Man flu is not a thing - Gender-specific secondary analysis of a prospective randomized-controlled trial for acute rhinosinusitis.

BACKGROUND: 'Man flu' is a popular term to describe hypersensitivity to acute rhinosinusitis (ARS) in men. While this pop-cultural description may influence the social perspective of ARS, so far, no prospective observational data on the gender-specific natural development of ARS is available. METHODS: Secondary data analyses were performed from the placebo arm of a prospective, interventional phase IV clinical trial. Objective measurement of ARS symptoms were assessed with the Major Symptom Score (MSS), a clinician-rated assessment tool. The Sino-Nasal Outcome Test-22 (SNOT-22) was used for symptom self-report. Repeated measures analysis of variance (ANOVA) with gender as a group variable were used to investigate changes in MMS and SNOT-22 total score and subscales over time. RESULTS: While MMS scores did not differ at baseline, women showed a significantly greater reduction than men with a medium effect size (p = .040) over time. In the patient-reported symptom score, women showed a significantly higher symptom load at baseline (p = .038), but also a significantly faster subjective improvement of symptoms than men during the course of time with a medium effect size (p = .020). However, when separately assessing the SNOT-22 subscales, a significant time*gender effect was only found for emotional symptoms (p = .047). No gender effect was found for neither nasal, otological, or sleep symptoms (all p > .05). DISCUSSION: Although a certain gender difference was found both in the clinician- as well as patient-rated ARS symptoms, the hypothesis of a 'man flu' should be disregarded. Gender differences in ARS symptomatology should be carefully evaluated without stigmatizing symptom distress based on gender perceptions.

Assessment of health-related quality-of-life in patients with chronic Rhinosinusitis - Validation of the German Sino-Nasal Outcome Test-22 (German-SNOT-22).

PURPOSE: The Sino-Nasal-Outcome-Test-22 (SNOT-22) represents the reference questionnaire to assess symptoms, health-related quality-of-life (HRQOL) and treatment-response in patients with chronic rhinosinusitis (CRS). The SNOT-22 has been validated for various languages, yet no validation is available for the German version. Thus, we provide a validation of the SNOT-22 for German. METHODS: In this prospective observational study 139 CRS-patients and 36 control-participants were included. CRS-patients completed the German-SNOT-22 before treatment (T0) and four (T1), twelve (T2) and 48 weeks after inclusion (T3). At T0, Mackay-Naclerio-, Lund-Mackay- and Brief-Symptom-Inventory-18 (BSI-18) scores were collected as external reference for the German-SNOT-22 and its subscales. At T1, T2, and T3 health-transition-items (HTIs) were raised to explore responsivity. Control-participants completed the German-SNOT-22 at T0. Reliability (internal consistency, item-total correlation), validity (concurrent validity, discriminatory validity) and responsiveness (distribution- and anchor-based) were explored for the German-SNOT-22. RESULTS: At T0, the mean German-SNOT-22 total-score for CRS patients was 38.0 (± 20.9) and responded to treatment (T1 = 26.3 ± 19.1; T2 = 25.8 ± 20.6; T3 = 20.5 ± 16.3). For control-participants, the mean total-score at T0 was 15.1 (±10.9). The German-SNOT-22 was reliable (excellent internal consistency α = 0.93; good overall item-total correlations r = 0.39-0.85), valid (significant correlations between Mackay-Naclerio-, Lund-Mackay- and BSI-18 scores, all r > 0.39, p < 0.01) and responsive (significant correlations between HTIs and mean change in German-SNOT-22 total-score F = 9.57, p < 0.001). CONCLUSION: The German-SNOT-22 validated here matches the original SNOT-22. It is a reliable, valid and responsive questionnaire to assess symptoms, HRQOL and treatment-response in CRS-patients. Good psychometric properties were observed.

Slug Is A Surrogate Marker of Epithelial to Mesenchymal Transition (EMT) in Head and Neck Cancer.

BACKGROUND: Epithelial to mesenchymal transition (EMT) promotes therapy resistance in head and neck cancer (HNC) cells. In this study, EMT was quantified in HNC tumor samples by the cellular co-localization of cytokeratin/vimentin, E­cadherin/ß­catenin and by Slug expression. METHODS: Tissue samples from HNC patients were stained with antibody pairs against cytokeratin/vimentin and E-cadherin/ß-catenin. Epithelial-mesenchymal co-localization was quantified using immunofluorescence multichannel image cytometry. Double positivity was confirmed using confocal microscopy. Slug was semi-quantified by 2 specialists and quantified by bright field image cytometry. RESULTS: Tumor samples of 102 patients were investigated. A loss of E-cadherin positive cells (56.9 ± 2.6% vs. 97.9 ± 1.0%; p < 0.0001) and E-cadherin/ß-catenin double positive cells (15.4 ± 5.7% vs. 85.4 ± 1.2%; p < 0.0001) was observed in tumor samples. The percentage of Slug positive cells was increased in tumor samples (12.1 ± 3.6% vs. 3.2 ± 2.6%; p = 0.001). Ordinal Slug scores judged by two specialists closely correlated with percentage of Slug-positive cells (Spearman's rho = 0.81; p < 0.001). Slug score correlated negatively with the percentage of E-cadherin positive cells (r = 0.4; p = 0.006), the percentage of E-cadherin/ß-catenin positive cells (r = 0.5; p = 0.001) and positively with cytokeratin/vimentin positive cells (r = 0.4, p = 0.003). CONCLUSION: EMT can be assessed in HNC tumor probes by cytokeratin/vimentin co-expression and loss of E-cadherin/ß-catenin co-expression. Slug score provides a convenient surrogate marker for EMT.

Surgical rescue for persistent head and neck cancer after first-line treatment.

PURPOSE: Surgical rescue is a treatment option for persistent disease after first-line treatment treatment of head and neck cancer (HNC). METHODS: Patients with persistent HNC treated with rescue surgery between 2008 and 2016 were included. Patients who received a rescue neck dissection (ND only) and who received primary site surgery ± ND were analysed separately (primary site surgery ± ND). RESULTS: During the observation period, 35 patients received ND only and 17 primary site surgery ± ND. No perioperative mortality was observed. In nine patients with ND only and 12 patients with primary site surgery ± ND at least one complication was encountered. 41/52 (79%) patients had a complete response. Median overall survival of patients receiving rescue surgery was 56 months (95% CI 44-69 months). Median overall survival was best for patients with initial laryngeal and oropharyngeal cancer and worst for patients with hypopharyngeal cancer (p = 0.02). Functional deficits following rescue surgery were mainly observed in the domains speech, nutrition, and shoulder/arm mobility. The risk of functional impairment was higher for patients with rescue surgery at the primary tumor site (OR 2.5 ± 2; p = 0.07). CONCLUSION: Rescue surgery offers patients with resectable, persistent disease a realistic chance to achieve long-term survival. Especially patients with laryngeal and oropharyngeal cancer profited from rescue surgery. Rescue neck dissection is an effective and safe procedure. Patients with rescue surgery at the primary tumor site ± ND should expect complications and permanent functional impairment.

Pleiotropic Effects of Epithelial Mesenchymal Crosstalk on Head and Neck Cancer: EMT and beyond.

Epithelial mesenchymal crosstalk (EMC) describes the interaction of the tumor stroma and associated fibroblasts with epithelial cancer cells. In this study we analysed the effects of EMC on head and neck cancer cells. In tumor cell lines EMC was induced using media conditioned from a mix-culture of cancer cells and fibroblasts. Cell proliferation and chemotherapy response were assessed using direct cell counting. Flow cytometry, immunohistochemistry of markers of epithelial-mesenchymal transition (EMT) and subsequent TissueFaxs™ acquisition and quantification and western blot analysis were performed. Holotomographic microscopy imaging was used to visualize the effects of EMC on Cisplatin response of SCC-25 cells. EMC induced a hybrid epithelial-mesenchymal phenotype in SCC-25 cells with co-expression of vimentin and cytokeratin. This hybrid phenotype was associated with chemotherapy resistance and increased proliferation of the cells. The EMC conditioned medium led to an activation of the IL-6/STAT3 pathway with subsequent phosphorylation of STAT3. EMC induced a hybrid epithelial-mesenchymal phenotype in HNSCC cells accompanied by increased therapy resistance and cell proliferation. The IL-6/STAT3 pathway might be one of the major pathways involved in these EMC-related effects.

Tavipec in acute rhinosinusitis: a multi-centre, doubleblind, randomized, placebo-controlled, clinical trial.

BACKGROUND: This randomized clinical trial was designed to evaluate the efficacy and safety of Tavipec® (Spicae aetheroleum), a phytomedicine obtained by steam distillation of the flowering tops of Lavandula latifolia, as compared to placebo in adult patients suffering from acute viral rhinosinusitis. METHODOLOGY: Patients with acute viral rhinosinusitis were randomly assigned to treatment with 2 capsules Tavipec® 150 mg or placebo thrice daily over a period of 7 days in a double-blind, parallel-group design. No additional treatment was admitted. The efficacy endpoints comprised the improvement of the main rhinosinusitis symptoms as per Major Symptom Score (MSS) and Sino-Nasal Outcome Test (SNOT-22) as well as of quality of life (QoL) by global assessment scale, evaluated at baseline, day 5 and day 8, respectively. RESULTS: 288 patients were enrolled and randomized to treatment. At day 8 the patients in the Tavipec® group had a significantly lower MSS compared to placebo and the impact of rhinosinusitis symptoms on QoL was significantly reduced. A significantly higher proportion of Tavipec® treated patients experienced a change in SNOT-22 score greater than or equal to 10 points at day 5 or day 8. No new safety signals were identified. CONCLUSIONS: The treatment with Tavipec® effectively reduced the symptoms of acute rhinosinusitis in adult patients.

Readout-Segmented Echo-Planar DWI for the Detection of Cholesteatomas: Correlation with Surgical Validation.

BACKGROUND AND PURPOSE: MR imaging has become an important tool for the detection of cholesteatomas of the middle ear. Various diffusion-weighted imaging sequences are available and have shown promising results. This study aimed to evaluate readout-segmented echo-planar DWI for the detection of cholesteatoma and compare the results with surgical validation. MATERIALS AND METHODS: Fifty patients with chronic otitis media (24 females and 26 males; range, 12-76 years of age; mean age, 41 years) who underwent MR imaging before an operation of the middle ear (1-169 days) were included. The MR imaging protocol consisted of axial and coronal readout-segmented echo-planar DWI with b-values of 0 and 1000 s/mm2 and 3-mm slice thickness. The readout-segmented echo-planar diffusion-weighted images were fused with standard T2-weighted sequences for better anatomic assignment. The results of the MR imaging evaluation were correlated with the results from the operation. RESULTS: Readout-segmented echo-planar DWI detected 22 of the 25 cases of surgically proved cholesteatoma. It has an accuracy of 92% (95% confidence interval, 80.8%-97.8%), a sensitivity of 88%, a specificity of 96%, a positive predictive value of 96%, and a negative predictive value of 89%. In 1 case, a positive finding for cholesteatoma with readout-segmented echo-planar DWI could not be proved by histology, and in 3 cases, histology yielded a cholesteatoma that was not detected with MR imaging. CONCLUSIONS: Readout-segmented echo-planar DWI is a promising and reliable MR imaging sequence for the detection and exclusion of cholesteatoma.

The SNOT-22 factorial structure in European patients with chronic rhinosinusitis: new clinical insights.

PURPOSE: The sino-nasal outcomes test-22 (SNOT-22) represents the reference questionnaire to assess patients with chronic rhinosinusitis (CRS). As weak correlations between objective CRS parameters and SNOT-22 total score have been observed, factor analyses have aimed to identify underlying factorial structures. However, ambiguous factor loadings and problematic item-domain assignments have resulted. Moreover, such factor analyses have mainly been performed in non-European CRS patients, while European data remain sparse. This study thus sought to address these issues. METHODS: Principal component analysis and confirmatory factor analysis were performed from SNOT-22 questionnaires completed by European CRS patients. Goodness of fit, internal consistencies, and factor loadings were calculated. Item-domain assignment was based on statistical grounds and clinical meaningfulness. Additionally, this study investigated correlations between SNOT-22 domains and external reference criteria, including Lund-Mackay score, Lund-Naclerio score and the brief symptom inventory 18 (BSI-18). RESULTS: One hundred and thirty-four European CRS patients were included. Principal component analysis proposed four SNOT-22 domains ("nasal symptoms", "otologic symptoms", "sleep symptoms", "emotional symptoms"), which explained 63.6% of variance. Observed item-domain-assignment differed from previously proposed item-domain assignments. All factor loadings were > 0.5, except "cough" (0.42) and "facial pain or pressure" (0.49). For confirmatory factor analysis, satisfactory goodness of fit (RMSEA = 0.66; CFI = 0.92; TLI = 0.90) and internal consistencies (Cronbach-α: total score = 0.93; domains = 0.75-0.91) were observed. Significant positive correlations were found between the "nasal symptoms" domain and both the Lund-Mackay score (r = 0.48; p < 0.001) and the Lund-Naclerio score (r = 0.27, p < 0.01). Significant positive correlations were also identified between "emotional symptoms" and BSI-18 total score (r = 0.64, p < 0.001). CONCLUSIONS: Principal component analysis performed for SNOT-22 questionnaires completed by European CRS patients indicated a different item-domain-assignment than previously reported. Confirmatory factor analysis suggested acceptable and clinically plausible psychometric properties for the resulting factorial structure. Significant correlations between the "nasal symptoms" and the "emotional symptoms" domains were observed with objective CRS parameters. The resulting factorial structure with different item-domain assignments may thus be more suitable for European CRS patients.

Cancer patients' wish for psychological support during outpatient radiation therapy : Findings from a psychooncological monitoring program in clinical routine.

BACKGROUND: Cancer patients frequently suffer from physical and psychosocial impairments due to their disease and its treatment. Psychooncology (PO) can help to cope with stress resulting from outpatient radiotherapy (RT) treatment. There are currently few data regarding patients' wishes for PO support. The aim of this study was to investigate the number of patients with a wish for PO, treatment paths, and predictors of the wish for PO among cancer patients at the beginning of RT. METHODS: The results of routine psychological stress screening (Hornheide screening instrument; cut-off  ≥ 4) of 944 cancer patients between 2015 and 2017 were analyzed in a retrospective cross-sectional study. Predictors for a wish for PO support were identified by stepwise binary logistic regression, in which sociodemographic and treatment data were included in addition to the screening items. RESULTS: Around 20% of patients had above-average stress levels and 13% expressed a wish for PO support (participation rate was approximately 55%). Low emotional wellbeing (OR = 11.3) and lack of social support (OR = 9.4) were strong predictors for this treatment wish. Among patients with pancreatic cancer, head and neck tumors, and hematologic disease, there was a substantial difference between the degree of psychological stress and the wish for treatment. Patients with urological (23.5%) and lung tumors (20.9%) most frequently expressed a wish for PO support. CONCLUSION: Patient-reported psychosocial problems were better predictors of a wish for PO support than sociodemographic or clinical data. Stress screening should thus be implemented in clinical routine.

Approximation of head and neck cancer volumes in contrast enhanced CT.

BACKGROUND: Tumor volume may serve as a predictor of response to radiochemotherapy (RCT) in head and neck squamous cell carcinoma (HNSCC). Computer assisted tumor volumetry requires time-consuming slice-by-slice manual or semi-automated segmentation. We questioned how accurately primary tumor and suspect cervical lymph node (LN) volumes can be approximated by the maximum tumor diameters in three dimensions. METHODS: In contrast-enhanced diagnostic CT scans of 74 patients with incident advanced HNSCC, manual slice-by-slice segmentation volumetry of primary tumor, total- and largest suspect cervical LN served as the reference method. In the same scans, maximum orthogonal diameters were measured using the distance measurement tool in standard visualization software in axial and coronal sections. From these diameters, approximate volumes were calculated using the cubic and ellipsoid formula. A second segmentation volumetry was performed in contrast enhanced radiotherapy-planning CT scans obtained prior to primary concurrent RCT 24 days (+/- 13 days) following the initial diagnostic CT scans. Intraclass correlation coefficients and Bland-Altman analyses were used to compare results. RESULTS: Slice-by-slice manual segmentation volumetry of primary and LN volumes revealed a lognormal distribution and ranged from 0 to 86 ml and 0 to 129 ml, respectively. Volume approximations in diagnostic CT scans with the ellipsoid formula resulted in an -8 % underestimation of tumor volumes (95 % CI -14 % to -1 %; p = 0.022) and an -18 % underestimation of suspect cervical LN volumes (95 % CI -25 % to -12 %; p = 0.001). Inter rater intraclass correlation for primaries was 0.95 (95 % CI +0.92 to +0.97; p = 0.001), and intra rater intraclass correlation was 0.99 (95 % CI +0.98 to +0.99; p = 0.001). The cubic formula resulted in pronounced overestimation of primary and LN volumes. Primary tumor volumes obtained by the second segmentation volumetry in radiotherapy-planning CT scans obtained on average 24 days following the initial volumetry resulted in larger primary tumor volumes (mean bias +28 %, 95 % CI +14 % to +41 %; p = 0.001). Tumor volume increase correlated with time between the diagnostic and planning CTs (r = 0.24, p = 0.05) and was approximately 1 % per day. DISCUSSION: Ellipsoid approximations of tumor and lymph node volumes in HNSCC using maximum orthogonal diameters underestimates volumes based on segmentation in multiple slices. Due to time difference and safety margins, segmented volumes in radiotherapy-planning CT scans tend to be larger than in diagnostic CT scans. CONCLUSION: Ellipsoid approximations of tumor and lymph node volumes in HNSCC are easily available from diagnostic CT scans. Volume estimates are applicable over a wide range of tumor and LN sizes and may be useful in clinical decision-making and oncologic research.

[Actinic Keratosis]. / Aktinische Keratose.

Actinic keratosis is a cutaneous lesion characterized by proliferation of atypical epidermal keratinocytes due to prolonged exposure to exogenous factors such as ultraviolet radiation. AKs are in-situ-squamous cell carcinomas (PEC) of the skin. AK typically presents as erythematous, scaly patch or papule (classic AK), occasionally as thick, adherent scale on an erythematous base. Mostly fair-skinned adults are affected. AKs typically occur in areas of frequent sun exposure (balding scalp, face, "H-region", lateral neck, décolleté, dorsum of the hand and lower extremities). Actinic Cheilitis is the term used for AKs appearing on the lips. The diagnosis of AK is based on clinical examination including inspection and palpation. The typical palpable rough surface of AK often precedes a visible lesion. Dermoscopy may provide additional information. If diagnosis is uncertain and invasion suspected, biopsy and histopathologic evaluation should be performed. The potential for progression to invasive PECs mandates therapeutic intervention. Treatment options include topical and systemic therapies. Topical therapies are classified into physical, medical and combined physical-chemical approaches and a sequential combination of treatment modalities is possible. Topical-physical cryotherapy is the treatment of choice for isolated, non-hypertrophic AK. Topical-medical treatment, e. g. 5-fluoruracil (5FU) cream or Imiquomod or Ingenolmebutat application is used for multiple, non-hypertrophic AKs. For hypertrophic AKs, a dehorning pretreatment with salicinated vaseline is recommended. Isolated hypertrophic AKs often need cryotherapy with prolonged freezing time or several consecutive applications. Sequentially combined approaches are recommended for multiple, hypertrophic AKs. Photodynamic therapy (PDT) as example for a combined physical-chemical approach is an established treatment for multiple, non-hypertrophic and hypertrophic AKs. Prevention includes avoidance of sun and application of sunscreen with high sun protection factor. Regular clinical checkups aid in early recognition of AKs.

Radiologic and functional evaluation of electrode dislocation from the scala tympani to the scala vestibuli in patients with cochlear implants.

BACKGROUND AND PURPOSE: Localization of the electrode after cochlear implantation seems to have an impact on auditory outcome, and conebeam CT has emerged as a reliable method for visualizing the electrode array position within the cochlea. The aim of this retrospective study was to evaluate the frequency and clinical impact of scalar dislocation of various electrodes and surgical approaches and to evaluate its influence on auditory outcome. MATERIALS AND METHODS: This retrospective single-center study analyzed a consecutive series of 63 cochlear implantations with various straight electrodes. The placement of the electrode array was evaluated by using multiplanar reconstructed conebeam CT images. For the auditory outcome, we compared the aided hearing thresholds and the charge units of maximum comfortable loudness level at weeks 6, 12, and 24 after implantation. RESULTS: In 7.9% of the cases, the electrode array showed scalar dislocation. In all cases, the electrode array penetrated the basal membrane within 45° of the electrode insertion. All 3 cases of cochleostomy were dislocated in the first 45° segment. No hearing differences were noted, but the charge units of maximum comfortable loudness level seemed to increase with time in patients with dislocations. CONCLUSIONS: The intracochlear dislocation rate of various straight electrodes detected by conebeam CT images is relatively low. Scalar dislocation may not negatively influence the hearing threshold but may require an increase of the necessary stimulus charge and should be reported by the radiologist.