Incidence and clinical outcome of primary carcinomas of the major salivary glands: 10-year data from a population-based state cancer registry in Germany.

PURPOSE: The aim of this project was to provide an overview of the epidemiology of primary salivary gland carcinomas (SGC) in terms of incidence, distribution of clinicopathological features and survival in one of the largest cancer registries in Europe. METHODS: Data were collected from patients with SGC of the major salivary glands registered in the population-based state cancer registry (Landeskrebsregister LKR) in North Rhine-Westphalia (NRW), Germany from 01/01/2009 to 12/31/2018. Age standardization of incidence was performed and relative survival estimates were computed by sex, histological group, age group and T-, N-, and M-stage. RESULTS: A total of 1680 patients were included in this analysis. The most frequent tumor localization was the parotid gland (78%). Adenocarcinoma (not otherwise specified) was the most common tumor entity (18.5%). Most tumors were found in stages T1-T3 (29% T1; 29% T2; 28% T3). The age-standardized incidence rate (ASR) for SGC was 0.65/100,000 and remained stable during the observation period. There was an age-dependent incidence increasing especially from the age 70 years and onwards. The overall 5-year relative survival (RS) for all patients with SGC was 69.2%. RS was 80-95.6% for T1-2 stage tumors, 60.3% for T3, 47.3% for T4 stage, 87.4% for N0 and 51.2% for N1-2, 74.4% for M0 and 44.9% for M1. CONCLUSION: Age-standardized incidence for SGC has been stable for the observed 10-year period. Smaller tumors and those without lymph node or distant metastases had a better RS than more advanced tumors.

[Tumor microenvironment in salivary gland carcinomas: Consequences for new therapeutic concepts]. / Das Tumormikromilieu bei Speicheldrüsenkarzinomen ­ mögliche Konsequenzen für neue Therapiekonzepte.

INTRODUCTION: Salivary gland carcinomas (SGCs) are rare tumors which represent a challenge for diagnosis and therapy due to their histological diversity and the different disease courses depending on the respective subtype. Little is known about the composition of the tumor microenvironment in SGCs. A more comprehensive understanding of the relevant molecular changes and immunological processes of the tumor and surrounding stroma could help to improve therapeutic efficiency, for example by adjuvant immunomodulation. METHODS: This manuscript highlights recent studies analyzing the composition of the tumor microenvironment in salivary gland carcinomas. RESULTS: The tumor microenvironment displays a significant diversity in the composition of immune cells among different tumor entities. In one third of the SGCs, an expression of cell surface molecule LAG3 on tumor infiltrating lymphocytes could be observed. LAG3-similar to CTLA­4 and PD-1-inhibits cellular proliferation, activation, and homeostasis of antitumor-effective T cells. Especially, prognostically less favorable entities such as salivary duct carcinomas and adenocarcinomas NOS (not otherwise specified) yielded higher expressions. CONCLUSIONS: LAG3 is particularly detectable in aggressive entities and advanced tumors. Hence, LAG3 inhibition poses a potential targeted therapy for advanced and metastatic SGCs.

[Salivary gland malignancies-highlights of the 2019 ASCO Annual Meeting]. / Maligne Speicheldrüsentumoren ­ Highlights der ASCO-Jahrestagung 2019.

BACKGROUND: Due to their comparatively low incidence, salivary gland carcinomas have only been the subject of isolated clinical studies in recent years. In addition, surgery with/without adjuvant radiotherapy is considered standard treatment. Systemic therapies have received little attention and are only used for advanced and distantly metastasized salivary gland malignancies. OBJECTIVE: The contributions with the highest relevance for this year's meeting of the American Society of Clinical Oncology (ASCO) were to be reviewed. MATERIALS AND METHODS: A total of 12 contributions pertaining to clinical studies on salivary gland malignancies were identified, eight of which were classified as relevant for future changes to the therapeutic landscape. RESULTS: Three studies dealt with different combinations of a checkpoint blockade, and each showed a low response rate. In addition, studies on targeted therapies depending on the results of a mutation analysis and expression of HER2 or the androgen receptor were presented. CONCLUSION: A favorable response of HER2-positive salivary gland carcinomas to an antibody-drug conjugate could be shown. Furthermore, no convincing data regarding response to programmed cell death protein 1 (PD1)/programmed death ligand 1 (PD-L1) inhibitors in advanced salivary gland cancer were presented. Further studies and ideas for new treatment approaches will be needed to improve the therapeutic options for patients with salivary gland carcinoma.

The relevance of the lymph node ratio as predictor of prognosis is higher in HPV-negative than in HPV-positive oropharyngeal squamous cell carcinoma.

OBJECTIVES: Lymph node ratio (LNR) is an established predictor in different entities of carcinoma, including head and neck malignancies. In oropharyngeal squamous cell carcinoma (OPSCC), lymph node involvement differs between human papilloma virus (HPV)-positive and HPV-negative tumours. Herein, we evaluate the impact of HPV association on the concept of LNR. METHODS: 88 surgically treated patients were included in this retrospective chart review. HPV-positive and HPV-negative OPSCC were evaluated for prediction of outcome by LNR separately. The endpoints were 5-year overall survival (OS) and recurrence-free survival (RFS). RESULTS: The OS of all patients was 60.1%. In univariate analysis, LNR was a significant predictor of overall survival rate (P=.008) in OPSCC independently of the HPV status, as well as extracapsular spread (ECS). T-classification was only a significant predictor in the univariate analysis in HPV-positive OPSCC carcinoma. However, in the multivariate analysis LNR remained predictor of prognosis in all OPSCC and in HPV-negative OPSCC. In patients with HPV-positive OPSCC, only T-classification reached significance to predict OS. CONCLUSION: Prognosis of primarily operated HPV-positive patients might be more dependent on the extent of primary tumour site, whereas prognosis of HPV-negative patients is based more on cervical metastatic spread, represented by LNR.

Reliability of Eustachian tube function measurements in a hypobaric and hyperbaric pressure chamber.

OBJECTIVES: Measurement of the Eustachian tube (ET) function is a challenge. The demand for a precise and meaningful diagnostic tool increases-especially because more and more operative therapies are being offered without objective evidence. The measurement of the ET function by continuous impedance recording in a pressure chamber is an established method, although the reliability of the measurements is still unclear. METHODS: Twenty-five participants (50 ears) were exposed to phases of compression and decompression in a hypo- and hyperbaric pressure chamber. The ET function reflecting parameters-ET opening pressure (ETOP), ET opening duration (ETOD) and ET opening frequency (ETOF)-were determined under exactly the same preconditions three times in a row. The intraclass correlation coefficient (ICC) and Bland and Altman plot were used to assess test-retest reliability. RESULTS: ICCs revealed a high correlation for ETOP and ETOF in phases of decompression (passive equalisation) as well as ETOD and ETOP in phases of compression (active induced equalisation). Very high correlation could be shown for ETOD in decompression and ETOF in compression phases. The Bland and Altman graphs could show that measurements provide results within a 95 % confidence interval in compression and decompression phases. CONCLUSIONS: We conclude that measurements in a pressure chamber are a very valuable tool in terms of estimating the ET opening and closing function. Measurements show some variance comparing participants, but provide reliable results within a 95 % confidence interval in retest. This study is the basis for enabling efficacy measurements of ET treatment modalities.

[The pressure-equalizing function of the Eustachian tube : Evaluation in a hypo-/hyperbaric pressure chamber]. / Druckausgleichende Funktion der Eustachischen Röhre : Evaluation in einer hypo-/hyperbaren Druckkammer.

BACKGROUND: The Eustachian tube connects the tympanic cavity (cavum tympani) and the nasopharynx, and enables pressure equalization between the middle ear and ambient pressure. Functional pressure compensation is very important for flying and diving in particular, due to non-physiologically large pressure differences. OBJECTIVE: Evaluation of the pressure-equalizing function of the Eustachian tube is still a clinical challenge. This review article evaluates the existing data. METHODS: Based on a selective literature search, different methods for evaluation of tube function are presented and evaluated, with special reference to evaluation of the pressure-equalizing function in a hypo-/hyperbaric pressure chamber. RESULTS: The pressure chamber enables the dynamics of active and passive pressure compensation to be provoked and also permits accurate measurement of pressures in the millibar range. CONCLUSION: A pressure chamber seems to be suitable to evaluate Eustachian tube function and therapeutic approaches to tube dysfunction. Further studies are needed to assess the value of the pressure chamber in combination with other functional tests.

Prediction of outcome by lymph node ratio in patients with parotid gland cancer.

OBJECTIVE: Lymph node ratio (LNR) has been shown to be an independent predictor of recurrence risk and survival in different entities of carcinoma. METHODS: In this retrospective chart review, 128 patients with parotid gland cancer (PGC) subsequently treated by primary surgery were included. About 64% (n = 82) of these patients were additionally treated with adjuvant radiotherapy. Five-year overall survival rates were determined by subgroups based on LNR value. RESULTS: Lymph node ratio was found to be significantly associated with overall survival rate (P < 0.001). Using univariate analyses, pathological tumour-node-metastasis (TNM)-stage, UICC-stage grouping and extracapsular spread were found to be significant predictors of overall survival (P < 0.001). However, with a multivariate analyses, LNR remained the only independent predictor of overall survival (P = 0.043). CONCLUSIONS: After surgery for PGC, evaluation of the neck using LNR was found to reliably stratify the overall survival rate.

[Spiradenocarcinoma of the forehead : A rare skin tumor in the head and neck region]. / Spiradenokarzinom der Stirn : Ein seltener Hauttumor im Kopf-Hals-Bereich.

Spiradenocarcinomas are rare malignant tumors that originate from the sweat glands of the skin and demonstrate aggressive growth. We report the case of an 86-year-old female patient presenting with a growth on the forehead which had been apparent for 2 years. After surgical removal of the tumor, histological workup culminated in the diagnosis of a spiradenocarcinoma. Surgical margins were free of tumor on pathological examination. Metastasis was excluded by positron-emission tomography-computed tomography (PET-CT). Due to the advanced age of the patient and the absence of metastatic disease, no adjuvant therapy was performed. Six months postoperatively there is no evidence of relapse.

[Relevance of the current discussion on prioritization for rheumatology]. / Bedeutung der gegenwärtigen Diskussion über Priorisierung für die Rheumatologie.

BACKGROUND: The increase in age-related diseases that can be expected due to demographic changes, the growing medicalization and the medical technological progress with new diagnostic and therapeutic methods, will probably lead to rising health expenditure in the coming years. The resulting financial problems have so far mostly been countered by an increase in health insurance contributions, tax subsidies, rationalization and hidden rationing. The potentials of explicit prioritization processes have so far not been made use of in Germany compared to some other countries where this is already in common use. METHODS: Prioritization in the healthcare system is a procedure of mental clarification and determination of the priority or subordination of certain indications, patient groups or methods with the result of multilevel ranking. Human dignity, equality and solidarity are fundamental values on which prioritization is based. The medical need, the urgency of treatment, the expected medical benefits, the treatment risk, the cost efficiency and the evidence level are criteria towards which prioritization is oriented. RESULTS: Prioritization processes lead to scientifically substantiated care recommendations which support decisions regarding the medically rational, ethically justifiable and economically meaningful use of limited resources. In order to gain broad public acceptance, prioritization guidelines should be developed in a transparent way by democratically justified committees the composition of which still needs to be clarified. Fundamental concepts, cornerstones of the current debate and efforts that have already been made to make progress in this field are presented in summarized form in this article.

[Systematic analysis of the readability of patient information on websites of German nonuniversity ENT hospitals]. / Systematische Analyse der Lesbarkeit von Patienteninformationstexten auf Internetseiten deutscher nichtuniversitärer HNO-Kliniken.

BACKGROUND: Besides their function as one of the main contact points, websites of hospitals serve as medical information portals. All patients should be able to understand medical information texts; regardless of their literacy skills and educational level. Online texts should thus have an appropriate structure to ease their comprehension. MATERIALS AND METHODS: Patient information texts on every German nonuniversity ENT hospital website (n = 125) were systematically analysed. For ten different ENT topics a representative medical information text was extracted from each website. Using objective text parameters and five established readability indices, the texts were analysed in terms of their readability and structure. Furthermore, we stratified the analysis in relation to the hospital organisation system and geographical region in Germany. RESULTS: Texts from 142 internet sites could be used for the definite analysis. On average, texts consisted of 15 sentences and 237 words. Readability indices congruously showed that the analysed texts could generally only be understood by a well-educated or even academic reader. CONCLUSION: The majority of patient information texts on German hospital websites are difficult to understand for most patients. In order to fulfil their goal of adequately informing the general population about disease, therapeutic options and the particular focal points of the clinic, a revision of most medical texts on the websites of German ENT hospitals is recommended.

[Characterizing the passive opening of the eustachian tube in a hypo-/hyperbaric pressure chamber]. / Charakterisierung der passiven Tubenöffnung in einer hypo-/hyperbaren Druckkammer.

BACKGROUND: Beside arbitrary and not arbitrary active pressure equalization systems there is a passive equalization system via the Eustachian tube (ET) at pressure difference between the epipharyngeal space and the middle ear. Aim of this study was to characterize this passive equalization system in a hypobaric/hyperbaric pressure chamber by continuously measuring the tympanic impedance. In contrast to other studies, which are measured only in a hypobaric pressure chamber it is possible to include participants with Eustachian tube dysfunction (ETD). MATERIAL AND METHODS: Following a fixed pressure profile 39 participants were exposed to phases of pressure rising and decompression. By continuously measuring the tympanic impedance in the pressure chamber it was possible to measure data of the Eustachian Tube opening Pressure (ETOP), Eustachian Tube closing pressure (ETCP) and Eustachian Tube opening duration (ETOD). In addition it was possible to characterize the gradient of pressure during decompression, while the ET was open. RESULTS: Beside the measurement of the arithmetic average of the ETOP (30.2 ± 15.1 mbar), ETCP (9.1 ± 7.7 mbar) and ETOD (0.65 ± 0.38 s) it was obvious that there are recurrent samples of pressure progression during the phase of tube opening. Generally it is possible to differentiate between the type of complete opening and partial opening. CONCLUSION: The fundamental characterization of the action of the passive tube opening, including the measurement of the ETOP, ETCP and ETOD, is a first step in understanding the physiological and pathophysiological function of the ET.

[Schwannoma in the epipharynx: a rare differential diagnosis]. / Schwannom im Epipharynx: Eine seltene Differenzialdiagnose.

There are many benign and malignant tumors of the epipharynx, which makes differential diagnosis difficult. As a very rare differential diagnosis, a schwannoma is possible. The origin of the tumor is most likely a small branch of a sensitive nerve of the glossopharyngeal nerve or the trigeminus nerve. A clear differentiation in the MRI scan is often not possible; especially differentiation from MPNST (malignant peripheral nerve sheath tumors) is difficult. To confirm the diagnosis and exclude malignancy, every tumor in the epipharynx should be surgically excised if possible, even if the patient has no discomfort.

Effects of a short-term improvement in glycaemic control on skin microvascular dysfunction in Type 1 and Type 2 diabetic patients.

AIMS: To investigate whether Type 1 and Type 2 diabetic patients differ in the effects of short-term improvement in glycaemic control on skin microvascular dysfunction. METHODS: Fourteen Type 1 and 14 Type 2 diabetic patients admitted to hospital to improve glycaemic control were investigated. Two age- and sex-matched groups of non-diabetic subjects served as controls. Capillary blood cell velocity (CBV) was assessed at the dorsal middle phalangeal area of the ring finger at rest and after 3-min arterial occlusion using laser Doppler anemometry. RESULTS: Comparing the measurements before and after improvement in glycaemic control, there were no significant changes in peak CBV, time to peak CBV and vasomotion amplitudes in Type 1 and Type 2 diabetic patients. On admission to hospital, time to peak CBV was prolonged in Type 1 (20.9 +/- 2.9 vs. 12.3 +/- 1.6 s, P = 0.003) and Type 2 diabetic patients (20.6 +/- 2.6 vs. 11.9 +/- 1.3 s, P = 0.021) compared with control subjects. After improvement in glycaemic control, there was no significant difference in time to peak CBV between Type 1 diabetic patients and their control subjects (17.8 +/- 4.2 vs. 12.3 +/- 1.6 s, P = 0.535). In Type 2 diabetic patients, the time to peak CBV increased non-significantly. CONCLUSIONS: Short-term improvement in glycaemic control did not appear to reverse microcirculatory dysfunction in Type 1 and Type 2 diabetes. However, there was an improvement of the delayed reactive hyperaemia in Type 1 diabetic patients.

Hepatitis C virus-specific T cell responses against conserved regions in recovered patients.

For the design of peptide-based vaccines against the hepatitis C virus it is essential to acquire more information on frequently recognized epitopes in patients with successful immune control of HCV in the context of different HLA types. A matrix approach using 393 15mer peptides from conserved HCV regions overlapping by 13 amino acids was applied in 52 HCV-recovered individuals. Candidate peptides were further tested in two independent laboratories. 38 peptides induced IFN-gamma responses in ELISPOT assays including 15 previously unknown epitopes. There was no particular immune dominance as only five peptides were recognized by more than three individuals. Seven out of 14 peptides tested in more detail could be confirmed to be immunogenic using ELISPOT and cytotoxicity assays. While only 33% of HCV-recovered individuals recognized recombinant HCV proteins, 81% of individuals tested positive in the matrix approach (p<0.001). The strength, frequency and breadth of HCV-specific T cell responses were similar in spontaneously recovered patients than in interferon-recovered patients. In conclusion (i) we identified novel HCV epitopes in conserved regions, (ii) confirmed the inter-individual diversity of HCV-specific T cell responses and (iii) found no significant differences in HCV-specific T cell responses between spontaneously recovered and IFN-recovered patients.

Impaired flow-mediated vasodilation in type 2 diabetes: lack of relation to microvascular dysfunction.

A reduced availability of nitric oxide (NO) is an important feature of endothelial dysfunction occurring early in the course of type 2 diabetes. The measurement of flow-mediated dilation (FMD) of the brachial artery after forearm ischemia is supposed to be a non-invasive method to assess endothelial production and release of NO. The impairment of reactive hyperemia due to microvascular dysfunction in diabetes might cause an insufficient increase in shear stress stimulating the endothelial NO release, thus leading to an underestimation of FMD. Therefore, the aim of the present study was to investigate the relationship between microcirculatory disturbances and the impairment of FMD in type 2 diabetic patients. 63 type 2 diabetic patients and 44 non-diabetic control subjects were investigated. Capillary blood cell velocity (CBV) was assessed at the dorsal middle phalangeal area of the left ring finger. Lumen diameter of the brachial artery was measured by high-resolution ultrasound. Patients were investigated at rest and after 5-min suprasystolic arterial compression. Percentage change of CBV during reactive hyperemia (CBV%) and flow-mediated dilation (FMD%) of the brachial artery relative to the baseline measurement were calculated. CBV% (63.4+/-10.7% vs. 124.0+/-18.5%; p<0.01) and FMD% (3.8+/-0.8% vs. 6.9+/-0.9%; p<0.01) were reduced in the diabetic patients compared to their control subjects. FMD% was not related to CBV% (r=0.14; p=0.139). The lack of an association between the reduction of endothelium-dependent vasodilation of the brachial artery and the impairment of postocclusive microvascular hyperemia observed in the present study contradicts the assumption that a reduced FMD is only the consequence of an impaired reactive hyperemia due to microvascular dysfunction. It also lends support to the suggestion that endothelial dysfunction in conduit vessels and impaired cutaneous microvascular responses to reactive hyperemia might at least partly develop independently due to several differences in their pathogenesis.

Influence of the duration of type 2 diabetes on early functional and morphological markers of atherosclerosis compared to the impact of coexisting classic cardiovascular risk factors.

AIM: The increased incidence of atherosclerotic macrovascular disease in type 2 diabetic patients is associated both with diabetes specific factors and coexisting classic cardiovascular risk factors as components of the metabolic syndrome. The aim of this study was to investigate the association between the duration of diabetes and early functional and morphological markers of atherosclerosis compared to the impact of coexisting cardiovascular risk factors such as hypertension, dyslipoproteinemia and cigarette smoking. METHODS: 63 type 2 diabetic patients and 25 non-diabetic control subjects were investigated. Lumen diameter of the brachial artery was measured by high-resolution ultrasound at rest and after 5-min suprasystolic arterial compression. Endothelium-independent dilatation of the brachial artery was measured 4 min after sublingual administration of 400 mug of glycerol trinitrate (GTN). Percentage change of arterial lumen diameter during reactive hyperemia (FMD%) and after GTN administration (GTN%) relative to the baseline measurements were calculated. The intima-media thickness (IMT) of the common carotid artery was measured bilaterally and averages were calculated. RESULTS: FMD% (3.8+/-0.8% vs. 6.9+/-0.9%; p<0.01) and GTN% (5.6+/-0.7% vs. 14.9+/-1.7%; p<0.01) were reduced in the diabetic patients compared to their control subjects. IMT was increased in diabetic patients compared to their controls (0.82+/-0.02 mm vs. 0.62+/-0.02 mm; p<0.01). The age-adjusted diabetes duration was inversely related to FMD% (r=-0.27; p=0.016). On multiple regression analysis including packyears, hypertension, hypercholesterolemia, and hypertriglyceridemia, only diabetes duration remained a significant independent determinant of FMD. GTN% and IMT were not associated with diabetes duration, packyears, hypertension, hypercholesterolemia, and hypertriglyceridemia when all variables were taken into account. CONCLUSION: The present data lend support to the suggestion that diabetic specific factors compared to coexisting cardiovascular risk factors such as hypertension, hyperlipoproteinemia, and smoking are of major importance for the pathogenesis of endothelial dysfunction in type 2 diabetes, because only the diabetes duration was shown to be related to endothelium-dependent vasodilation when all variables were taken into account.