Flexible endoscopic evaluation of swallowing in children with type 1 spinal muscular atrophy.

PURPOSE: This study aimed to report on implementing flexible endoscopic evaluation of swallowing (FEES) in infants and toddlers with type 1 spinal muscular atrophy (SMA). In addition, a comparison of FEES results and clinical scores was carried out. METHODS: A prospective pilot study was conducted including ten symptomatic children with SMA type 1 (two SMN2 copies). They started treatment with one of the three currently approved therapies for SMA at a median age of 3.8 months (range 0.7-8.9). FEES was performed according to a standard protocol using Penetration-Aspiration Scale (PAS) and Murray Secretion Scale as a primary outcome. The Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) for motor function, Neuromuscular Disease Swallowing Status Scale (NdSSS), Oral and Swallowing Abilities Tool (OrSAT), and single clinical swallowing-related parameters were also assessed. RESULTS: Distinct swallowing disorders were already evident in eight children at inclusion. The most common findings from FEES were pharyngeal secretion pooling, penetration, and aspiration of saliva and food as well as delayed initiation of swallowing. Despite an average increase in motor function, no comparable improvement was found in swallowing function. None of the surveyed clinical scores showed a significant dependence on PAS in a mixed linear model. CONCLUSIONS: Valuable information regarding the status of dysphagia can be gathered endoscopically, particularly concerning secretion management and when oral intake is limited. Currently available clinical tools for children with type 1 may represent a change in nutritional status but are not yet mature enough to conclude swallowing ability. Further development is still required.

European white paper: oropharyngeal dysphagia in head and neck cancer.

PURPOSE: To develop a European White Paper document on oropharyngeal dysphagia (OD) in head and neck cancer (HNC). There are wide variations in the management of OD associated with HNC across Europe. METHODS: Experts in the management of specific aspects of OD in HNC across Europe were delegated by their professional medical and multidisciplinary societies to contribute to this document. Evidence is based on systematic reviews, consensus-based position statements, and expert opinion. RESULTS: Twenty-four sections on HNC-specific OD topics. CONCLUSION: This European White Paper summarizes current best practice on management of OD in HNC, providing recommendations to support patients and health professionals. The body of literature and its level of evidence on diagnostics and treatment for OD in HNC remain poor. This is in the context of an expected increase in the prevalence of OD due to HNC in the near future. Contributing factors to increased prevalence include aging of our European population (including HNC patients) and an increase in human papillomavirus (HPV) related cancer, despite the introduction of HPV vaccination in various countries. We recommend timely implementation of OD screening in HNC patients while emphasizing the need for robust scientific research on the treatment of OD in HNC. Meanwhile, its management remains a challenge for European professional associations and policymakers.

The ability of the eating assessment tool-10 to detect penetration and aspiration in Parkinson's disease.

PURPOSE: Dysphagia is common in patients with Parkinson's disease (PD) and often leads to pneumonia, malnutrition, and reduced quality of life. This study investigates the ability of the Eating Assessment Tool-10 (EAT-10), an established, easy self-administered screening tool, to detect aspiration in PD patients. This study aims to validate the ability of the EAT-10 to detect FEES-proven aspiration in patients with PD. METHODS: In a controlled prospective cross-sectional study, a total of 50 PD patients completed the EAT-10 and, subsequently, were examined by Flexible Endoscopic Evaluation of Swallowing (FEES) to determine the swallowing status. The results were rated through the Penetration-Aspiration Scale (PAS) and data were analyzed retrospectively. RESULTS: PAS and EAT-10 did not correlate significantly. Selected items of the EAT-10 could not predict aspiration or residues. 19 (38%) out of 50 patients with either penetration or aspiration were not detected by the EAT-10. The diagnostic accuracy was established at only a sufficient level (AUC 0.65). An optimal cut-off value of ≥ 6 presented a sensitivity of 58% and specificity of 82%. CONCLUSIONS: The EAT-10 is not suited for the detection of penetration and aspiration in PD patients. Therefore, it cannot be used as a screening method in this patient population. There is still a need for a valid, simple, and efficient screening tool to assist physicians in their daily diagnostics and to avoid clinical complications.

Dysphagia Screening in Parkinson's Disease. A diagnostic accuracy cross-sectional study investigating the applicability of the Gugging Swallowing Screen (GUSS).

BACKGROUND: Simple water-swallowing screening tools are not predictive of aspiration and dysphagia in patients with Parkinson's Disease (PD). We investigated the diagnostic accuracy of a multi-texture screening tool, the Gugging Swallowing Screen (GUSS) to identify aspiration and dysphagia/penetration in PD patients compared to flexible endoscopic evaluation of swallowing (FEES). METHODS: Swallowing function was evaluated in 51 PD participants in clinical 'on-medication' state with the GUSS and a FEES examination according to standardized protocols. Inter-rater reliability and convergent validity were determined and GUSS- and FEES-based diet recommendations were compared. KEY RESULTS: Inter-rater reliability of GUSS ratings was high (rs  = 0.8; p < 0.001). Aspiration was identified by the GUSS with a sensitivity of 50%, and specificity of 51.35% (PPV 28%, NPV 73%, LR+ 1.03, LR- 0.97), dysphagia/penetration was identified with 72.97% sensitivity and 35.71% specificity (PPV 75%, NPV 33.33%, LR+ 1.14, LR- 0.76). Agreement between GUSS- and FEES-based diet recommendations was low (rs  = 0.12, p = 0.42) with consistent NPO (Nil per Os) allocation by GUSS and FEES in only one participant. CONCLUSIONS AND INFERENCES: The multi-texture screening tool GUSS in its current form, although applicable with good inter-rater reliability, does not detect aspiration in PD patients with acceptable accuracy. Modifications of the GUSS parameters "coughing," "voice change" and "delayed swallowing" might enhance validity. The GUSS' diet recommendations overestimate the need for oral intake restriction in PD patients and should be verified by instrumental swallowing examination.

Dipping and rotating: two maneuvers to achieve maximum magnification during indirect transnasal laryngoscopy.

BACKGROUND: Since many years, office-based flexible transnasal laryngoscopy is a common routine procedure. The development of new technical equipment such as high-definition cameras and flexible tip-chip endoscopes nowadays allows for much more precise examination than a few years ago. In contrast to rigid laryngoscopy, it is possible to move the tip of the endoscope close to the vocal folds and to other structures of interest. Nevertheless, without professional handling of the equipment, one cannot benefit from the potential of the newest technology. METHOD: Two easily performed and very helpful maneuvers in flexible endoscopy are described. The "dipping maneuver" enables a maximum magnification of the mucosal surfaces of the endolarynx as well as the examination of the subglottal region and the trachea by positioning the tip of the endoscope very close to the vocal folds or even in the upper trachea during long transnasal inspiration. During the "rotation laryngoscopy", the tip of the endoscope is positioned in the posterior interarytenoid region by rotating the flexible endoscope by 180° and advancing it close to the glottis. This allows a close-up examination of the anterior commissure, the inferior aspect of the vocal folds and the inside of the Morgagni's ventricle. Before performing transnasal flexible endoscopy, we routinely apply topical anesthesia sprayed intranasally. CONCLUSION: The described techniques of flexible endoscopy are easily performed and allow a maximum magnification of the mucosal surfaces and otherwise not visible regions of the endolarynx.

[Training Curriculum for the Certificate "Diagnostics and Therapy of Oropharyngeal Dysphagia, including FEES", of the German Society for Phoniatrics and Pedaudiology and the German Society for Otolaryngology, Head and Neck Surgery]. / Ausbildungscurriculum zum Zertifikat "Diagnostik und Therapie oropharyngealer Dysphagien, inklusive FEES" der Deutschen Gesellschaft für Phoniatrie und Pädaudiologie und der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie.

BACKGROUND: In Germany, about 5 million people of all ages suffer from dysphagia. Due to demographic change and improved medical care, the incidence of swallowing disorders is expected to increase. Dysphagia is associated with an increased morbidity and mortality and leads to a considerable financial burden on the health systems. The two most common causes of dysphagia are neurological disorders and head and neck cancer. Diagnostics and therapy have developed continuously over the past decades. In particular, the flexible endoscopic evaluation of swallowing (FEES) has become an established part of dysphagia diagnostics. RESULTS: The certificate "Diagnostics and Therapy of Oropharyngeal Dysphagia, incl. FEES" was developed by the German Society for Phoniatrics and Pedaudiology (DGPP) and the German Society for Otolaryngology, Head and Neck Surgery (DGHNO KHC) in cooperation with the German Professional Association for Phoniatrics and Pedaudiology and the German Professional Association of Otolaryngologists.It consists of three parts: the modules (A, B and C), the indirect supervision and a practical examination. Structure, detailed contents and requirements for obtaining the certificate are described in the following article. The qualification of the lecturers and auditors are also defined. CONCLUSION: The systematic training serves the quality assurance and establishment of standards in the diagnostics and therapy of oropharyngeal dysphagia in the area of phoniatrics and ear, nose and throat medicine.

Swallowing speed is no adequate predictor of aspiration in Parkinson's disease.

BACKGROUND: There is still a lack of a clinical test to reliably identify patients with Parkinson's disease (PD) being at risk for aspiration. METHODS: In this prospective, controlled, cross-sectional study, we assessed if swallowing speed for water is a useful clinical test to predict aspiration proven by flexible endoscopic evaluation of swallowing (FEES). Due to this, we measured the swallowing speed for 90 mL water in 115 consecutive and unselected PD outpatients of all clinical stages and 32 healthy controls. KEY RESULTS: Average swallowing speed was lower in patients compared with controls (6.5 ± 3.9 mL/s vs 8.5 ± 3.2 mL/s; P < .01). The disease-independent widely used threshold of <10 mL/s showed insufficient sensitivity of 88% and specificity of 19% with high false-positive rates of 63% for patients and 69% for controls. Receiver operating characteristic (ROC) analysis was carried out to define a suitable cutoff value for detection of aspiration of water (area under the curve 0.72, P < .001) in PD patients. The optimized cutoff value was 5.5 mL/s with a sensitivity of 69% and a specificity of 64%. CONCLUSION AND INFERENCES: Measuring swallowing speed is prone to methodological errors and not suitable as a screening instrument to predict aspiration in PD patients.

Pin-up Glottoplasty: Feasibility Study of a Novel Approach Medializing or Lateralizing Immobile Vocal Folds.

Principles in medializing and lateralizing vocal folds have not changed a lot within the last decades (Isshiki et al, 1974; Bruenings, 1911). We present a feasibility study for a completely new approach to perform medialization and lateralization of immobile vocal folds. The method was tested on 20 human larynges by inserting a 21G needle into the vocal fold, medializing (or, in other cases, lateralizing) the vocal cord and fixing the needle at the cricoid cartilage posteriorly. The anterior and posterior fixation points of the needle allow for a stable positioning of the needle, which we consider necessary in both cases of medialization or lateralization. The needle position was examined visually as well as three-dimensionally via cone beam computed tomography.

EZH2 overexpression in head and neck cancer is related to lymph node metastasis.

BACKGROUND: Enhancer of zeste homolog 2 (EZH2), the catalytic subunit of the polycomb repressive complex 2, plays an important role in tumor development and progression by interacting with histone and non-histone proteins. EZH2 represents a putative therapeutic target and has been suggested as a prognostic marker in several cancer types. MATERIAL AND METHODS: This study investigates the prognostic relevance of immunohistochemical EZH2 expression in head and neck squamous cell carcinoma. Tissue microarray sections with 667 cancers of oral cavity, oro- and hypopharynx and larynx were analyzed for EZH2 expression. RESULTS: Nuclear EZH2 staining was recorded in 322 (81.8%) of 394 cases. Staining was weak in 33 (10.2%), moderate in 128 (39.6%), and strong in 103 (32.0%) cancers. The prevalence of EZH2 expression in tumors of the oral cavity and the orohypopharynx was higher as compared to cancers of the larynx (P = .0023). EZH2 expression was correlated to presence of lymph node metastasis (P = .0089) but was unrelated to histological grade, tumor stage, surgical margin, or distant metastasis. EZH2 expression had no impact on patient survival. CONCLUSION: The high prevalence of EZH2 expression in head and neck squamous cell carcinoma stresses its capability as a therapeutic target.

High-level ßIII-tubulin overexpression occurs in most head and neck cancers but is unrelated to clinical outcome.

BACKGROUND: ßIII-tubulin (TUBB3) is an isotype of microtubules, which are involved in crucial cellular roles including maintenance of cell shape, intracellular transport, and mitosis. Overexpression of TUBB3 was found to be associated with poor prognosis and resistance to tubulin-binding drugs and in several solid tumors including head and neck squamous cell carcinomas (HNSCC). Considering the potential high importance of a prognostic biomarker in these cancers, this study aimed to investigate the clinical relevance of immunohistochemical TUBB3 expression in HNSCC. METHODS: Tissue microarray (TMA) sections containing samples from 667 cancers of oral cavity, oro- and hypopharynx, and larynx for which follow-up data were available were analyzed for TUBB3 expression by immunohistochemistry. RESULTS: Over 90% of our analyzed cancers showed unequivocal cytoplasmic TUBB3 expression. Staining was considered weak in 69 (15.5%), moderate in 149 (33.5%), and strong in 188 (42.2%) of cancers. The frequent TUBB3 overexpression showed no significant correlation with pathological grading, tumor stage, nodal status, or surgical margin and had no impact on patient outcomes. CONCLUSION: Despite lacking prognostic utility in HNSCC, the remarkable high prevalence of TUBB3 expression in HNSCC emphasizes its putative relevance as a target for future drugs targeting TUBB3.

Lack of evidence for prognostic value of epidermal growth factor receptor intron-1 CA repeats for oral carcinomas.

Epidermal growth factor receptor (EGFR) expression is altered in several malignancies, including oral squamous cell carcinoma. A CA-repeat polymorphism in intron-1 (CA-SSR-1) of the EGFR gene is reported to influence EGFR expression and is associated with features of various solid tumors and outcomes of cancer patients. In the present study we evaluated the influence of length and zygosity of CA-SSR-1 on the survival of patients with oral squamous cell carcinoma. The length and zygosity of CA-SSR-1 was obtained through microsatellite analysis in 91 patients with oral cancer, who were treated in the Department of Oral and Maxillofacial Surgery of the University Medical Centre Hamburg Eppendorf, Germany, during the years 1998-2008. Follow up was conducted until 2016. Outcome measures were age, gender, tumor stage, occurrence of metastases, and date of recurrence or death. Statistical analysis was conducted using the chi-square test and the log-rank test. Neither length nor zygosity of the CA-SSR-1 in patients with oral squamous cell carcinoma was significantly correlated with sex, age, tumor size, tumor localization, lymph node involvement, metastasis status, disease-free survival, or overall survival. Length and zygosity of the CA-SSR-1 polymorphism in EGFR is not able to serve as a prognostic biomarker in White European patients with oral squamous cell carcinoma.

CD151 expression is frequent but unrelated to clinical outcome in head and neck cancer.

OBJECTIVES: CD151 is a plasma membrane protein belonging to the tetraspanin family. CD151 represents a putative therapeutic target and has been suggested as a prognostic marker in several cancer types. The present study aims to investigate the prognostic relevance of immunohistochemical CD151 expression in head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: Tissue microarray (TMA) sections containing samples from 667 cancers of oral cavity, oro- and hypopharynx and larynx, for which follow-up data were available, were analyzed for CD151 expression by immunohistochemistry. RESULTS: Membranous CD151 immunostaining was recorded in 269 (60.3 %) of 446 analyzable cases. Staining was considered weak in 129 (28.9 %), moderate in 98 (22.0 %), and strong in 42 (9.4 %) of cancers. CD151 expression was unrelated to histological grade, tumor stage, nodal status, or surgical margin. There was a tendency towards a somewhat lower prevalence of CD151 expression in tumors of the oral cavity (52.9 % positive) as compared to cancers of the oro-hypopharynx (62.1 %) and larynx (63.3 %; p = 0.0100). CD151 expression had no impact on patient survival. CLINICAL RELEVANCE: In summary, immunohistochemical analysis of CD151 lacks prognostic utility in HNSCC. The high prevalence of CD151 expression in HNSCC emphasizes its putative relevance as a therapeutic target for further development of anti-CD151 drugs.