Impact of 18F-FDG PET Intensity Normalization on Radiomic Features of Oropharyngeal Squamous Cell Carcinomas and Machine Learning-Generated Biomarkers.

We aimed to investigate the effects of 18F-FDG PET voxel intensity normalization on radiomic features of oropharyngeal squamous cell carcinoma (OPSCC) and machine learning-generated radiomic biomarkers. Methods: We extracted 1,037 18F-FDG PET radiomic features quantifying the shape, intensity, and texture of 430 OPSCC primary tumors. The reproducibility of individual features across 3 intensity-normalized images (body-weight SUV, reference tissue activity ratio to lentiform nucleus of brain and cerebellum) and the raw PET data was assessed using an intraclass correlation coefficient (ICC). We investigated the effects of intensity normalization on the features' utility in predicting the human papillomavirus (HPV) status of OPSCCs in univariate logistic regression, receiver-operating-characteristic analysis, and extreme-gradient-boosting (XGBoost) machine-learning classifiers. Results: Of 1,037 features, a high (ICC ≥ 0.90), medium (0.90 > ICC ≥ 0.75), and low (ICC < 0.75) degree of reproducibility across normalization methods was attained in 356 (34.3%), 608 (58.6%), and 73 (7%) features, respectively. In univariate analysis, features from the PET normalized to the lentiform nucleus had the strongest association with HPV status, with 865 of 1,037 (83.4%) significant features after multiple testing corrections and a median area under the receiver-operating-characteristic curve (AUC) of 0.65 (interquartile range, 0.62-0.68). Similar tendencies were observed in XGBoost models, with the lentiform nucleus-normalized model achieving the numerically highest average AUC of 0.72 (SD, 0.07) in the cross validation within the training cohort. The model generalized well to the validation cohorts, attaining an AUC of 0.73 (95% CI, 0.60-0.85) in independent validation and 0.76 (95% CI, 0.58-0.95) in external validation. The AUCs of the XGBoost models were not significantly different. Conclusion: Only one third of the features demonstrated a high degree of reproducibility across intensity-normalization techniques, making uniform normalization a prerequisite for interindividual comparability of radiomic markers. The choice of normalization technique may affect the radiomic features' predictive value with respect to HPV. Our results show trends that normalization to the lentiform nucleus may improve model performance, although more evidence is needed to draw a firm conclusion.

[Revision surgery after stapedectomy]. / Revisionsoperationen nach Stapesplastik.

Revision stapes surgery is considered to be significantly more demanding than primary stapes surgery, both in terms of the indication and the surgical approach. This article reviews common indications for revision after stapedectomy as well as the surgical approaches and intraoperative findings. A distinction is made between revision surgeries, which are usually carried out because of conductive hearing loss a long time after stapes surgery, and acute or subacute revisions that become necessary in the immediate postoperative course. With the shortening of postoperative observation times under inpatient conditions as a result of increasing economization and the associated shift of the immediate postoperative phase to the outpatient setting, the recognition of postoperative irregularities is also becoming increasingly important for otorhinolaryngologists in private practice, even if they do not perform these highly specialized interventions themselves.

Primary injection laryngoplasty after chordectomy for small glottic carcinomas.

OBJECTIVES: The purpose of this study was to analyze the short- and middle-term effects of primary injection laryngoplasty in patients having tumor resection within the same surgery concerning the vocal outcome. Injection laryngoplasty was performed after harvesting autologous adipose tissue via lipoaspiration. METHODS: A prospective study was performed with 16 patients (2 female; 14 male) who received tumor resection and an injection laryngoplasty using autologous adipose tissue during a single stage procedure. Multidimensional voice evaluation including videostroboscopy, patient self-assessment, voice perception, aerodynamics, and acoustic parameters was performed preoperatively, as well as 1.5, 3 and 6 months postoperatively. RESULTS: Results show an improvement in the roughness-breathiness-hoarseness (RBH) scale, voice dynamics and subjective voice perception 6 months postoperatively. Maintenance of Voice Handycap Index, jitter and shimmer could be observed 6 months postoperatively. There was no deterioration in RBH and subjective voice perception 2 and 6 weeks postoperatively. No complications occurred in the fat harvesting site. CONCLUSIONS: Using the lipoaspiration and centrifugation approach, primary fat injection laryngoplasty shows short-term maintenance und middle-term improvement in voice quality in patients with vocal fold defect immediately after chordectomy 6 months postoperatively. Cancer recurrence rate is comparable to the reported cancer recurrence rate for laryngeal carcinoma and thus not elevated through primary augmentation.

A Rejected Hypothesis: Phenomenon of High Treatment Adherence in Direct-to-Consumer Teledermatology Despite Lack of Direct Physician-Patient Interaction.

Background: Adherence to dermatological treatment is described as poor. Empathy and open communication in the physician-patient relationship has been proven to improve adherence. As direct-to-consumer teledermatology enables patients to access dermatological consultations without in-person interactions, we hypothesized treatment adherence in teledermatology to be low. Methods: The objective of the study was to examine treatment adherence in teledermatology. This retrospective cross-sectional study used data from patients treated through a German direct-to-consumer teledermatology platform between July 2021 and April 2022. Additional information was collected through voluntary follow-up questionnaires provided to patients to assess individual treatment success, treatment-related adverse events, and treatment adherence. Results: Data collection included 771 patients; 61.6% (475/771) were women (mean age 35 years). In 46% (355/771), skin disease had been present for <3 months before teleconsultation. Of all patients who answered the follow-up questionnaire (n = 228), 28.5% (65/228) reported treatment-related adverse events, with skin dryness being the most common (56.9%, 37/65). Adverse events resulting in treatment discontinuation were reported in 1.3% (3/228) of all cases. Improvement in skin condition on therapy was described by 75.4% (172/228). In 85.5% (195/228), full treatment adherence was reported. Conclusion: This is the first study worldwide to examine data on treatment adherence in direct-to-consumer-teledermatology. Despite the lack of doctor-patient interaction, the results of our study demonstrate that most patients show high treatment adherence. Possible drivers contributing to high compliance rates could be the high proportion of new-onset skin diseases, the high treatment success of the prescribed therapies, and the low rate of serious adverse events.

Misjudgment of Skills in Clinical Examination Increases in Medical Students Due to a Shift to Exclusively Online Studies during the COVID-19 Pandemic.

In medical school, practical capacity building is a central goal. During the COVID-19 pandemic, a shift to online teaching methods in university was mandated in many countries to reduce risk of SARS-CoV-2 transmission. This severely affected the teaching of psychomotor ability skills such as head and neck examination skills, resulting in a share of students that have only been taught such ENT-specific examination skills with online courses; our study aimed to measure performance and capacity of self-evaluation in these students. After completing a new extensive online Ear Nose Throat (ENT) examination course, we conducted a standardized clinical skills exam for nine different ENT examination items with 31 students. Using Likert scales, self-evaluation was based on questionnaires right before the clinical skills exam and objective evaluation during the exam was assessed following a standardized regime. Self-evaluation and objective evaluation were correlated. To compare the exclusive online teaching to traditional hands-on training, a historic cohort with 91 students was used. Objective examination performance after in-classroom or online teaching varied for single examination items while overall assessment remained comparable. Overall, self-evaluation did not differ significantly after online-only and in-classroom ENT skill teaching. Nevertheless, misjudgment of one's skill level increased after online-only training compared to in-classroom teaching. Highest levels of overestimation were observed after online training in simple tasks. While gender and interest in ENT did not influence self-evaluation and misjudgment, higher age of participants was associated with an overestimation of skills. Medical students with online-only training during the COVID-19 pandemic achieved similar ENT examination skills to those with traditional on-campus training before the pandemic. Nevertheless, students with online-only training were more prone to misjudge their skills when they assessed their skills. Due to the COVID-19 pandemic, current medical students and graduates might therefore lack individual specific psychomotor skills such as the ENT examination, underlining the importance of presence-based teaching.

[Child with a vascularized throat mass]. / Kind mit gefäßreichem "Kloß" im Hals.

We report the case of an 11-year-old girl with difficultly speaking and a history of singular, self-limiting oral bleeding. Clinical and radiological examination in the emergency room showed a vascularized tumor of the base of the tongue, which almost completely occluded the oropharynx. After complex anesthesiologic preparation and endoluminal embolization, the tumor was safely removed by transoral laser microsurgery. Histology revealed a rare benign schwannoma of the oropharynx. Further clinical examinations and genetic screening were recommended.

[Artificial intelligence in otorhinolaryngology]. / Künstliche Intelligenz in der Hals-Nasen-Ohren-Heilkunde.

BACKGROUND: The continued advancement of digitalization increasingly allows deployment of artificial intelligence (AI) algorithms, leveraging profound effects on society and medicine. OBJECTIVE: This article aims to provide an overview of current developments and futures perspectives of AI in otorhinolaryngology. MATERIALS AND METHODS: Scientific studies and expert analyses were evaluated and discussed. RESULTS: AI can increase the value of current diagnostic tools in otorhinolaryngology and enhance surgical precision in head and neck surgery. CONCLUSION: AI has the potential to further improve diagnostic and therapeutic procedures in otorhinolaryngology. This technology, however, is associated with challenges, for example in the domain of privacy and data security.

[ToSkORL: self- and objective assessment of examination skills in the head and neck region]. / ToSkORL: Selbst- und Fremdeinschätzung bei der Untersuchung des Kopf-Hals-Bereichs.

BACKGROUND: A central goal of medical school is acquisition of theoretical and practical competences. However, evidence on how capacity acquisition can be measured for special examination techniques is scarce. ToSkORL (Teaching of Skills in Otorhinolaryngology) is a project aimed at scientifically and didactically investigating students' self-evaluation skills in otorhinolaryngologic and head and neck examination techniques. METHODS: During the examination techniques course, a standardized oral and practical exam for nine different techniques was conducted. Using Likert scales, self-evaluation was based on questionnaires before the clinical skills exam and objective evaluation was performed by the examiners during the examination using a checklist. Self- and objective evaluation were correlated. Nine different examination skills were assessed 42 times each by a total of 91 students. RESULTS: Self-evaluation of competence in the different examination skills varied widely. Nevertheless, self- and objective evaluation correlated well overall, independent of age and gender. Students highly interested in otorhinolaryngology rated their own skills higher but tended toward overestimation. For examination items with intermediate difficulty, the highest divergences between self- and objective evaluation were found. CONCLUSION: Student self-evaluations are an appropriate instrument for measuring competences in otorhinolaryngologic examinations. Instructors should focus on items with allegedly intermediate difficulty, which are most often over- and underestimated.

Cannabinoid Receptor 2 Agonism is Capable of Preventing Lipopolysaccharide Induced Decreases of Cochlear Microcirculation - A Potential Approach for Inner Ear Pathologies.

HYPOTHESIS: The ability of JWH-133, an agonist at the cannabinoid receptor 2, to abrogate the effects of lipopolysaccharide on cochlear microcirculation was investigated. BACKGROUND: Cochlear inflammation and subsequent impairment of microcirculation is part of numerous pathologies affecting inner ear function, including suppurative labyrinthitis, noise trauma, and sudden sensorineural hearing loss. One way of causing cochlear inflammation is exposing the cochlea to lipopolysaccharide, a bacterial endotoxin. METHODS: Twenty Dunkin-hartley guinea pigs were divided into four groups of five animals each. Two groups received topic treatment with JWH-133 and two received treatment with placebo. One group that had been treated with JWH-133 and one with placebo were then exposed to lipopolysaccharide or placebo, respectively. Cochlear microcirculation was quantified before, in between and after treatments by in vivo fluorescence microscopy. RESULTS: Significantly different changes in cochlear blood flow were only seen in the group that was treated with placebo and subsequently lipopolysaccharide. Every other group showed no significant change in cochlear blood flow. CONCLUSION: JWH-133 is capable of abrogating the effects of lipopolysaccharide on cochlear microcirculation. It may therefore be clinical interest in treating numerous inflammation associated cochlear pathologies.

Human Adipose-Derived Stem/Stromal Cells Promote Proliferation and Migration in Head and Neck Cancer Cells.

Human adipose-derived stem/stromal cells (ASCs) are increasingly used as auto-transplants in regenerative medicine to restore tissue defects or induce wound healing, especially in cancer patients. The impact of ASCs on squamous cell carcinoma of the upper aerodigestive tract (UAT) including head and neck and esophageal squamous cell carcinoma (HNSCC and ESCC) is not yet fully understood. ASCs were cultured from subcutaneous, abdominal lipoaspirates of five patients, who received auto-transplants to the head and neck. Supernatants were tested for paracrine effects in functional in vitro assays of proliferation of HNSCC tumor cell line FaDu and ESCC cell line Kyse30, and their cell migration/invasion capacities in Boyden chambers, in addition to endothelial tube formation assay using human umbilical vein endothelial cells (HUVECs). All ASC-derived supernatants enhanced proliferation of FaDu cells, invasive migration, and tube formation by HUVECs, compared to controls. Of five patients' lipoaspirates, ASC-derived supernatants of four patients increased proliferation and invasive migration in Kyse30 cells. The data suggests that ASCs can promote tumor cell proliferation, invasiveness, and neo-angiogenesis in these tumor cell lines of the UAT and HUVEC in a paracrine manner. Although clinical studies on the subject of oncological safety are still needed, these findings emphasize the importance of complete tumor removal before ASCs are used in the head and neck.

Discrimination of Cancer Stem Cell Markers ALDH1A1, BCL11B, BMI-1, and CD44 in Different Tissues of HNSCC Patients.

Cancer stem cells (CSCs) are accountable for the progress of head and neck squamous cell carcinoma (HNSCC). This exploratory study evaluated the expression of molecular CSC markers in different tissues of HNSCC patients. Tissue specimens of primary tumor, lymph node metastases and macroscopically healthy mucosa of 12 consecutive HNSCC patients, that were treated with surgery and adjuvant radio(chemo)therapy upon indication, were collected. Samples were assessed for the expression of p16 as a surrogate for HPV-related disease and different molecular stem cell markers (ALDH1A1, BCL11B, BMI-1, and CD44). In the cohort, seven patients had HPV-related HNSCC; six thereof were oropharyngeal squamous cell carcinoma. While expression of BMI-1 and BCL11B was significantly lower in healthy mucosa than both tumor and lymph node metastasis, there were no differences between tumor and lymph node metastasis. In the HPV-positive sub-cohort, these differences remained significant for BMI-1. However, no significant differences in these three tissues were found for ALDH1A1 and CD44. In conclusion, this exploratory study shows that CSC markers BMI-1 and BCL11B discriminate between healthy and cancerous tissue, whereas ALDH1A1 and CD44 were expressed to a comparable extent in healthy mucosa and cancerous tissues.

Stapes and Stapes Revision Surgery: Preoperative Air-Bone Gap Is a Prognostic Marker.

OBJECTIVE: Stapes surgery is considered an effective treatment in otosclerosis, but controversy remains regarding predictors of surgical outcome. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary referral center. PATIENTS: One hundred sixty three cases of stapes surgery between 2012 and 2019 were reviewed. MAIN OUTCOME MEASURES: Primary outcome measures were relative hearing improvement (relHI), defined as preoperative minus postoperative air conduction divided by preoperative air-bone gap (ABG), as well as relative ABG closure (relABGc), defined as preoperative ABG minus postoperative ABG divided by preoperative ABG. Univariate and multivariate linear regression analyses were performed to determine independent predictors for these outcomes. RESULTS: Higher preoperative bone conduction (BC) and primary surgery (compared with revision) were independently associated with increased relHI (p = 0.001 and p = 0.004, respectively). Lower preoperative BC, higher preoperative ABG, primary surgery, and age were independently associated with increased relABGc (p = 0.0030, p < 0.001, p = 0.0214, and p = 0.0099, respectively). Sex did not predict surgical outcome. In patients with less than 20 dB preoperative ABG, likelihood of negative relABGc was increased (compared with 20-30 dB or >30 dB preoperative ABG, p = 0.0292, Fisher's exact test). This tendency was not significant for relHI (p = 0.074). CONCLUSIONS: Our findings demonstrate that calculating HI and ABGc in relation to preoperative ABG can reliably predict outcomes of stapes surgery. Both primary and revision stapes surgery are effective treatment options, but relative improvement is higher in primary cases. Preoperative BC, preoperative ABG, and age predict surgical outcomes as well. Otosclerosis patients with low preoperative ABG, especially less than 20 dB, should be counseled and selected cautiously regarding stapes surgery.

Prediction of post-radiotherapy locoregional progression in HPV-associated oropharyngeal squamous cell carcinoma using machine-learning analysis of baseline PET/CT radiomics.

Locoregional failure remains a therapeutic challenge in oropharyngeal squamous cell carcinoma (OPSCC). We aimed to devise novel objective imaging biomarkers for prediction of locoregional progression in HPV-associated OPSCC. Following manual lesion delineation, 1037 PET and 1037 CT radiomic features were extracted from each primary tumor and metastatic cervical lymph node on baseline PET/CT scans. Applying random forest machine-learning algorithms, we generated radiomic models for censoring-aware locoregional progression prognostication (evaluated by Harrell's C-index) and risk stratification (evaluated in Kaplan-Meier analysis). A total of 190 patients were included; an optimized model yielded a median (interquartile range) C-index of 0.76 (0.66-0.81; p = 0.01) in prognostication of locoregional progression, using combined PET/CT radiomic features from primary tumors. Radiomics-based risk stratification reliably identified patients at risk for locoregional progression within 2-, 3-, 4-, and 5-year follow-up intervals, with log-rank p-values of p = 0.003, p = 0.001, p = 0.02, p = 0.006 in Kaplan-Meier analysis, respectively. Our results suggest PET/CT radiomic biomarkers can predict post-radiotherapy locoregional progression in HPV-associated OPSCC. Pending validation in large, independent cohorts, such objective biomarkers may improve patient selection for treatment de-intensification trials in this prognostically favorable OPSCC entity, and eventually facilitate personalized therapy.

Role of cancer stem cell markers ALDH1, BCL11B, BMI-1, and CD44 in the prognosis of advanced HNSCC.

PURPOSE: Cancer stem cells (CSCs) are held accountable for the progress of head and neck squamous cell carcinoma (HNSCC). In the presented study, the authors evaluated the prognostic value of CSC markers in two particular HNSCC cohorts. METHODS: This two cohort study consisted of 85 patients with advanced stage HNSCC, treated with primary radio(chemo)therapy (pRCT), and 95 patients with HNSCC, treated with surgery and partially adjuvant radio(chemo)therapy. Overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) were assessed. Samples were assessed for the expression of different molecular stem cell markers (ALDH1, BCL11B, BMI­1, and CD44). RESULTS: In the pRCT cohort, none of the baseline patient and tumor features exhibited a statistically significant relation with survival in either the cohort or the human papillomavirus (HPV)-stratified subcohorts. High expression of BMI­1 significantly decreased OS and DFS, while high expression of CD44 decreased all modes of survival. Multivariate analysis showed significant prognostic influence for all tested CSC markers, with high BMI­1 and CD44 decreasing survival (BMI-1: OS, DFS, DSS; CD44: OS, DFS) and high ALDH1 and BCL11B showing a beneficial effect on survival (ALDH1: OS, DFS; BCL11B: OS, DSS). In the surgical cohort, classical prognosticators such as HPV status, R1 resection, and nodal status in HPV-negative HNSCC played a significant role, but the tested CSC markers showed no significant effect on prognosis. CONCLUSION: Although validation in independent cohorts is still needed, testing for CSC markers in patients with advanced or late stage HNSCC might be beneficial, especially if many comorbidities exist or disease is irresectable. The findings might guide the development and earlier use of targeted therapies in the future.

Potential Added Value of PET/CT Radiomics for Survival Prognostication beyond AJCC 8th Edition Staging in Oropharyngeal Squamous Cell Carcinoma.

Accurate risk-stratification can facilitate precision therapy in oropharyngeal squamous cell carcinoma (OPSCC). We explored the potential added value of baseline positron emission tomography (PET)/computed tomography (CT) radiomic features for prognostication and risk stratification of OPSCC beyond the American Joint Committee on Cancer (AJCC) 8th edition staging scheme. Using institutional and publicly available datasets, we included OPSCC patients with known human papillomavirus (HPV) status, without baseline distant metastasis and treated with curative intent. We extracted 1037 PET and 1037 CT radiomic features quantifying lesion shape, imaging intensity, and texture patterns from primary tumors and metastatic cervical lymph nodes. Utilizing random forest algorithms, we devised novel machine-learning models for OPSCC progression-free survival (PFS) and overall survival (OS) using "radiomics" features, "AJCC" variables, and the "combined" set as input. We designed both single- (PET or CT) and combined-modality (PET/CT) models. Harrell's C-index quantified survival model performance; risk stratification was evaluated in Kaplan-Meier analysis. A total of 311 patients were included. In HPV-associated OPSCC, the best "radiomics" model achieved an average C-index ± standard deviation of 0.62 ± 0.05 (p = 0.02) for PFS prediction, compared to 0.54 ± 0.06 (p = 0.32) utilizing "AJCC" variables. Radiomics-based risk-stratification of HPV-associated OPSCC was significant for PFS and OS. Similar trends were observed in HPV-negative OPSCC. In conclusion, radiomics imaging features extracted from pre-treatment PET/CT may provide complimentary information to the current AJCC staging scheme for survival prognostication and risk-stratification of HPV-associated OPSCC.

PET/CT radiomics signature of human papilloma virus association in oropharyngeal squamous cell carcinoma.

PURPOSE: To devise, validate, and externally test PET/CT radiomics signatures for human papillomavirus (HPV) association in primary tumors and metastatic cervical lymph nodes of oropharyngeal squamous cell carcinoma (OPSCC). METHODS: We analyzed 435 primary tumors (326 for training, 109 for validation) and 741 metastatic cervical lymph nodes (518 for training, 223 for validation) using FDG-PET and non-contrast CT from a multi-institutional and multi-national cohort. Utilizing 1037 radiomics features per imaging modality and per lesion, we trained, optimized, and independently validated machine-learning classifiers for prediction of HPV association in primary tumors, lymph nodes, and combined "virtual" volumes of interest (VOI). PET-based models were additionally validated in an external cohort. RESULTS: Single-modality PET and CT final models yielded similar classification performance without significant difference in independent validation; however, models combining PET and CT features outperformed single-modality PET- or CT-based models, with receiver operating characteristic area under the curve (AUC) of 0.78, and 0.77 for prediction of HPV association using primary tumor lesion features, in cross-validation and independent validation, respectively. In the external PET-only validation dataset, final models achieved an AUC of 0.83 for a virtual VOI combining primary tumor and lymph nodes, and an AUC of 0.73 for a virtual VOI combining all lymph nodes. CONCLUSION: We found that PET-based radiomics signatures yielded similar classification performance to CT-based models, with potential added value from combining PET- and CT-based radiomics for prediction of HPV status. While our results are promising, radiomics signatures may not yet substitute tissue sampling for clinical decision-making.

Oropharyngeal HPV Detection Techniques in HPV-associated Head and Neck Cancer Patients.

BACKGROUND/AIM: The incidence of human papilloma virus (HPV)-related head and neck squamous cell carcinoma (HNSCC) has been increasing in the last decades. Analysis of oral brushing or rinsing samples for screening or stratification could potentially improve screening and prevention. PATIENTS AND METHODS: Oral brushes and mouthwashes were taken from 20 patients with HPV-associated HNSCC before definite therapy. HPV genotyping was performed for the detection of 14 high-risk HPV subtypes and correlated to DNA isolated from tumor tissue. RESULTS: Ten of 20 patients were tested HPV positive by using either method. There was a significant correlation between macroscopic visibility of tumor and positive HPV detection (p<0.001) and HPV detection and tumor size (p<0.001). HPV was detected in all macroscopically visible tumors. Half of the HPV cases who had macroscopically invisible tumors were missed by both methods. CONCLUSION: Both techniques are limited in the detection of macroscopically non-visible and small tumors. Therefore, the application of these techniques for screening or diagnosis of HNSCC is not recommended.