OBJECTIVE: This study introduces a hybrid training model for endolaryngeal surgeries integrating a porcine larynx into a plastic airway manikin. The study explores interventions with a conventional rigid laryngoscope as well as with the novel hyperangulated laryngoscope for surgery (sMAC). METHODS: We integrated a porcine larynx into a plastic airway manikin with blue markings on vocal folds simulating lesions and utilized a conventional rigid laryngoscope and the sMAC for endolaryngeal cordectomies and biopsies. RESULTS: The setup provided clear visual exposure of the glottic plane, enabling precise surgical interventions. Trained surgeons and residents successfully performed cordectomies and biopsies on the model. CONCLUSION: The hybrid model offers a realistic, cost-effective solution for training and testing endolaryngeal surgical procedures, particularly with the sMAC. Despite anatomical differences between porcine and human larynges, the model’s affordability and tissue similarity render it a valuable training tool. Further studies are warranted to evaluate its efficacy for training.

Head and neck squamous cell carcinoma (HNSCC) is the seventh most common cancer worldwide with a poor prognosis for survival. Risk factors include alcohol and tobacco abuse and infection with human papilloma virus (HPV). To enhance anti-tumor immune responses immunotherapeutic approaches are approved for recurrent metastatic disease but only approx. 20% of patients respond to checkpoint blockade of the PD-1/PD-L1 axis. Therefore, preclinical research is needed to better understand molecular and cellular processes and to identify new therapeutic targets. Immunocompetent mouse models can serve these purposes but only few are currently available for HPV-positive HNSCC. Here, we established a mouse cell line overexpressing the oncogenes E6/E7 of the HPV16 genome as well as a constitutively active form of H-Ras and studied the anti-tumor immune response upon orthotopic tumor growth at the floor of the mouth. Moreover, we analyzed the same immunoregulatory pathways in samples of HPV-positive cancer patients. T cells in the tumor of mice and humans exhibited high expression of CD39 and CD73, two ectoenzymes involved in the production of immunosuppressive adenosine from ATP, along with increased expression of PD-1, LAG-3 and GITR. Additionally, B cell responses were elevated in tumor-bearing mice, seen as an increase of germinal center, immunoregulatory marginal zone and follicular B cell subtypes. Taken together, this study suggests that the generated mouse model shares characteristics with human disease and can thus be used as a platform to study anti-tumor responses in HPV-positive HNSCC which will help to identify novel therapeutic targets.

Background: Head and neck cancers, constituting 3-5% of all cancer cases, often require surgical resection for optimal outcomes. Achieving complete resection (R0) is crucial, but current methods, relying on white light endoscopy and microscopy, have limitations. Hyperspectral imaging (HSI) offers potential benefits by capturing detailed spectral information beyond human vision. Material and methods: This study enrolled 32 patients with head and neck squamous cell carcinoma (HNSCC). Following surgical resection specimens underwent ex vivo HSI imaging. Annotated regions were utilized to train a Convolutional Neural Network (CNN) and Graph Neural Network (GNN). Imaging parameters were carefully optimized for efficiency. Results: Our HSI imaging setup required around 12 min per measurement and demonstrated feasibility with promising accuracy. The combination of HSI and artificial intelligence (AI) achieved an 86% accuracy in predicting tumor tissue. Challenges included data volume and extended capture times. Conclusion: Hyperspectral imaging, complemented by AI, shows promise in enhancing tissue differentiation for HNSCC. The study envisions real-time integration of HSI into surgery for margin assessment. Challenges such as data volume and capture times warrant further exploration, emphasizing the need for ongoing investigations to refine clinical applications.

This retrospective study examined overall survival (OS), recurrence free survival (RFS), and laryngeal preservation time in a large cohort of 663 patients with T1/2 N0 M0 glottic cancer after transoral laser or open surgery vs radiotherapy. A total of 595 surgically treated patients and 68 individuals after definitive radio(chemo)therapy (R (C)–T) were studied. Patient characteristics including sociological, surgical, and pathological data, OS and RFS as well as laryngeal preservation time were recorded and compared between various groups/cohorts. There were no significant differences in OS and RFS between surgically treated and conservatively treated patients. However, laryngeal preservation time was significantly higher in surgically treated patients (p < 0.001) (mean: 138.3 ± 2.2 months, versus 102.8 ± 7.6 months) than those under conservative treatment. The surgical treatment method (transoral vs. open partial resection) did not influence OS or RFS. Additionally, the rate of transoral vs. open surgery did not change over a decade. T2-stage patients showed significantly lower RFS than T1-stage patients. Initial R status significantly influenced OS and tumor recurrence. The findings of this study exhibited a significantly longer laryngeal preservation time in patients with T1/2 N0 M0 glottic cancer treated surgically than in those treated with radiotherapy. No significant differences in OS or RFS were observed between open partial laryngectomy and transoral laser surgery. The R status had a significant impact on OS and RFS, with OS being significantly associated with an R0 status, regardless of T status or the surgical approach (open versus transoral). Laryngeal preservation surgery is recommended as a central therapeutic strategy for T1/2 N0 M0 glottic cancer because it has a higher laryngeal preservation rate than the conservative treatment. Given the high recurrence rate (18.5

BACKGROUND:Metastases are associated with poor survival in head and neck squamous cell carcinoma (HNSCC) patients and tumour-associated macrophages (TAMs) are important drivers in tumour progression and metastasis formation. Small extracellular vesicles (sEVs) are another important factor that contribute to systemic immunosuppression and pre-metastatic niche formation. Here, we investigate the effect of plasma sEVs from HNSCC patients on pre-metastatic niche formation, directly or through modulation of macrophages. METHODS:Primary macrophages were incubated with sEVs from plasma of HNSCC patients or healthy donors (HD). RNA profiles and inflammatory properties of macrophages were evaluated. Direct and indirect effects of sEVs on chemotaxis, T cell activation, proliferation and epithelial-to-mesenchymal transition (EMT) of tumour cells were investigated. RESULTS:sEVs of HNSCC patients and HD induced different RNA profiles in macrophages. sEVs induced apoptosis and inhibition of T cell activation, while tumour cells were attracted by sEV-treated macrophages, but not sEVs directly. Proliferation was inhibited by both, sEVs and supernatant of EV-treated macrophages in HNSCC. Additionally, EMT in tumour cells was reversed by HNSCC sEV-treated macrophages. CONCLUSION:sEVs from plasma of HNSCC patients transformed macrophages into metastasis-promoting TAMs and inhibited anti-tumour T cells, highlighting the potential of sEVs and TAMs as targets for therapeutic approaches.

Introduction: The analysis of exhaustion marker expression, like immune checkpoint molecules (ICMs) on tumor-infiltrating lymphocytes as well as peripheral immune cells of patients with head and neck squamous cell carcinoma (HNSCC), is of high interest since it reveals information about the patient’s immune status and the effectiveness of immune modulation. However, data regarding age-dependent expression are lacking. Here, we demonstrate an increase in most ICMs associated with age and disease, suggesting immune checkpoint modulation as an evidence-based option for the treatment of aged HNSCC patients. Material and Methods: Peripheral blood mononuclear cells (PBMCs) (healthy: n = 30 with an age range from 21 to 84 years/HNSCC: n = 37 with an age range from 37 to 94 years) were analyzed via flow cytometry following (density gradient separation) standard protocol. Flow cytometry was performed using CD4 and CD8 as backbone markers as well as co-stimulatory molecules like CD137, OX40, GITR, and CD27 or ICM like PD-1, CTLA4, BTLA, LAG3, or TIM3 using a Gallios flow cytometer (Beckman Coulter, Brea, CA, USA). Results: We found a statistically significant decreased ICM expression on the PBMCs of healthy donors with increasing age. However, the expression of ICMs in HNSCC was significantly increased (PD1 on CD4+ T cells: p = 0.001), while we found a decreased co-stimulatory molecule expression (e.g., CD27 on CD4+ T cells and CD39+ T cells: p = 0.003 and p = 0.009, respectively). Immune cells of HPVneg HNSCC have a significant age-dependent decrease in CD27 expression on CD8+, CD4+, and CD39+ T cells (p = 0.0426, p = 0.0078, and p = 0.0078, respectively). Conclusions: This study sheds light on the changing co-stimulatory molecule/ICM expression regarding the patient’s age and reveals an increase in most immune checkpoint molecules for HNSCC patients according to their age. This new evidence is valuable in ensuring individualized therapeutic approaches in the increasingly relevant field of checkpoint inhibition, even in old age.

Background Patients with hereditary angioedema (HAE) experience recurrent, unpredictable episodes of edema. These swellings are often preceded by prodromal symptoms. HAE management includes acute treatment, long-term prophylaxis (LTP), and short-term prophylaxis (STP) before procedures with a risk of swelling. The effects of LTP on prodromal symptoms and the necessity for STP in patients on LTP remain unclear. Methods A questionnaire-based study involving HAE and AAE patients receiving LTP was conducted. Changes in prodromal symptoms and the incidence of procedures with an increased risk of swelling, including surgeries, dental procedures, and endoscopies were assessed. Results A total of 26 patients were included in the study. Among them, 18 experienced zero to three attacks since starting LTP. Abdominal attacks constituted 60% of all attacks, followed by swellings of the extremities and head and neck. The most frequently reported trigger factors were stress and mechanical stimuli, followed by infections. 9 patients reported surgical procedures, with 8 using STP. Of these, 4 experienced breakthrough attacks, including one laryngeal attack. 105 dental procedures were reported, with STP used for only one. Only one angioedema attack occurred after an intervention without STP. For endoscopies, 7 procedures were reported, 3 of which were performed under STP. Two abdominal attacks were reported by the same patient, both without prior STP. Prodromal symptoms remained consistent in type but varied in intensity and frequency under LTP. Conclusions For dental procedures, the mandatory use of STP in HAE patients on effective LTP should be reconsidered, provided acute treatment is available and other trigger factors are absent.

The guideline is being drawn up as a joint guideline for oropharyngeal and hypopharyngeal carcinoma. Oropharyngeal carcinoma in particular has experienced the greatest increase in incidence among all head and neck carcinomas in the last 20 years and is now the sixth most common cancer in men in Germany. Together with hypopharyngeal carcinoma, these tumors are currently the most common cancer entity in the head and neck region. Due to the association with human papillomavirus type 16 (HPV16), we now distinguish two groups of oropharyngeal carcinomas in Germany: HPV16-positive (approx. 35%) and HPV-negative (approx. 65%). A HPV16 association with hypopharyngeal carcinoma has not been described. The therapy covers the entire spectrum of head and neck surgery, including diversified reconstructive procedures, transoral and external approaches, the options for primary and adjuvant radiotherapy (possibly in combination with chemotherapy) and the current recommendations for drug-based tumor therapy, which range from classic chemotherapy to immuno-oncology. In addition, measures for early detection and prevention are carried out, with particular consideration of the HPV16-associated genesis of oropharyngeal carcinoma, as well as adequate rehabilitation after the primary treatment of oropharyngeal and hypopharyngeal carcinomas. Finally, the treatment options for recurrences or distant metastases that cannot be cured in the further course of the disease are shown and classified.

BACKGROUND/AIM:Head and neck squamous cell carcinoma (HNSCC) is an aggressive epithelial malignancy of the upper aerodigestive tract, associated with poor survival. As part of the HNSCC microenvironment, the interleukin-18 (IL-18)/IL-18 binding protein (IL-18BP) signaling is becoming increasingly interesting as a potential biomarker and therapeutic target. However, the systemic expression levels of IL-18BP in the context of the immunological environment in HNSCC patients remain unexplored. MATERIALS AND METHODS:ELISA measurements of plasma IL-18-BP were carried out with regard to associated inflammatory markers such as C-reactive protein, acute phase protein ferritin, and IL-18 in 34 patients with HNSCC before and during the course of radio(chemo)therapeutic treatment and in correlation to the clinicopathological parameters. RESULTS:Plasma IL-18BP concentrations were significantly elevated in HNSCC patients compared to healthy controls and correlated strongly with IL-18 levels before and after treatment. However, plasma ferritin levels, which were also elevated, showed no correlation with IL-18 or IL-18BP. Notably, changes in IL-18BP and IL-18 levels following therapy exhibited a well-maintained balance, indicating a functional feedback mechanism. CONCLUSION:The results demonstrate a robust IL-18/IL-18BP feedback regulation in HNSCC, which likely aids tumor cells in evading anti-tumor immune responses. This balance, unaffected by radiotherapy or chemoradiotherapy, underscores the potential of IL-18BP as a therapeutic target and a prognostic biomarker in HNSCC.

The field of otorhinolaryngology and head and neck surgery comprises both conservative and surgical domains. Specialist training is often followed by in-depth surgical specialization, in the past reflected by, among other things, continued education in "specialized surgical otorhinolaryngology." This qualification was discontinued, however, by the German Medical Association's reform of the continuing medical education (CME) regulations ([Muster-]Weiterbildungsordnung, MWBO, 2003). Although it is still possible to obtain additional certification in "plastic and esthetic surgery," another advanced surgical qualification in, for example, oncology, otology, or rhinology, is currently not possible within the scope of the WBO of the medical associations. It would not appear possible to implement additional (Sect. C of the WBO) or specialist (Sect. B) CME qualifications in the near future, despite the fact that surgical specialization-in light of the necessity of sustainable quality assurance (e.g., certified cancer centers, cochlear implantation facilities, skull base centers) or the fundamental changes to the healthcare landscape (hospital reform)-seems more important than ever. On the initiative of the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery (DGHNO-KHC), and the German Academy of Oto-Rhino-Laryngology (DAHNO), a concept to enable expert certification is to be developed in collaboration with specialist working groups. This initiative initially addresses "head and neck surgical oncology" as well as perspectives for "oto- and lateral skull base surgery" and "rhino- and anterior skull base surgery." Relevant content is stored in a logbook. The goal is to present the applicants' expertise in "head and neck surgical oncology" analogously to international standards. The certificate can be used as evidence of individual oncosurgical skills, e.g., for other certification procedures. The practical implementation is carried out by an independent certification body (ClarCert GmbH) on behalf of the DGHNO-KHC in collaboration with the DAHNO and the Oncology Working Group. Applications for the expert certificate "head and neck surgical oncology" are now open for members of the DGHNO-KHC and the DAHNO.

A fundamental hospital reform is urgently needed due to the existing shortage of specialists, postpandemic productivity changes, and increasing financial deficits faced by hospitals in Germany. Starting from a hospital reform initiated in North-Rhine Westphalia (NRW), the so-called Hospital Care Improvement Act ("Krankenhausversorgungsverbesserungsgesetz", KHVVG) was launched at the federal level with the aim of ensuring more adequate funding, safeguarding and improving treatment quality, and reducing bureaucracy. This was passed by the Federal Council and officially came into force on 1 January 2025. For the specialty of Otorhinolaryngology, two categories-general ENT and cochlear implants-were selected for future hospital planning. The new law also established minimum physician requirements (e.g., 3 full-time physicians including 24/7 on-call duty) and defines so-called "oncological capping" as well as minimum number of cases for each defined entity. These measures are expected to lead to significant changes in the hospital landscape, including centralization of highly specialized services, with potential implications for specialist training. In summary, the KHVVG will ultimately alter patient care, thus, requiring flexible adaptation processes, which will be supported by professional societies. For this reason, we have simulated and discussed the effects of the KHVVG on our field to better assess possible consequences and initiate adjustment processes at an early stage.

Due to their high developmental diversity and different regulatory and functional roles, B cell subpopulations can promote or inhibit tumor growth. An orthotopic murine HNSCC model was applied to investigate the B cell composition and function in HNSCCs. Using flow cytometry approaches, cells from the spleen, lymph nodes and tumors were analyzed. Additionally, immunoglobulin (Ig) levels post-tumor induction were tracked via enzyme-linked immunosorbent assays (ELISA). Following tumor induction, GCs, as well as increasing numbers of GL7+CD95+ GC B cells in the spleen and tumor tissues, were detected. In parallel, we observed CD39+CD73+ B cells in tumors and spleens of tumor-bearing mice. Notably, CD39+CD73+ expression was primarily detected on MZ B cells and to a lesser extent on follicular (FO) and non-follicular, newly formed (NF) B cells, supposing an immunosuppressive function of MZ B cells in the TME. Parallel to increased MZ B cell numbers in secondary lymphoid organs (SLOs) as well as in the tumor tissue, IgM antibody (Ab) levels rose continuously. In contrast, IgG1, IgG2, and IgG3 levels increased at later time points. Understanding the complex interactions between B cell subsets and the TME could lead to new strategies for enhancing the treatment and prognosis of HNSCC patients.

Segmenting the boundary between tumor and healthy tissue during surgical cancer resection poses a significant challenge. In recent years, Hyperspectral Imaging (HSI) combined with Machine Learning (ML) has emerged as a promising solution. However, due to the extensive information contained within the spectral domain, most ML approaches primarily classify individual HSI (super-)pixels, or tiles, without taking into account their spatial context. In this paper, we propose an improved methodology that leverages the spatial context of tiles for more robust and smoother segmentation. To address the irregular shapes of tiles, we utilize Graph Neural Networks (GNNs) to propagate context information across neighboring regions. The features for each tile within the graph are extracted using a Convolutional Neural Network (CNN), which is trained simultaneously with the subsequent GNN. Moreover, we incorporate local image quality metrics into the loss function to enhance the training procedure's robustness against low-quality regions in the training images. We demonstrate the superiority of our proposed method using a clinical ex vivo dataset consisting of 51 HSI images from 30 patients. Despite the limited dataset, the GNN-based model significantly outperforms context-agnostic approaches, accurately distinguishing between healthy and tumor tissues, even in images from previously unseen patients. Furthermore, we show that our carefully designed loss function, accounting for local image quality, results in additional improvements. Our findings demonstrate that context-aware GNN algorithms can robustly find tumor demarcations on HSI images, ultimately contributing to better surgery success and patient outcome.

Zusammenfassung Hintergrund Eine schwere, nicht kontrollierte chronische Rhinosinusitis mit nasalen Polypen (CRSwNP) kann sich unter Dupilumab 300 mg 2‑wöchentlich komplett zurückbilden. Spätestens dann folgt die Frage der Patienten nach einer möglichen Therapiedeeskalation. Eine Beendigung der Antikörpertherapie nach 24 Wochen führte zum Rezidiv, hingegen blieb unter reduzierter Dupilumab-Dosis durch Streckung des Intervalls auf 4 Wochen die Kontrolle erhalten. Eine vom Zulassungstext abweichende Verlängerung der Therapieintervalle wird jedoch aktuell nicht empfohlen. Methoden Es erfolgte eine retrospektive Untersuchung des Verlaufs von 29 Patienten mit schwerer CRSwNP, mit Typ-2-Inflammation assoziierten Komorbiditäten und bestehender Indikation zur Biologikatherapie. Nach Rückbildung der CRSwNP und der Beschwerden unter Dupilumab 300 mg 2‑wöchentlich war das Applikationsintervall individuell zunächst auf 4 Wochen, danach ggf. auf 6 Wochen verlängert worden. Erfasst wurden u. a. die Lebensqualität (Sinonasal Outcome Test, SNOT-22), der nasale Polypenscore (NPS) und das Riechvermögen (Sniffinʼ Sticks, Fa. Burghart Messtechnik, Holm, Deutschland). Ergebnisse Alle Patienten zeigten innerhalb der ersten 3 Monate ein sehr gutes Therapieansprechen. Eine Verlängerung des Dupilumab-Intervalls auf 4 Wochen erfolgte nach 7–31 Monaten (median 13 Monate), auf 6 Wochen ( n = 9) nach 17–35 Monaten (median 23 Monate). Im Verlauf traten bei keinem Patienten ein Rezidiv, eine Verschlechterung der Lebensqualität oder des Riechens auf. Schlussfolgerung Eine Verlängerung der Dupilumab-Injektionsintervalle auf 4 evtl. auch 6 Wochen ist individuell nach weitestgehender Rückbildung der Polypen und Beschwerden ohne klinische Verschlechterung möglich. Weitere Studien zur Deeskalation bzw. Beendigung der Biologikatherapie bei erzielter CRSwNP-Kontrolle sind unabdingbar.

Gene set enrichment analysis output

BACKGROUND AND OBJECTIVES:This paper presents an overview on nasal packing materials which are available in Germany. The current literature is analyzed whether there are robust criteria regarding use nasal packing after sinonasal surgery, whether there are fundamental and proven advantages or disadvantages of products, and what this means in clinical practice.MATERIALS AND METHODS:Selective literature analysis using the PubMed database (key words "nasal packing", "nasal tamponade", "nasal surgery", "sinonasal surgery", or "sinus surgery"), corresponding text books and resulting secondary literature.RESULTS AND CONCLUSIONS:Because of systematic methodological shortcomings, the literature does not help in the decision-making about which nasal packing should be used after which kind of sinonasal surgery. In fact, individual approaches for the many different clinical scenarios are recommended. In principle, nasal packing aims in hemostasis, should promote wound healing, and should not result in secondary morbidity. Nasal packing materials should be smooth (non-absorbable materials), inert (absorbable materials), and should not exert excessive pressure. Using non-absorbable packing entails the risk of potentially lethal aspiration and ingestion. For safety reasons inpatient control is recommended as long as this packing is in situ. With other, uncritical packing materials and in patients with special conditions, outpatient control could be justified.

BACKGROUND:Transoral laser microsurgery, the standard surgical approach for early-stage laryngeal cancer, necessitates an unobstructed line of sight to the operating field. However, achieving adequate laryngeal exposure can be challenging, potentially compromising treatment outcomes. METHODS:We developed a 3D-printed curved laryngoscope (sMAC), designed to match the upper airway anatomy. In a user study (n = 15) with a human body donor we compared the sMAC system to conventional microlaryngoscopy regarding laryngeal exposure and accessibility in a difficult exposure scenario. RESULTS:All 15 participants achieved complete glottic exposure and successfully manipulated laryngeal landmarks using the sMAC system. Only four participants achieved partial exposure using microlaryngoscopy. Positioning of the sMAC system was significantly faster (p = 0.023). A vocal cord resection was conducted successfully (n = 2) using the sMAC system. CONCLUSION:The sMAC system effectively addresses challenges associated with transoral laryngeal surgery. Ongoing development aims to overcome current limitations of the system and prepare first clinical trials.