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BACKGROUND: Precise preoperative radiological evaluation of aural atresia is of utmost importance for surgical planning. Until now, multislice computed tomography (MSCT) has been used but it cannot adequately visualize small structures such as the stapes. Flat-panel volume CT (fpVCT) with its secondary reconstructions (fpVCTSECO) offers a high-resolution visualization of the middle ear. New otosurgical planning software also enables detailed 3D reconstruction of the middle ear anatomy. AIM OF THE WORK: Evaluation of the use of fpVCTSECO in combination with an otosurgical planning software for a more accurate diagnosis and treatment of congenital aural atresia. MATERIAL AND METHODS: Seven patients with congenital aural atresia underwent preoperative MSCT (600 µm slice thickness) and corresponding fpVCT (466 µm slice thickness). In addition, fpVCTSECO (99 µm slice thickness) were reconstructed. The Jahrsdoerfer and Siegert grading scores were determined and their applicability in the abovementioned imaging modalities was evaluated. In addition, the malleus incus complex was analyzed in 3D rendering. RESULTS: Imaging with fpVCTSECO enabled reliable visualization of the abnormalities, in particular the ossicular chain. A significant difference in the Siegert grading score was found. In addition, the malleus-incus complex could be visualized better in 3D. DISCUSSION: The introduction of new imaging techniques and surgical planning techniques into the diagnostic concept of aural atresia facilitates the identification of malformed anatomy and enables systematic analysis. This combination can also help to more accurately classify the pathology and thus increase the safety and success of the surgical procedure.

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INTRODUCTION: Multidisciplinary tumor boards are meetings where a team of medical specialists, including medical oncologists, radiation oncologists, radiologists, surgeons, and pathologists, collaborate to determine the best treatment plan for cancer patients. While decision-making in this context is logistically and cost-intensive, it has a significant positive effect on overall cancer survival. METHODS : We evaluated the quality and accuracy of predictions by several large language models for recommending procedures by a Head and Neck Oncology tumor board, which we adapted for the task using parameter-efficient fine-tuning or in-context learning. Records were divided into two sets: n=229 used for training and n=100 records for validation of our approaches. Randomized, blinded, manual human expert classification was used to evaluate the different models. RESULTS : Treatment line congruence varied depending on the model, reaching up to 86%, with medically justifiable recommendations up to 98%. Parameter-efficient fine-tuning yielded better outcomes than in-context learning, and larger/commercial models tend to perform better. CONCLUSION: Providing precise, medically justifiable procedural recommendations for complex oncology patients is feasible. Extending the data corpus to a larger patient cohort and incorporating the latest guidelines, assuming the model can handle sufficient context length, could result in more factual and guideline-aligned responses and is anticipated to enhance model performance. We, therefore, encourage further research in this direction to improve the efficacy and reliability of large language models as support in medical decision-making processes.

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α-solanine is a glycoalkaloid that is commonly found in nightshades (Solanum) and has a toxic effect on the human organism. Among other things, it is already known to inhibit tumor cell proliferation and induce apoptosis in tumor cell lines. Due to its potential as a tumor therapeutic, the current study investigated the effect of α-solanine on head and neck squamous cell carcinoma (HNSCC). In addition, genotoxic and antiangiogenic effects on human umbilical vein endothelial cells (HUVECs) were evaluated at subtoxic α-solanine concentrations. Cytotoxicity and apoptosis rates were measured in two human HNSCC cell lines (FaDu pharynx carcinoma cells and CAL-33 tongue carcinoma cells), as well as in HUVECs. MTT and Annexin V analyses were performed 24 h after α-solanine treatment at increasing doses up to 30 µM to determine cytotoxic concentrations. Furthermore, genotoxicity at subtoxic concentrations of 1, 2, 4 and 6 µM in HUVECs was analyzed using single-cell gel electrophoresis (comet assay). The antiangiogenic effect on HUVECs was evaluated in the capillary tube formation assay. The MTT assay indicated an induction of concentration-dependent viability loss in FaDu and CAL-33 cancer cell lines, whereas the Annexin V test revealed α-solanine-induced cell death predominantly independent from apoptosis. In HUVECs, the cytotoxic effect occurred at lower concentrations. No genotoxicity or inhibition of angiogenesis were detected at subtoxic doses in HUVECs. In summary, α-solanine had a cytotoxic effect on both malignant and non-malignant cells, but this was only observed at higher concentrations in malignant cells. In contrast to existing data in the literature, tumor cell apoptosis was less evident than necrosis. The lack of genotoxicity and antiangiogenic effects in the subtoxic range in benign cells are promising, as this is favorable for potential therapeutic applications. In conclusion, however, the cytotoxicity in non-malignant cells remains a severe hindrance for the application of α-solanine as a therapeutic tumor agent in humans.

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Chronic rhinosinusitis is a common disease. Due to the significant reduction of the quality of life, possible serious complications and economic consequences, a sufficient therapy is essential. With the entry of biologics into the treatment of chronic rhinosinusitis, relevant innovations have emerged in recent years. This article is aimed at providing an up-to-date overview of the conservative and surgical treatment options for chronic rhinosinusitis.

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INTRODUCTION: Cochlear duct length (CDL) measurement plays a role in the context of individualized cochlear implant (CI) surgery regarding an individualized selection and implantation of the CI electrode carrier and an efficient postoperative anatomy-based fitting process. The level of detail of the preoperative temporal bone CT scan depends on the imaging modality with major impact on CDL measurements and CI electrode contact position determination. The aim of this study was to evaluate the accuracy of perioperative CDL measurements and electrode contact determination in photon-counting CT (PCCT). METHODS: Ten human fresh-frozen petrous bone specimens were examined with a first-generation PCCT. A clinically applicable radiation dose of 27.1 mGy was used. Scans were acquired before and after CI insertion. Postoperative measurement of the CDL was conducted using an otological planning software and 3D-curved multiplanar reconstruction. Investigation of electrode contact position was performed by two respective observers. Measurements were compared with a conventional multislice CT and to a high-resolution flat-panel volume CT with secondary reconstructions. RESULTS: Pre- and postoperative CDL measurements in PCCT images showed no significant difference to high-resolution flat-panel volume CT. Postoperative CI electrode contact determination was also as precise as the flat-panel CT-based assessment. PCCT and flat-panel volume CT were equivalent concerning interobserver variability. CONCLUSION: CDL measurement with PCCT was equivalent to flat-panel volume CT with secondary reconstructions. PCCT enabled highly precise postoperative CI electrode contact determination with substantial advantages over conventional multislice CT scanners.

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OBJECTIVE: Education in microsurgery of the ear includes staged training to allow for mastering of the complex microsurgical procedures, particularly in the context of middle ear reconstruction and cochlear implantation. Traditional surgical training includes temporal bone preparations by cadaver dissection and supervised operating room practice. As these on-site trainings are limited, there is a need to broaden education facilities in an on-line format. Therefore, a first basic on-line training for otosurgery was developed. MATERIALS AND METHODS: The system consists of an artificial temporal bone model together with a set of basic surgical instruments and implant dummies. As an essential part of the training kit, a high-resolution camera set is included that allows for connection to a video streaming platform and enables remote supervision of the trainees' surgical steps by experienced otological surgeons. In addition, a pre-learning platform covering temporal bone anatomy and instrumentation and pre-recorded lectures and instructional videos has been developed to allow trainees to review and reinforce their understanding before hands-on practice. RESULTS: Over the three courses held to date, 28 participants with varying levels of prior surgical experience took part in this otological surgical training program. The immediate feedback of the participants was evaluated by means of a questionnaire. On this basis, the high value of the program became apparent and specific areas could by identified where further refinements could lead to an even more robust training experience. CONCLUSION: The presented program of an otosurgical online training allows for basal education in practical exercises on a remote system. In this way, trainees who have no direct access to on-site instruction facilities in ear surgery now have the chance to start their otosurgical training in an educational setting adapted to modern technologies.

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OBJECTIVE: Confocal laser endomicroscopy (CLE) is an optical imaging technique that allows in vivo, real-time, microscope-like assessment of superficial lesions. Although there is substantial data on CLE use in the upper GI tract, there is limited information regarding its application in the nasal cavity and paranasal sinuses. This study aims to assess the feasibility and diagnostic metrics of CLE in the nasal cavity and paranasal sinuses regarding differentiation between healthy/benign and malignant tissue. These structures show, however, a wider variety of frequent and concomitant benign and malignant pathologies, which could pose an increased challenge for optical biopsy by CLE. METHODS: We performed CLE on a case series of six patients with various findings in the nose (three chronic rhinosinusitis, adenocarcinoma, meningoenzephalozele, esthesionneuroblastoma). Forty-two sequences (3792 images) from various structures in the nasal cavity and/or paranasal sinuses were acquired. Biopsies were taken at corresponding locations and analyzed in hematoxylin and eosin staining as a standard of reference. Three independent examiners blinded to the histopathology assessed the sequences. RESULTS: Healthy and inflamed mucosa could be distinguished from malignant lesions with an accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of 84.1%, 85.4%, 83.1%, 72.5%, and 92.1%, respectively, with a substantial agreement between raters (Fleiss κ = 0.62). CONCLUSION: This technique shows, despite its limitations, potential as an adjunctive imaging technique during sinus surgery; however, the creation of a scoring system based on reproducible and defined characteristics in a larger more diverse population should be the focus of further research to improve its diagnostic value and clinical utility. LEVEL OF EVIDENCE: NA Laryngoscope, 2024.

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The following review article highlights key topics in pediatric rhinology that are currently the focus in research and at conferences as well as in the interdisciplinary discussion between otorhinolaryngologists and pediatricians. In particular, congenital malformations such as choanal atresia or nasal dermoid cysts are discussed, followed by statements on the current procedures for sinogenic orbital complications as well as on the diagnosis and therapy of chronic rhinosinusitis in children. Furthermore, updates on the role of the ENT specialist in the care for children with cystic fibrosis and primary ciliary dyskinesia are provided.

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Head and neck squamous-cell carcinoma (HNSCC) is associated with aggressive local invasiveness, being a main reason for its poor prognosis. The exact mechanisms underlying the strong invasive abilities of HNSCC remain to be elucidated. Therefore, there is a need for in vitro models to study the interplay between cancer cells and normal adjacent tissue at the invasive tumor front. To generate oral mucosa tissue models (OMM), primary keratinocytes and fibroblasts from human oral mucosa were isolated and seeded onto a biological scaffold derived from porcine small intestinal submucosa with preserved mucosa. Thereafter, we tested different methods (single tumor cells, tumor cell spots, spheroids) to integrate the human cancer cell line FaDu to generate an invasive three-dimensional model of HNSCC. All models were subjected to morphological analysis by histology and immunohistochemistry. We successfully built OMM tissue models with high in vivo-in vitro correlation. The integration of FaDu cell spots and spheroids into the OMM failed. However, with the integration of single FaDu cells into the OMM, invasive tumor cell clusters developed. Between segments of regular epithelial differentiation of the OMM, these clusters showed a basal membrane penetration and lamina propria infiltration. Primary human fibroblasts and keratinocytes seeded onto a porcine carrier structure are suitable to build an OMM. The HNSCC model with integrated FaDu cells could enable subsequent investigations into cancer cell invasiveness.

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Nasal xenobiotic metabolizing enzymes (XMEs) are important for the sense of smell because they influence odorant availability and quality. Since the major part of the human nasal cavity is lined by a respiratory mucosa, we hypothesized that this tissue contributed to nasal odorant metabolism through XME activity. Thus, we built human respiratory tissue models and characterized the XME profiles using single-cell RNA sequencing. We focused on the XMEs dicarbonyl and l-xylulose reductase, aldehyde dehydrogenase (ALDH) 1A1, and ALDH3A1, which play a role in food odorant metabolism. We demonstrated protein abundance and localization in the tissue models and showed the metabolic activity of the corresponding enzyme families by exposing the models to the odorants 3,4-hexandione and benzaldehyde. Using gas chromatography coupled with mass spectrometry, we observed, for example, a significantly higher formation of the corresponding metabolites 4-hydroxy-3-hexanone (39.03 ± 1.5%, p = 0.0022), benzyl alcohol (10.05 ± 0.88%, p = 0.0008), and benzoic acid (8.49 ± 0.57%, p = 0.0004) in odorant-treated tissue models compared to untreated controls (0 ± 0, 0.12 ± 0.12, and 0.18 ± 0.18%, respectively). This is the first study that reveals the XME profile of tissue-engineered human respiratory mucosa models and demonstrates their suitability to study nasal odorant metabolism.

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OBJECTIVE: Education in microsurgery of the ear includes staged training to allow for mastering of the complex microsurgical procedures, particularly in the context of middle ear reconstruction and cochlear implantation. Traditional surgical training includes temporal bone preparations by cadaver dissection and supervised operating room practice. As these on-site trainings are limited, there is a need to broaden education facilities in an on-line format. Therefore, a first basic on-line training for otosurgery was developed. MATERIALS AND METHODS: The system consists of an artificial temporal bone model together with a set of basic surgical instruments and implant dummies. As an essential part of the training kit, a high-resolution camera set is included that allows for connection to a video streaming platform and enables remote supervision of the trainees' surgical steps by experienced otological surgeons. In addition, a pre-learning platform covering temporal bone anatomy and instrumentation and pre-recorded lectures and instructional videos has been developed to allow trainees to review and reinforce their understanding before hands-on practice. RESULTS: Over the three courses held to date, 28 participants with varying levels of prior surgical experience took part in this otological surgical training program. The immediate feedback of the participants was evaluated by means of a questionnaire. On this basis, the high value of the program became apparent and specific areas could by identified where further refinements could lead to an even more robust training experience. CONCLUSION: The presented program of an otosurgical online training allows for basal education in practical exercises on a remote system. In this way, trainees who have no direct access to on-site instruction facilities in ear surgery now have the chance to start their otosurgical training in an educational setting adapted to modern technologies.

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Background: The subtotal petrosectomy procedure may be useful for cochlear implantation in selected patient groups. Although it is highly effective, complications can arise, which may have economic implications for the patient due to the high cost of the device. Therefore, several authors have attempted to identify the most effective concept for obliteration. Methods: We present a pilot descriptive study of application techniques for obliterating cavities after subtotal petrosectomy using a temporoparietal fascial flap (TPFF) modified with injectable platelet-rich fibrin (IPRF+) for three cochlear implant (CI) patients. Results: Our concept preserves important anatomical structures, such as the temporalis muscle, which covers the CI receiver-stimulator. Injection of IPRF+ also increases the available tissue volume for obliteration and enhances its anti-inflammatory and regenerative potential. Conclusions: To the best of our knowledge, the use of TPFF for filling the cavity has not been adopted for CI with SP and for blind sac closure. Our literature review and our experience with this small group of patients suggest that this procedure, when combined with IPRF+ injections, may reduce the risk of potential infection in the obliterated cavity, particularly when used with CI. This technique is applicable only in cases when the surgeons are convinced that the middle ear cavity is purged of cholesteatoma.

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INTRODUCTION: The middle cranial fossa (MCF) approach is a well-established procedure in surgery of the internal auditory canal, as well as with the retrosigmoid and translabyrinthine approaches. It is commonly used in the hearing-preserving microsurgery of small vestibular schwannomas (VS). The debate about the "best" approach for the microsurgery of small VS without contact to the brainstem is controversial. It has been stated that the MCF approach leads to irreversible damage to the temporal lobe, which may be evident in follow-up magnet resonance imaging (MRI) as gliosis in up to 70% of patients. MATERIALS AND METHODS: This study represents a retrospective chart analysis conducted at a tertiary university hospital. Here, 76 postoperative MRIs were re-evaluated by an experienced neuroradiologist and compared with the preoperative images. Temporal lobe gliosis was classified on an ordinal scale as absent, slight, moderate or severe. Occurrence of gliosis was matched to the clinical predictors (tumor stage, tumor volume, sex, age, and side). RESULTS: No case of severe or moderate gliosis was found in the patient group. Slight gliosis of the temporal lobe was rare and was only detected in four patients (5%). There was no relation between clinical predictors and the incidence of gliosis. CONCLUSIONS: In our cohort, postoperative MR imaging did not reveal relevant damage to the temporal lobe parenchyma. This confirms the safe concept of microsurgery of small tumors via the middle fossa approach. The severe glioses described in other studies may be caused by a forced insertion of the retractor or by more extended approaches. However, further prospective neurocognitive studies seem to be necessary in order to assess functional changes in the temporal lobe.

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Neural stem cells (NSCs) have been recently identified in the neonatal rat medial geniculate body (MGB). NSCs are characterized by three cardinal features: mitotic self-renewal, formation of progenitors, and differentiation into all neuroectodermal cell lineages. NSCs and the molecular factors affecting them are particularly interesting, as they present a potential target for treating neurologically based hearing disorders. It is unclear whether an NSC niche exists in the rat MGB up to the adult stage and which neurogenic factors are essential during maturation. The rat MGB was examined on postnatal days 8, 12, and 16, and at the adult stadium. The cardinal features of NSCs were detected in MGB cells of all age groups examined by neurosphere, passage, and differentiation assays. In addition, real-time quantitative polymerase chain reaction arrays were used to compare the mRNA levels of 84 genes relevant to NSCs and neurogenesis. In summary, cells of the MGB display the cardinal features of NSCs up to the adult stage with a decreasing NSC potential over time. Neurogenic factors with high importance for MGB neurogenesis were identified on the mRNA level. These findings should contribute to a better understanding of MGB neurogenesis and its regenerative capacity.

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Sinonasal mucosal melanoma (SNMM) is a rare and aggressive disease representing only 4% of all sinonasal malignancies and 1.4% of all melanomas. With an incidence of approximately 0.2 to 2 cases per million, the disease represents a very rare cancer type. As a result, there is a lack of data and most of the evidence for this highly aggressive disease is based on retrospective observations and analyses. The standard of care is radical tumor resection followed by an adjuvant radiotherapy. Nevertheless, the rate of local recurrence is high, up to 50%. In addition, the majority of patients (up to 70%) develop distant metastases during the course of their disease. Both contribute to the extremely poor prognosis of the disease. Mucosal melanomas (SM) and cutaneous melanomas (CM) behave differently with respect to biology, clinic presentation and prognosis. Compared to CM, survival rates are significantly lower for SM. The 5-year survival rate is around 25% in SNMM but 39-97% in cutaneous melanoma. Similar to CM, immune checkpoint inhibitors achieve promising results in SM. However, response rates are lower in SM compared to CM. The goal of this CME article is to provide an overview on biology, diagnosis, therapy, and prognosis of SNMM.

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BACKGROUND: German university otorhinolaryngology has a need for digital teaching content. Case-based e­learning represents a digital teaching methodology. The data on student use of case-based e­learning in university teaching of ENT medicine are limited. OBJECTIVE: The aim of this work was to determine the extent to which voluntary case-based e­learning is used by otolaryngology students and what influence the quality of the e­learning has on motivation to use e­learning and on the interest in otolaryngology. MATERIALS AND METHODS: Fifteen voluntary e­learning cases were created based on the content of the ENT lecture in the winter semester 2022/2023. Subsequently, a descriptive evaluation of the usage statistics of the cases of 157 students was conducted. Likewise, an evaluation of the quality of the e­learning as well as the motivation to complete it and the interest in otorhinolaryngology was carried out using a voluntary questionnaire. RESULTS: Voluntary case-based e­learning was used to varying degrees by 66% of the students. The quality of e­learning correlated significantly with the motivation and the interest in otolaryngology. CONCLUSION: The teaching content of otorhinolaryngology can be implemented sufficiently in case-based e­learning and is characterized by satisfactory student acceptance. Integration should be accomplished in a high-quality manner to increase motivation and interest in otorhinolaryngology.

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BACKGROUND: In patients with iodine-negative thyroid cancer (TC), current guidelines endorse an [18F]FDG PET/CT to identify dedifferentiated sites of disease. We aimed to determine the rate of oncological management changes triggered by such a molecular imaging approach, along with the impact on outcome. METHODS: 42 consecutive patients with negative findings on [131I] whole body scan were scheduled for [18F]FDG PET/CT and treatment based on PET results were initiated. To determine the impact on oncological management, we compared the therapeutic plan prior to and after molecular imaging. Based on imaging follow-up, the rate of controlled disease (CD, defined as stable disease, complete or partial response) was also recorded, thereby allowing to assess whether [18F]FDG-triggered management changes can also lead to favorable outcome. RESULTS: We observed no alterations of the treatment plan in 9/42 (21.4%) subjects (active surveillance in 9/9 [100%]). Oncological management was changed in the remaining 33/42 (78.6%; systemic treatment in 9/33 [27.3%] and non-systemic treatment in 24/33 [72.7%]). Among patients receiving non-systemic therapy, the following changes were noted: surgery in 20/24 (83.3%) and radiation therapy in 4/24 (16.7%). In the systemic group, tyrosine kinase inhibitor (TKI) was prescribed in 8/9 (88.9%), while radioiodine therapy based on a TKI-mediated redifferentiation approach was conducted in 1/9 (11.1%). In 26 subjects with available follow-up, rate of CD was 22/26 (84.6%) and among those, 15/22 (68.1%) had experienced previous management changes based on PET/CT findings. CONCLUSIONS: In subjects with iodine-negative TC, [18F]FDG PET/CT triggered relevant management changes along with disease control in the vast majority of patients. As such, in dedifferentiated TC, [18F]FDG PET/CT may serve as a relevant management tool and therapeutic decision-aid in the clinic.

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Pediatric chronic rhinosinusitis (PCRS) differs from adult chronic rhinosinusitis (CRS) in several aspects. The confrontation with the environment takes place in the growing sinus system, and the immune system is also developing. The inflammatory mechanisms differ to some extent from those of adult CRS patients. The adenoid vegetations play an important role, particularly during the first 6 years of life. Other pathogenetic aspects are important (e.g., asthma, gastroesophageal reflux disease, immunodeficiency). Genetically determined systemic diseases such as cystic fibrosis cause specific challenges in diagnostics and treatment already in childhood. Consistent conservative therapy is often successful, but surgical procedures that have been proven to be effective and associated with few complications are also increasingly used.

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INTRODUCTION: Oligometastatic disease (OMD) is a metastatic stage that could benefit maximally from local therapies. Patients in this state have a better prognosis relative to those with disseminated metastases. Stereotactic radiotherapy provides a non-invasive ablative tool for primary malignant tumors and metastases. MATERIALS AND METHODS: We searched our register for patients with oligometastatic or recurrent head and neck cancer (OMD/R-HNC) who received stereotactic radiotherapy to manage their OMD/R. We evaluated the survival outcomes and prognostic factors that affected the survival of those patients. RESULTS: In all, 31 patients with 48 lesions met the inclusion criteria for the analysis. The lesions comprised various metastatic sites, with the majority being pulmonary (37 lesions). Squamous cell cancer was the most common histology (26 patients). The median overall survival (mOS) was 33 months, with a progression-free survival (PFS) of 9.6 months. Eight patients received subsequent stereotactic radiotherapy after disease progression. The local control (LC) rates were 91.3, 87.7, and 83% at 6, 12, and 36 months. Patients with the de novo OMD who received stereotactic radiotherapy as their initial treatment had a median systemic treatment-free survival of 23.9 months. In univariate analysis, a trend for better OS was observed in patients with p16-positive squamous cell tumors; patients who progressed within 150 days after diagnosis had a significantly lower OS. De novo OMD showed significantly better PFS compared to induced OMD. Multivariate analyses identified p16-positive squamous cell cancer, metachronous OMD and a longer time to progression as positive predictors of OS, while de novo OMD was the only positive predictor for PFS. Treatment-related toxicities were generally mild, with two cases of grade 3 dysphagia reported. CONCLUSION: Stereotactic radiotherapy demonstrated favorable outcomes in patients with OMD/R-HNC with limited toxicities. Further studies are warranted to validate these findings and optimize treatment strategies for this patient population.

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Background: The cochlear aqueduct (CA), which connects the scala tympani and the subarachnoid space, and its accompanying structures appear to have a significant relevance during cochlear implantation and an accurate visualization in clinical imaging is of great interest. Aims and Objective: This study aims to determine which potential and limitations clinically available imaging modalities have in the visualization of the CA. Methods: Micro-CT, flat-panel volume computed tomography with and without secondary reconstruction (fpVCT, fpVCTseco) and multislice computed tomography (MSCT) of 10 temporal bone specimen were used for 3D analysis of the CA. Results: FpVCTseco proved superior in visualizing the associated structures and lateral portions of the CA, which merge into the basal turn of the cochlea. All clinical imaging modalities proved equal in analyzing the length, total volume of the CA and its area of the medial orifice. Conclusion: The choice of the most accurate clinical imaging modality to evaluate the CA and its associated structures depends on the clinical or scientific question. Furthermore, this study should provide a basis for further investigations analyzing the CA.

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