Exosomal Serum Biomarkers as Predictors for Laryngeal Carcinoma.

BACKGROUND: The lack of screening methods for LSCC is a critical issue, as treatment options and the treatment outcome greatly depend on the stage of LSCC at initial diagnosis. Therefore, the objective of this study was to identify potential exosomal serum biomarkers that can diagnose LSCC and distinguish between early- and late-stage disease. METHODS: A multiplexed proteomic array was used to identify differentially expressed proteins in exosomes isolated from the serum samples of LSCC patients compared to the control group (septorhinoplasty, SRP). The most promising proteins for diagnosis and differentiation were calculated using biostatistical methods and were validated by immunohistochemistry (IHC), Western blots (WB), and ELISA. RESULTS: Exosomal insulin-like growth factor binding protein 7 (IGFBP7) and Annexin A1 (ANXA1) were the most promising exosomal biomarkers for distinguishing between control and LSCC patients and also between different stages of LSCC (fold change up to 15.9, p < 0.001 for all). CONCLUSION: The identified proteins represent potentially novel non-invasive biomarkers. However, these results need to be validated in larger cohorts with a long-term follow-up. Exosomal biomarkers show a superior signal-to-noise ratio compared to whole serum and may therefore be an important tool for non-invasive biomarker profiling for laryngeal carcinoma in the future.

Case-tailored indicated extracapsular dissection versus "one-size-fits-all" nerve dissection: Has the bet been won?

OBJECTIVE: The aim of the study was to trace the development of surgical therapy in a large cohort, examine its changes at one single institution that has been specializing in salivary gland pathologies over the last 22 years, and to determine the extent to which a possible shift in the surgical therapy of parotid benign tumors towards less radical methods was correlated with a change in the incidence of facial palsy and Frey's syndrome. STUDY DESIGN: Retrospective clinical study. METHODS: A retrospective evaluation of the records of all patients treated for benign parotid tumors at a tertiary referral center between 2000 and 2022 was carried out. Surgical methods were classified into four groups: extracapsular dissection, partial superficial parotidectomy, superficial parotidectomy and complete parotidectomy. RESULTS: A total of 4037 patients were included in the study. Our analysis demonstrated an increase in the total number of parotidectomies for benign lesions from 71 (2000) to 298 (2022), mostly due to the increase in extracapsular dissections (from 9 to 212). The increased performance of less radical surgery was associated with a significantly decreased incidence of perioperative complications. CONCLUSIONS: Our study showed that the increased performance of less radical surgery was associated with better functional outcomes over the years.

Diagnosis of malignancy in oropharyngeal confocal laser endomicroscopy using GPT 4.0 with vision.

PURPOSE: Confocal Laser Endomicroscopy (CLE) is an imaging tool, that has demonstrated potential for intraoperative, real-time, non-invasive, microscopical assessment of surgical margins of oropharyngeal squamous cell carcinoma (OPSCC). However, interpreting CLE images remains challenging. This study investigates the application of OpenAI's Generative Pretrained Transformer (GPT) 4.0 with Vision capabilities for automated classification of CLE images in OPSCC. METHODS: CLE Images of histological confirmed SCC or healthy mucosa from a database of 12 809 CLE images from 5 patients with OPSCC were retrieved and anonymized. Using a training data set of 16 images, a validation set of 139 images, comprising SCC (83 images, 59.7%) and healthy normal mucosa (56 images, 40.3%) was classified using the application programming interface (API) of GPT4.0. The same set of images was also classified by CLE experts (two surgeons and one pathologist), who were blinded to the histology. Diagnostic metrics, the reliability of GPT and inter-rater reliability were assessed. RESULTS: Overall accuracy of the GPT model was 71.2%, the intra-rater agreement was κ = 0.837, indicating an almost perfect agreement across the three runs of GPT-generated results. Human experts achieved an accuracy of 88.5% with a substantial level of agreement (κ = 0.773). CONCLUSIONS: Though limited to a specific clinical framework, patient and image set, this study sheds light on some previously unexplored diagnostic capabilities of large language models using few-shot prompting. It suggests the model`s ability to extrapolate information and classify CLE images with minimal example data. Whether future versions of the model can achieve clinically relevant diagnostic accuracy, especially in uncurated data sets, remains to be investigated.

Lymphatic Vessels in Chronic Rhinosinusitis.

Purpose: The purpose of this study was to analyze the nasal lymphatic system in order to uncover novel factors that might be involved in pathogenesis of chronic rhinosinusitis (CRS) with (CRSwNP) and without nasal polyps (CRSsNP). Patients and Methods: Lymphatic vessels (LVs) and macrophages were localized and counted in the inferior and middle turbinate, the uncinate process and the ethmoid of CRSwNP and CRSsNP patients, the NP and the inferior turbinate of controls (n≥6 per group). Lysates of the same tissue types (n=7 per group) were analyzed for lymphatic vessel endothelial receptor 1 (LYVE-1), for matrix metalloproteinase 14 (MMP-14) and for Hyaluronic acid (HA) using ELISA. HA was localized in sections of CRSwNP NP, CRSsNP ethmoid and control inferior turbinate (n=6 per group). The results of HA levels were correlated to the number of macrophages in tissues. The nasal secretions of CRSwNP (n=28), CRSsNP (n=30), and control (n=30) patients were analyzed for LYVE-1 and HA using ELISA. Results: The number of LVs was significantly lower in tissues of both CRS groups compared to the control. In the tissue lysates, LYVE-1 expression differed significantly between the CRSwNP tissues with a particularly high level in the NP. MMP-14 was significantly overexpressed in CRSwNP uncinate process. There were no significant differences in tissue HA expression. In the mucus LYVE-1 was significantly underexpressed in CRSsNP compared to CRSwNP and control, while HA was significantly underexpressed in both CRS groups. In the NP, HA and macrophages were accumulated particularly below the epithelium. Tissue levels of HA revealed a significant positive correlation with the number of macrophages. Conclusion: CRS might be associated with an insufficient clearing of the nasal mucosa through the lymphatics. The accumulation of HA and macrophages might promote inflammation, fluid retention, and polyp formation. These results may provide novel CRS-associated factors.

Ultrasound Changes in Salivary Glands after Radioactive Iodine Treatment in Benign Diseases and Differentiated Cancer of Thyroid Glands in Consideration of Dose and Time Dependency.

PURPOSE: To assess ultrasound (US) features observed in salivary glands after radioactive iodine treatment (RAIT) in relation to the dose and time interval after RAIT. MATERIALS AND METHODS: A retrospective analysis of US findings regarding the salivary glands of patients presenting after RAIT due to thyroid cancer (Group 1, n=99) or benign thyroid diseases (Group 2, n=25). The control group consisted of randomly selected patients (no RAIT, Group 3, n=100). Groups were compared regarding RAIT dose, symptoms, and US findings (duct dilation, hypoechoic/heterogeneous parenchyma, parenchymal loss). The association of the presence of US parameters after RAIT with various dose levels (2000-15000MBq) and time intervals (24, 60, 120 months) and the differences between the groups was evaluated. RESULTS: Significant differences between US parameters were noted when comparing Group 1 with Group 2 or 3. Nothing of relevant significance was noted when Groups 2 and 3 were compared. US features indicating a slight or moderate sialadenitis showed the most significant associations with doses <4000MBq and time intervals <24 months after RAIT. US changes indicating a serious sialadenitis or even gland atrophy showed the most significant association at doses between >7000-9000MBq and when US was performed >60 months after RAIT. CONCLUSION: Our results point to a dose and time dependency of pathologic US findings in RAIT-induced effects on the major salivary glands. Based on the US findings, a better estimation of the current impact of RAIT on the salivary glands and the further prognosis appears possible.

Risk stratification of thyroid nodules: Assessing the suitability of ChatGPT for text-based analysis.

PURPOSE: Accurate risk stratification of thyroid nodules is essential for optimal patient management. This study aimed to assess the suitability of ChatGPT for risk stratification of thyroid nodules using a text-based evaluation. METHODS: A dataset was compiled comprising 50 anonymized clinical reports and associated risk assessments for thyroid nodules. The Chat Generative Pre-trained Transformer (ChatGPT) was used to classify sonographic patterns in accordance with the Thyroid Imaging Reporting and Data System (TI-RADS). The model's performance was assessed using various criteria, including sensitivity, specificity, and accuracy. A comparative analysis was conducted, evaluating the model against investigator-based risk stratification as well as histology. RESULTS: With an overall agreement rate of 42 % in comparison with examiner-based evaluation (TI-RADS 1-5), the results show that ChatGPT has moderate potential for predicting the risk of malignancy in thyroid nodules using text-based reports. The chatbot model achieved a sensitivity of 86.7 %, a specificity of 10.7 %, and an overall accuracy of 68 % when distinguishing between low-risk (TI-RADS 2 and 3) and high-risk (TI-RADS 4 and 5) categories. Interrater reliability was calculated with a Cohen's kappa of 0.686. CONCLUSION: This study highlights the potential of ChatGPT in assisting clinicians with risk stratification of thyroid nodules. The results suggest that ChatGPT can facilitate personalized treatment decisions, although the agreement rate is still low. Further research and validation studies are necessary to establish the clinical applicability and generalizability of ChatGPT in routine practice. The integration of ChatGPT into clinical workflows has the potential to enhance thyroid nodule risk assessment and improve patient care.

The modified Polsby-Popper score, a novel quantitative histomorphological biomarker and its potential to predict lymph node positivity and cancer-specific survival in oral tongue squamous cell carcinoma.

BACKGROUND: The significance of different histological spreading patterns of tumor tissue in oral tongue squamous cell carcinoma (TSCC) is well known. Our aim was to construct a numeric parameter on a continuous scale, that is, the modified Polsby-Popper (MPP) score, to describe the aggressiveness of tumor growth and infiltration, with the potential to analyze hematoxylin and eosin-stained whole slide images (WSIs) in an automated manner. We investigated the application of the MPP score in predicting survival and cervical lymph node metastases as well as in determining patients at risk in the context of different surgical margin scenarios. METHODS: We developed a semiautomated image analysis pipeline to detect areas belonging to the tumor tissue compartment. Perimeter and area measurements of all detected tissue regions were derived, and a specific mathematical formula was applied to reflect the perimeter/area ratio in a comparable, observer-independent manner across digitized WSIs. We demonstrated the plausibility of the MPP score by correlating it with well-established clinicopathologic parameters. We then performed survival analysis to assess the relevance of the MPP score, with an emphasis on different surgical margin scenarios. Machine learning models were developed to assess the relevance of the MPP score in predicting survival and occult cervical nodal metastases. RESULTS: The MPP score was associated with unfavorable tumor growth and infiltration patterns, the presence of lymph node metastases, the extracapsular spread of tumor cells, and higher tumor thickness. Higher MPP scores were associated with worse overall survival (OS) and tongue carcinoma-specific survival (TCSS), both when assessing all pT-categories and pT1-pT2 categories only; moreover, higher MPP scores were associated with a significantly worse TCSS in cases where a cancer-free surgical margin of <5 mm could be achieved on the main surgical specimen. This discriminatory capacity remained constant when examining pT1-pT2 categories only. Importantly, the MPP score could successfully define cases at risk in terms of metastatic disease in pT1-pT2 cancer where tumor thickness failed to exhibit a significant predictive value. Machine learning (ML) models incorporating the MPP score could predict the 5-year TCSS efficiently. Furthermore, we demonstrated that machine learning models that predict occult cervical lymph node involvement can benefit from including the MPP score. CONCLUSIONS: We introduced an objective, quantifiable, and observer-independent parameter, the MPP score, representing the aggressiveness of tumor growth and infiltration in TSCC. We showed its prognostic relevance especially in pT1-pT2 category TSCC, and its possible use in ML models predicting TCSS and occult lymph node metastases.

Comparison of mucus and serum biomarker sampling in chronic rhinosinusitis with nasal polyps.

OBJECTIVE: The objective of this study was to analyze advantages and disadvantages of mucus and serum for biomarker analysis. METHODS: This study includes prospective study of 61 CRS with nasal polyps patients who were followed over 24 months and over nine time points after functional endoscopic sinus surgery. At each time points, the nasal polyp score (NPS) was assessed and mucus as well as serum was collected. Selected were measured in mucus and serum. Mean, standard deviation and variance, undetectable values, and the correlation of the biomarkers to the NPS over time and to early recurrences were calculated, and the effect of surgery on the biomarkers was assessed. Additionally, the diurnal rhythm of all biomarkers was measures in order to assure stable biomarker values during sampling times. RESULTS: All biomarkers showed stable values during sampling times. Serum biomarker levels displayed higher percentages of undetectable values compared to mucus biomarkers. Mucus periostin (p < 0.001, r = 0.89), mucus IgE (p < 0.001, r = 0.51), serum periostin (p < 0.001, r = 0.53), mucus CST1 (p < 0.001, r = 0.27), and serum IgE (p < 0.01, r = -0.18) were the best marker and medium combinations to track the NPS over time and to predict recurrences. Mucus serpinF2 was negatively correlated and predicted early recurrences (p = 0.026, R2  = 0.015). CONCLUSIONS: Serum and mucus both represent viable mediums for "liquid biopsies." The most promising biomarker/medium combinations over time to track disease severity were mucus periostin, mucus IgE, serum periostin, mucus CST1, and serum IgE. Mucus serpinF2 was the best biomarker to predict early recurrences.

Surgical Versus Noninvasive Manual Repositioning After Cochlear Implant Partial Magnet Dislocation.

Objectives: To compare surgical magnet repositioning (SMR) and noninvasive manual magnet repositioning (MMR) as treatments for partial magnet dislocation (PMD) of the internal magnet in a cochlear implant (CI) caused by magnetic resonance imaging (MRI). The primary objective was the success rate, while the secondary objectives were total postinterventional CI downtime and complications. Methods: This single-center retrospective study was conducted at a tertiary referral medical center. Patients with CI treated for PMD between January 1, 2007 and September 30, 2022 were included. SMR served as primary treatment until June 2019 and as secondary treatment after the introduction of MMR. Results: A total of 51 cases of PMD were observed in 42 patients and 43 devices (18 ♀; 24 ♂; 12 with bilateral CI). MMR was performed successfully in 19 out of 20 cases (95%), while 32 cases were managed successfully by SMR. The median age at first magnet repositioning was 53.8 years (minimum 19 years, maximum 93 years). When MMR was performed, the mean time from diagnosis to treatment (0.5 ± 1.5 days vs 9.8 ± 7.6 days; P < .01), the mean time from repositioning to CI reactivation (1.4 ± 4.3 days vs 13.1 ± 6.7 days; P < .01), and the mean total CI downtime (1.9 ± 4.8 days vs 22.9 ± 11.9 days; P < .01) were significantly shorter compared to SMR. Significantly fewer complications were experienced with MMR [n = 0 (0%) vs n = 8 (25%); P = .04]. Conclusion: In case of PMD caused by MRI, noninvasive MMR shows a high success rate with a shorter total CI downtime as well as a lower complication rate compared to SMR. Therefore, MMR should be considered as first line treatment with SMR as a second option in case of failure.

A comparison between p16-positive head and neck cancer of unknown primary (HPV-HNCUP) and oropharyngeal squamous cell carcinoma (HPV-OPSCC): are they the same disease?

INTRODUCTION: The following study aimed to answer the question if HPV-HNCUP and HPV-OPSCC are the same disease. Propensity score matching (PSM) was used to compare the oncological outcomes of both groups, in particular the 5-year overall survival rate (OS), the 5-year disease specific survival rate (DSS) and the 5-year progression free survival rate (PFS). MATERIALS AND METHODS: Firstly, between January 1st, 2007, and March 31st, 2020 a total of 131 patients were treated with HNCUP at our Department. Out of these, 21 patients with a confirmed positive p16 status were referred to surgery followed by adjuvant therapy. Secondly, between January 1st, 2000, and January 31st, 2017, a total of 1596 patients were treated with an OPSSC at our Department. Out of these, 126 patients with a confirmed positive p16 status were referred to surgery followed by adjuvant therapy. After PSM, 84 patients with HPV-OPSCC and 21 HPV-HNCUP remained in the study for further comparison. RESULTS: The OS was 63.5% (95% CI 39.4-87.6) for HPV-HNCUP and 88.9% (95% CI 90.4-100.0) for HPV-OPSCC patients and therefore, significantly lower for the first mentioned (p = 0.013). The DSS was also significantly impaired for HPV-HNCUP (71.0%, 95% CI 46.3-95.7), in comparison with HPV-OPSCC patients (95.5%, 95% CI 90.4-100.0; p = 0.002). The PFS for HPV-HNCUP patients was lower (75.6%, 95% CI 54.0-97.2) yet not significantly different to HPV-OPSCC (90.4%, 95% CI 83.5-97.3; p = 0.067). CONCLUSIONS: The results presented demonstrate a significant reduced OS and DSS for HPV-HNCUP patients. Accordingly, in our study HPV-HNCUP and HPV-OPSCC are two different entities with a different oncological outcome.

Effect of postoperative systemic prednisolone on short-term and long-term outcomes in chronic rhinosinusitis with nasal polyps: A multi-centered randomized clinical trial.

Introduction: The objective of this study was to determine whether postoperative additive systemic steroid administration in chronic rhinosinusitis with nasal polyps (CRSwNP) impacted selected endoscopic, subjective and objective outcome measures. Methods: This was a prospective, randomized, double-blind, placebo-controlled, noninferiority multicenter trial of n=106 patients with CRSwNP. All patients underwent primary functional endoscopic sinus surgery (FESS) followed by topical nasal steroids. Patients were randomized to a systemic steroid or placebo for 1 month. Patients were followed up for 2 years over 9 time points. The primary outcome measures were the differences between groups with respect to the nasal polyp score (NPS) and sinonasal quality of life (SNQoL). Secondary outcome measures included interactions with respect to the Lund-Kennedy score (LKS), sinonasal symptoms, general quality of life (GQoL), 16-item odor identification test scores, recurrence rates, need for revision surgery and mucus biomarker levels. Results: 106 patients were randomized to either the placebo or the systemic steroid group (n=53 per group). Postoperative systemic steroids were not superior to placebo with respect to all primary (p= 0.077) and secondary outcome measures (p>0.05 for all). Reported adverse events were similar between the two groups. Conclusion: In conclusion, the addition of postoperative systemic steroids after primary FESS did not confer a benefit over topical steroid nasal spray alone with respect to NPS, SNQOL, LKS, GQOL, sinonasal symptoms, smell scores, recurrence rates, the need for revision surgery or biomarkers over a short-term follow-up of up to 9 months and a long-term follow-up of up to 24 months in CRSwNP patients. Functional endoscopic surgery did, however, show a strong effect on all outcome measures, which remained relatively stable up to the endpoint at 2 years.

Differences in Need for Opioids After Sinonasal Surgery at Day of Surgery and in the Postoperative Period.

INTRODUCTION: In the last years, the use of opioid analgesics has increased, as well as their morbidity and mortality, especially in the United States. Most patients after sinonasal surgery receive opioid analgesics, although up to 90% have leftover opioid pills. Around 70% of these patients keep the opioid analgesics, which could possibly lead to improper use. The objective of the following study was the investigation of the need for, use of, timing and side effects of opioid and non-opioid analgesics after sinonasal surgery. METHODS: This was a retrospective study of (n = 280) patients who underwent sinonasal surgery in the Otolaryngology Department of the University Erlangen-Nürnberg between January and December 2018. The postoperative pain (3-5 days after surgery) using the numeric rating scale and the postoperative need for on-demand opioids and non-opioid analgesics in relation to demographic and surgical parameters were evaluated. RESULTS: Of total, 59.64% of all patients received opioid analgesics postoperatively on the day of surgery. On the first postoperative day (POD1), the mean pain score yielded the highest values; however, only 0.71% of the patients needed opioid analgesics, and pain was sufficiently controlled with non-opioids or no pain medication at all. There was a significant reduction of the pain score from POD2 to 5 (P = .01; P < .01, respectively). Only 1.8% of the patients needed an opioid analgesic from POD1-5. Of total, 2.1% of the patients presented with a postoperative bleeding complication, and only 1 (0.4%) patient needed endoscopic coagulation. CONCLUSION: Our results indicate that the majority of patients need opioid analgesics almost exclusively on the day of surgery. There were no major complications in patients taking either opioid or non-opioids. Our results indicate that the postoperative pain regimen from POD1 should initially be started using non-opioid analgesics and be further escalated to opioid analgesics in individual cases.

Pneumoparotid: Practical impact of Surgeon performed Ultrasound in an effective Diagnostic Approach.

OBJECTIVES: Pneumoparotid is characterized by air inclusions in the parotid duct system. Use of ultrasound has proved valuable for evaluating air inclusions in various parts of the body; the diagnostics of this condition has not been systematically analyzed, however. The aim of this study was to evaluate the value of ultrasound in the detection of air inclusions along the parotid duct system and its closer characterization. METHODS: Retrospective analysis was carried out of patients diagnosed with pneumoparotid between 2005 and 2020 in a salivary gland center. Ultrasound was performed in all cases, and features of air inclusions were described. Reference standard was the clinical demonstration of foamy saliva after gland massage and/or sialendoscopic evidence of intraductal air inclusions. RESULTS: Twenty-one patients were identified (48.8 ± 3.8 years). Two were associated with wind instruments; seven were iatrogenic, following treatment for duct stenosis; one after radiotherapy; four with known bruxism and seven were idiopathic and without associated conditions. On ultrasound examination, pneumoparotid was characterized by three phenomena: flattened, mobile hyperechoic reflexes, dirty shadows with reverberation or "sunbeam effect," and shifting shadows during gland massage. CONCLUSIONS: Ultrasound was useful for characterizing pneumoparotid in a fast and practical way and could serve as imaging tool of first choice.

Analysis of CRSsNP Proteome Using a Highly Multiplexed Approach in Nasal Mucus.

BACKGROUND: Chronic rhinosinusitis without nasal polyps (CRSsNP) represents a phenotype of CRS, whose immunological mechanisms are still unclear. So far there are neither suitable biomarkers to determine the course of the disease nor an individual therapy. OBJECTIVE: The purpose of this study was to characterize the CRSsNP endotype by identifying and validating non-invasive proteomic biomarkers. METHODS: A highly-multiplexed proteomic array consisting of antibodies against 2000 proteins was used to identify proteins that are differentially expressed in the nasal mucus of the CRSsNP and control groups (n = 7 per group). The proteins identified to be most differentially expressed were validated in matched nasal mucus samples using western blots and enzyme-linked immunosorbent assay (ELISA). Validation was also done in a second cohort using western blots (CRSsNP n = 25, control n = 23) and ELISA (n = 30 per group). Additionally, immunohistochemistry in CRSsNP and control tissue samples was performed to characterize the selected proteins further. RESULTS: Out of the 2000 proteins examined, 7 from the most differentially expressed proteins were chosen to be validated. The validation results showed that 4 proteins were significantly upregulated in CRSsNP mucus, including macrophage inflammatory protein-1beta (MIP-1ß), resistin, high mobility group box 1 (HMGB1), and forkhead box protein 3 (FOXP3). Cartilage acidic protein 1 (CRTAC1) was not significantly upregulated. Two proteins were significantly downregulated including scavenger receptor class F member 2 (SCARF2) and P-selectin. All proteins selected are mainly associated with inflammation, cell proliferation/differentiation, apoptosis and cell-cell or cell-matrix interaction. CONCLUSION: Proteomic analysis of CRSsNP and control mucus has confirmed known and revealed novel disease-associated proteins that could potentially serve as a new biosignature for CRSsNP. Analysis of the associated pathways will specify endotypes of CRSsNP and will lead to an improved understanding of the pathophysiology of CRSsNP. Furthermore, our data contribute to the development of a reproducible, non-invasive, and quantitative "liquid biopsy" for rhinosinusitis.

Synthetic mucus for an ex vivo phonation setup: Creation, application, and effect on excised porcine larynges.

Laryngeal mucus hydrates and lubricates the deformable tissue of the vocal folds and acts as a boundary layer with the airflow from the lungs. However, the effects of the mucus' viscoelasticity on phonation remain widely unknown and mucus has not yet been established in experimental procedures of voice research. In this study, four synthetic mucus samples were created on the basis of xanthan with focus on physiological frequency-dependent viscoelastic properties, which cover viscosities and elasticities over 2 orders of magnitude. An established ex vivo experimental setup was expanded by a reproducible and controllable application method of synthetic mucus. The application method and the suitability of the synthetic mucus samples were successfully verified by fluorescence evidence on the vocal folds even after oscillation experiments. Subsequently, the impact of mucus viscoelasticity on the oscillatory dynamics of the vocal folds, the subglottal pressure, and acoustic signal was investigated with 24 porcine larynges (2304 datasets). Despite the large differences of viscoelasticity, the phonatory characteristics remained stable with only minor statistically significant differences. Overall, this study increased the level of realism in the experimental setup for replication of the phonatory process enabling further research on pathological mucus and exploration of therapeutic options.

Validation of a classification and scoring system for the diagnosis of laryngeal and pharyngeal squamous cell carcinomas by confocal laser endomicroscopy

Abstract Introduction: Confocal laser endomicroscopy is an optical imaging technique that allows in vivo, real-time, microscope-like images of the upper aerodigestive tract's mucosa. The assessment of morphological tissue characteristics for the correct differentiation between healthy and malignant suspected mucosa requires strict evaluation criteria. Objective: This study aims to validate an eight-point score for the correct assessment of malignancy. Methods: We performed confocal laser endomicroscopy between March and October 2020 in 13 patients. 197 sequences (11.820 images) originated from the marginal area of pharyngeal and laryngeal carcinomas. Specimens were taken at corresponding locations and analyzed in H&E staining as a standard of reference. A total of six examiners evaluated the sequences based on a scoring system; they were blinded to the histopathological examination. The primary endpoints are sensitivity, specificity, and accuracy. Secondary endpoints are interrater reliability and receiver operator characteristics. Results: Healthy mucosa showed epithelium with uniform size and shape with distinct cytoplasmic membranes and regular vessel architecture. Confocal laser endomicroscopy of malignant cells demonstrated a disorganized arrangement of variable cellular morphology. We calculated an accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of 83.2%, 81.3%, 85.5%, 86.7%, and 79.7%, respectively, with a κ-value of 0.64, and an area under the curve of 0.86. Conclusion: The results confirm that this scoring system is applicable in the laryngeal and pharyngeal mucosa to classify benign and malignant tissue. A scoring system based on defined and reproducible characteristics can help translate this experimental method to broad clinical practice in head and neck diagnosis.

Evaluation of Respiratory Particle Emission during Otorhinolaryngological Procedures in the Context of the SARS-CoV-2 Pandemic.

Understanding the risk of infection by routine medical examination is important for the protection of the medical personnel. In this study we investigated respiratory particles emitted by patients during routine otolaryngologic procedures and assessed the risks for the performing physician. We developed two experimental setups to measure aerosol and droplet emission during rigid/flexible laryngoscopy, rhinoscopy, pharyngoscopy, otoscopy, sonography and patient interview for subjects with and without masks. A high-speed-camera setup was used to detect ballistic droplets (approx. > 100 µm) and an aerosol-particle-sizer was used to detect aerosol particles in the range of 0.3 µm to 10 µm. Aerosol particle counts were highly increased for coughing and slightly increased for heavy breathing in subjects without masks. The highest aerosol particle counts occurred during rigid laryngoscopy. During laryngoscopy and rhinoscopy, the examiner was exposed to increased particle emission due to close proximity to the patient's face and provoked events such as coughing. However, even during sonography or otoscopy without a mask, aerosol particles were expelled close to the examiner. The physician's exposure to respiratory particles can be reduced by deliberate choice of examination technique depending on medical indication and the use of appropriate equipment for the examiners and the patients (e.g., FFP2 masks for both).

Cystatin SN is a potent upstream initiator of epithelial-derived type 2 inflammation in chronic rhinosinusitis.

BACKGROUND: Cystatin SN (CST1) and cystatin SA (CST2) are cysteine protease inhibitors that protect against allergen, viral, and bacterial proteases. Cystatins are overexpressed in the setting of allergic rhinitis and chronic rhinosinusitis with nasal polyps (CRSwNP); however, their role in promoting type 2 inflammation remains poorly characterized. OBJECTIVE: The purpose of this study was to use integrated poly-omics and a murine exposure model to explore the link between cystatin overexpression in CRSwNP and type 2 inflammation. METHODS: In this institutional review board- and institutional animal care and use committee-approved study, we compared tissue, exosome, and mucus CST1 and CST2 between CRSwNP and controls (n = 10 per group) by using matched whole exome sequencing, transcriptomic, proteomic, posttranslational modification, histologic, functional, and bioinformatic analyses. C57/BL6 mice were dosed with 3.9 µg/mL of CST1 or PBS intranasally for 5 to 18 days in the presence or absence of epithelial ABCB1a knockdown. Inflammatory cytokines were quantified by using Quansys multiplex assays or ELISAs. RESULTS: Of the 1305 proteins quantified, CST1 and CST2 were among the most overexpressed protease inhibitors in tissue, exosome, and mucus samples; they were localized to the epithelial layer. Multiple posttranslational modifications were identified in the polyp tissue. Exosomal CST1 and CST2 were strongly and significantly correlated with eosinophils and Lund-Mackay scores. Murine type 2 cytokine secretion and TH2 cell infiltration increased in a time-dependent manner following CST1 exposure and was abrogated by epithelial knockdown of ABCB1a, a regulator of epithelial cytokine secretion. CONCLUSION: CST1 is a potent upstream initiator of epithelial-derived type 2 inflammation in CRSwNP. Therapeutic strategies targeting CST activity and its associated posttranslational modifications deserve further interrogation.

Systematic classification of confocal laser endomicroscopy for the diagnosis of oral cavity carcinoma.

INTRODUCTION: Confocal laser endomicroscopy (CLE) is an optical imaging technique that allows in vivo microscope-like images of the upper aerodigestive tract's mucosa in 1000-fold magnification. The assessment of morphological tissue characteristics for the correct differentiation between healthy and malignoma suspected mucosa requires strict evaluation criteria. This study aims to validate a score for oral cavity squamous cell carcinoma (OCSCC) diagnostic. METHODS: We performed CLE and examined a total of twelve patients. All 95 sequences (778 s, 6224 images) originate from the area of the primary tumor 260 s, 2080 images) and unsuspicious mucosa of the oral cavity (518 s, 4144 images). Specimen were taken at corresponding locations and analyzed histologically in H&E staining as a reference standard. A total of eight examiners (four experienced and four inexperienced) evaluated the sequences based on a scoring system. The primary endpoints are sensitivity, specificity, and accuracy. Secondary endpoints are inter-rater reliability and receiver operator characteristics. RESULTS: Healthy mucosa showed epithelium with uniform size and shape with distinct cytoplasmic membranes and regular vessel architecture. CLE of malignant cells demonstrated a disorganized arrangement of variable cellular morphology. We calculated an accuracy, sensitivity, specificity, PPV, and NPV of 88.7 %, 90.1 %, 87.4 %, 87.5 %, and 90.0 %, respectively, with inter-rater reliability and κ-value of 0.775, and an area under the curve of 0.935. CONCLUSIONS: The results confirm that this scoring system is applicable in the oral cavity mucosa to classify benign and malignant tissue.

Radio(chemo)therapy in anaplastic thyroid cancer-high locoregional but low distant control rates-a monocentric analysis of a tertiary referral center.

BACKGROUND: Anaplastic thyroid cancer (ATC) is a lethal disease with highly aggressive disease progression. This study analyses the influence of radio(chemo)therapy, R(C)T, on disease control, survival rates and predictors for survival. PATIENTS AND METHODS: A total of 33 patients with ATC, treated at a tertiary referral center between May 2001 and April 2020 were included. Univariate and multivariate analysis were used to investigate correlates of R(C)T and predictors on disease control and survival rates. RESULTS: Median follow-up was 4 months. In UICC stage IVA and IVB median overall survival (OS) was 8 months, median progression-free survival (PFS) was 6 months. Patients with UICC stage IVA and IVB and patients being irradiated with a radiation dose of more than 60 Gy showed increased OS. Of these patients, 3 were alive and free from disease. All of them receiving cisplatin-based radiochemotherapy and a minimum radiation dose of 66 Gy. UICC stage IVC showed a median OS of 2.5 months and a median PFS of 1 month. Only 2 of 16 patients had local failure. CONCLUSION: Depending on UICC stage, RT with high radiation dose can lead to improved OS or at least higher locoregional control. A limiting factor is the high incidence of distant metastases; therefore modern systemic treatment options should be integrated into multimodal therapy concepts.