Bacterial biofilm formation on headpieces of Cochlear implants.

INTRODUCTION: Bacterial biofilm formation on medical devices, such as Cochlear implants (CI), can lead to chronic infections. Not only the inner parts of the implant but also the externally located headpiece might be associated with prolonged superficial skin eczema resulting in the inability of wearing the headpiece. In this study, the surface of three CI headpieces from different manufacturers were examined for bacterial biofilm formation. MATERIALS AND METHODS: Two bacterial species associated with implant-related infections were tested: Pseudomonas aeruginosa (ATCC9027) and Staphylococcus aureus (ATCC6538). Biofilms were formed over 24 h in tryptic soy broth at 36 °C. Biofilm formation was detected in form of biomass measurement by crystal violet staining. CI headpiece dummies of three manufacturers were used. RESULTS: Both tested bacterial species formed biofilms on the examined CI headpiece-surfaces in a species-dependent manner with higher biofilm formation of P. aeruginosa. For both, S. aureus and P. aeruginosa, biofilm formation on the CI components was comparable to a polystyrene control surface. Between the three manufacturers, no significant difference in biofilm formation was found. DISCUSSION: The tested bacteria displayed biofilm formation on the CI headpieces in a species-specific manner with higher amount of biofilm formed by P. aeruginosa. The biofilm formation was comparable between the manufacturers. In this study, an enhanced biofilm formation on CI headpieces could not be demonstrated. These in vitro tests suggest a minor role of bacterial biofilm on the CI headpiece in skin infections under the CI headpiece.

[Results of a survey on the current management of chronic rhinosinusitis with nasal polyps in Germany]. / Ergebnisse einer Umfrage zur aktuellen Behandlung der chronischen Rhinosinusitis mit nasalen Polypen.

INTRODUCTION: With a prevalence of 0.55% to 4%, chronic rhinosinusitis with nasal polyps (CRSwNP) is a relevant part of the daily work of German otolaryngologists. The aim of the questionnaire-based data collection was to assess the current treatment status of CRSwNP in Germany. MATERIAL AND METHODS: For this purpose, 24 questions within an anonymized online questionnaire were sent to all German ENT departments. RESULTS: Of 160 contacted ENT departments, 50 participated in the survey (31.3%). Among these, 76% performed more than 100 sinus surgeries annually and 38% treated more than 50 patients with biologics. Saline irrigations (80%) and intranasal glucocorticoids (GCS, 96%) were the most common conservative therapies. Systemic GCSs (52%) and intranasal GCS irrigation (20%) were less common. 80% of departments used biologics in the therapy of CRSwNP with an overall preference for dupilumab (70%). For therapy of aspirin intolerance, biologics (52%) were preferred to aspirin desensitization (26%). Prior to treatment with biologics clinical workup included the nasal polyp score (90%), the SNOT-22 questionnaire (84%), surrogate markers of type 2 inflammation (60%-72%), and computer tomography (50%). Final treatment success was assessed after 24 weeks (50%). CONCLUSION: Mostly, the responding departments followed German and European recommendations for diagnosis and therapy of CRSwNP. Therapy with biologics is widely used. The value of preoperative systemic GCS and the frequent performance of CT before initiation of therapy with a biologic should be debated in regard to its currently widespread use.

[Nodal metastasis and value of neck dissection in T1/2 oropharyngeal and hypopharyngeal carcinomas]. / Nodale Metastasierung und Stellenwert der Neck Dissection bei T1/2-Oro- und Hypopharynxkarzinomen.

BACKGROUND: Due to heterogeneous data, the indication for elective neck dissection (END) in patients with squamous cell carcinoma of the hypopharynx and oropharynx (HPSCC and OPSCC) in stages T1/2N0 is somewhat unclear. Therefore, in this multicenter study, we performed detailed analysis of the metastatic behavior of HPSCC and OPSCC. MATERIAL AND METHODS: The nodal metastatic patterns of 262 HPSCC and OPSCC patients who had undergone surgery was retrospectively investigated. In addition, recurrence-free and overall survival were recorded. Furthermore, a systematic literature review on the topic was completed. RESULTS: In patients with HPSCC, a discrepancy between clinical and pathologic N status was recorded in 62.1% of patients vs. 52.4% for p16- OPSCC, and 43.6% for p16+ OPSCC. The occult metastasis rate in cT1/2cN0 primary tumors was 38.9% for HPSCC vs. 17.8% (p16- OPSCC) and 11.1% (p16+ OPSCC). Contralateral metastases occurred in 22.2% of cases for HPSCC at stages cT1/2cN0, compared to only 9.1% for p16- OPSCC, and 0% for p16+ OPSCC patients.Patients with p16+ OPSCC had better recurrence-free and overall survival than p16- OPSCC and HPSCC patients. A direct association between patient survival and the extent of neck surgical therapy could not be demonstrated in our patients. CONCLUSION: Patients with HPSCC are at risk for bilateral neck metastases from stage cT1/2cN0, justifying bilateral END. Patients with T1/2 OPSCC present with occult metastases ipsilaterally in >20% of cases; however, the risk for contralateral occult metastasis is <10%. Hence, in strictly lateralized cT1/2CN0 tumors, omission of contralateral END may be considered.

[Results of a nationwide survey on the treatment of salivary gland diseases in German hospitals]. / Ergebnisse einer deutschlandweiten Umfrage zur Behandlung von Speicheldrüsenerkrankungen im Krankenhaus.

BACKGROUND: Salivary gland diseases are an important part of the work of ENT physicians in hospitals. The treatment strategies depend, among other things, on the doctrine at the respective location. OBJECTIVE: The aim of this questionnaire-based study was to assess the current diagnostic workup and therapeutic strategies for salivary gland diseases in German otorhinolaryngology departments. MATERIALS AND METHODS: A survey was performed using a 25-question online questionnaire sent to all German otorhinolaryngology department directors. RESULTS: The questionnaire was answered by 92 of 175 otorhinolaryngology departments (52.6%). In the diagnosis of salivary gland tumors, a dominance of sonography and MRI was shown. Fine- and core-needle aspiration were not performed by more than 50% of the clinics. The dominant technique for parotidectomy was under microscopic control (82%). In 99% of clinics, EMG was used during resection of the parotid gland for intraoperative monitoring of the facial nerve. There was a trend towards performing partial parotidectomies (85%), lateral parotidectomies (70%), and extracapsular dissections (57%) for benign tumors of the parotid gland. The treatment concepts for malignant tumors were inconsistent. CONCLUSION: In particular, the treatment strategy and extent of surgery for benign and malignant salivary gland tumors differed depending on location. The choice of palliative (drug) therapy was also diverse. Prospective multicenter studies could help to develop evidence-based treatment strategies.

Identification of cytokeratin24 as a tumor suppressor for the management of head and neck cancer.

To improve management of head and neck squamous cell carcinoma patients, we need to increase our understanding of carcinogenesis, to identify biomarkers, and drug targets. This study aimed to identify novel biomarkers by providing transcriptomics profiles of matched primary tumors, lymph node metastasis, and non-malignant tissue of 20 HNSCC patients as well as by bioinformatic analyses of a TCGA HNSCC cohort, comprising 554 patients. We provide cancer cell signaling networks differentially expressed in tumors versus metastases, such as mesenchymal-epithelial transition, and structural integrity networks. As a proof of principle study, we exploited the data sets and performed functional analyses of a novel cytokeratin, cytokeratin24 (cKRT24), which had not been described as biomarker for tumors before. Survival analysis revealed that low cKRT24 expression correlated with poor overall survival in HNSCC. Experimentally, downregulation of cKRT24 in primary tumors, metastases, and HNSCC cell lines was verified on mRNA and protein level. Cloning and ectopic overexpression of cKRT24 not only affected viability and growth of HNSSC cell lines, but also inhibited tumor growth in murine xenograft studies. We conclude that cKRT24 functions as a tumor suppressor in HNSCC, and may serve as an additional prognostic biomarker and novel target to support current HNSCC treatments.

The accuracy of clinical neck staging for p16-positive and negative oropharyngeal cancer and its therapeutic implications.

PURPOSE: Oropharyngeal squamous cell carcinoma (OPSCC) may be treated with primary surgery or primary (chemo)radiation. While surgery with concurrent neck dissection provides definitive pathological staging of the neck, non-surgical treatment relies on clinical staging for treatment planning. To assess the accuracy of clinical neck staging, we compared clinical to surgical staging after primary surgery in patients with p16-negative and p16-positive OPSCC. METHODS: Retrospective analysis of clinical, pathological, and oncologic outcome data of patients with OPSCC treated with primary surgery and bilateral neck dissection. Clinical and pathological nodal status were compared for p16-negative and p16-positive patients. Patients with occult metastatic disease were analyzed in detail. RESULTS: 95 patients were included. 60.5% of p16-negative patients and 66.6% of p16-positive patients had pathologically confirmed metastatic neck disease. p16-positive patients had improved 24-month recurrence-free survival compared to p16-negative patients at 93.3% vs. 69.6%. Pathological N-status differed from clinical N-status in 36.8% of p16-negative patients vs. 31.6% of p16-positive patients. Occult metastatic disease was more common in p16-negative patients at 18.4% vs. 8.8% for p16-positive patients. Clinical detection sensitivity for extranodal extension was low overall; sensitivity was 27.3% and specificity was 91.6% for p16-negative patients vs. 61.5% and 80.0% for p16-positive patients, respectively. CONCLUSION: Our data show a considerable degree of inaccuracy of clinical neck staging results in all OPSCC patients which needs to be taken into consideration during therapy planning. For p16-positive patients, these findings warrant attention in the context of therapy deintensification to avoid undertreatment.

Patterns of cervical lymph node metastasis in supraglottic laryngeal cancer and therapeutic implications of surgical staging of the neck.

PURPOSE: Accurate therapeutic management of the neck is a challenge in patients with supraglottic laryngeal cancer. Nodal metastasis is common at all disease stages, and treatment planning relies on clinical staging of the neck, for both surgical and non-surgical treatment. Here, we compared clinical and surgical staging results in supraglottic carcinoma patients treated with primary surgery to assess the accuracy of pre-therapeutic clinical staging and guide future treatment decisions. METHODS: Retrospective analysis of clinical, pathological, and oncologic outcome data of 70 patients treated with primary surgery and bilateral neck dissection for supraglottic laryngeal cancer. Patients where clinical and pathological neck staging results differed, were identified and analyzed in detail. RESULTS: On pathologic assessment, patients with early stage (pT1/2) primaries showed cervical lymph node metastases in 55% (n = 17/31) of cases, compared to 67% (n = 26/39) of patients with pT3/4 tumors. In 24% (n = 17/70) of all patients, cN status differed from pN status, resulting in an upstaging in 16% of cases (n = 11/70) and a downstaging in 9% (n = 6/70) of cases. 14% of patients with cN0 status had occult metastases (n = 5/30). As assessed by a retrospective tumor board, in case of a non-surgical treatment approach, the inaccurate clinical staging of the neck would have led to an over- or undertreatment of the neck in 20% (n = 14/70) of all patients. CONCLUSION: Our data re-emphasize the high cervical metastasis rates of supraglottic laryngeal cancer across all stages. Inaccurate clinical staging of the neck is common and should be taken into consideration when planning treatment.

Concordance Analysis of the Pressure Chamber and Tubomanometer According to Estève for the Determination of Eustachian Tube Opening Pressure.

INTRODUCTION: For the diagnosis of Eustachian tube dysfunction (ETD), clinical procedures such as tympanometry, micro-otoscopy, and maneuvers according to Toynbee and Valsalva only allow an indirect assessment for the moment. With a prevalence of up to 5%, the selection of patients with ETD and its subtypes is clinically relevant. Dynamic methods of Eustachian tube function assessment include a hypo/hyperbaric pressure chamber and Estève's tubomanometer (TMM). One method of assessing ETD is the evaluation of Eustachian tube opening pressure (ETOP). MATERIAL AND METHODS: We performed a concordance analysis between pressure chamber and TMM to determine ETOP. For this purpose, we analyzed the measurements of both methods from 28 healthy subjects using Bland-Altman plots, regression according to Passing-Bablok and Lin's concordance correlations coefficient. The maximum tolerated clinical deviation of measured values was set at 10%. RESULTS: A maximum of 53 measurements of ETOP between pressure chamber and TMM were compared. Mean ETOP for TMM was 28.7 hPa, passive opening was 32 hPa, Toynbee maneuver was 28.4 hPa, and Valsalva maneuver was 54.6 hPa. Concordance analysis revealed following results: passive opening versus TMM: Bland-Altman mean difference 3.3 hPa, limits of agreement ±31.8 hPa; Passing-Bablok regression y = 0.67 x + 9.36; Lin's rccc = 0.18. Toynbee versus TMM: Bland-Altman mean difference 0.7 hPa, limits of agreement ±35.8 hPa; Passing-Bablok regression y = 0.47x + 14.03; Lin's rccc = 0.14. Valsalva versus TMM: Bland-Altman mean difference 24.2 hPa, limits of agreement ±117.5 hPa; Passing-Bablok regression y = 0.17x + 25.12; Lin's rccc = 0.18. CONCLUSION: Estève's tubomanometer and pressure chamber measurements of ETOP are not concordant. The two methods cannot be interchanged without reservation.

Standardized Digital Image Analysis of PD-L1 Expression in Head and Neck Squamous Cell Carcinoma Reveals Intra- and Inter-Sample Heterogeneity with Therapeutic Implications.

For practical reasons, in many studies PD-L1 expression is measured by combined positive score (CPS) from a single tumor sample. This does not reflect the heterogeneity of PD-L1 expression in head and neck squamous cell carcinoma (HNSCC). We investigated the extent and relevance of PD-L1 expression heterogeneity in HNSCC analyzing primary tumors and recurrences (LRs), as well as metastases. Tumor tissue from 200 HNSCC patients was immunohistochemically stained for PD-L1 and analyzed using image-analysis software QuPath v3.4 with multiple specimens per patient. CPS was ≥20 in 25.6% of primary tumors. Intra-tumoral heterogeneity led to a therapeutically relevant underestimation of PD-L1 expression in 28.7% of patients, when only one specimen per patient was analyzed. Inter-tumoral differences in PD-L1 expression between primary tumors and lymph node metastasis (LNM) or LR occurred in 44.4% and 61.5% (CPS) and in 40.6% and 50% of cases (TPS). Overall survival was increased in patients with CPS ≥ 1 vs. CPS < 1 in primary tumors and LNM (hazard ratio: 0.46 and 0.35; p < 0.005); CPS in LR was not prognostic. Our analysis shows clinically relevant intra- and inter-sample heterogeneity of PD-L1 expression in HNSCC. To account for heterogeneity and improve patient selection for immunotherapy, multiple sample analyses should be performed, particularly in patients with CPS/TPS < 1.

Growth Factor Receptor Expression in Oropharyngeal Squamous Cell Cancer: Her1-4 and c-Met in Conjunction with the Clinical Features and Human Papillomavirus (p16) Status.

This study aimed to assess the distribution of growth factor receptors in oropharyngeal squamous cell cancer (OPSCC) and evaluate their role in the context of human papillomavirus (HPV) status, prognosis and potential relevance for targeted therapy. The protein expression of human epidermal growth factor receptor (Her)1-4 and c-Met were retrospectively assessed using semiquantitative immunohistochemistry on tissue microarrays and analyzed for correlations as well as differences in the clinicopathological criteria. Her1-4 and c-met were overexpressed compared to normal mucosa in 46%, 4%, 17%, 27% and 23%, respectively. Interestingly, most receptors were coexpressed. Her1 and c-Met were inversely correlated with p16 (p = 0.04; p = 0.02). Her2 and c-Met were associated with high tobacco consumption (p = 0.016; p = 0.04). High EGFR, Her3, Her4 and c-Met expression were associated with worse overall and disease-free survival (p ≤ 0.05). Furthermore, EGFR and c-Met expression showed raised hazard ratios of 2.53 (p = 0.02; 95% CI 1.24-5.18) and 2.45 (p = 0.02; 95% CI 1.13-5.35), respectively. Her4 was expressed less in distant metastases than in corresponding primary tumors and was correlated to a higher T category. EGFR and c-Met are relevant negative prognostic factors in OPSCC, independent of known clinicopathological parameters. We suggest dual targeting of EGFR and c-Met as a promising strategy for OPSCC treatment.