The extracellular matrix landscape in salivary gland carcinomas is defined by cellular differentiation via expression of three distinct protein modules.

The extracellular matrix (ECM) is an integral part of the tumor microenvironment of carcinomas. Even though salivary gland carcinomas (SGCs) display a range of tumor cell differentiation and distinct extracellular matrices, their ECM landscape has not been characterized in depth. The ECM composition of 89 SGC primaries, 14 metastases, and 25 normal salivary gland tissues was assessed using deep proteomic profiling. Machine learning algorithms and network analysis were used to detect tumor groups and protein modules that explain specific ECM landscapes. Multimodal in situ studies to validate exploratory findings and to infer a putative cellular origin of ECM components were applied. We revealed two fundamental SGC ECM classes which align with the presence or absence of myoepithelial tumor differentiation. We describe the SGC ECM through three biologically distinct protein modules that are differentially expressed across ECM classes and cell types. The modules have a distinct prognostic impact on different SGC types. Since targeted therapy is rarely available for SGC, we used the proteomic expression profile to identify putative therapeutic targets. In summary, we provide the first extensive inventory of ECM components in SGC, a difficult-to-treat disease that encompasses tumors with distinct cellular differentiation. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

The extent of androgen receptor and HER2 expression allows for targeted therapy in most cases of salivary duct carcinoma: analysis of clinical and histopathological data in a tertiary care center.

PURPOSE: The incidence of salivary duct carcinoma (SDC) seems to be underestimated due to inaccurate classification. Further, the frequency of SDC patients with targeted therapy options according to current guidelines is unclear. Therefore, this study aimed at (a) describing the proportion of SDC among salivary gland carcinoma (SGC) before and after reclassification of cases initially classified as adenocarcinoma, not otherwise specified (ANOS); and (b) quantifying the frequency of SDC patients with targeted therapy options. METHODS: All patients with SDC or ANOS treated in a tertiary care center between 1996 and 2023 were identified. Histopathological diagnosis was verified for patients primarily diagnosed with SDC and reviewed for patients initially diagnosed with ANOS. Clinical data for SDC patients were retrieved from clinical charts. Immunohistochemical (IHC) androgen receptor (AR) and HER2 staining was performed. RESULTS: Among 46 SDC, 34 were primarily diagnosed as SDC and 12 had initially been classified as ANOS. The proportion of SDC among SGC was 12.1% and was rising when comparing the time periods 2000-2015 (7.1-11.5%) versus 2016-2023 (15.4-18.1%). Nuclear AR staining in > 70% of tumor cells was found in 56.8% and HER2 positivity (IHC 3 +) in 36.4% of cases. 70.5% of patients showed AR staining in > 70% of tumor cells and/or HER2 positivity and therefore at least one molecular target. 5-year overall and disease-free survival (DFS) were 62.8% and 41.0%. Multivariate Cox regression revealed positive resection margins (HR = 4.0, p = 0.03) as independent negative predictor for DFS. CONCLUSIONS: The results suggest a rising SDC incidence and show that the extent of the AR and HER2 expression allows for targeted therapy in most SDC cases.

Combination of nivolumab with standard induction chemotherapy in children and adults with EBV-positive nasopharyngeal carcinoma : Protocol of a prospective multicenter phase 2 trial.

BACKGROUND: Treatment of Epstein-Barr virus(EBV)-positive nasopharyngeal carcinoma (NPC) with cisplatin/5-fluorouracil (5-FU) induction chemotherapy, followed by radiochemotherapy and subsequent interferon­ß, has yielded high survival rates in children, adolescents, and young adults. A previous study has shown that reduction of radiation dose from 59.4 to 54.0 Gy appears to be safe in patients with complete response (CR) to induction chemotherapy. As immune checkpoint-inhibitors have shown activity in NPC, we hypothesize that the addition of nivolumab to standard induction chemotherapy would increase the rate of complete tumor responses, thus allowing for a reduced radiation dose in a greater proportion of patients. METHODS: This is a prospective multicenter phase 2 clinical trial including pediatric and adult patients with their first diagnosis of EBV-positive NPC, scheduled to receive nivolumab in addition to standard induction chemotherapy. In cases of non-response to induction therapy (stable or progressive disease), and in patients with initial distant metastasis, treatment with nivolumab will be continued during radiochemotherapy. Primary endpoint is tumor response on magnetic resonance imaging (MRI) and positron emission tomography (PET) after three cycles of induction chemotherapy. Secondary endpoints are event-free (EFS) and overall survival (OS), safety, and correlation of tumor response with programmed cell death ligand 1 (PD-L1) expression. DISCUSSION: As cure rates in localized EBV-positive NPC today are high with standard multimodal treatment, the focus increasingly shifts toward prevention of late effects, the burden of which is exceptionally high, mainly due to intense radiotherapy. Furthermore, survival in patients with metastatic disease and resistant to conventional chemotherapy remains poor. Primary objective of this study is to investigate whether the addition of nivolumab to standard induction chemotherapy in children and adults with EBV-positive NPC is able to increase the rate of complete responses, thus enabling a reduction in radiation dose in more patients, but also offer patients with high risk of treatment failure the chance to benefit from the addition of nivolumab. TRIAL REGISTRATION: EudraCT (European Union Drug Regulating Authorities Clinical Trials Database) No. 2021-006477-32.

[ENT in zero g: the cosmic challenges of otolaryngology]. / Hals, Nase und Ohren in der Schwerelosigkeit: die kosmischen Herausforderungen der HNO-Heilkunde.

Manned spaceflight places special demands on the human body, including the organs in the ENT region. These organs play a critical role in maintaining the health and safety of astronauts in space. In this paper, we review common ENT problems of spaceflight, including upper airway edema, middle ear and mastoid effusions, hearing loss, and dizziness with nausea. We discuss the underlying mechanisms contributing to these complaints, their clinical manifestations, and potential treatment strategies. In addition, we examine the potential impact of these conditions on astronaut health and mission outcomes. Finally, we emphasize the importance of preventive measures and future research in this area to optimize astronaut health and safety on future missions.

[Update: Epidemiology and Prevention of Oropharyngeal Cancer]. / Update: Epidemiologie und Prävention des Oropharynxkarzinoms.

Due to the association with the causal HPV-16 infection, the oropharyngeal carcinoma spreads into two separate entities depending on HPV-16 positivity. More recent data show a diversified picture of the importance and prevalence of the surrogate parameter p16 (discordance) for a definitive HPV-16 association, which varies worldwide. In the context of prevention options, vaccination is of major and HPV screening of healthy people only of little importance.

[Vestibular Schwannoma: Factors in Therapy Decision-Making]. / Vestibularisschwannom: Faktoren bei der Therapieentscheidung.

The treatment of vestibular schwannomas (VS) has always posed a challenge for physicians. Three essential treatment principles are available: wait-and-scan, surgery, and stereotactic radiotherapy. In addition to the type of treatment, decisions must be made regarding the optimal timing of therapy, the combination of different treatment modalities, the potential surgical approach, and the type and intensity of radiation. Factors influencing the therapy decision include tumor location and size or stage, patient age, comorbidities, symptoms, postoperative hearing rehabilitation options, patient preferences, and, not least, the experience of the surgeons and the personnel and technical capabilities of the clinical site. This article begins with a brief overview of vestibular schwannomas, then outlines the fundamental interdisciplinary treatment options, and finally discusses the ENT (ear, nose, and throat)-relevant factors in the therapy decision.

Prognostic implications of p16 and HPV discordance in oropharyngeal cancer (HNCIG-EPIC-OPC): a multicentre, multinational, individual patient data analysis.

BACKGROUND: p16INK4a (p16) immunohistochemistry is the most widely used biomarker assay for inferring HPV causation in oropharyngeal cancer in clinical and trial settings. However, discordance exists between p16 and HPV DNA or RNA status in some patients with oropharyngeal cancer. We aimed to clearly quantify the extent of discordance, and its prognostic implications. METHODS: In this multicentre, multinational individual patient data analysis, we did a literature search in PubMed and Cochrane database for systematic reviews and original studies published in English between Jan 1, 1970, and Sept 30, 2022. We included retrospective series and prospective cohorts of consecutively recruited patients previously analysed in individual studies with minimum cohort size of 100 patients with primary squamous cell carcinoma of the oropharynx. Patient inclusion criteria were diagnosis with a primary squamous cell carcinoma of oropharyngeal cancer; data on p16 immunohistochemistry and on HPV testing; information on age, sex, tobacco, and alcohol use; staging by TNM 7th edition; information on treatments received; and data on clinical outcomes and follow-up (date of last follow-up if alive, date of recurrence or metastasis, and date and cause of death). There were no limits on age or performance status. The primary outcomes were the proportion of patients of the overall cohort who showed the different p16 and HPV result combinations, as well as 5-year overall survival and 5-year disease-free survival. Patients with recurrent or metastatic disease or who were treated palliatively were excluded from overall survival and disease-free survival analyses. Multivariable analysis models were used to calculate adjusted hazard ratios (aHR) for different p16 and HPV testing methods for overall survival, adjusted for prespecified confounding factors. FINDINGS: Our search returned 13 eligible studies that provided individual data for 13 cohorts of patients with oropharyngeal cancer from the UK, Canada, Denmark, Sweden, France, Germany, the Netherlands, Switzerland, and Spain. 7895 patients with oropharyngeal cancer were assessed for eligibility. 241 were excluded before analysis, and 7654 were eligible for p16 and HPV analysis. 5714 (74·7%) of 7654 patients were male and 1940 (25·3%) were female. Ethnicity data were not reported. 3805 patients were p16-positive, 415 (10·9%) of whom were HPV-negative. This proportion differed significantly by geographical region and was highest in the areas with lowest HPV-attributable fractions (r=-0·744, p=0·0035). The proportion of patients with p16+/HPV- oropharyngeal cancer was highest in subsites outside the tonsil and base of tongue (29·7% vs 9·0%, p<0·0001). 5-year overall survival was 81·1% (95% CI 79·5-82·7) for p16+/HPV+, 40·4% (38·6-42·4) for p16-/HPV-, 53·2% (46·6-60·8) for p16-/HPV+, and 54·7% (49·2-60·9) for p16+/HPV-. 5-year disease-free survival was 84·3% (95% CI 82·9-85·7) for p16+/HPV+, 60·8% (58·8-62·9) for p16-/HPV-; 71·1% (64·7-78·2) for p16-/HPV+, and 67·9% (62·5-73·7) for p16+/HPV-. Results were similar across all European sub-regions, but there were insufficient numbers of discordant patients from North America to draw conclusions in this cohort. INTERPRETATION: Patients with discordant oropharyngeal cancer (p16-/HPV+ or p16+/HPV-) had a significantly worse prognosis than patients with p16+/HPV+ oropharyngeal cancer, and a significantly better prognosis than patients with p16-/HPV- oropharyngeal cancer. Along with routine p16 immunohistochemistry, HPV testing should be mandated for clinical trials for all patients (or at least following a positive p16 test), and is recommended where HPV status might influence patient care, especially in areas with low HPV-attributable fractions. FUNDING: European Regional Development Fund, Generalitat de Catalunya, National Institute for Health Research (NIHR) UK, Cancer Research UK, Medical Research Council UK, and The Swedish Cancer Foundation and the Stockholm Cancer Society.

Sex-specific aspects in patients with oropharyngeal squamous cell carcinoma: a bicentric cohort study.

BACKGROUND: Oropharyngeal squamous cell carcinoma (OPSCC) is the only subgroup of head neck cancer that presents with an increased incidence. Gender-specific studies in other cancer entities have revealed differences in treatment response and prognosis. However, only limited data in OPSCC according to gender and human papillomavirus (HPV) status exist. Therefore, we aimed to investigate sex-specific differences in OPSCC and how these may be distributed in relation to HPV and other risk factors. METHODS: This retrospective, bicentric study included 1629 patients with OPSCC diagnosed between 1992 and 2020. We formed subgroups based on TNM status, American Joint Cancer Committee 8th edition (AJCC8), HPV status, treatment modality (surgery (± radio(chemo)therapy (RCT) vs. definitive RCT) and patient-related risk factors and investigated gender differences and their impact on patients survival via descriptive-,uni- and multivariate analysis. RESULTS: With the exception of alcohol abuse, no significant differences were found in risk factors between men and women. Females presented with better OS than males in the subgroup T1-2, N + , independent of risk factors (p = 0.008). Males demonstrated significant stratification through all AJCC8 stages (all p < 0.050). In contrast, women were lacking significance between stage II and III (p = 0.992). With regard to therapy (surgery (± R(C)T) - vs. definitive RCT) women treated with surgery had better OS than men in the whole cohort (p = 0.008). Similar results were detected in the HPV-negative OPSCC sub-cohort (p = 0.042) and in high-risk groups (AJCC8 stage III and IV with M0, p = 0.003). CONCLUSION: Sex-specific differences in OPSCC represent a health disparity, particularly according to staging and treatment, which need to be addressed in future studies.

Impact of COVID-19-Mediated Olfactory Loss on Quality of Life.

INTRODUCTION: COVID-19 can be associated with a variety of longer-lasting impairments that can have a significant impact on patients' quality of life (QoL). While this is well described in the literature for limitations in lung capacity or permanent headaches, there is little research on the impact of olfactory dysfunction in the context of COVID-19 on patients' QoL. METHODS: In 65 patients with a history of COVID-19, the present olfactory ability was assessed using the Sniffin' Sticks test. In addition, olfactory QoL was assessed by the Questionnaire of Olfactory Disorders. Self-assessment was performed with visual analogue scales. The data were compared with the results obtained in healthy individuals and in patients with hyposmia due to other viral infections. RESULTS: The QoL of COVID-19 patients was significantly lower compared to the healthy control group. Even recovered subjects whose olfaction had already returned to the normal range still had a reduced QoL. The severity of the olfactory impairment correlated with the reduction in QoL. However, the olfactory QoL of COVID-19 patients was not worse than that of patients' olfactory loss due to other viral infections. Patients with parosmia had reduced QoL and rated their situation worse than patients without parosmia. CONCLUSION: QoL appears to be impaired in patients with long-lasting COVID-19 olfactory disorders several months after overcoming acute symptoms, even if olfaction has normalized. However, the impairment is not more pronounced than in patients with other postviral olfactory disorders of the same duration.

Peroxisomes Are Highly Abundant and Heterogeneous in Human Parotid Glands.

The parotid gland is one of the major salivary glands producing a serous secretion, and it plays an essential role in the digestive and immune systems. Knowledge of peroxisomes in the human parotid gland is minimal; furthermore, the peroxisomal compartment and its enzyme composition in the different cell types of the human parotid gland have never been subjected to a detailed investigation. Therefore, we performed a comprehensive analysis of peroxisomes in the human parotid gland's striated duct and acinar cells. We combined biochemical techniques with various light and electron microscopy techniques to determine the localization of parotid secretory proteins and different peroxisomal marker proteins in parotid gland tissue. Moreover, we analyzed the mRNA of numerous gene encoding proteins localized in peroxisomes using real-time quantitative PCR. The results confirm the presence of peroxisomes in all striated duct and acinar cells of the human parotid gland. Immunofluorescence analyses for various peroxisomal proteins showed a higher abundance and more intense staining in striated duct cells compared to acinar cells. Moreover, human parotid glands comprise high quantities of catalase and other antioxidative enzymes in discrete subcellular regions, suggesting their role in protection against oxidative stress. This study provides the first thorough description of parotid peroxisomes in different parotid cell types of healthy human tissue.

[Diagnostics and treatment of secondary malignancies of the parotid gland-An overview]. / Diagnostik und Therapie sekundärer Malignome der Ohrspeicheldrüse ­ eine Übersicht.

BACKGROUND: Secondary malignancies of the parotid gland frequently have a cutaneous origin and the incidence in central Europe is increasing. OBJECTIVE: The aim of this review article was to present the epidemiology, (differential) diagnostics and treatment of secondary malignancies of the parotid gland. MATERIAL AND METHODS: A literature search of the current guidelines and evidence was carried out in the web-based databank PubMed. RESULTS: The incidence of secondary malignancies of the parotid gland seems to be increasing in Europe, mainly due to a rising incidence of metastases of cutaneous squamous cell carcinomas. Except for malignant lymphomas, parotidectomy is the treatment of choice in the curative situation. In the absence of clear evidence, in the case of an intact facial nerve lateral or total parotidectomy with ipsilateral neck dissection seems to be indicated, depending on the entity of the secondary malignancy. CONCLUSION: The differential diagnostics of squamous cell carcinoma (in) of the parotid gland can be complicated. When a squamous cell carcinoma of the parotid gland is diagnosed for the first time, a dermatological full body examination and a detailed medical history should be taken with respect to skin tumors of the head and neck region. In addition to surgical treatment of the parotid gland and neck, adjuvant radiotherapy is usually indicated.

[Predatory journals in otorhinolaryngology]. / Raubtier-Journale im HNO-Fachgebiet.

BACKGROUND: Pseudo-scientific predatory journals have been making a commercially lucrative business with scientific manuscripts for many years misusing the "open access" model by offering a fast and uncomplicated publication of scientific manuscripts in return for publication fees. The question arises as to whether the specialty field of otorhinolaryngology has already been infiltrated by this bad practice. MATERIAL AND METHODS: A pseudo-scientific fake manuscript was sent to 20 journals in which the journal title indicated an otorhinolaryngological content. Half of the journals were traditional otorhinolaryngology journals, which publish a print edition and which are mainly financed by subscriptions and advertisements. The other half were journals that published exclusively according to the "open access" model. Various parameters of the journals and of the review process were evaluated. RESULTS: All 10 traditional ORL journals refused to publish the fake manuscript. Among the journals that published exclusively according to the "open access" model, there was one rejection of the manuscript, while 2 journals recommended a revision and 7 journals accepted the manuscript directly for publication. CONCLUSION: Predatory publishers and journals are also active in the field of otorhinolaryngology. Especially at journals that publish articles exclusively "open access" for a publication or processing fee, scientific authors should be careful and check the seriousness of the journal in advance by using recommended hints and tools.

[Otolaryngology-knowledge among ORL-physicians: An analysis of the quiz questions in the ORL-App]. / HNO-Wissen bei HNO-Ärzten: Eine Analyse der Quizfragen in der HNO-App.

BACKGROUND: The ORL-App, a smartphone app for further education and training for ORL doctors and those interested in ORL, complements existing offers in medical education and training. The principle of game-based e-learning can open up new perspectives in times of digitalisation and pandemic. The heart of the app is a large ORL quiz, in which app users compete against each other. This paper analyses the performance of app users in the quiz module, taking into account the questions' categories and the users' level of education. MATERIAL AND METHODS: Retrospectively, an evaluation of the quiz questions was carried out for the first 24 months after the introduction of the app. There were 3593 different questions to choose from in 16 different categories. Based on the level of training, a distinction was made between doctors in further training, specialists, senior physicians, chief physicians and professors in the field of ORL. In addition, data on students and non-medical staff were available. RESULTS: There was a significant difference in the level of knowledge of the users considering the level of training. The group of doctors in further training (n = 1013) represented the largest group, with an average of 244 questions per user and 65.1% of the questions answered correctly. They thus achieved a significantly better answer rate than the group of specialists (n = 566), who were able to answer 61.0 % of the questions correctly. CONCLUSION: The game-based form of training through the quiz-part of the ORL-App seems to be particularly attractive for doctors in further training. In addition, this user group achieved better answer rates than the specialists.

[Salivary gland carcinomas - Monocentric experience on subtypes and their incidences over 42 years]. / Speicheldrüsenkarzinome ­ Monozentrische Erfahrung zu Subtypen und deren Inzidenz über 42 Jahre.

OBJECTIVE: Salivary gland carcinomas are rare and heterogeneous. More than 20 subtypes are recognized and risk factors are diverse. The aim of this work was to evaluate the subtype and other risk factors in a monocentric population from more than four decades. MATERIAL AND METHODS: 205 cases (diagnosis period 1972-2014) were retrospectively collected and analyzed with regard to the distribution of risk factors and their influence on overall survival (OS). RESULTS: 19/24 (79.2%) of the subtypes listed in the WHO classification occurred rarely in the cohort (< 5%). 10/24 (41.7%) of all subtypes were never diagnosed. With a total of 145/205 cases (70.7%), squamous cell carcinoma (PEC), adenocarcinoma (AdenoCa), acinar cell carcinoma (AcinarCa), mucoepidermoid carcinoma (MEC), and adenoid cystic carcinoma (ACC) were by far the most common subtypes. Risk factors are significantly different in these groups (e.g., lymphogenic metastasis and degree of differentiation in AdenoCa and age, T and UICC stage in PEC). The 5-year overall survival of all patients was 66.9% and differed significantly within the most common subtypes. An independent impact on overall survival was detectable for patient age (p<0.001), and T- (p=0.003) and N-stage (p=0.046) in multivariate analysis. CONCLUSIONS: Most subtypes occurred markedly rarely or not at all within decades. The most common diagnoses differ with respect to risk factors as well as OS and 3 risk groups can be defined based on histology. In conclusion, considering TNM alone is insufficient for prognosis estimation in salivary gland carcinoma.

[ctHPV-DNA based precision oncology for patients with oropharyngeal cancer - Where are we?] / ctHPV-DNA-basierte Präzisionsonkologie für Patienten mit Oropharynxkarzinom ­ wo stehen wir?

Human papillomavirus (HPV) is an established etiologic factor for cancers in the head and neck region, specifically for Oropharyngeal Squamous Cell Carcinoma (OPSCC). The comparatively good overall survival justifies the current discussion regarding therapy de-escalation for patients with a low-risk profile. In addition to the immunohistochemistry-based biomarker p16INK4a, there is still a need for diagnostic and prognostic biomarkers that allow risk stratification and monitoring during therapy and follow-up of these patients. In recent years, liquid biopsy, especially in the form of plasma samples, has gained importance and is already used to monitor viral DNA in patients with Epstein-Barr virus-associated nasopharyngeal carcinoma. Circulating DNA (ctDNA) released by the tumor into the bloodstream is particularly suitable for a high specificity in detecting virus-associated tumors. Detection of viral E6 and E7 oncogenes in HPV-positive OPSCC is predominantly performed by droplet digital/quantitative PCR as well as next generation sequencing. Detection of circulating HPV-DNA derived from tumor cells (ctHPV-DNA) at diagnosis is associated with advanced tumor stage, locoregional and distant metastases. Longitudinal studies have further demonstrated that detectable and/or increasing ctHPV-DNA levels are associated with treatment failure and disease relapse. However, a standardization of the diagnostic procedure is necessary before introducing liquid biopsy into the clinical routine. In the future, this might allow a valid reflection of disease progression in HPV-positive OPSCC.

Prospective study on the Eustachian tube function during Frenzel maneuver in a hypobaric/hyperbaric pressure chamber.

INTRODUCTION: The Frenzel maneuver describes a technique for middle ear equalizing which is frequently used by apnea divers. It offers advantages compared to the most commonly used techniques such as the Valsalva or Toynbee maneuver. Until now, there is insufficient literature about the pressure dynamics and Eustachian tube (ET) function during the Frenzel maneuver. The aim of the present study was to characterize the ET function during the Frenzel maneuver. MATERIALS AND METHODS: By means of an established standardized profile of compression and decompression in a hypo/hyperbaric pressure chamber, we examined different parameters such as the ET opening pressure (ETOP), ET opening duration (ETOD), and ET opening frequency (ETOF) in 11 experienced apnea divers and compared them to the parameters during the Valsalva and Toynbee maneuver. RESULTS: Standard values for ETOP, ETOD, and ETOF could be established for the Frenzel maneuver under standardized conditions in a hypo/hyperbaric pressure chamber. Compared to the Frenzel maneuver, ETOP was higher and ETOD longer (both p < 0.001) during the Valsalva maneuver whereas ETOP was lower and ETOD shorter (both p < 0.001) during the Toynbee maneuver. No difference regarding ETOF was observed between the Frenzel, Valsalva, and Toynbee maneuver. DISCUSSION: The Frenzel maneuver was shown to be at least as effective as the Valsalva maneuver concerning ET opening. We believe that knowledge of the Frenzel technique might facilitate the pressure equalization during diving and recommend implementation of an appropriate equalization training in apnea and scuba diving education.

CD138 Is Expressed in Different Entities of Salivary Gland Cancer and Their Lymph Node Metastases and Therefore Represents a Potential Therapeutic Target.

Advanced salivary gland carcinomas (SGC) often lack therapeutic options. Agents targeting CD138 have recently shown promising results in clinical trials for multiple myeloma and a preclinical trial for triple-negative breast cancer. Immunohistochemistry for CD138 was performed for all patients who had undergone primary surgery for SGC with curative intent. Findings were validated using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) imaging. Overall, 111 primary SGC and 13 lymph node metastases from salivary duct carcinomas (SaDu) were evaluated. CD138 expression was found in 60% of all SGC with differing expression across entities (p < 0.01). A mean of 25.2% of the tumor cells in mucoepidermoid carcinoma (MuEp) were positive, followed by epithelial-myoepithelial carcinoma (20.9%), acinic cell carcinoma (16.0%), and SaDu (15.2%). High-/intermediate-grade MuEp showed CD138 expression in a mean of 34.8% of tumor cells. For SaDu, lymph node metastases showed CD138 expression in a mean of 31.2% of tumor cells which correlated with CD138 expression in their primaries (p = 0.01; Spearman's ρ = 0.71). MALDI-MS imaging confirmed the presence of the CD138 protein in SGC. No significant association was found between clinicopathological data, including progression-free survival (p = 0.50) and CD138 expression. CD138 is expressed in the cell membrane of different entities of SGC and SaDu lymph node metastases and therefore represents a potential target for CD138 targeting drugs.

[Novel therapeutic approaches for salivary gland carcinomas]. / Neue Therapieansätze für Speicheldrüsenmalignome.

Novel therapeutic options for the treatment of salivary gland malignancies have emerged due to the improvement and distribution of molecular pathological testing methods and the availability of targeted therapies. Since they are less toxic, these new agents are a valuable alternative to conventional cytotoxic chemotherapy. On the one hand, there are new entity-specific therapies such as NTRK inhibitor therapy for secretory carcinomas and axitinib therapy for adenoid cystic carcinomas. Moreover, cross-entity therapeutics such as antiandrogenic therapy, HER2 inhibition, and PI3K inhibition are also coming to the fore. For metastatic/recurrent salivary gland carcinomas that cannot be treated with targeted therapy, platinum-based chemotherapies continue to be therapy of choice.

[Is Flying or Diving risky after cochlear implantation? Examination in a pressure chamber]. / Ist Fliegen oder Tauchen riskant für CI-Träger? ­ Untersuchungen in einer Druckkammer.

OBJECTIVE: Complications after cochlear implantation are relatively rare but patients are asked to follow certain behavioral rules. Until now there is no evidence if pressure changes that occur during flying and diving are safe for patients after cochlear implantation. For example, no recommendation exists for SCUBA- diving activities. MATERIALS AND METHODS: In a hypo-/hyperbaric pressure chamber patients after cochlear implantation were exposed to a standardized profile of decompression and compression simulating a flight in a common airplane and a dive. Pre and after the exposure in the pressure chamber, ENT examination and a control of impedances of the cochlear implant were performed. Additionally, patients filled in a questionnaire about complaints they had experienced in the pressure chamber or after. RESULTS: A total of 11 subjects (17 ears with CI) were examined in the pressure chamber. 2/3 of the subjects stated that they had slight complaints during the examination. Only in one patient the measurement needed to be stopped due to pain. Seven patients showed a vascular injection of the malleus in ear microscopy. In none of the patients there was a subjective change in hearing after the examination. Objective measurements of the impedance did not show relevant changes. CONCLUSION: The exposure of cochlear implanted patients to overpressure and underpressure in a pressure chamber did not result in any significant deviation of the impedances, so that no further adjustment was necessary. Since there are no certified in vivo studies on pressure changes while diving and flying with a cochlear implant, further studies are required in order to be able to adequately advise CI patients about diving and flying.

Round window accessibility during cochlear implantation.

OBJECTIVE: To assess data regarding round window (RW) visibility and surgical approaches in cochlear implant cases, and to describe and analyze surgical steps relevant for the RW approach in cochlear implantation. STUDY DESIGN: Prospective clinical study. METHODS: A questionnaire was completed by surgeons after each of altogether 110 cochlear implantations. Round window membrane (RWM) visibility was graded according to the St Thomas Hospital (STH) classification. RESULTS: Performing different surgical steps during the preparation of the RW niche, the RWM could be fully exposed (STH Type I) in 87%. A RW approach could be used for electrode insertion in 89% of the adult and 78% of the pediatric cases. The distribution of RW types differed significantly between adults and children. Drilling of the superior bony lip was the surgical step most frequently needed in adult as well as pediatric cases to obtain optimal RW exposure. CONCLUSION: In children, optimized surgical exposure of the RW niche resulted in only 52% full RWM visibility; whereas in adults, this could be achieved in 87%. The facial nerve (FN) had to be exposed at the level of the posterior tympanotomy in more than 70% of pediatric cases with full RWM visibility; while in adult cases with 100% visibility, such specific exposure was necessary in only 33%. Thus, surgical preparation of the RW niche seems to be more demanding in children than in adults.