[Update on HPV-associated head and neck cancers-highlights of the 2024 ASCO Annual Meeting]. / Update zu HPV-assoziierten Kopf-Hals-Karzinomen ­ Highlights der ASCO-Jahrestagung 2024.

BACKGROUND: Human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) is becoming increasingly important in head and neck oncology. At this year's conference of the American Society of Clinical Oncology (ASCO), a large number of papers were presented on the topic of HPV-associated HNSCC, particularly with regard to neoadjuvant treatment approaches, radiation de-escalation strategies, therapeutic vaccines, and treatment monitoring. In this context, study results on the treatment of HPV-related recurrent respiratory papillomatosis (RRP) were also presented. OBJECTIVE: Based on contributions to the 2024 ASCO Annual Meeting, an insight into the latest developments in HPV-associated diseases of the head and neck is provided. METHODS: The papers were reviewed for clinical relevance and contextualized based on current therapeutic concepts. RESULTS AND CONCLUSION: A large number of studies on liquid biopsies (LB) were presented. It was shown that although the methods for analyzing LBs for HPV-positive patients are well developed and can be used for diagnostics, risk classification, treatment management, or tumor follow-up, the methods vary considerably, and their clinical application has not yet been sufficiently validated. With regard to therapeutic HPV vaccination, three large studies were presented for the treatment of recurrent/metastatic HPV-positive oropharyngeal squamous cell carcinoma (OPSCC). The only randomized study was on the vaccine ISA101b (peltopepimut-S) and did not reach its primary endpoint; however, the vaccine seemed to be highly effective in patients with a combined positive score (CPS) ≥ 20. Furthermore, data from a phase I study on PRGN2012, an adenovirus-based immunotherapy used therapeutically for the treatment of recurrent respiratory papillomatosis (RRP), were presented. PRGN2012 led to a reduction in surgical interventions for RRP, and the US Food and Drug Administration (FDA) designated PRGN2012 as a breakthrough therapy and orphan drug. However, the vaccine is not yet approved for the treatment of RRP.

[Chronic rhinosinusitis with nasal polyposis : A retrospective analysis of therapeutic approaches in 463 patients]. / Chronische Rhinosinusitis mit Polyposis nasi : Retrospektive Analyse des therapeutischen Vorgehens bei 463 Patienten.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease, the treatment of which has undergone significant changes in recent years. In addition to surgical approaches, topical and systemic steroids, and adaptive acetylsalicylic acid (ASA) desensitization, three specific antibodies have complemented the therapeutic portfolio since 2019. METHODS: A retrospective evaluation of all patients who presented as outpatients for the first time due to CRSwNP in 2007 and 2008 (collective A) and 2017 and 2018 (collective B) was performed, up to and including June 2023. RESULTS: The clinical courses of 463 patients (mean age 49.1 years, range 5-82 years; 65.9% male) were included in the analysis. Conservative treatment with nasal corticosteroids started before initial presentation was more frequent in collective B (collective A 43.9% vs. collective B 72.2%). In 278 of the 463 patients (60%; A: 62%, B: 58%), at least one operation on the nasal sinuses had been performed after initial presentation; in 101 of these patients (36.3%) recurrent polyposis (within mean follow-up of 2.4 years) required further treatment. The indication for ASA provocation/desensitization was applied less frequently in collective B, also due to a high discontinuation rate (at least 38%) of the maintenance therapy. Of the total cohort, 16 patients (3.5%; A: n = 8, B: n = 8) were meanwhile switched to antibody therapy at recurrence. CONCLUSION: A step-by-step guideline-orientated approach is recommended in the treatment of CRSwNP. Systemic antibodies as an add-on to nasal corticosteroids are a relatively new therapeutic option for treatment-refractory CRSwNP, which reduces the indication for ASA desensitization, which is associated with a relatively high incidence of side effects and poor compliance.

[Chronic rhinosinusitis with nasal polyps-extension of dupilumab treatment intervals]. / Chronische Rhinosinusitis mit nasalen Polypen ­ Verlängerung der Dupilumab-Therapieintervalle.

BACKGROUND: In patients with severe, uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP), dupilumab 300 mg every 2 weeks can completely resolve nasal polys, sinus disease, and symptoms. In this case, patients ask for de-escalation. Although trials have demonstrated recurrence after stopping the biologic at 24 weeks, reducing the dose of dupilumab to once every 4 weeks did not result in deterioration of control. An extension of the treatment intervals would, however, diverge from the approval text, and is currently not recommended. METHODS: The course of 29 patients with severe CRSwNP, type­2 inflammation-associated comorbidities, and an indication for biologic was retrospectively analyzed. After resolution of CRSwNP and symptoms under biweekly dupilumab 300 mg, the dupilumab interval had been prolonged individually, initially up to 4 weeks, thereafter up to 6 weeks, if applicable. Control was assessed via quality of life (22-item sinonasal outcome test, SNOT-22), nasal polyp score, and smell identification test (Sniffin' Sticks; Burghart Messtechnik, Holm, Germany). RESULTS: All patients showed an excellent improvement within the first 3 months. The dupilumab application interval was extended to 4 weeks after 7-31 months (median 13 months) and to 6 weeks (n = 9) after 17-35 months (median 23 months). No recurrent polyps or symptoms were subsequently observed. CONCLUSION: In case of maximal regression of polyps and discomfort, extension of dupilumab injection intervals to 4 and potentially 6 weeks is possible without clinical worsening. Further studies on de-escalation or termination of biologic treatment when CRSwNP control is achieved are essential.

[Statement on the lower age limit for outpatient adenotomies and tonsillotomies]. / Stellungnahme zur Altersuntergrenze bei der ambulanten Durchführung von Adenotomien und Tonsillotomien.

At the beginning of 2023, there have been significant changes to the regulations for outpatient surgery in Germany, which were set out in a trilateral self-administration agreement between the umbrella association of statutory health insurance companies, the German Hospital Association and the Federal Association of Statutory Health Insurance Physicians. Among other things, a catalog stated circumstances under which an operation should not be carried out on an outpatient basis or should only be carried out with doubt. This catalog explains the patient's age: up to the first year of life, inpatient performance of a service can be justified. This formulation in itself means that children from one year of age on should regularly undergo outpatient surgery.In the german scientific societies for otolaryngology, head and neck surgery as well as for anesthesiology and intensive care medicine, doubts arose as to whether this age limit could also be scientifically justified for operations in the throat such as adenotomy or tonsillotomy.A search was carried out in international guidelines and in the international literature and the statements were evaluated. The results of this literature search were discussed with representatives of the Pediatric Otorhinolaryngology Working Group (AG PädHNO) of the German Society for Otorhinolaryngology, Head and Neck Surgery (DGHNO-KHC) and the scientific working group for pediatric anesthesia (WAKKA) of the German Society for Anesthesiology and Intensive Care Medicine (DGAI) in conferences.The consensus revealed that a strict age limit of the first year of life is not appropriate for the outpatient performance of adenotomies and tonsillotomies. First of all, specifying a strict age limit is questionable because, regardless of age, a number of other medical and social factors influence the responsible performance of outpatient operations. Furthermore, the age limit of one year is not considered appropriate in view of literature, guidelines and practical experience in the international area. The assessment of the literature and the consideration of the implementation in the international area make an age limit in the range of 2-3 years seem more appropriate.This review provides the responsible doctors with a variety of insights, aspects and arguments so that they can make their decision to carry out these operations on an outpatient or inpatient basis appropriately and responsibly.

Continuous investigation of the nasal cycle over 48 hours.

BACKGROUND: Previous results on the nasal cycle refer to measurements over up to 24h. The long-term rhinoflowmetry (LRFM) allows continuous observations over a longer period. The aim of the study was to observe the nasal cycle for the first time over 48h under everyday conditions. METHODOLOGY: The LRFM was continuously applied to 30 rhinologically healthy subjects (20 female, 10 male) over 48h. The different types of nasal cycle were classified as follows: "classic", "in concert", "one-sided", "no-cycle" and "mixed". The focus of this study was on the results over the entire 48 hours. The comparison of the two consecutive days was also made. RESULTS: A nasal cycle could be detected in 100% of the subjects over 48h. With 97%, the mixed type most commonly occurred as a combination of classical and in concert components. In all subjects, classical cycle components could be detected at least once. The no-cycle type was not observed. In the awake state, the mixed type dominated (80%), as a combination of classical and in concert parts. In the sleep state, the classical type was the most common type (97%). The average phase duration was 206 ± 83 minutes. CONCLUSIONS: In the very first continuous 48-hour study on the nasal cycle, 100% of the subjects presented a nasal cycle. The LRFM method is the only one that offers the possibility to perform continuous measurements over a longer period during daily routine. The results of previous single-stage examination methods should thus be questioned.

[Skull base surgery in the German DRG system-New categorization of important procedures]. / Die Schädelbasischirurgie im deutschen DRG-System ­ Neue Zuordnung wichtiger Prozeduren.

Surgery of the skull base includes interventions between the nose or paranasal sinuses (anterior skull base) or ear/temporal bone (lateral skull base) and the intracranial space. As interventions at the anterior skull base almost exclusively involve complex pathologies in a demanding anatomical region, in many cases two experienced surgeons from different disciplines are required who should be experienced in operating together. The technical and time requirements are also considerable in many cases; however, for many procedures there are no specific skull base operational and procedural keys (OPS) codes that take the considerable personnel and structural effort into account. A change in the diagnosis-related groups (DRG) system, implemented since the beginning of 2023, now adjusts the remuneration of the abovementioned effort for malignant pathologies of the anterior and lateral skull base. The reallocation of procedures 5­015.0/1/3/4 and 5­016.0/2/4/6 results in a significant upgrade of anterior and lateral skull base surgery. Since the beginning of 2023 skull base surgery will no longer be charged under DRG D25C with a (former) relative weight of 1.893, but with DRG D25B with a current relative weight of 3.753 when a code of the aforementioned groups is used. Nevertheless, further adjustments are necessary, for example, in the available reconstructive steps in order to provide the Institute for the Remuneration System in Hospitals (InEK) with the most differentiated data possible on the procedural effort of the intervention and to achieve a more balanced distribution of the reimbursements of skull base surgery in the long term.

[Diagnosis and Treatment in frontobasal fractures]. / Vorgehen bei frontobasalen Frakturen.

Traumatic brain injury can result in frontobasal fractures (FBF). The goals of treatment for FBF are to eliminate primary morbidity and/or prevent secondary morbidity. Of particular importance in this regard is the proximity of important sensory organs for hearing, vision, smell, and taste, as well as their supplying nervous structures. Medical history, clinical findings, or CT scan are necessary and should lead to an individual evaluation. Depending on the severity of the fractures, the following disciplines may be involved in the treatment of FBF: neurosurgery, plastic surgery, oral and maxillofacial surgery, and/or otorhinolaryngology. Particularly less invasive endoscopic endonasal therapy is a specialty of otorhinolaryngologic surgeons and has not been widely established in other disciplines. The present work provides an overview of the current state of the art in terms of the following aspects, taking into account the current literature: anatomic principles, classification of fractures, diagnostics (in particular clinical examination, imaging, and laboratory chemistry tests), clinical symptoms, and treatment.

[Radiation or Surgery for HPV-positive oropharyngeal cancer? The ORATOR2 Trial - Comparing apples and oranges]. / Strahlentherapie oder Operation bei HPV-positiven Oropharynxkarzinomen? Die ORATOR2-Studie ­ ein Vergleich von Birnen und Äpfeln.

ORATOR2 was a randomized phase II trial aiming to assess an optimal approach for therapy de-escalation in early (T1-T2, N0-N2) human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OPSCC). Radiotherapy (RT) (consisting of a reduced dose of 60 Gy with concurrent weekly cisplatin in N+ patients) was compared to trans-oral surgery (TOS) and neck dissection (ND) (with adjuvant reduced-dose RT depending on pathologic findings) in 61 patients. The primary endpoint, overall survival, favored the radiotherapy approach. This was mainly due to 3 mortality events in the surgery arm (2 surgery-related) which resulted in an early trial termination. The authors, who speak on behalf of the German Society of Otorhinolaryngology, Head & Neck Surgery (working group for oncology) warn to draw conclusions for clinical practice pointing out the main shortages/weaknesses of this trial especially in the surgery arm (at least 1 cm margins, recommending re-operation if not achieved, prohibition of regional or free flaps, high rates of tracheotomy, low rate of TLM). Small patient numbers, a highly selected patient cohort and a short follow-up time further limit this study's relevance. Therefore, patients with HPV-related OPSCC should not receive de-escalating (radiation) therapy outside of clinical trials. When deciding between a surgical or a radio-therapeutical approach, patients should be informed about the pros and cons of both modalities after interdisciplinary consent in a tumor board, as long as clinical trial results` (e. g. EORTC 1420) are pending.

Empfehlungen zur Überprüfung der Wirksamkeit und Verlaufsdokumentation von Mepolizumab bei chronischer Rhinosinusitis mit Nasenpolypen (CRSwNP) im deutschen Gesundheitssystem ­ Empfehlungen des Ärzteverbandes Deutscher Allergologen (AeDA) und der AGs Klinische Immunologie, Allergologie und Umweltmedizin und Rhinologie und Rhinochirurgie der Deutschen Gesellschaft für HNO-Heilkunde, Kopf- und Halschirurgie (DGHNOKHC).

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the mucous membranes of the nose and sinuses. Eosinophilic inflammation is described as a common endotype. The anti-IL5 antibody mepolizumab was approved in November 2021 as an add-on therapy to intranasal glucocorticosteroids for the treatment of adults with severe chronic rhinosinusitis with nasal polyps when systemic glucocorticosteroids or surgery do not provide adequate disease control. While national and international recommendations exist for the use of mepolizumab in CRSwNP, it has not yet been adequately specified how this therapy is to be monitored, what follow-up documentation is necessary, and when it should be terminated if necessary. METHODS: A literature search was performed to analyze previous data on the treatment of CRSwNP with mepolizumab and to determine the available evidence by searching Medline, Pubmed, the national and international trial and guideline registries and the Cochrane Library. Human studies published in the period up to and including 10/2022 were considered. RESULTS: Based on the international literature and previous experience by an expert panel, recommendations for follow-up, adherence to therapy intervals and possible therapy breaks, as well as termination of therapy when using mepolizumab for the indication CRSwNP in the German health care system are given on the basis of a documentation sheet. CONCLUSIONS: Understanding the immunological basis of CRSwNP opens up new non-surgical therapeutic approaches with biologics for patients with severe, uncontrolled courses. Here, we provide recommendations for follow-up, adherence to therapy intervals, possible therapy pauses, or discontinuation of therapy when mepolizumab is used as add-on therapy with intranasal glucocorticosteroids to treat adult patients with severe CRSwNP that cannot be adequately controlled with systemic glucocorticosteroids and/or surgical intervention.

Treatment success after rhinosurgery: an evaluation of subjective and objective parameters.

PURPOSE: Septal deviation and nose deformities are widely prevalent. As a consequence, patients may complain about difficulties in nasal breathing leading to a perception of diminished disease-specific quality of life. In a prospective randomized trial, we aimed to analyse the outcome of septoplasty (SPL) and septorhinoplasty (SRP) on patient satisfaction. METHODS: Patients with functional indication for SPL (n = 19) or SRP (n = 54) were included and randomized for additional turbinoplasty. Preoperative clinical symptoms were collected with SNOT-20 GAV (Sinu-nasal outcome test-20-German adapted version) and NOSE© (nasal obstruction symptom evaluation) questionnaires. The final evaluation of treatment success was performed 9 months after surgery with SNOT-20 GAV, NOSE© and a self-established feedback questionnaire. Nasal breathing and obstruction were objectively measured with rhinomanometry and acoustic rhinometry [minimum cross-sectional area 2 (MCA2)]. RESULTS: Minimum cross-sectional area 2 was statistically improved compared to the pre-treatment value in SPL (p = 0.0004) and SRP (p = 0.0001). Regarding MCA2 values of matched patient groups, similar findings were detected (SPL: p = 0.0013, SRP: p < 0.0001). Sinu-nasal outcome test-20 GAV and NOSE© scores were significantly reduced after both surgical procedures (NOSE©: SPL: p < 0.0001, SRP: p < 0.0001; SNOT-20 GAV: SPL: p = 0.0068, SRP: p < 0.0001). Evaluation of patient satisfaction in a self-established feedback questionnaire revealed a motivation of 81% of patients to redo the surgery (SPL 13/16, SRP 34/42) and a notably general satisfaction of 86% for SPL and 80% for SRP. CONCLUSION: Rhinosurgery leads to quantitative better nasal breathing and increased disease-specific satisfaction. However, this study implies the importance of the right selection of patients and the correct indication of the surgical technique.

[Typical emergencies in otorhinolaryngology-a monocentric analysis of the seasonal course]. / Typische Notfälle in der Hals-Nasen-Ohren-Heilkunde ­ eine monozentrische Evaluation über den jahreszeitlichen Verlauf.

BACKGROUND: The incidence of acute ear, nose, and throat (ENT) diagnoses is influenced by multiple parameters, for example meteorological and seasonal influences. By better understanding the triggering factors, prophylactic approaches can be developed. MATERIALS AND METHODS: A retrospective analysis was performed over 6 years of all patients who presented to the university hospital because of typical and minor ENT emergencies. The diagnoses impacted cerumen, acute otitis media, acute otitis externa, nasal bone fracture, epistaxis, acute tonsillitis, acute rhinosinusitis, and peritonsillar abscess were analyzed. RESULTS: A total of 32,968 cases were analyzed. Epistaxis was the most common of the investigated emergency diagnoses, accounting for 24.5% (8082 cases). Epistaxis, acute otitis media, and acute rhinosinusitis occurred significantly more frequently in the colder half of the year. There was no significant correlation of the incidence of nasal bone fracture with public holidays. Acute otitis externa correlated significantly with the local summer vacations. In calendar week 38, the fewest total emergency presentations occurred, whereas in calendar week 52, the most emergency presentations occurred. CONCLUSION: Seasonal and meteorological factors play a significant role in the pathogenesis of many emergency ENT diagnoses.

[Definition and illustration of the different types of nasal cycle using long-term rhinometry]. / Definition und Darstellung der verschiedenen Typen des Nasenzyklus mittels Langzeitrhinometrie.

BACKGROUND: A reciprocal swelling of the nasal mucosa is often referred to as the classical nasal cycle; however, reports in the literature suggest a more complex picture. Most of the research on the nasal cycle is based on individual measurements. The long-term rhinometry (LRM) now makes it possible to continuously examine the cyclic swelling of the nasal mucosa over 24 h. The aim of this study was therefore to evaluate the nasal cycle with LRM over 24 h. MATERIAL AND METHODS: An LRM was performed in 55 rhinologically healthy subjects over 24 h using the portable measuring system Rhino-Move© (Happersberger Otopront; Hohenstein, Germany). RESULTS: In addition to the expected strictly reciprocal swelling of the nasal mucosa in the sense of the classical nasal cycle, the following cycle types were detected: in-concert type with simultaneous rise and drop of the air flow on both sides of the nose, the one-sided type with significant congestion and decongestion of the mucous membrane only on one side and no detectable changes on the other side of the nose and the non-cycle type without any change in airflow on both sides. Most subjects showed a complex picture with multiple cycle types within the 24 h measurement (mixed nasal cycle). The types often differed during the day and night. CONCLUSION: This study confirms the assumption that the nasal cycle measured over 24 h is much more complex than often described in the literature. Most subjects showed several of the 5 cycle types described here. The LRM has proven to be an easy to- use and reliable measurement method. The relationship between cycle type and physical activity as well as other factors remains to be investigated.

[Oncologic follow-up in head and neck cancer patients]. / Onkologische Nachsorge von Kopf-Hals-Tumor-Patienten.

Despite medical treatment according to evidence-based guidelines, approximately 25-30% of all head and neck tumor patients suffer a disease relapse, depending on tumor stage and entity. The primary goal of systematic follow-up examinations is early detection and treatment of recurrent tumors or metachronous secondary tumors, but it also serves to rule out distant metastasis. Secondary goals are the diagnosis and management of treatment-associated side effects to optimize quality of life. Because of an especially high relapse risk in the first 2 years after treatment, close-knit clinical controls are recommended, e.g., quarterly. Later on, the clinical control interval can be extended to 6 months. Cross-sectional diagnostic imaging of the primary tumor region is performed annually and when screening for possible distant metastases, or upon clinical suspicion of recurrence. After 5 years without tumor recurrence, the structured clinical follow-up is usually completed.

[Infrasound - implications for human medicine]. / Infraschall ­ humanmedizinische Implikationen.

Infrasound describes ubiquitous, low-frequency sound (< 20 Hz) in the environment with a long wavelength below the median hearing threshold, which can nevertheless be heard and tactilely perceived, depending on the sound pressure level and frequency spectrum. In nature, infrasound emissions usually occur only in the low-threshold range. Nevertheless, after strong and chronic exposure to usually artificially generated infrasound emissions, various effects on the ear and the body, sometimes questionably critical to health, can be observed. Correct measurement and assessment of infrasound sources is complex and controversial. Established guidelines are scarce. Innovative research areas include infrasound monitoring for evaluation of natural events and infrasound applications in medicine. In the future, it is hoped that new insights will be gained from infrasound research and that a more extensive classification in occupational medicine will be possible.

Positionspapier: Empfehlungen zur Anwendung von Mepolizumab bei chronischer Rhinosinusitis mit Polyposis nasi (CRSwNP) im deutschen Gesundheitssystem ­ Empfehlungen des Ärzteverbandes Deutscher Allergologen (AeDA) und der AGs Klinische Immunologie, Allergologie und Umweltmedizin und Rhinologie und Rhinochirurgie der Deutschen Gesellschaft für HNO-Heilkunde, Kopf- und Hals-Chirurgie (DGHNO-KHC).

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the paranasal sinus mucosa with eosinophilic inflammation as the most common endotype. The anti-IL5 antibody mepolizumab was approved for the treatment of severe CRSwNP in the EU in November 2021. METHODS: A literature search was performed to analyze the immunology of CRSwNP and determine the available evidence by searching Medline, Pubmed, and the German national and international trial and guideline registries and the Cochrane Library. Human studies published in the period up to and including 12/2021 that investigated the effect of mepolizumab in CRSwNP were considered. RESULTS: Based on the international literature and previous experience, recommendations for the use of mepolizumab in CRSwNP in the German health care system are given by an expert panel on the basis of a documentation form. CONCLUSIONS: Understanding about the immunological basis of CRSwNP opens new non-surgical therapeutic approaches with biologics for patients with severe courses. Mepolizumab is approved since November 2021 for add-on therapy with intranasal corticosteroids for the treatment of adult patients with severe CRSwNP who cannot be adequately controlled with systemic corticosteroids and/or surgical intervention.

Empfehlungen zur Überprüfung der Wirksamkeit und Verlaufsdokumentation von Dupilumab bei chronischer Rhinosinusitis mit Nasenpolypen (CRSwNP) im deutschen Gesundheitssystem.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the nasal and paranasal mucosa. A Type-2 inflammation is described as the most common endotype. Since October 2019 the anti-IL-4/-IL-13 antibody dupilumab has been approved in Germany as an add-on therapy to intranasal corticosteroids for the treatment of adults with severe chronic rhinosinusitis with nasal polyps, when systemic corticosteroids alone or surgery do not provide adequate disease control. While recommendations for the use of dupilumab in CRSwNP exist at both national and international levels, until now it has not been adequately established, how therapy should be monitored and when it should be discontinued in the German Health Care System. METHODS: A literature search was performed analyzing previous data on the treatment of CRSwNP with dupilumab and to determine the available evidence by searching Medline, Pubmed, the national and international trial and guideline registries and the Cochrane Library. Human studies published in the period up to 05/2022 were included. RESULTS: Based on international literature and previous experience, recommendations are given by an expert panel for follow-up and possible therapy breaks, therapy intervals or termination of therapy when using dupilumab for the indication CRSwNP in the German health care system based on a documentation form. CONCLUSIONS: Understanding the immunological basis of CRSwNP opens new non-surgical therapy approaches with biologics for patients with severe courses. The authors give recommendations for follow-up, possible therapy breaks, therapy intervals and a termination for dupilumab treatment as add-on therapy with intranasal corticosteroids for the treatment of adult patients with severe CRSwNP that cannot be adequately controlled with systemic corticosteroids and/or surgical intervention.

Changes in circulating exosome molecular profiles following surgery/(chemo)radiotherapy: early detection of response in head and neck cancer patients.

BACKGROUND: Head and neck cancers (HNSCC) are highly immunosuppressive. Plasma-derived exosomes of HNSCC patients carry immunomodulatory molecules, and their cargo correlates with clinical parameters. Here, we evaluated the exosomal molecular profile for early detection of treatment failure in locally advanced HNSCC patients treated with conventional therapy. METHODS: Plasma from 17 HNSCC patients was collected before, during, and after treatment by surgery with adjuvant (chemo)radiation and at recurrence. Exosomes were isolated by size-exclusion chromatography. Total exosomal protein (TEP) was used to estimate exosome load and on-bead flow cytometry to evaluate relative fluorescence intensity (RFI) of tumour-associated and immunoregulatory proteins on exosomes. Exosomal effects on the activity of and adenosine production by T cells was assessed by flow cytometry and mass spectrometry. RESULTS: TEP and the ratio of tumour-/immune-cell-derived exosomes varied during and after therapy with an overall decrease in the tumour-free follow-up but an increase at recurrence. RFI values of immunoregulatory proteins on exosomes, their ability for T cell inhibition and adenosine production changed during and after therapy. PD-L1 was the earliest discriminator for treatment failure and disease-free survival. CONCLUSIONS: Monitoring of plasma exosomes during therapy represents a promising opportunity for early detection of treatment failure and risk stratification to delay/avoid recurrence.

Influence of travel burden on tumor classification and survival of head and neck cancer patients.

PURPOSE: Cancer patients have to overcome various barriers to obtain diagnostics and treatment at head and neck cancer centers. Travel distance to a specialized hospital may result in psychosocial and financial distress, thus interfering with diagnostics, treatment, and follow-up care. In this study, we have aimed to analyze the association of travel distance with cTNM status, UICC stage at primary diagnosis, and survival outcomes of head and neck cancer (HNC) patients. METHODS: We have analyzed data of 1921 consecutive HNC patients diagnosed between 2014 and 2019 at the head and neck cancer center of the Comprehensive Cancer Center Ulm (CCCU), Germany. Postal code-based travel distance calculation in kilometers, TNM status, and UICC stage were recorded at initial diagnosis. The assembly of travel distance-related groups (short, intermediate, long-distance) has been investigated. Moreover, group-related survival and recurrence analysis have been performed. RESULTS: In contrast to observations from overseas, no association of travel distance and higher cTNM status or UICC stage at primary diagnosis has been observed. Furthermore, no significant differences for recurrence-free survival and overall survival by travel distance were detected. CONCLUSION: In southern Germany, travel distance to head and neck cancer centers seems to be tolerable. Travel burden is not synonymous with travel distance alone but also involves sociodemographic, monetary, and disease-specific aspects as well as accessibility to proper infrastructure of transport and health care system.

Evaluation of a curved surgical prototype in a human larynx.

PURPOSE: It is not always possible to create linear access to the larynx using a rigid operating laryngoscope for microlaryngoscopy. In this study, we evaluate the usability of a novel curved surgical prototype with flexible instruments for the larynx (sMAC) in a simulation dummy and human body donor. METHODS: In a user study (n = 6), head and neck surgeons as well as medical students tested the system for visualization quality and accessibility of laryngeal landmarks on an intubation dummy and human cadaver. A biopsy of the epiglottis was taken from the body donor. Photographic and time documentation was carried out. RESULTS: The sMAC system demonstrated general feasibility for laryngeal surgery. Unlike conventional microlaryngoscopy, all landmarks could be visualized and manipulated in both setups. Biopsy removal was possible. Visibility of the surgical field remained largely unobstructed even with an endotracheal tube in place. Overall handling of the sMAC prototype was satisfactorily feasible at all times. CONCLUSION: The sMAC system could offer an alternative for patients, where microlaryngoscopy is not applicable. A clinical trial has to clarify if the system benefits in clinical routine.

Re-evaluating the nasal cycle by long-term rhinoflowmetry: most individuals demonstrate a 'mixed' nasal cycle.

BACKGROUND: The nasal cycle seems to be more complex than a strictly alternating swelling of the nasal mucosa. Long-term rhinoflowmetry (LRFM) allows continuous investigation of changes in nasal airflow over 24 hours (24h). We evaluated the various types of nasal cycle with LRFM over 24 hours and investigated the influence of age and gender. METHODS: LRFM was continuously performed over 24h in 55 rhinologically healthy subjects (36 female, 19 male). The LRFM flow curves were examined for phases of the 'classical' 'in-concert' 'one-side' and'no-cycle' cycle types. Subjects were divided into 4 age subgroups (19-29; 30-49; 50-69; >70 years). Correlations of age and gender with the individual cycle forms were analyzed. RESULTS: 85.5% of the subjects presented a 'mixed' nasal cycle within 24h. 'classical' nasal cycle was seen most often (92.7% vs. 'in-concert' 56.4% vs. 'one-sided' 18.2% vs. 'no-cycle' 5.5%). Older age groups significantly more often presented the 'no-cycle' type. A tendency was seen towards a mixed nasal cycle with increasing age. The mixed nasal cycle was significantly more often seen in the female subjects. CONCLUSIONS: LRFM is an easy-to-use measurement tool. The 'mixed' nasal cycle predominates. However, all 4 different cycle types can be detected, alternating over 24h in each subject. Moreover, the cycle type varies with age.