucosal waves was 0.96 and 0.90, respectively. Following surgical intervention, the recovery rate of the mucosal wave and amplitude was 12% in the invasive carcinoma group, 36% in the SIN III group and up to 80% for both these parameters in the SIN I, SIN II, and hyperkeratosis groups. CONCLUSION: LVS is a valid tool to identify early glottic carcinoma and its high risk premalignancy carcinoma in situ (CIS). Even when there is no definitive differentiation between SIN I and II, the invasive character of a CIS and an invasive glottic carcinoma can be identified. Especially strobosopic signs of abnormal amplitude and/or mucosal waves, particularly phoniatric halt, are an early indication for a CIS or an invasive carcinoma.

[Evaluation of Universal Newborn Hearing Screening and follow-up]. / Evaluation des Neugeborenen-Hörscreenings und der pädaudiologischen Konfirmationsdiagnostik.

BACKGROUND: Universal newborn hearing screening (UNHS) was established in Germany in 2009. Even compliance was tested in early studies, there is little knowledge regarding the follow-up examination of children with suspected hearing disorder. METHODS: A retrospective evaluation was performed in 570 cases of children who failed newborn hearing screening for the years between 2009-2016. Hearing deficiency was defined as having a hearing threshold ≥ 35 dB. Compliance with national guidelines was checked. Every child received brainstem evoked response audiometry (BERA). RESULTS: Permanent hearing disorder was found in 24 %, of whom about half (51 %) had an inner ear hearing loss (of these in 73 % bilateral). Only 27 % of high risk children born in peripheral hospitals were tested immediately by the envisaged automated auditory brainstem response (AABR) method. They often presented tardy, leading to a delayed diagnosis and therapy. Children tracked by the Bavarian health office presented little earlier but had less cases who were lost to follow-up. DISCUSSION: In 93 % a diagnosis was made during first examination and therapy (e. g. prescription of hearing aids) initiated on average within four months age. The rate of deafness corresponded with national averages. The quality of primary screenings is crucial in revealing problems and avoiding delay in dealing with them.

[Subglottic pathologies]. / Subglottische Pathologien.

Subglottic pathologies are rare and show a clinical unspecific appearance i. e. through tissue increase around the cricoid or the cranial trachea. Typical symptoms are hoarseness, an overstimulated coughing, a globus laryngeus feeling as well as dyspnea or a stridor. Differential diagnosis include benign diseases like involving a posttraumatic status (e. g. stenosis), infection (i. e. pseudocroup), rheumatic disease (i. e. granulomatosis with polyangiitis) or benign tumor (i. e. papilloma, hemangioma or granular cell tumor). On the other hand, malignant diseases like the squamous cell carcinoma, a chondrosarcoma or the very rare laryngeal lymphoma manifestation must be considered as well. Idiopathic causes should also be taken into account. To secure the final diagnosis of such tumor formation a tissue sample should be histologically analyzed. The therapy is multimodal e. g. in close collaboration with internal medicine and ENT specialists.

Quality of Voice and Prognostic Markers for the Recovery of Vocal Fold Paralysis After Thyroid Surgery.

OBJECTIVES: This study is set to analyze clinicopathological factors predicting the recovery of unilateral vocal fold paralysis (UVP) in patients after thyroid gland surgery. The quality of voice was additionally assessed in these patients. METHODS: The charts and videolaryngostroboscopy (VLS) examinations of 84 consecutive patients with a complete UVP after surgery of the thyroid gland were retrospectively reviewed. Patients were divided into 2 groups: patients who fully recovered from vocal fold paralysis and those who failed to recover after a follow-up of 12 months. The quality of voice was analyzed among other things by determining the Voice Handicap Index (VHI). RESULTS: The UVP fully recovered in 52 of 84 (61.9%) patients. Positive mucosal waves (pMWs) on the paralyzed side, a minimal glottic gap <3 mm seen at the first postoperative VLS, age ≤50 years, and surgery duration ≤120 minutes were associated factors for a complete recovery of nerve function. The voice parameters improved independently from recovery of the paralysis in 90% of the patients. CONCLUSIONS: For patients with a poor prognosis of a UVP, early intervention may be beneficial. Thus, predicting factors for a full recovery of vocal fold motion would be a valuable tool. In our cohort, about 60% of recoveries could have been predicted using the above-mentioned parameters. Good quality of voice was independently reached in 90% of the cases.

[Evaluation of treatment modalities for contact granulomas]. / Evaluation des Therapieerfolges bei Kontaktgranulomen.

INTRODUCTION: There are merely heterogenous therapy modalities for contact granulomas (CG) without evidenced efficacy. The intention of our study was to evaluate possible risk factors as well as to demonstrate therapeutic successful approaches. METHODS: Based on a retrospective analysis on 79 patients with CG we evaluated personal data for the first patient contact, for the first follow-up appointment (FA) averaged 3-4 months after the first contact, for the second follow-up appointment (SA) averaged 6-8 months after the first contact and for the last follow-up (LA) averaged 13 months after the first contact with collecting information concerning a possible gastrolaryngeal reflux disease as well as symptoms like harrumphing, hoarseness, hyperfunctional dysphonia as well as videostroboscopic signs. The therapeutic methods were prohibition of harrumphing, speech therapy, antazida therapy, surgical resection or a combination of therapy modalities. The group of FA and SA were divided into groups of complete remission group and incomplete remission group, symptoms and stroboscopic signs were statistically compared. RESULTS: Harrumphing was an important cofactor in developing a CG. Although we couldn't verify a superior therapy modality a complete remission was archieved in 2/3rd of the reviewed cases. Even if there was an incomplete remission of the contact granuloma we were able to show a reduction of symptoms. Surgical resections of CG showed a significantly higher recurrence rate. DISCUSSION: Even if we couldn't confirm a superior therapy modality we recommend a symptomatic therapy of CG with overall good remission rates. Primary surgical interventions are not advised owing to high recurrence rates.

Sequencing the GRHL3 Coding Region Reveals Rare Truncating Mutations and a Common Susceptibility Variant for Nonsyndromic Cleft Palate.

Nonsyndromic cleft lip with/without cleft palate (nsCL/P) and nonsyndromic cleft palate only (nsCPO) are the most frequent subphenotypes of orofacial clefts. A common syndromic form of orofacial clefting is Van der Woude syndrome (VWS) where individuals have CL/P or CPO, often but not always associated with lower lip pits. Recently, ∼5% of VWS-affected individuals were identified with mutations in the grainy head-like 3 gene (GRHL3). To investigate GRHL3 in nonsyndromic clefting, we sequenced its coding region in 576 Europeans with nsCL/P and 96 with nsCPO. Most strikingly, nsCPO-affected individuals had a higher minor allele frequency for rs41268753 (0.099) than control subjects (0.049; p = 1.24 × 10(-2)). This association was replicated in nsCPO/control cohorts from Latvia, Yemen, and the UK (pcombined = 2.63 × 10(-5); ORallelic = 2.46 [95% CI 1.6-3.7]) and reached genome-wide significance in combination with imputed data from a GWAS in nsCPO triads (p = 2.73 × 10(-9)). Notably, rs41268753 is not associated with nsCL/P (p = 0.45). rs41268753 encodes the highly conserved p.Thr454Met (c.1361C>T) (GERP = 5.3), which prediction programs denote as deleterious, has a CADD score of 29.6, and increases protein binding capacity in silico. Sequencing also revealed four novel truncating GRHL3 mutations including two that were de novo in four families, where all nine individuals harboring mutations had nsCPO. This is important for genetic counseling: given that VWS is rare compared to nsCPO, our data suggest that dominant GRHL3 mutations are more likely to cause nonsyndromic than syndromic CPO. Thus, with rare dominant mutations and a common risk variant in the coding region, we have identified an important contribution for GRHL3 in nsCPO.

Prognostic Relevance of Mucosal Waves in Patients With Unilateral Vocal Fold Paralysis.

OBJECTIVES: To analyze the prognostic relevance of mucosal waves (MWs) for recovery of unilateral vocal fold paralysis (UVP). METHODS: The charts and stroboscopic examinations of 100 consecutive patients with a complete UVP were reviewed retrospectively. All had a minimal (estimated <3 mm) mucosal gap on stroboscopy. A positive or negative MW on the paralyzed vocal fold was associated with complete recovery to full adduction and abduction. All patients were followed for at least 12 months. RESULTS: Causes of the paralysis were iatrogenic/traumatic (n = 82), malignancy associated (n = 10), and idiopathic (n = 8). In patients with positive MW at diagnosis (n = 80), the chance of recovery of unilateral vocal fold paralysis was 91.25%, whereas the chance of recovery with a negative mucosal wave (n = 20) was only 10%. CONCLUSION: Positive MWs in stroboscopy are a predictor for recovery of (iatrogenic/traumatic) unilateral vocal fold paralysis and should be used in routine diagnostic assessment.

Hoarseness-causes and treatments.

BACKGROUND: Hoarseness (dysphonia) is the reason for about 1% of all consultations in primary care. It has many causes, ranging from self-limited laryngitis to malignant tumors of the vocal cords. METHODS: This review is based on literature retrieved by a selective search in PubMed employing the terms "hoarseness," "hoarse voice," and "dysphonia," on the relevant guideline of the American Academy of Otolaryngology -Head and Neck Surgery, and on Cochrane reviews. RESULTS: Hoarseness can be caused by acute (42.1%) and chronic laryngitis (9.7%), functional vocal disturbances (30%), and benign (10.7-31%) and malignant tumors (2.2-3%), as well as by neurogenic disturbances such as vocal cord paresis (2.8-8%), physiologic aging of the voice (2%), and psychogenic factors (2-2.2 %). Hoarseness is very rarely a manifestation of internal medical illness. The treatment of hoarseness has been studied in only a few randomized controlled trials, all of which were on a small scale. Voice therapy is often successful in the treatment of functional and organic vocal disturbances (level 1a evidence). Surgery on the vocal cords is indicated to treat tumors and inadequate vocal cord closure. The only entity causing hoarseness that can be treated pharmacologically is chronic laryngitis associated with gastro-esophageal reflux, which responds to treatment of the reflux disorder. The empirical treatment of hoarseness with antibiotics or corticosteroids is not recommended. CONCLUSION: Voice therapy, vocal cord surgery, and drug therapy for appropriate groups of patients with hoarseness are well documented as effective by the available evidence. In patients with risk factors, especially smokers, hoarseness should be immediately evaluated by laryngos - copy.

Do orofacial clefts represent different genetic entities?

OBJECTIVE: To contribute to the understanding of potential genetic differences between different cleft types. METHOD: Analysis of family history concerning cleft type and search for cleft-type-specific associations in candidate genes performed in 98 individuals from 98 families. RESULTS: In a given family, the cleft type of a second case was more often identical to the index case than expected by chance. Each type of cleft (cleft lip [CL], cleft lip and palate [CLP], cleft palate only [CP], and submucous cleft palate only [SMCP]) was associated with different genes. CONCLUSION: Family history indicates some specificity of cleft types. The observed phenotype-genotype associations were compatible with this interpretation in that significant associations occurred with disjoint sets of genes in each cleft type. These observations indicate that CL, CLP, CP, and SMCP might represent genetically different entities.

Long term outcome of psychogenic voice disorders.

OBJECTIVES: To evaluate different therapy for psychogenic voice disorders. METHODS: Epidemiological data, organic and psychological symptoms, therapeutic options and outcome were prospectively analyzed in 40 consecutive patients with psychogenic voice disorders. Their voice was evaluated by subjective means and self assessment (voice handicap index) and an organic or functional disorder was excluded by videolaryngostroboscopy. Additionally, a detailed psychological examination and exploration were made. Every patient received intensive voice exercises with biofeedback by a phoniatrician and counseling by a clinical psychologist. Following this, therapy options of psychotherapy or a combination of psychotherapy and voice therapy were given. After an interval (average 16 months) from first contacting our section, every patient was asked to complete a questionnaire about their therapies and quality of voice. RESULTS: Patients had previously received insufficient voice therapy or antibiotics. The psychological examination detected psychological disorders as a basic problem. Overall, in 70% of patients there was either an improvement or resolution of voice problems. For all patients psychotherapy or a combination of voice therapy and psychotherapy was recommended, but only accepted in 37.5%. In all cases, when psychotherapy in combination with speech therapy took place, it was successful, whereas speech therapy alone provided improvement only in 12.5%. CONCLUSION: Psychogenic voice disorders are often misdiagnosed, leading to inadequate therapy. Psychotherapy (often in combination with voice therapy) was most effective also in the long term, but is often not accepted by patients. Voice therapy alone had a poor success rate.

Laryngoplasty with hyaluronic acid in patients with unilateral vocal fold paralysis.

OBJECTIVES: Augmentation of vocal fold with hyaluronic acid (Restylane; Q-Med AB, Uppsala, Sweden) is used as a therapeutic option for insufficient glottic closure in unilateral vocal fold paralysis (UVP). Analysis of the optimal glottic width, effectiveness (long-term voice improvement as a consequence of longevity of Restylane), and safety of this new method was made. STUDY DESIGN/METHODS: In a prospective clinical cohort study, 19 consecutive patients with UVP who received vocal fold augmentation with hyaluronic acid (Restylane) were examined preoperatively; 6 weeks, 6, and 12 months postoperatively by laryngostroboscopy; and their voice was evaluated by subjective, objective, and self-assessment (Voice Handicap Index). RESULTS: In 11 of 19 (58%) patients, a subjectively and objectively acceptable voice quality was observed in a follow-up of 12 months. Eight of 19 (42%) patients had a considerable impairment of the voice after 6 weeks (range: 1-24 weeks). Therefore, another intervention (eg, injection laryngoplasty or thyroplasty) was recommended. An impairment of voice was mainly observed if the preoperative glottal gap during phonation was more than 1 mm. CONCLUSION: A long duration (up to 12 months) of acceptable quality of voice was achieved by augmentation with Restylane, if the glottal gap was 1 mm or less videolaryngostroboscopically during phonation. The authors recommend this therapy for temporary voice improvement and to augment vocal therapy, if spontaneous recovery of voice is likely. Long-term results remain to be seen.

Genetic and environmental risk factors for submucous cleft palate.

A multifactorial aetiology with genetic and environmental factors is assumed for orofacial clefts. Submucous cleft palate (SMCP), a subgroup of cleft palates with insufficient median fusion of the muscles of the soft palate hidden under the mucosa, has a prevalence of 1:1,250-1:5,000. We described the prevalence of risk factors among 103 German patients with the subtype SMCP and genotyped 24 single nucleotide polymorphisms (SNPs) from 12 candidate genes for orofacial clefts. Analysis of risk factors yielded a positive history for maternal cigarette smoking during pregnancy in 25.2% of the patients, and this was significantly more frequent than in the normal population. The group of patients differed in allele frequencies at SNP rs3917192 of the gene TGFB3 (nominal P = 0.053) and at SNP rs5752638 of the gene MN1 (nominal P = 0.075) compared with 279 control individuals. Our results indicate a potential role of maternal smoking during pregnancy for the formation of SMCP. The analysis of genetic variants hints at the contribution of TGFB3 and MN1 in the aetiology of SMCPs.

Long-term outcome in preterm children with human cytomegalovirus infection transmitted via breast milk.

AIM: To investigate neurodevelopmental outcome and hearing in preterm children with breast milk transmitted human cytomegalovirus (HCMV) infection. METHODS: Forty-one preterm children (born before 32 weeks of gestation or birth weight <1500 g; 20 HCMV positive, 21 HCMV negative) from an original cohort of 44 children were examined at school age. Assessments included neurological examination, assessment of motor [Movement Assessment Battery for Children (M-ABC)] and cognitive function [Kaufman Assessment Battery for Children (K-ABC)], audiological tests and anthropometric measures. RESULTS: In both groups, irrespective of the presence or absence of a history of HCMV infection, performance in assessments of cognitive and motor function was within the normal range. However, significant differences between the HCMV-positive and the HCMV-negative group were found in both motor and cognitive function, with poorer performance in the HCMV-positive group. There were no significant differences in anthropometric parameters, and all 20 HCMV-positive children had normal hearing function. CONCLUSIONS: In this study, cognitive and motor function in preterm children with early postnatally acquired HCMV infection transmitted via breast milk was within the normal range. However, the findings suggest that their outcome is poorer than outcome in preterm children without HCMV infection. These findings need to be replicated in larger scale studies.

Discrimination of native and non-native vowel contrasts in bilingual Turkish-German and monolingual German children: Insight from the Mismatch Negativity ERP component.

The development of native-like memory traces for foreign phonemes can be measured by using the Mismatch Negativity (MMN), a component of the auditory event-related potential. Previous studies have shown that the MMN is sensitive to changes in neural organization depending on language experience. Here we measured the MMN response in 5-6year-old monolingual German and bilingual Turkish-German kindergarten children growing up in Germany. MMN was investigated to a German vowel contrast and to a vowel contrast that exists in Turkish and in German. The results show that compared to a German control group, the MMN response is less robust in Turkish-German children to the German vowel contrast. The response to the contrast that exists in both languages does not differ between groups. Overall, the results suggest that the Turkish-German children have not yet fully acquired the German phonetic inventory despite living in Germany since birth and being immersed in a German-speaking environment.

Repaired cleft palate and ventilation tubes and their associations with cholesteatoma in children and adults.

OBJECTIVE: To determine the influence of ventilation tubes (VTs) on the formation of cholesteatoma and hearing in operated cleft palate patients with chronic ear problems. DESIGN: Retrospective 72-month follow-up of 116 operated cleft palate patients. PATIENTS AND INTERVENTIONS: Demographic data, clinical examination, and hearing were evaluated. The patients were divided according to age and type of cleft and subdivided in a subgroup with (VT+) or without ventilation tube (VT-). MAIN OUTCOME MEASURES: The effect of ventilation tubes (VT) on the incidence of cholesteatoma formation and degree of hearing loss in operated cleft palate patients with chronic ear problems. RESULTS: The overall incidence of cholesteatoma was 15.5% (VT+, 14.0%; VT-, 16.7%; not significant). Bilateral hearing loss of >20 dB remained in 14.0% of the VT+ patients and in 22.7% of the VT- patients (p < .05). Submucous cleft palate (SM CP) adults (n = 15) developed high rates of cholesteatoma and hearing loss of >20 dB (both 26.7%). CONCLUSIONS: Tube insertion had no influence on the development of cholesteatoma. Adults with submucous cleft palate especially require periodic otologic evaluation because they have Eustachian tube-related otologic disease and hearing loss at a higher rate than expected.

Breathing and voice quality after surgical treatment for bilateral vocal cord paralysis.

OBJECTIVE: To evaluate long-term results of surgical treatment for bilateral vocal cord paralysis using objective and subjective measures of breathing and voice quality. DESIGN: Prospective cross-sectional case series. SETTING: Tertiary care otolaryngology and speech pathology referral center. PATIENTS: Ten patients with bilateral vocal cord paralysis who underwent surgical treatment between October 1996 and May 2006 at the Department of Otorhinolaryngology-Head and Neck Surgery, University of Würzburg, were examined at a mean of 27.2 months after surgery. MAIN OUTCOME MEASURES: Glottal area, voice range profile, Voice Handicap Index, pulmonary function test results, Göttingen Hoarseness Diagram, microlaryngostroboscopic findings, chronic respiratory disease questionnaire, and European Organization for Research and the Treatment of Cancer quality-of-life questionnaire, including the head and neck module. RESULTS: Residual recurrent nerve function was seen in 9 of 10 patients. Pulmonary data varied widely and did not correlate with the size of the glottal area. Quality of life, subjective dyspnea, and physical functioning correlated with expiratory airflow measures. Voice range was reduced in all patients. High breathiness and reduced maximum phonation time led to increased Voice Handicap Index scores. CONCLUSIONS: Microlaryngostroboscopic findings did not necessarily correlate with subjective dyspnea and vocal complaints. Reduction of inspiratory speaking efforts and acquisition of special breathing techniques improve airflow stability and effectiveness of respiration, leading to enhanced quality of life.

A novel IRF6 nonsense mutation (Y67X) in a German family with Van der Woude syndrome.

Van der Woude syndrome (VWS) is the most common type of syndromic orofacial cleft, which accounts for approximately 2% of all cleft lip and palate cases. It is characterised by variable association of lower lip pits, cleft lip and cleft palate, and hypodontia. VWS arises as the result of mutations in the gene encoding interferon regulatory factor 6 (IRF6). The disorder is transmitted in an autosomal dominant manner, with high penetrance and variable expressivity. Very recently, mutations of the IRF6 gene in exons 2-9 have been found in VWS patients, suggesting that this gene plays an important role in orofacial development. We report a novel mutation of the IRF6 gene in a German family. Five out of the 12 persons affected were able to be investigated. The mutation produced a stop codon within exon 4 of the IRF6 gene. All 5 patients were heterozygous for a base substitution c.201C>A changing the tyrosine codon at amino acid position 67 into a stop codon (p.Y67X) in exon 4. The premature stop codon was responsible for a truncated protein lacking parts of the DNA- binding domain and the complete Smad-interferon regulatory factor-binding domain probably essential for interactions with the Smad transcription factors.