Bilateral vs Unilateral Hypoglossal Nerve Stimulation in Patients With Obstructive Sleep Apnea.

Objective: Unilateral hypoglossal nerve stimulation (uniHNS) is an effective treatment for obstructive sleep apnea. Bilateral hypoglossal nerve stimulation (biHNS) is a novel therapeutic option and a different approach to hypoglossal nerve stimulation. The aim of this study was to analyze the clinical outcome of the first 10 biHNS cases vs the first 10 uniHNS cases ever implanted. Study Design: Prospective data analysis. Setting: International multicenter comparative clinical trial. Methods: The first 10 patients in 2020 who received a biHNS device (Genio System; Nyxoah) and the first 10 patients in 2014 who received a uniHNS system (Inspire II; Inspire Medical Systems) were included. Treatment outcome was evaluated at 3 months after surgery. Data collection included demographics, apnea hypopnea index (AHI), oxygen saturation and desaturation index, Epworth Sleepiness Scale, and adverse events. Results: The mean ± SD age was 52.1 ± 9.6 years (biHNS) and 58.3 ± 8.6 years (uniHNS). The mean body mass index was 26.4 ± 5.6 kg/m2 (biHNS) and 26.2 ± 2.2 kg/m2 (uniHNS). The mean preimplantation AHI (biHNS, 39.9 ± 14.8/h; uniHNS, 32.2 ± 11.0/h) decreased in both groups after 3 months (biHNS, 19.2 ± 14.0/h, P = .008; uniHNS, 13.1 ± 16.8/h, P = .037) with no significant difference between groups (P = .720). The mean preimplantation Epworth Sleepiness Scale (biHNS, 11.8 ± 6.2; uniHNS, 11.1 ± 4.9) decreased as well after 3 months (biHNS, 9.4 ± 6.3; uniHNS, 6.0 ± 5.0). Conclusion: Preliminary postmarket data suggest that biHNS may be as safe and effective as uniHNS. Long-term follow-up in a larger sample size is required to assess the stability of biHNS.

NOTCH1 Intracellular Domain and the Tumor Microenvironment as Prognostic Markers in HNSCC.

(1) Background: NOTCH1 is the second most common mutated gene in whole-exome sequencing of HNSCC. The aim of this project was to gain further insight into the relevance of NOTCH1 in HNSCC, potentially establishing NOTCH1 as a prognostic marker or therapeutic target; (2) Methods: NOTCH1 was silenced via RNA interference in six HNSCC cell lines and the impact was evaluated in migration and proliferation assays. Subsequently, the protein expression of NOTCH1 intracellular domain (NICD) and NOTCH1 mRNA expression were examined in 70 oropharyngeal squamous cell cancer tissue samples. Lastly, the NICD expression was compared with the local infiltration of lymphocytes, measured with the immunoscore; (3) Results: Knockdown of NOTCH1 decreased migration and proliferation. A high NICD expression was associated with lower OS. A high immunoscore resulted in significantly better OS. NICD expression was independent of the immunoscore and as a whole differentiated three distinct prognostic groups; (4) Conclusions: These data suggest that NOTCH1 is involved in migration and proliferation of HNSCC cell lines. In vivo, NICD expression was associated with overall survival and could, therefore, be used as a prognostic marker. NICD expression differs from NOTCH1 mRNA levels, potentially explaining the previously suggested bimodal role as an oncogene and tumor suppressor in HNSCC.

[GERD and adjuvant radio-chemotherapy predespose to recurrent voice prosthesis leakage]. / GERD und adjuvante Radiochemotherapie prädisponieren für rezidivierende Stimmprotheseninsuffizienz.

After total laryngectomy, regaining ability to speech is a keystone in regards of life quality. Voice prostheses have been shown to be a sufficient tool for satisfying communication, although frequent replacements of prostheses are burdening certain patients. Therefore, a more accurate understanding of mechanisms of prosthetic leakage is urgently needed. METHODS: We performed a retrospective analysis of 58 Patients after laryngectomy. Additionally, we analyzed pre- and post-therapeutic CT-scans of 22 Patients regarding pharyngeal stenosis. RESULTS: In 40 Patients, at least one replacement of voice prosthesis was documented during observation period, median device life was 235 days. Patients treated with adjuvant radiotherapy (RT) showed a significantly longer device life than patients with adjuvant radio-chemotherapy (RCT, p = 0.002). Furthermore, patients suffering of gastroesophageal reflux disease (GERD) showed a significantly shortened device life (p = 0.04).17 patients (42.5 %) suffered of clinically relevant stenosis of the neopharynx, which was treated with dilatation in 14 patients (82 %) and did not affect prosthesis device life. CONCLUSION: GERD is a risk factor for shortened voice prosthesis' device life and therefore should be treated effectively after laryngectomy. Also, adjuvant RCT predisposes a shortened device life.Stenosis is observed frequently after laryngectomy but does not affect device life when effectively treated.

High NOTCH1 mRNA Expression Is Associated with Better Survival in HNSCC.

The clinical impact of the expression of NOTCH1 signaling components in squamous cell carcinoma of the pharynx and larynx has only been evaluated in subgroups. The aim of this study was therefore to evaluate NOTCH1 expression in head and neck squamous cell cancer (HNSCC) patient tissue and cell lines. We analyzed tissue from 195 HNSCCs and tissue from 30 normal patients for mRNA expression of NOTCH1, NOTCH3, HES1, HEY1, and JAG1 using quantitative real-time PCR. Association of expression results and clinical orpathological factors was examined with multivariate Cox regression. NOTCH1 expression was determined in three Human Papilloma Virus (HPV)-positive and nine HPV-negative HNSCC cell lines. High expression of NOTCH1 was associated with better overall survival (p = 0.013) and disease-free survival (p = 0.040). Multivariate Cox regression confirmed the significant influence of NOTCH1 expression on overall survival (p = 0.033) and disease-free survival (p = 0.029). A significant correlation was found between p16 staining and NOTCH1 mRNA expression (correlation coefficient 0.28; p = 0.01). NOTCH1 was expressed at higher levels in HPV-positive HNSCC cell lines compared with HPV-negative cell lines, which was not statistically significant (p = 0.068). We conclude that NOTCH1 expression is associated with overall survival, and that inhibition of NOTCH1 therefore seems less promising.

HES1 mRNA expression is associated with survival in sinonasal squamous cell carcinoma.

OBJECTIVE: In squamous cell carcinoma of the pharynx and larynx, NOTCH1 downstream signaling has been shown to be activated. The NOTCH1 signaling pathway has not been examined in detail for sinonasal squamous cell carcinomas (SNSCCs). The aim of this study was to evaluate NOTCH1 signaling by mRNA expression analysis and to examine the occurrence of NOTCH1 mutations in SNSCC. STUDY DESIGN: In a retrospective study, we analyzed tissues from 44 SNSCCs and 56 head and neck squamous cell carcinomas (HNSCCs) at other locations. Expression of NOTCH1, NOTCH3, HES1, HEY1, and JAG1 mRNA were measured by using quantitative real-time polymerase chain reaction (q-rtPCR). In SNSCC, NOTCH1 mutations were evaluated with sequencing of seven selected exons. RESULTS: Expression of NOTCH1, HEY1, and JAG1 at the mRNA level were significantly higher in tumor tissue compared with normal tissue. In SNSCC, the subgroup of patients with high expression (5th quintile) of HES1 mRNA was associated with better survival (P = .04); however these patients with high expression of HES1 mRNA had also a more favorable tumor stage and grade and more unfavorable resections representing potential confounders. CONCLUSIONS: Key components of NOTCH1 are upregulated at the mRNA level in HNSCCs. The mechanism, clinical significance, and potential therapeutic options should therefore be further evaluated.