The value of biomarkers in the therapy of CRSwNP with biologicals-a long-term follow-up of dupilumab therapy.

PURPOSE: Since its release, Dupilumab has shown great results in treating severe uncontrolled CRSwNP. However, there is a lack of real-world data beyond 12 months of follow-up, and it is not clear to what extent biomarkers are appropriate for monitoring and predicting the Dupilumab therapy success. Hence, this study aims to analyze biomarkers for monitoring therapy, predicting therapy success and assess the effect of Dupilumab in real-world settings. METHODS: The follow-up was performed with 104 patients retrospectively up to 22 months, assessing SNOT-22, NPS, olfactometry, ACS, FEV-1, and blood biomarkers (total serum IgE, Eosinophils, ECP). Patients were divided into subgroups depending on their pretherapeutic biomarker levels and subsequent development was analyzed. RESULTS: There was substantially improvement in all clinical parameters up to 1 year and then continuously up to month 22. Patients with initially elevated baseline blood eosinophil counts (> 0.5 billion/L) had a trend of better SNOT-22 development after 1 year (- 12.19 points, p = 0.03). The course of total serum IgE showed moderate correlation with almost all clinical variables obtained. Therapy was well tolerated with only mild and transient adverse events. CONCLUSION: Dupilumab has considerably reduced symptoms and disease severity even beyond 1 year of treatment, supporting its role as targeted and effective treatment option for CRSwNP. Our data shows that total serum IgE is a promising biomarker for the monitoring during the treatment with Dupilumab. Elevated pre-therapeutic serum eosinophil counts may be a predictor of good subjective response to therapy. Larger cohorts and a long-term-follow-up over years are needed to further consolidate these findings.

The "fascia taco" for nasal septum perforation closure-A retrospective Cohort study on success rates and patient reported outcomes.

Objective: Nasal septum perforation (NSP) is a common condition affecting ~1.2% of the general population and is still considered challenging to treat. Therapeutic strategies range from conservative local treatments and septal button closures to over 40 different surgical approaches. This study aimed to present a novel secure approach. Methods: We describe our novel and unique NSP closure approach using a "fascia taco," in which conchal cartilage is enveloped by temporalis fascia like a taco and splints are left in place for 6-8 weeks. A review of patient charts was conducted and questionnaires including the German-SNOT-22 and D-NOSE were sent by mail to all eligible patients who received a fascia taco between 2016 and 2021. Results: Thirty-three patients were identified. The questionnaire response rate was 54.5%. The mean operative time (cut to sew) for all patients who only underwent NSP closure was 90.4 min. The overall success rate in terms of postoperative NSP closure was 81.8%. We found an apparent but nonsignificant association between closure failure and smoking (failure rate 66.6% in smokers vs. 15.4% in nonsmokers; X 2 = 3.4188, p = .064). Questionnaire analysis showed a significant postoperative reduction of mean values in D-NOSE from 60.8 to 33.1 (p = .009) and in German-SNOT-22 from 38.6 to 21.2 (p = .005). Conclusion: The fascia taco technique is an easy-to-apply, safe procedure for NSP closure that is short in duration and associated with a low morbidity, resulting in excellent patient satisfaction. Level of Evidence: 4.

Computer-Aided Diagnosis of Maxillary Sinus Anomalies: Validation and Clinical Correlation.

OBJECTIVE: Computer aided diagnostics (CAD) systems can automate the differentiation of maxillary sinus (MS) with and without opacification, simplifying the typically laborious process and aiding in clinical insight discovery within large cohorts. METHODS: This study uses Hamburg City Health Study (HCHS) a large, prospective, long-term, population-based cohort study of participants between 45 and 74 years of age. We develop a CAD system using an ensemble of 3D Convolutional Neural Network (CNN) to analyze cranial MRIs, distinguishing MS with opacifications (polyps, cysts, mucosal thickening) from MS without opacifications. The system is used to find correlations of participants with and without MS opacifications with clinical data (smoking, alcohol, BMI, asthma, bronchitis, sex, age, leukocyte count, C-reactive protein, allergies). RESULTS: The evaluation metrics of CAD system (Area Under Receiver Operator Characteristic: 0.95, sensitivity: 0.85, specificity: 0.90) demonstrated the effectiveness of our approach. MS with opacification group exhibited higher alcohol consumption, higher BMI, higher incidence of intrinsic asthma and extrinsic asthma. Male sex had higher prevalence of MS opacifications. Participants with MS opacifications had higher incidence of hay fever and house dust allergy but lower incidence of bee/wasp venom allergy. CONCLUSION: The study demonstrates a 3D CNN's ability to distinguish MS with and without opacifications, improving automated diagnosis and aiding in correlating clinical data in population studies. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

[How much digitization do ENT curricula need? : Opportunities and limits from the perspective of students and teachers]. / Wieviel Digitalisierung braucht die HNO-Lehre? : Chancen und Grenzen aus Sicht von Studierenden und Lehrenden.

BACKGROUND: Digitalization has long been an integral part of students' everyday lives and increasingly also of their medical training. It seems to be an unwritten law that "digital natives" want as much digitalization as possible. This study aims to shed more light on how students in the clinical phase of medical studies perceive the increasing digitalization of teaching and what they need for good education. MATERIALS AND METHODS: This study analyzed two surveys that were conducted using an online questionnaire. On the one hand, students in the 5th-9th semesters of the medical faculty at the University of Hamburg (n = 282) were surveyed (survey 1). Another survey addressed all employees of ENT clinics in Germany (n = 175; survey 2). RESULTS: A total of 76 students took part in survey 1 and 123 lecturers in survey 2. The results show that both students and lecturers do not want face-to-face teaching to be completely replaced by digital formats. A total of 72.7% of students reject the possibility of teaching practical skills through digital formats. The majority of students surveyed stated that offline formats improve their concentration (61.1%), participation probability (63.9%), and motivation to learn (76.6%). In contrast, 40.2% of lecturers see digitalization as a way to reduce the workload without any relevant loss in teaching quality. CONCLUSION: Digital teaching formats have a negative impact on the medical education of the students surveyed. Interaction and physical presence are needed to increase the motivation to learn. This leads to the first conclusion that students are critical of the increasing digitalization of medical studies.

[Decision-making in the treatment of chronic rhinosinusitis with nasal polyps in the era of biologics]. / Entscheidungsfindung bei der Behandlung der chronischen Rhinosinusitis mit Nasenpolypen in der Ära der Biologika.

Chronic rhinosinusitis is one of the most common chronic diseases in the population. Chronic rhinosinusitis with nasal polyps (CRSwNP) in adults is predominantly characterized by a type 2 inflammatory endotype. If sufficient control cannot be achieved through primary drug therapy, surgical intervention is usually recommended as the next stage of treatment. Nowadays, various biologics are available that have been or will be approved for use in these patients. This review summarizes the presentations from the 29th Congress of the European Rhinologic Society in Sofia 2023 and the latest findings on decision-making in the treatment of CRSwNP. Standard therapy with medication and sinus surgery fails in some patients with CRSwNP. Biologics that act on the type 2 inflammatory pathway led to a reduction in the nasal polyp score (NPS), an improvement in nasal obstruction, and an improvement in quality of life without significant side effects. Biomarkers such as total IgE, serum eosinophils, and Osteoprotegerin (OPG) can provide indications of the success of the treatment. In summary, it can be said that for many patients with recurrent CRSwNP, a combination of paranasal sinus surgery and treatment with a biologic that is precisely tailored to the patient's endotype is the best option. However, the question of which surgical approach and which biologic at which time and for which patient is still ongoing and requires further studies.

[Endoscopic endonasal anterior skull base surgery : Presentation of a monocentric entity profile]. / Endonasal-endoskopische anteriore Schädelbasischirurgie : Darstellung eines monozentrischen Entitätenprofils.

BACKGROUND: Extended endoscopic endonasal surgery (EEES) is an essential part of treatment of various pathologies of the anterior skull base. In addition to significant improvements in the quality of life of affected patients and a lower complication profile compared to open skull base surgery, the therapeutic results are comparable if the indications are correct. MATERIALS AND METHODS: Data of all endoscopic endonasal skull base procedures performed at the University Skull Base Center Hamburg under the direction of the Department of Otorhinolaryngology between June 2018 and November 2022 were retrospectively collected. RESULTS: A total of 50 cases were identified. Of these, 56% (28/50) were malignant tumors, 24% (12/50) were benign pathologies with direct skull base involvement, and 20% (10/50) were anterior skull base defects with rhinoliquorrhea. In 96% (48/50) of cases, the preoperatively set goal of surgery (representative biopsy, complete resection, closure of the skull base defect) could be achieved. Complications grade III or higher according to Clavien-Dindo occurred in 4/50 cases. During the observation period, n = 5 olfactory neuroblastomas were diagnosed, all of which were exclusively and successfully operated on endoscopically. CONCLUSION: In recent years, the spectrum of endoscopically resectable pathologies of the anterior skull base has steadily expanded. In particular, midline-related tumors such as olfactory neuroblastoma or iatrogenic/idiopathic skull base defects with cerebrospinal fluid rhinorrhea are treated completely endoscopically with very good results. Nevertheless, there are also limitations to this technique. Due to high variance in the scope of frontobasal surgery, the extent, and the complex anatomy, as well as the overlapping responsibilities of the specialist disciplines, establishment of certified skull base centers and bundling of frontobasal surgery at these centers is highly relevant for quality assurance.

A Novel Diagnostic and Treatment Algorithm for Acute Mastoiditis in Children Based on 109 Cases.

BACKGROUND: Acute mastoiditis (AM) is a potentially life-threatening condition primarily affecting children. To date, there are no consistent criteria or valid guidelines for the diagnosis and treatment of pediatric AM. Therefore, this study evaluates the clinical course of AM in terms of clinical signs and treatment. In addition, a novel classification scheme for the disease and a treatment algorithm is being proposed. METHODS: Patient records over a 12-year period from a single center were reviewed to identify confirmed cases of AM in children. Data collected included clinical signs, body temperature, and infection parameters during the disease, as well as radiological imaging, antibiotics, and surgical as well as conservative treatment. In addition, a classification of the AM stages was established in accordance with the findings described and practical experience, consisting of four stages (1, mastoidal irritation; 2, mild AM; 3, advanced AM; 4, advanced AM and additional complications) with corresponding treatment recommendations. In the retrospective cohort, those AM cases that were treated alongside the classification were compared with the rest concerning clinical course and outcome. RESULTS: A total of 109 patients (mean age, 3.8 ± 3.8 years) were included. The main symptoms at hospital admission were auricular protrusion (n = 73; 67.0%), fever (n = 56; 51.4%) with a mean temperature of 38.3 ± 1.1°C, and otalgia (n = 28; 25.7%). The mean laboratory-tested levels of leukocytes and C-reactive protein at the time of hospital admission were 15.96 ± 8.7/nl and 59.6 ± 54.0 mg/L, respectively. During winter, there was a higher prevalence of AM, with peak hospital admissions in April (n = 22). The most common pathogen was Streptococcus pyogenes (32 cases). Treatment was purely conservative in four cases, whereas the remaining cases underwent surgery (41× grommet insertion, 64× plus mastoidectomy). The outcome was generally good, but in eight patients a second surgical procedure had to be performed as they showed signs of clinical deterioration. A total of 101 patients were treated according to the proposed algorithm, and all of which had a good outcome without the need for further interventions. CONCLUSION: Based on clinical experience in a large cohort of pediatric AM patients, a novel diagnostic and treatment algorithm has been developed and successfully tested in a retrospective cohort for AM in children to prevent further complications and to ease its management by pediatricians and otorhinolaryngologists in the emergency setting.

Multiple instance ensembling for paranasal anomaly classification in the maxillary sinus.

PURPOSE: Paranasal anomalies are commonly discovered during routine radiological screenings and can present with a wide range of morphological features. This diversity can make it difficult for convolutional neural networks (CNNs) to accurately classify these anomalies, especially when working with limited datasets. Additionally, current approaches to paranasal anomaly classification are constrained to identifying a single anomaly at a time. These challenges necessitate the need for further research and development in this area. METHODS: We investigate the feasibility of using a 3D convolutional neural network (CNN) to classify healthy maxillary sinuses (MS) and MS with polyps or cysts. The task of accurately localizing the relevant MS volume within larger head and neck Magnetic Resonance Imaging (MRI) scans can be difficult, but we develop a strategy which includes the use of a novel sampling technique that not only effectively localizes the relevant MS volume, but also increases the size of the training dataset and improves classification results. Additionally, we employ a Multiple Instance Ensembling (MIE) prediction method to further boost classification performance. RESULTS: With sampling and MIE, we observe that there is consistent improvement in classification performance of all 3D ResNet and 3D DenseNet architecture with an average AUPRC percentage increase of 21.86 ± 11.92% and 4.27 ± 5.04% by sampling and 28.86 ± 12.80% and 9.85 ± 4.02% by sampling and MIE, respectively. CONCLUSION: Sampling and MIE can be effective techniques to improve the generalizability of CNNs for paranasal anomaly classification. We demonstrate the feasibility of classifying anomalies in the MS. We propose a data enlarging strategy through sampling alongside a novel MIE strategy that proves to be beneficial for paranasal anomaly classification in the MS.

International Consensus Statement on Allergy and Rhinology: Sinonasal Tumors.

BACKGROUND: Sinonasal neoplasms, whether benign and malignant, pose a significant challenge to clinicians and represent a model area for multidisciplinary collaboration in order to optimize patient care. The International Consensus Statement on Allergy and Rhinology: Sinonasal Tumors (ICSNT) aims to summarize the best available evidence and presents 48 thematic and histopathology-based topics spanning the field. METHODS: In accordance with prior International Consensus Statement on Allergy and Rhinology documents, ICSNT assigned each topic as an Evidence-Based Review with Recommendations, Evidence-Based Review, and Literature Review based on the level of evidence. An international group of multidisciplinary author teams were assembled for the topic reviews using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses format, and completed sections underwent a thorough and iterative consensus-building process. The final document underwent rigorous synthesis and review prior to publication. RESULTS: The ICSNT document consists of four major sections: general principles, benign neoplasms and lesions, malignant neoplasms, and quality of life and surveillance. It covers 48 conceptual and/or histopathology-based topics relevant to sinonasal neoplasms and masses. Topics with a high level of evidence provided specific recommendations, while other areas summarized the current state of evidence. A final section highlights research opportunities and future directions, contributing to advancing knowledge and community intervention. CONCLUSION: As an embodiment of the multidisciplinary and collaborative model of care in sinonasal neoplasms and masses, ICSNT was designed as a comprehensive, international, and multidisciplinary collaborative endeavor. Its primary objective is to summarize the existing evidence in the field of sinonasal neoplasms and masses.

["Radical" versus "functional" surgery of the paranasal sinuses-A contradiction?] / "Radikale" vs. "funktionelle" Chirurgie der Nasennebenhöhlen ­ ein Widerspruch?

BACKGROUND AND OBJECTIVE: The terms "functional" and "radical" paranasal sinus surgery were often considered to be different operations which were mutually exclusive. This overview aims to look at the basics of these terms and surgical procedures and to work out the resulting surgical concepts for clinically relevant indications. MATERIAL AND METHODS: Selective literature analysis using the data base PubMed, corresponding textbooks and resulting secondary literature regarding functional and radical or extended paranasal sinus surgery. Similarly, the current literature regarding clinically relevant indications for sinus surgery were analyzed. RESULTS AND CONCLUSION: Modern pathophysiological knowledge, anatomically and pathophysiologically substantiated endoscopic surgical procedures and the usage of up to date technical possibilities have resulted in concepts which combine functional and so-called radical or extended surgery of the paranasal sinuses that complement each other and sometimes even overlap. The preoperative diagnosis and definition of underlying diseases are decisive and should be as precise as possible, as the extent and surgical details mainly depend on them: a sole creation of free drainage pathways, an additional creation of anatomical access for subsequent topical treatment or a complete (radical) removal of a pathological process.

Tissue Classification During Needle Insertion Using Self-Supervised Contrastive Learning and Optical Coherence Tomography.

Needle positioning is essential for various medical applications such as epidural anaesthesia. Physicians rely on their instincts while navigating the needle in epidural spaces. Thereby, identifying the tissue structures may be helpful to the physician as they can provide additional feedback in the needle insertion process. To this end, we propose a deep neural network that classifies the tissues from the phase and intensity data of complex OCT signals acquired at the needle tip. We investigate the performance of the deep neural network in a limited labelled dataset scenario and propose a novel contrastive pretraining strategy that learns invariant representation for phase and intensity data. We show that with 10% of the training set, our proposed pretraining strategy helps the model achieve an F1 score of 0.84±0.10 whereas the model achieves an F1 score of 0.60±0.07 without it. Further, we analyse the importance of phase and intensity individually towards tissue classification.

[Special tumor entities in the head and neck region: nasopharyngeal, salivary gland, and thyroid cancer]. / Spezielle Tumorentitäten im Kopf-Hals-Bereich: Nasopharynxkarzinom, Speicheldrüsenkarzinom und Schilddrüsenkarzinom.

BACKGROUND: At the meetings of the American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO) in 2022, studies were presented which suggest changes in the clinical routine of nasopharyngeal, salivary gland, and thyroid cancer. OBJECTIVE: Therapeutic innovations for special otorhinolaryngological tumor entities with potential clinical relevance were assessed after reviewing the studies presented at the ASCO 2022/ESMO 2022 meetings. MATERIALS AND METHODS: The presented clinical phase II and phase III studies were analyzed. Results were classified according to their potential clinical importance, taking into account current treatment standards. RESULTS: Three studies were presented that dealt with the topic of risk-adapted treatment stratification in advanced nasopharyngeal cancer. Dose-reduced radiotherapy (60 Gy) in low-risk patients resulted in a favorable toxicity profile with promising oncological results in a single-arm phase II study. In a phase III study, intensity-modulated radiotherapy alone showed comparable survival to combined radiochemotherapy with cisplatin in selected low-risk patients. In high-risk patients, addition of the EGFR antibody nimotuzumab to definitive radiochemotherapy showed an increased 5­year survival rate compared to placebo (phase III study). Although an immediate change in clinical practice in Europe based on these studies is questionable, the concept of risk-adapted therapy taking into account biological characteristics (Epstein-Barr virus [EBV] DNA level) is future orientated. Similar to previous years, the contributions on recurrent/metastatic salivary gland and thyroid cancer emphasized the importance of targeted therapies based on vulnerable molecular target lesions.

Evaluation of a short instrument for measuring health-related quality of life in oncological patients in routine care (HELP-6): an observational study.

Purpose: Patient-reported outcomes have not been sufficiently implemented into the routine care of cancer patients because the existing instruments are often too long and complex or not cancer-specific. The aim of this study is the determination of psychometric properties and item reduction of a newly developed health-related quality of life (HrQoL) questionnaire for use in oncological clinical routines. Methods: This observational study with a repeated measurements design included oncological inpatients and outpatients. A total of 630 patients participated at the first point of measurement and 404 at the second point of measurement. To evaluate the instrument, we conducted hierarchical confirmative factor analyses and for further validation correlated the resulting factors with standardized and validated HrQoL measurements. Test-retest reliability and responsiveness to change were tested. Results: The developed questionnaire "HELP-6" ("Hamburg Inventory for Measuring Quality of Life in Oncological Patients") has a six-factor structure and has moderate-to-good convergent validity (r= -0.25 --0.68). Test-retest reliability was moderate-to-good (r =0.56-0.81, p < 0.001). Indications for responsiveness to change were found for three dimensions. The final version of the questionnaire HELP-6 has six dimensions with one item each. Conclusion: With the HELP-6 instrument for measuring HrQoL in cancer patients, we provide a short and practical patient-reported outcome instrument. Though responsiveness to change could not be confirmed for all dimensions in this study, the HELP-6 includes time-efficient completion and evaluation and is informative in relevant HrQoL dimensions of cancer patients. Therefore, the HELP-6 poses an important addition to inpatient and outpatient routine cancer care. Trial registration: This study was registered at Open Science Framework (https://osf.io/y7xce/), on 9 June 2018.

Characteristics of smell and taste disorders depending on etiology: a retrospective study.

PURPOSE: This study investigates the impact of etiology on the epidemiologic profile, disease severity, type of treatment and therapy outcome in smell and taste disorders. METHODS: This is a retrospective analysis of 270 patients that presented with a smell or taste disorder in a specialized, tertiary care center. An established questionnaire was used to collect data from patients and physicians. Olfactometry was performed with the Sniffin' Sticks test kit, while gustometry was performed by taste strips. RESULTS: Post-traumatic etiology was associated with young age (median 46 years) and male sex, and showed the most severe degrees of smell loss compared to other etiologies (64.3% anosmia). Postinfectious causes occurred more frequently in females (77.3%) and correlated with a history of pharyngeal surgery, suggesting a vulnerability for virally mediated sensory dysfunction following adenoid/tonsil removal. Parosmia also correlated with both postinfectious etiology (62.5%) and female sex. In sinunasal etiology, the presence of nasal polyps worsened the overall olfactory test score by approximately 50%. In particular, smell threshold and discrimination were reduced, while smell identification was not significantly impacted by nasal polyp obstruction. Sinunasal dysfunction was the only etiology to show significant improvement after therapy (73.9% improved). Finally, we could establish good correlations between the subjective impairment and objective dysfunction for each sensory modality. CONCLUSION: Each etiology of chemosensory dysfunction shows particular distributions of variables like sex, age, comorbidities and operations, disease severity, sensory threshold, discrimination and identification. This paper offers a detailed account of the correlations between the cause and the characteristics of smell and taste loss.

Outcomes following oropharyngeal squamous cell carcinoma resection and bilateral neck dissection with or without contralateral postoperative radiotherapy of the pathologically node-negative neck.

PURPOSE: There are no consensus guidelines regarding the postoperative treatment of the contralateral pathologically node-negative neck in oropharyngeal squamous cell carcinoma. This study aimed to determine if omission of postoperative irradiation of the contralateral pathologically node-negative neck affects oncological outcomes. METHODS: We retrospectively identified 84 patients with primary surgical treatment including bilateral neck dissection and postoperative (chemo-)radiotherapy (PO(C)RT). Survival was analyzed using the log-rank test and the Kaplan-Meier method. RESULTS: Patients showed no decrease in tumor-free, cause-specific (CSS), or overall survival (OS) when PO(C)RT of the contralateral pathologically node-negative neck was omitted. Increased OS was found in patients with unilateral PO(C)RT and especially an increased OS and CSS was found in unilateral PO(C)RT and in tumors arising from lymphoepithelial tissue. CONCLUSIONS: Omitting the contralateral pathologically node-negative neck appears to be safe in terms of survival and our retrospective study advocates further prospective randomized control de-escalation trials.

Impaired DNA double-strand break repair and effective radiosensitization of HPV-negative HNSCC cell lines through combined inhibition of PARP and Wee1.

Objectives: In head and neck squamous cell carcinoma (HNSCC), tumors negative for Human Papillomavirus (HPV) remain a difficult to treat entity and the morbidity of current multimodal treatment is high. Radiotherapy in combination with molecular targeting could represent suitable, less toxic treatment options especially for cisplatin ineligible patients. Therefore, we tested dual targeting of PARP and the intra-S/G2 checkpoint through Wee1 inhibition for its radiosensitizing capacity in radioresistant HPV-negative HNSCC cells. Materials and methods: Three radioresistant HPV-negative cell lines (HSC4, SAS, UT-SCC-60a) were treated with olaparib, adavosertib and ionizing irradiation. The impact on cell cycle, G2 arrest and replication stress was assessed through flow cytometry after DAPI, phospho-histone H3 and γH2AX staining. Long term cell survival after treatment was determined through colony formation assay and DNA double-strand break (DSB) levels were assessed through quantification of nuclear 53BP1 foci in cell lines and patient-derived HPV± tumor slice cultures. Results: Wee1 and dual targeting induced replication stress but failed to effectively inhibit radiation-induced G2 cell cycle arrest. Single as well as combined inhibition increased radiation sensitivity and residual DSB levels, with the largest effects induced through dual targeting. Dual targeting also enhanced residual DSB levels in patient-derived slice cultures from HPV-negative but not HPV+ HNSCC (5/7 vs. 1/6). Conclusion: We conclude that the combined inhibition of PARP and Wee1 results in enhanced residual DNA damage levels after irradiation and effectively sensitizes radioresistant HPV-negative HNSCC cells. Ex vivo tumor slice cultures may predict the response of individual patients with HPV-negative HNSCC to this dual targeting approach.

Lipidome Analysis of Oropharyngeal Tumor Tissues Using Nanosecond Infrared Laser (NIRL) Tissue Sampling and Subsequent Mass Spectrometry.

Ultrashort pulse infrared lasers can simultaneously sample and homogenize biological tissue using desorption by impulsive vibrational excitation (DIVE). With growing attention on alterations in lipid metabolism in malignant disease, mass spectrometry (MS)-based lipidomic analysis has become an emerging topic in cancer research. In this pilot study, we investigated the feasibility of tissue sampling with a nanosecond infrared laser (NIRL) for the subsequent lipidomic analysis of oropharyngeal tissues, and its potential to discriminate oropharyngeal squamous cell carcinoma (OPSCC) from non-tumorous oropharyngeal tissue. Eleven fresh frozen oropharyngeal tissue samples were ablated. The produced aerosols were collected by a glass fiber filter, and the lipidomes were analyzed with mass spectrometry. Data was evaluated by principal component analysis and Welch's t-tests. Lipid profiles comprised 13 lipid classes and up to 755 lipid species. We found significant inter- and intrapatient alterations in lipid profiles for tumor and non-tumor samples (p-value < 0.05, two-fold difference). Thus, NIRL tissue sampling with consecutive MS lipidomic analysis is a feasible and promising approach for the differentiation of OPSCC and non-tumorous oropharyngeal tissue and may provide new insights into lipid composition alterations in OPSCC.

Hereditary head and neck paraganglioma: from basics to practical consequences.

PURPOSE OF REVIEW: This review summarizes practical recommendations for screening, work-up, and management of hereditary head and neck paragangliomas based on the growing molecular and empirical understanding of this disease. RECENT FINDINGS: The proportion of hereditary cases among head and neck paragangliomas is significant (∼33 to 50%), and specific genetic alterations may increase the risk of malignancy. Genotyping should be performed for each case, and patients carrying a pathological mutation should be regularly screened for new tumors. Computed tomography (CT), magnetic resonance imaging (MRI), digital subtraction angiography (DSA), and functional positron emission tomography (PET) can provide a reliable preoperative diagnosis in the absence of histology. Comparative data on therapeutic outcome and morbidity now render radiation, stereotactic radiosurgery, and active surveillance preferable over surgery in highly advanced cases of jugulotympanic and vagal paragangliomas, whereas surgery remains the first choice for most carotid body paragangliomas. SUMMARY: Complete paraganglioma removal continues to be the primary therapeutic goal; however, this is sometimes impossible to accomplish with acceptable morbidity. In these cases, therapy selection should focus on preserving cranial nerve function and minimizing both tumor-associated and therapy-associated complications, particularly in genetically predisposed patients. An interdisciplinary approach to the management of hereditary head and neck paragangliomas is strongly recommended.

Dupilumab (Dupixent®) tends to be an effective therapy for uncontrolled severe chronic rhinosinusitis with nasal polyps: real data of a single-centered, retrospective single-arm longitudinal study from a university hospital in Germany.

INTRODUCTION: Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory disease, which is usually type 2-mediated in the western hemisphere, associated with severe therapeutic and socioeconomic challenges. The first targeted systemic treatment option for severe uncontrolled CRSwNP is a human monoclonal antibody against the interleukin-4 receptor α (IL-4Rα) subunit called dupilumab, which was approved for subcutaneous administration in Germany in October 2019. The purpose of this study is to investigate the efficacy of dupilumab in real life in patients treated with dupilumab in label according to license in our department in 2019-2021. MATERIALS AND METHODS: Since October 2019, we have investigated 40 patients (18 men, 22 women) treated with dupilumab in a single-center, retrospective single-arm longitudinal study. The following parameters were collected before treatment (baseline), at 1 month, 4 months, 7 months, 10 months, and 13 months: the Sino-Nasal Outcome Test-22 (SNOT-22), the forced expiratory pressure in 1 s (FEV-1), the olfactometry using Sniffin' Sticks-12 identification test (SSIT), a visual analog scale of the total complaints, the Nasal Polyp Score (NPS), histologic findings as well as total serum IgE, eosinophilic cationic protein in serum and blood eosinophils. RESULTS: The average age was 52.7 years (± 15.3). The follow-up period was 13 months. The SNOT-22 average was 60 points (± 22.2) at the first visit, 28.2 points (± 17.1) after 4 months and 20.8 points (± 17.7) after 13 months. The NPS was 4.3 points (± 1.5), after 4 months 2.1 points (± 1.3) and after 13 months 1.4 points (± 1.1). Olfactometry showed 3.2 points (± 3.7) at the baseline, 7.0 points (± 4.0) after 4 months and 7.8 points (± 3.5) after 13 months. The other parameters also improved. Most parameters showed linear dependence in the slopes under therapy (p < 0.001). Adverse side effects were mostly only mild, and no rescue therapy was needed. CONCLUSION: There is a clear improvement in the medical condition and symptoms in all categories mentioned under therapy with dupilumab, as well as a reduction in the need for systemic glucocorticoids and revision surgery as rescue treatment. Our results show that dupilumab tends to be an effective therapy alternative for severe CRSwNP.

Src family kinase targeting in head and neck tumor cells using SU6656, PP2 and dasatinib.

BACKGROUND: We have recently shown a frequent upregulation of Src-family kinases (SFK) in head and neck squamous cell carcinoma (HNSCC). Here we tested, if SFK targeting is effective especially in HNSCC cells with upregulated SFK signaling. METHODS: The impact of SFK inhibitors SU6656, PP2 and dasatinib on three HNSCC cell lines with different SFK activity levels was analyzed using proliferation and colony formation assays, Western blot and functional kinomics. RESULTS: Proliferation was blocked by all inhibitors in a micro-molar range. With respect to cell kill, dasatinib was most effective, while SU6656 showed moderate and PP2 minor effects. Cellular signaling was affected differently, with PP2 having no effect on SFK signaling while dasatinib probably has non-SFK specific effects. Only SU6656 showed clear SFK specific effects on signaling. CONCLUSION: The results demonstrate potential benefit of SFK inhibition in HNSCC but they also highlight challenges due to non-specificities of the different drugs.