Prediction of lymph node status in patients with surgically treated head and neck squamous cell carcinoma via neck lavage cytology: A pilot study.

BACKGROUND: Neck dissection is a standardized surgical procedure for patients with head and neck squamous cell carcinoma (HNSCC) and plays a critical role in the choice of adjuvant treatment based on histopathological findings. Saline irrigation is routinely performed at the end of surgery. However, this irrigant is not used for diagnostic purposes. METHODS: Intraoperative irrigation of the neck dissection wound was performed in 56 patients with HNSCC (N = 93 neck dissections), and the cytological suspension obtained was processed via the liquid-based cytology (LBC) technique, Papanicolaou staining, and immunocytochemical staining. Microscopic preparations were screened for the presence of tumor cells and classified as positive, borderline, or negative. These results were correlated with the histopathological and clinical data. RESULTS: Neck lavage LBC demonstrated high diagnostic value in detecting lymph node metastases (N+) with extracapsular spread (ECS), with a specificity, sensitivity, negative predictive value, and positive predictive value of 93.1%, 100%, 100%, and 80%, respectively. Tumor cells were detected in 4.8% of N- cases, 20% of N+ cases without ECS, and 100% of N+ cases with ECS. Receiver operating characteristic curve analysis showed an area under the curve of 0.8429 for the prediction of N+ (p < .0001) and 0.9658 for the prediction of N+ with ECS (p < .0001). CONCLUSIONS: Differential lavage cytology can provide valid and rapid information on the lymph node status in patients with HNSCC and showed an excellent correlation with histopathology. Thus, neck lavage LBC may facilitate faster and more reasonable planning of adjuvant treatment and help improve the therapeutic management of patients with HNSCC.

Dual Sec62/Ki67 immunocytochemistry of liquid-based cytological preparations represents a highly valid biomarker for non-invasive detection of head and neck squamous cell carcinomas.

BACKGROUND: Head and neck squamous cell carcinomas (HNSCC) are frequently diagnosed in advanced stages, which limits therapeutic options and results in persistently poor patient outcomes. The aim of this study was to use liquid-based swab cytology (LBC) in combination with dual immunocytochemical detection of migration and proliferation markers Sec62 and Ki67 in order to allow non-invasive early detection of HNSCC as well as to analyse the diagnostic validity of this method for predicting the malignancy of suspicious oral lesions. METHODS: 104 HNSCC patients and 28 control patients, including healthy patients (n = 17), papilloma (n = 1) and leukoplakia patients (n = 10), were included in this study. For all patients, an LBC swab followed by simultaneous immunocytochemical detection of Sec62 and Ki67 was performed. Immunocytochemical as well as cytopathological results were correlated with histological diagnoses and clinical findings. RESULTS: All HNSCC patients (100%) showed dual Sec62/Ki67 positivity, and all control patients except for the papilloma patient were negative for Sec62/Ki67 (96.4%), resulting in a 100% sensitivity and 96.4% specificity of Sec62/Ki67 dual stain for non-invasive detection of HNSCC. The positive predictive value was 99% and the negative predictive value was 100%. Sec62 expression levels showed a positive correlation with tumour de-differentiation (p = 0.0489). CONCLUSION: Simultaneous immunocytochemical detection of Sec62/Ki67 using LBC represents a promising non-invasive and easy-to-apply tool for the early detection of HNSCC in routine clinical practice. This novel technique can help to avoid incisional biopsies and reduce the frequency with which general anaesthesia is used in diagnostic procedures in patients with suspicious oral lesions.

Alterations in pathogen-specific cellular and humoral immunity associated with acute peripheral facial palsy of infectious origin.

BACKGROUND: Peripheral facial palsy (PFP) is a common neurologic symptom which can be triggered by pathogens, autoimmunity, trauma, tumors, cholesteatoma or further local conditions disturbing the peripheral section of the nerve. In general, its cause is often difficult to identify, remaining unknown in over two thirds of cases. As we have previously shown that the quantity and quality of pathogen-specific T cells change during active infections, we hypothesized that such changes may also help to identify the causative pathogen in PFPs of unknown origin. METHODS: In this observational study, pathogen-specific T cells were quantified in blood samples of 55 patients with PFP and 23 healthy controls after stimulation with antigens from varicella-zoster virus (VZV), herpes-simplex viruses (HSV) or borrelia. T cells were further characterized by expression of the inhibitory surface molecule CTLA-4, as well as markers for differentiation (CD27) and proliferation (Ki67). Pathogen-specific antibody responses were analyzed using ELISA. Results were compared with conventional diagnostics. RESULTS: Patients with PFP were more often HSV-seropositive than controls (p = 0.0003), whereas VZV- and borrelia-specific antibodies did not differ between groups. Although the quantity and general phenotypical characteristics of antigen-specific T cells did not differ either, expression of CTLA-4 and Ki67 was highly increased in VZV-specific T cells of 9 PFP patients, of which 5 showed typical signs of cutaneous zoster. In the remaining 4 patients, a causal relationship with VZV was possible but remained unclear by clinical standard diagnostics. A similar CTLA-4- and Ki67-expression profile of borrelia-specific T cells was also found in a patient with acute neuroborreliosis. DISCUSSION: In conclusion, the high prevalence of HSV-seropositivity among PFP-patients may indicate an underestimation of HSV-involvement in PFP, even though HSV-specific T cell characteristics seem insufficient to identify HSV as a causative agent. In contrast, striking alterations in VZV- and borrelia-specific T cell phenotype and function may allow identification of VZV- and borrelia-triggered PFPs. If confirmed in larger studies, antigen-specific immune-phenotyping may have the potential to improve specificity of the clinical diagnosis.

Assessing the Use of Telepresence-Guided Video-Based Head and Neck Ultrasound Training: A Step towards Minimizing Dependence on Human Resources?

The acquisition of ultrasound skills is an essential part of any medical student's education. University access restrictions in the context of the COVID-19 pandemic have highlighted the need for digitization in teaching. However, teaching manual skills in online courses has proven to be challenging, not least in terms of human resources. Therefore, the aim of this study was to set up a hybrid head and neck ultrasound course consisting of a preface of video-based self-study followed by supportive instruction by a tutor in telepresence and to evaluate the quality, effectiveness, and feasibility of this teaching method. Thirty-five students were shown video tutorials on systematic ultrasound of the neck course. Learning outcomes were analyzed using self-assessment questionnaires and external assessment by an experienced ultrasonographer. All participants demonstrated statistically significant learning improvement (p < 0.001) when comparing self-assessment scores before and after training. The mean self-assessment scores increased from 13.8 to 26.6 for the telepresence-guided group, from 16.6 to 27.3 for the web-based group, and from 14.0 to 26.2 for the in-person group. The external observer assessment also showed improvement, with mean scores of 46.7, 48.1, and 46.5, respectively. Overall results did not significantly differ when comparing different instruction modalities. A telepresence-guided video-based ultrasound course is well suited to teaching ultrasound skills similar to in-person courses and allows a more resource-efficient targeting of student needs.

[Experiences with endoscopic ear surgery of a German tertiary hospital for otolaryngology]. / Erfahrungen mit der endoskopischen Ohrchirurgie an einer deutschen Hals­, Nasen­, Ohrenklinik der Maximalversorgung.

BACKGROUND: The aim of this article is to report on the integration of endoscopic ear surgery (EES) into daily clinical practice. MATERIAL AND METHODS: In a monocentric prospective study, the endoscopy unit was set up during even weeks over a period of 10 months and the procedure was primarily started endoscopically via a transmeatal approach. In odd weeks, the endoscopy was omitted. A total of 60 procedures in 59 patients were evaluated. Points of comparison were intraoperative vision, incision-suture time, postoperative hearing outcome, and postoperative otoscopic findings. RESULTS: With the exception of the facial nerve (p = 0.15 Mann-Whitney U­test), the EES showed significantly improved visualization of all areas in the middle ear. The incision-suture times were similar in both methods. If bimanual placement of an ossicular prosthesis was necessary, the incision-suture time increased disproportionately (MES: 57.18 ± 9.7 min, EES: 76.83 ± 24.99 min; p = 0.019, *). There were no statistically significant changes related to hearing outcomes when comparing EES with the microscopic technique. There were no postoperative complications in the EES surgery group. CONCLUSION: Integration of EES proved to be successful and advantageous in a real patient collective at this location.

Immunohistochemistry Reveals TRPC Channels in the Human Hearing Organ-A Novel CT-Guided Approach to the Cochlea.

TRPC channels are critical players in cochlear hair cells and sensory neurons, as demonstrated in animal experiments. However, evidence for TRPC expression in the human cochlea is still lacking. This reflects the logistic and practical difficulties in obtaining human cochleae. The purpose of this study was to detect TRPC6, TRPC5 and TRPC3 in the human cochlea. Temporal bone pairs were excised from ten body donors, and the inner ear was first assessed based on computed tomography scans. Decalcification was then performed using 20% EDTA solutions. Immunohistochemistry with knockout-tested antibodies followed. The organ of Corti, the stria vascularis, the spiral lamina, spiral ganglion neurons and cochlear nerves were specifically stained. This unique report of TRPC channels in the human cochlea supports the hypothesis of the potentially critical role of TRPC channels in human cochlear health and disease which has been suggested in previous rodent experiments.

Prognostic impact of intra- and peritumoral immune cell subpopulations in head and neck squamous cell carcinomas - comprehensive analysis of the TCGA-HNSC cohort and immunohistochemical validation on 101 patients.

Background: Due to the expanding role of immune checkpoint inhibition in the treatment of head and neck squamous cell carcinoma, understanding immunological processes in the tumor microevironment (TME) has strong translational importance. Though analytical methods for a comprehensive analysis of the immunological TME have constantly improved and expanded over the past years the prognostic relevance of immune cell composition in head and neck cancer TME largely remains ambiguous with most studies focusing on one or a small subset of immune cells. Methods: The overall survival (OS) of the TCGA-HNSC patient cohort comprising 513 head and neck cancer patients was correlated with a total of 29 different immune metrics including a wide spectrum of immune cell subpopulations as well as immune checkpoint receptors and cytokines using RNAseq based immune deconvolution analyses. The most significant predictors of survival among these 29 immune metrics were validated on a separate HNSCC patient cohort (n=101) using immunohistochemistry: CD3, CD20+CXCR5, CD4+CXCR5, Foxp3 and CD68. Results: Overall immune infiltration irrespective of immune cell composition showed no significant correlation with the patients' overall survival in the TCGA-HNSC cohort. However, when focusing on different immune cell subpopulations, naïve B cells (p=0.0006), follicular T-helper cells (p<0.0001), macrophages (p=0.0042), regulatory T cells (p=0.0306), lymphocytes (p=0.0001), and cytotoxic T cells (p=0.0242) were identified as highly significant predictors of improved patient survival. Using immunohistochemical detection of these immune cells in a second independent validation cohort of 101 HNSCC patients, we confirmed the prognostic relevance of follicular T helper cells, cytotoxic T cells and lymphocytes. In multivariable analysis, HPV negativity and advanced UICC stages were identified as additional prognostic biomarkers associated with poor outcome. Conclusion: Our study highlights the prognostic relevance of the immunological tumor environment in head and neck cancer and demonstrates that a more detailed analysis of immune cell composition and immune cell subtypes is necessary to accurately prognosticate. We observed the highest prognostic relevance for lymphocytes, cytotoxic T cells, and follicular T helper cells, suggesting further investigations focusing on these specific immune cell subpopulations not only as predictors of patient prognosis but also as promising targets of new immunotherapeutic strategies.

Differential nasal swab cytology represents a valuable tool for therapy monitoring but not prediction of therapy response in chronic rhinosinusitis with nasal polyps treated with Dupilumab.

Introduction: Chronic Rhinosinusitis with nasal polyps (CRSwNP) is a common chronic disease with a high impact on patients' quality of life. If conservative and surgical guideline treatment cannot sufficiently control disease burden, biologicals can be considered as a comparably new treatment option that has revolutionized CRSwNP therapy since the first approval of Dupilumab in 2019. With the aim to select patients who benefit from this new treatment and to find a marker for therapy monitoring, we investigated the cellular composition of nasal mucous membranes and inflammatory cells of patients suffering from CRSwNP and undergoing Dupilumab therapy using non-invasive nasal swab cytology. Methods: Twenty CRSwNP patients with the indication for Dupilumab therapy have been included in this prospective clinical study. In total, five study visits were conducted with ambulatory nasal differential cytology using nasal swabs starting with the beginning of therapy and followed by visits every 3 months for 12 months. First, these cytology samples were stained with the May-Grunwald-Giemsa method (MGG) and the percentage of ciliated cells, mucinous cells, eosinophil cells, neutrophil cells, and lymphocytes was analyzed. Secondly, an immunocytochemical (ICC) ECP-staining was performed to detect eosinophil granulocytes. Additionally, during each study visit the nasal polyp score, SNOT20 questionnaire, olfactometry, the total IgE concentration in peripheral blood as well as the eosinophil cell count in peripheral blood were recorded. The change of parameters was evaluated over one year and the correlation between clinical effectiveness and nasal differential cytology was analyzed. Results: In both MGG (p<0.0001) and ICC analysis (p<0.001) a significant decrease of eosinophils was seen under Dupilumab treatment. When patients were divided into a Eo-low- (<21%) and Eo-high- (≥21%) group according to the percentage eosinophils in nasal swab catology in the first study visit, the Eo-high-group showed a greater change of eosinophils over time (Δ17.82) compared to the Eo-low-group (Δ10.67) but, however, no better response to therapy. The polyp score, SNOT20 questionnaire, and total IgE concentration in peripheral blood showed a significant decrease during the observation period (p<0.0001). Discussion: Nasal swab cytology as an easy-to-apply diagnostic method allows detection and quantification of the different cell populations within the nasal mucosa at a given time. The nasal differential cytology showed a significant decrease of eosinophils during Dupilumab therapy and can therefore be used as non-invasvive method for monitoring therapy success of this cost intensive therapy and potentially can allow an optimized individual therapy planning and management for CRSwNP patients. Since the validity of initial nasal swab eosinophil cell count as a predictive biomarker for therapy response was limited in our study, additional studies including larger number of participants will be necessary to further evaluate the potential benefits for clinical practice of this new diagnostic method.

Effect of postoperative systemic prednisolone on short-term and long-term outcomes in chronic rhinosinusitis with nasal polyps: A multi-centered randomized clinical trial.

Introduction: The objective of this study was to determine whether postoperative additive systemic steroid administration in chronic rhinosinusitis with nasal polyps (CRSwNP) impacted selected endoscopic, subjective and objective outcome measures. Methods: This was a prospective, randomized, double-blind, placebo-controlled, noninferiority multicenter trial of n=106 patients with CRSwNP. All patients underwent primary functional endoscopic sinus surgery (FESS) followed by topical nasal steroids. Patients were randomized to a systemic steroid or placebo for 1 month. Patients were followed up for 2 years over 9 time points. The primary outcome measures were the differences between groups with respect to the nasal polyp score (NPS) and sinonasal quality of life (SNQoL). Secondary outcome measures included interactions with respect to the Lund-Kennedy score (LKS), sinonasal symptoms, general quality of life (GQoL), 16-item odor identification test scores, recurrence rates, need for revision surgery and mucus biomarker levels. Results: 106 patients were randomized to either the placebo or the systemic steroid group (n=53 per group). Postoperative systemic steroids were not superior to placebo with respect to all primary (p= 0.077) and secondary outcome measures (p>0.05 for all). Reported adverse events were similar between the two groups. Conclusion: In conclusion, the addition of postoperative systemic steroids after primary FESS did not confer a benefit over topical steroid nasal spray alone with respect to NPS, SNQOL, LKS, GQOL, sinonasal symptoms, smell scores, recurrence rates, the need for revision surgery or biomarkers over a short-term follow-up of up to 9 months and a long-term follow-up of up to 24 months in CRSwNP patients. Functional endoscopic surgery did, however, show a strong effect on all outcome measures, which remained relatively stable up to the endpoint at 2 years.

Thunder and lightning-a report on firework-associated acoustic trauma at New Year 2021/2022.

BACKGROUND: This cross-sectional study aimed to assess the frequency and type of firework-associated acoustic trauma occurring in Germany on New Year's Eve 2021, despite the ban on firework sales due to the COVID-19 pandemic. MATERIALS AND METHODS: The survey period lasted 7 days, from 28 December 2021 to 03 January 2022. A questionnaire inquired date, type and treatment of trauma, sex, and age of the patient, and whether the trauma occurred when lighting or watching fireworks. Hearing impairment was classified according to the World Health Organization (WHO grades 0 to 4), and concomitant tinnitus, vertigo, or other injuries were recorded. The questionnaire was sent to the otorhinolaryngology departments of 171 hospitals in Germany. RESULTS: Of 37 otorhinolaryngology departments, 16 reported no and 21 reported 50 patients with firework-associated acoustic trauma. Mean age was 29 ± 16 years and 41 of 50 patients were males. Of these 50 patients, 22 presented without and 28 with hearing loss, 32 reported tinnitus and 3 vertigo; 20 patients were injured when lighting fireworks and 30 when watching. Hearing impairment was classified as 14â€¯× WHO grade 0, 5â€¯× WHO grade 1, 4â€¯× WHO grade 2, 2â€¯× WHO grade 3, and 3â€¯× WHO grade 4. Inpatient treatment was received by 8 patients and 11 suffered from concomitant burn injuries. CONCLUSION: Despite the sales ban, some firework-associated acoustic traumas occurred at New Year 2021/2022 in Germany. Some instances led to hospitalization, but an even higher number of unreported cases can be assumed. This study can serve as a baseline for further annual surveys to raise the awareness of the danger of seemingly harmless fireworks for the individual.

[Thunder and lightning-a report on firework-associated acoustic trauma at New Year 2021/2022 (German version)]. / Schlag auf Schlag ­ Bericht über feuerwerksbedingte Knalltraumata zum Jahreswechsel 2021/2022.

BACKGROUND: This cross-sectional study aimed to assess the frequency and type of firework-associated acoustic trauma occurring in Germany on New Year's Eve 2021, despite the ban on firework sales due to the COVID-19 pandemic. MATERIALS AND METHODS: The survey period lasted 7 days, from 28 December 2021 to 03 January 2022. A questionnaire inquired date, type and treatment of trauma, sex, and age of the patient, and whether the trauma occurred when lighting or watching fireworks. Hearing impairment was classified according to the World Health Organization (WHO grades 0 to 4), and concomitant tinnitus, vertigo, or other injuries were recorded. The questionnaire was sent to the otorhinolaryngology departments of 171 hospitals in Germany. RESULTS: Of 37 otorhinolaryngology departments, 16 reported no and 21 reported 50 patients with firework-associated acoustic trauma. Mean age was 29 ± 16 years and 41 of 50 patients were males. Of these 50 patients, 22 presented without and 28 with hearing loss, 32 reported tinnitus and 3 vertigo; 20 patients were injured when lighting fireworks and 30 when watching. Hearing impairment was classified as 14â€¯× WHO grade 0, 5â€¯× WHO grade 1, 4â€¯× WHO grade 2, 2â€¯× WHO grade 3, and 3â€¯× WHO grade 4. Inpatient treatment was received by 8 patients and 11 suffered from concomitant burn injuries. CONCLUSION: Despite the sales ban, some firework-associated acoustic traumas occurred at New Year 2021/2022 in Germany. Some instances led to hospitalization, but an even higher number of unreported cases can be assumed. This study can serve as a baseline for further annual surveys to raise the awareness of the danger of seemingly harmless fireworks for the individual.

[From the nose to the ear: field cancerization via the Eustachian tube]. / Von der Nase ins Ohr: Feldkanzerisierung über die Tuba auditiva.

We report on the metachronic appearance of an inverted papilloma in the ipsilateral middle ear after resection of an endonasal inverted papilloma and its malignant transformation. After multiple surgical interventions and adjuvant radiation and chemotherapy, there was recurrence with intracerebral growth, which ultimately led to the patient's death 3 years after the initial presentation.

Transorbital embolization of cavernous sinus dural arterio-venous malformations with surgical exposure and catheterization of the superior ophthalmic vein.

PURPOSE: Cavernous sinus dural arterio-venous malformations (dAVF) represent a pathologic connection between branches of the internal and/or external carotid artery and the cavernous sinus. Standard endovascular approaches for dAVF treatment are transvenous embolization through the inferior petrosal sinus or the facial vein and transarterial embolization. These approaches are not always successful or feasible, and alternative techniques are required. Here, we present a case series of a minimally invasive transorbital approach with surgical exposure and catheterization of the superior ophthalmic vein for transvenous fistula coiling. METHODS: 14 patients with dAVFs (Barrow Type B to D) that were treated at a tertiary care medical center over a period of 13 years were included in the study. Patients with persisting dAVF associated symptoms were selected for this approach when conventional endovascular interventions were not successful or not feasible. The surgical procedure was performed under general anaesthesia. RESULTS: A successful transorbital approach was performed in all 14 cases. In 12 of 14 patients a catheter assisted successful embolization of the fistula was performed using platinum coils with no relevant residual fistula flow. In two cases, a spontaneous thrombosis of the fistula during the surgical procedure required no further embolization. No postoperative therapy-associated complications were observed. CONCLUSION: The described approach is an effective method to embolize dAVFs in selected cases when catheter assisted transvenous and/or transarterial embolization is not successful or not feasible. In this case series we demonstrate an excellent success rate with no therapy-associated major complications.

[Outpatient Antibiotic Prescription Rates and Mastoiditis in Children and Adolescents, Saarland, 2014-2019]. / Ambulante Antibiotika-Verordnungsrate und Mastoiditis-Fälle bei Kindern und Jugendlichen im Saarland, 2014­2019.

BACKGROUND: Infections of the respiratory tract are the main indication for outpatient antibiotic therapy in children and adolescents. In recent years the antibiotic prescription rate (APR) in the pediatric population has decreased significantly. OBJECTIVES: The aim of the retrospective mastoiditis audit in the PaedineSaar network is to investigate the incidence of inpatient acute mastoiditis (AM) in Saarland (2014-2019) regarding to the decreasing APRs in children, as well as to gather data of the clinical course of AM. METHODS: All inpatient AM cases 2014-2019 were analyzed retrospectively from 6 hospitals for pediatrics and/or otorhinolaryngology in Saarland and Trier. Children and adolescents aged 0-17 years and residing in Saarland were included in the study. RESULTS: 2014-2019 53 inpatient treated AM cases have been recorded. During the study period there was no significant increase of AM incidence (mean incidence 2014-2019: 6.1/100,000). 34% (18/53) of the patients received prehospital antibiotic treatment (main indication: acute otitis media (AOM) 15/18, 83%). At least one complication occurred in 30% of the patients (16/53). There was a slight trend to more complications in children without oral antibiotic treatment before admission (14/35 (40%) vs. 2/18 (11%) p=0.056). CONCLUSIONS: The incidence of AM leading to inpatient treatment in children in Saarland did not increase 2014-2019 despite a significant and sustained decline in the outpatient APRs. The results of this audit should be used for the development of a more standardized approach concerning the diagnostics and treatment of children with AM.

Expression of 3q Oncogene SEC62 Predicts Survival in Head and Neck Squamous Cell Carcinoma Patients Treated with Primary Chemoradiation.

Primary chemoradiotherapy (CRT) is an established treatment option for locally advanced head and neck squamous cell carcinomas (HNSCC) usually combining intensity modified radiotherapy with concurrent platinum-based chemotherapy. Though the majority of patients can be cured with this regimen, treatment response is highly heterogeneous and can hardly be predicted. SEC62 represents a metastasis stimulating oncogene that is frequently overexpressed in various cancer entities and is associated with poor outcome. Its role in HNSCC patients undergoing CRT has not been investigated so far. A total of 127 HNSCC patients treated with primary CRT were included in this study. The median follow-up was 5.4 years. Pretherapeutic tissue samples of the primary tumors were used for immunohistochemistry targeting SEC62. SEC62 expression, clinical and histopathological parameters, as well as patient outcome, were correlated in univariate and multivariate survival analyses. High SEC62 expression correlated with a significantly shorter overall survival (p = 0.015) and advanced lymph node metastases (p = 0.024). Further significant predictors of poor overall and progression-free survival included response to therapy (RECIST1.1), nodal status, distant metastases, tobacco consumption, recurrence of disease, and UICC stage. In a multivariate Cox hazard proportional regression analysis, only SEC62 expression (p = 0.046) and response to therapy (p < 0.0001) maintained statistical significance as independent predictors of the patients' overall survival. This study identified SEC62 as an independent prognostic biomarker in HNSCC patients treated with primary CRT. The role of SEC62 as a potential therapeutic target and its interaction with radiation-induced molecular alterations in head and neck cancer cells should further be investigated.

Identification of Neural Mechanisms in First Single-Sweep Analysis in oVEMPs and Novel Normative Data.

BACKGROUND: Bone-conducted (BC) VEMPs provide important tools for measuring otolith function. However, two major drawbacks of this method are encountered in clinical practice-small n10 amplitude and averaging technique. In this study, we present the results of a new VEMP setup measuring technique combined with a novel single-sweep analysis. METHODS: The study included BC oVEMP data from 92 participants for the evaluation of normative data using a novel analysis technique. For evaluating test-retest reliability, the intraclass correlation coefficient (ICC) was used. RESULTS: We found significant n10 amplitude differences in single-sweep analyses after the first and second measurements. Thereby, mathematical analyses of the head movement did not show any differences in the first or second measurements. The normative n10 amplitude was 20.66 µV with an asymmetric ratio (AR) of 7%. The new value of late shift difference (LSD) was 0.01 ms. The test retest-reliability showed good to excellent ICC results in 9 out of 10 measurements. CONCLUSIONS: Our results support a phenomenon in single-sweep analysis of the first stimuli independent of head movement and signal morphology. Furthermore, the values obtained with the new measurement method appear to be more sensitive and may allow an extended diagnostic range due to the new parameter LSD.

Antagonizing Sec62 function in intracellular Ca2+ homeostasis represents a novel therapeutic strategy for head and neck cancer.

Various cancer types including head and neck squamous cell carcinomas (HNSCC) show a frequent amplification of chromosomal region 3q26 that encodes, among others, for the SEC62 gene. Located in the ER membrane, this translocation protein is known to play a critical role as a potential driver oncogene in cancer development. High SEC62 expression levels were observed in various cancer entities and were associated with a poor outcome and increased metastatic burden. Because of its intracellular localization the SEC62 protein is poorly accessible for therapeutic antibodies, therefore a functional SEC62 knockdown represents the most promising mechanism of a potential antineoplastic targeted therapy. By stimulating the Ca2+ efflux from the ER lumen and thereby increasing cellular stress levels, a functional inhibition of SEC62 bears the potential to limit tumor growth and metastasis formation. In this study, two potential anti-metastatic and -proliferative agents that counteract SEC62 function were investigated in functional in vitro assays by utilizing an immortalized human hypopharyngeal cancer cell line as well as a newly established orthotopic murine in vivo model. Additionally, a CRISPR/Cas9 based SEC62 knockout HNSCC cell line was generated and functionally characterized for its relevance in HNSCC cell proliferation and migration as well as sensitivity to SEC62 targeted therapy in vitro.

Schwannoma of the Hypoglossal Nerve Mimicking Carotid Body Paraganglioma.

Carotid body paragangliomas (CBPs) clinically present as highly vascularized cervical masses with a pathognomonic localization at the carotid artery bifurcation. Following ultrasonography and MRI/CT imaging, surgical resection with optional preoperative embolization is considered as the treatment of choice in most cases. We herein present the case of a 60-year-old female with characteristic clinical signs and imaging findings of a right-sided CBP who finally went to surgical treatment. Intraoperatively, the tumor showed an adherent growth to the hypoglossal nerve that had to be partially resected, resulting in a postoperative nerve palsy. Histological examination of the resected tumor revealed the unexpected diagnosis of a hypoglossal nerve schwannoma. To the best of our knowledge, we herein present the third case reported in the literature of a unilateral hypoglossal schwannoma located at the carotid bifurcation mimicking clinical symptoms, imaging and intraoperative findings of a CBP.

Podoplanin expression in lymph node metastases of head and neck cancer and cancer of unknown primary patients.

INTRODUCTION: Head and neck squamous cell carcinomas (HNSCCs) are cancers with generally poor prognosis. Outcomes have not improved in decades, with more than half of the patients presenting with lymph node metastases at the time of diagnosis. A unique subtype of HNSCC, cancer of unknown primary of the head and neck (HNCUP) is associated with a poor outcome. Increased expression of the D2-40 gene (podoplanin) has been described for several human malignancies and has been associated with increased metastatic potential of cancer cells. METHODS: In order to examine the role of podoplanin in lymph node metastasis of HNSCC generally and HNCUP specifically, we evaluated the prognostic impact of podoplanin expression in HNSCC- (n = 68) and HNCUP-associated lymph node metastases (n = 30). The expression of podoplanin was analyzed by immunohistochemical staining of lymph node tissue samples and correlated with clinical and histopathological data. RESULTS: We found a non-significant tendency towards a higher podoplanin expression in HNCUP compared to HNSCC lymph node metastases and a significant correlation between a high podoplanin expression and advanced node-stage classification. Podoplanin expression had no significant impact on overall survival for both groups and did not correlate with human papillomavirus tumor status. CONCLUSION: Taken together, our results suggest that upregulation of podoplanin may be associated with a stimulation of lymphatic metastasis in head and neck cancer.