The extent of androgen receptor and HER2 expression allows for targeted therapy in most cases of salivary duct carcinoma: analysis of clinical and histopathological data in a tertiary care center.

PURPOSE: The incidence of salivary duct carcinoma (SDC) seems to be underestimated due to inaccurate classification. Further, the frequency of SDC patients with targeted therapy options according to current guidelines is unclear. Therefore, this study aimed at (a) describing the proportion of SDC among salivary gland carcinoma (SGC) before and after reclassification of cases initially classified as adenocarcinoma, not otherwise specified (ANOS); and (b) quantifying the frequency of SDC patients with targeted therapy options. METHODS: All patients with SDC or ANOS treated in a tertiary care center between 1996 and 2023 were identified. Histopathological diagnosis was verified for patients primarily diagnosed with SDC and reviewed for patients initially diagnosed with ANOS. Clinical data for SDC patients were retrieved from clinical charts. Immunohistochemical (IHC) androgen receptor (AR) and HER2 staining was performed. RESULTS: Among 46 SDC, 34 were primarily diagnosed as SDC and 12 had initially been classified as ANOS. The proportion of SDC among SGC was 12.1% and was rising when comparing the time periods 2000-2015 (7.1-11.5%) versus 2016-2023 (15.4-18.1%). Nuclear AR staining in > 70% of tumor cells was found in 56.8% and HER2 positivity (IHC 3 +) in 36.4% of cases. 70.5% of patients showed AR staining in > 70% of tumor cells and/or HER2 positivity and therefore at least one molecular target. 5-year overall and disease-free survival (DFS) were 62.8% and 41.0%. Multivariate Cox regression revealed positive resection margins (HR = 4.0, p = 0.03) as independent negative predictor for DFS. CONCLUSIONS: The results suggest a rising SDC incidence and show that the extent of the AR and HER2 expression allows for targeted therapy in most SDC cases.

Nectin-4 is frequently expressed in primary salivary gland cancer and corresponding lymph node metastases and represents an important treatment-related biomarker.

Many locally advanced and metastatic salivary gland carcinomas (SGC) lack therapeutic targets. Enfortumab vedotin, an antibody-drug conjugate binding to Nectin-4, recently gained FDA approval for third-line urothelial carcinoma. Therefore, the aim of this study was to assess the expression of Nectin-4 in primary SGC and corresponding lymph node metastases and to correlate it with clinicopathological data. Immunohistochemical staining for Nectin-4 was performed for patients who had undergone surgery with curative intent for primary SGC of the parotid or submandibular gland in a tertiary referral center between 1990 and 2019. One hundred twenty-two primary SGC and twenty corresponding lymph node metastases were included. Nectin-4 was expressed in 80.3% of primary SGC with a mean Histo(H-)score of 61.2 and in 90.0% of lymph node metastases with a mean H-score of 75.6. A moderate or high Nectin-4 expression was found in 25.9% of salivary duct carcinomas (SaDu) and in 30.7% of adenoid cystic carcinomas (ACC). SaDu patients with a lower T-stage (p = 0.04), no loco-regional lymph node metastases (p = 0.049), no vascular invasion (p = 0.04), and no perineural spread (p = 0.03) showed a significantly higher mean Nectin-4 H-score. There was a statistical tendency towards a more favorable disease-free survival among SaDu patients with a higher Nectin-4 expression (p = 0.09). Nectin-4 is expressed in SGC and therefore represents a potential therapeutic target, especially in entities with a high rate of local recurrence and metastatic spread such as SaDu and ACC.

Analysis of the Quality of Parotidectomy Videos on YouTube Using the IVORY-Grading-System.

OBJECTIVE: The aim of this study was to evaluate the quality and the educational content of YouTube videos showing parotidectomy. METHODS: We searched for videos displaying parotidectomy on YouTube. To rate parotidectomy videos, we introduced the "Instructional Videos in Otorhinolaryngology by YO-IFOS (IVORY)-grading-system (GS)" derived from the IVORY Guidelines, which pose established consensus recommendations for the production of educational surgical videos in otolaryngology. The videos were rated using the IVORY-GS, and the total score was tested for statistical association with views, likes, likes/dislikes-ratio, age, and length of the videos for validation of the IVORY-GS. RESULTS: Overall, 50 parotidectomy videos were identified. Sixty-eight (68%) of the videos showed a superficial parotidectomy. The mean IVORY-GS total score was 24.9 (out of a maximum of 44 points). Video education quality was rated as moderate in 22% and high in 4%. There was a statistically significant correlation between the total score and the number of views (p = 0.03), the total score and the number of likes (p < 0.01), and the total score and the likes/dislikes ratio (p < 0.01). A higher total score was a significant predictor of more likes (p = 0.01) and a higher likes/dislikes ratio (p < 0.01). CONCLUSION: Our modification of the IVORY Guidelines is otolaryngology-specific, suitable, and recommended to evaluate parotidectomy videos. To date, most videos are of poor educational quality. Future efforts in otolaryngology surgical video education could focus on the establishment of an online video platform. LEVEL OF EVIDENCE: NA Laryngoscope, 133:2631-2637, 2023.

The extracellular matrix landscape in salivary gland carcinomas is defined by cellular differentiation via expression of three distinct protein modules.

The extracellular matrix (ECM) is an integral part of the tumor microenvironment of carcinomas. Even though salivary gland carcinomas (SGCs) display a range of tumor cell differentiation and distinct extracellular matrices, their ECM landscape has not been characterized in depth. The ECM composition of 89 SGC primaries, 14 metastases, and 25 normal salivary gland tissues was assessed using deep proteomic profiling. Machine learning algorithms and network analysis were used to detect tumor groups and protein modules that explain specific ECM landscapes. Multimodal in situ studies to validate exploratory findings and to infer a putative cellular origin of ECM components were applied. We revealed two fundamental SGC ECM classes which align with the presence or absence of myoepithelial tumor differentiation. We describe the SGC ECM through three biologically distinct protein modules that are differentially expressed across ECM classes and cell types. The modules have a distinct prognostic impact on different SGC types. Since targeted therapy is rarely available for SGC, we used the proteomic expression profile to identify putative therapeutic targets. In summary, we provide the first extensive inventory of ECM components in SGC, a difficult-to-treat disease that encompasses tumors with distinct cellular differentiation. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

[Diagnostics and treatment of secondary malignancies of the parotid gland-An overview]. / Diagnostik und Therapie sekundärer Malignome der Ohrspeicheldrüse ­ eine Übersicht.

BACKGROUND: Secondary malignancies of the parotid gland frequently have a cutaneous origin and the incidence in central Europe is increasing. OBJECTIVE: The aim of this review article was to present the epidemiology, (differential) diagnostics and treatment of secondary malignancies of the parotid gland. MATERIAL AND METHODS: A literature search of the current guidelines and evidence was carried out in the web-based databank PubMed. RESULTS: The incidence of secondary malignancies of the parotid gland seems to be increasing in Europe, mainly due to a rising incidence of metastases of cutaneous squamous cell carcinomas. Except for malignant lymphomas, parotidectomy is the treatment of choice in the curative situation. In the absence of clear evidence, in the case of an intact facial nerve lateral or total parotidectomy with ipsilateral neck dissection seems to be indicated, depending on the entity of the secondary malignancy. CONCLUSION: The differential diagnostics of squamous cell carcinoma (in) of the parotid gland can be complicated. When a squamous cell carcinoma of the parotid gland is diagnosed for the first time, a dermatological full body examination and a detailed medical history should be taken with respect to skin tumors of the head and neck region. In addition to surgical treatment of the parotid gland and neck, adjuvant radiotherapy is usually indicated.

CD138 Is Expressed in Different Entities of Salivary Gland Cancer and Their Lymph Node Metastases and Therefore Represents a Potential Therapeutic Target.

Advanced salivary gland carcinomas (SGC) often lack therapeutic options. Agents targeting CD138 have recently shown promising results in clinical trials for multiple myeloma and a preclinical trial for triple-negative breast cancer. Immunohistochemistry for CD138 was performed for all patients who had undergone primary surgery for SGC with curative intent. Findings were validated using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) imaging. Overall, 111 primary SGC and 13 lymph node metastases from salivary duct carcinomas (SaDu) were evaluated. CD138 expression was found in 60% of all SGC with differing expression across entities (p < 0.01). A mean of 25.2% of the tumor cells in mucoepidermoid carcinoma (MuEp) were positive, followed by epithelial-myoepithelial carcinoma (20.9%), acinic cell carcinoma (16.0%), and SaDu (15.2%). High-/intermediate-grade MuEp showed CD138 expression in a mean of 34.8% of tumor cells. For SaDu, lymph node metastases showed CD138 expression in a mean of 31.2% of tumor cells which correlated with CD138 expression in their primaries (p = 0.01; Spearman's ρ = 0.71). MALDI-MS imaging confirmed the presence of the CD138 protein in SGC. No significant association was found between clinicopathological data, including progression-free survival (p = 0.50) and CD138 expression. CD138 is expressed in the cell membrane of different entities of SGC and SaDu lymph node metastases and therefore represents a potential target for CD138 targeting drugs.

Cancer-specific and overall survival of patients with primary and metastatic malignancies of the parotid gland - A retrospective study.

The aim of this study was to display the cancer-specific and overall survival of patients with primary and metastatic malignancies of the parotid gland. In this retrospective study all patients with primary parotid malignancy and metastatic cutaneous squamous cell carcinoma (cSCC) of the parotid gland treated surgically with curative intent at a tertiary care institution were included. Patients were followed with regards to their oncologic outcome for a minimum of two years. Management approaches, overall, and cancer-specific survival were compared between patients with primary and secondary parotid gland carcinomas. Ninety-four patients (43 patients with primary parotid malignancy; 51 patients with metastatic cSCC of the parotid gland) were included. Patients with metastatic cSCC were older (p = 0.001) and more frequently male (p = 0.002). Adjuvant therapy (p = 0.001) and neck dissection (p = 0.009) were more frequently performed among patients with metastatic cSCC of the parotid gland than among those with primary parotid malignancy. Mean follow-up was 50 (95% CI: 40-65) months. Five-year cancer-specific survival was 87.3% among patients with primary parotid malignancies and 54.5% among patients with metastatic cSCC (p = 0.006). Cancer-specific survival of patients with metastatic cSCC of the parotid gland is still low. An earlier diagnosis of parotid metastases of cSCC may potentially lead to a better prognosis.

Status quo after one year of COVID-19 pandemic in otolaryngological hospital-based departments and private practices in Germany.

PURPOSE: The COVID-19 pandemic has affected healthcare systems worldwide. Data on the impact on otolaryngological clinics and private practices is sparse. This study aimed to present data on healthcare worker (HCW) screening, status of HCW, pre-interventional testing, the use of personal protective equipment (PPE) and the economic impact of the pandemic. METHODS: Otolaryngological private practices and hospital-based departments were surveyed nationwide using an online questionnaire. Participating facilities were recruited via the German Society for Oto-Rhino-Laryngology and the German Association for Otolaryngologists in Bavaria. RESULTS: 365 private practices (2776 employees) and 65 hospitals (2333 employees) were included. Significantly more hospitals (68.7%) than practices (40.5%) performed pre-interventional testing in their outpatients (p < 0.00). Most inpatients were tested in practices and hospitals (100.0% and 95.0%; p = 0.08). HCW screening was performed in 73.7% of practices and in 77.3% of hospitals (p = 0.54). Significantly more HCW infections were reported in private practices (4.7%) than in hospital (3.6%; p = 0.03). The private or home environment was the most frequent source of infection among HCW in hospitals (44%) and practices (63%). The use of PPE increased over the course of the pandemic. The number of procedures and the revenue decreased in 2020. CONCLUSION: The rate of pre-interventional testing among outpatients in otolaryngological practices is low and HCW infections were found to be more frequent in practices than in hospitals. In addition, a high rate of infections in otolaryngological HCW seems to stem from the private or home environment.

Diagnostic Accuracy and Post-Procedural Complications Associated with Ultrasound-Guided Core Needle Biopsy in the Preoperative Evaluation of Parotid Tumors.

Correct diagnosis of a parotid neoplasm based on histology preoperatively is of utmost importance in order to guide patient management. The aim of this study was to evaluate the diagnostic accuracy of an ultrasound-guided core needle biopsy of a parotid lesion and to describe associated post-procedural complications. A retrospective study was conducted between January 2015 and March 2021 of all patients who were referred to a tertiary care center for evaluation of a parotid lesion and who underwent core needle biopsy due to high-risk features or when malignancy was suspected on clinical examination or ultrasonography. Patient characteristics, histological findings, and post-procedural complications were recorded and evaluated. Among 890 patients referred for evaluation of a parotid lesion, in 138 patients a core needle biopsy was undertaken. On the basis of core needle biopsy findings, 11 lymphomas and 82 non-lymphoma malignancies were diagnosed in the parotid gland. The sensitivity of the core needle biopsy predicting the accurate tumor type was 97.56% (95% CI 91.47-99.70%) and the specificity 94.64% (95% CI 85.13-98.88%). The accuracy for the correct histopathological diagnosis was 93.48% (95% CI 87.98-96.97%). Post-procedural minor complications occurred in 19 patients (13.8%). In conclusion, a core needle biopsy can identify malignancy in the parotid gland with high sensitivity and specificity in a safe manner and therefore guide surgical treatment.

Prospective study on complications using different techniques for parotidectomy for benign tumors.

OBJECTIVES: Long-term prospective studies on procedure-related complications after parotid surgery for benign neoplasms (BNs) are scarce. This is the first prospective study on the use of extracapsular dissection (ECD) for BNs, and it aimed to examine the incidence of postoperative complications after parotid surgery for BN. METHODS: We collected data obtained in a prospective study of parotidectomy for BN at a university hospital and analyzed the transient and long-term complications. RESULTS: The incidence rates of transient facial palsy immediately and 18 months after surgery were 15.0% and 3.7%, respectively. The rates of immediate postoperative facial palsy in patients who underwent ECD, partial superficial, superficial, and total parotidectomy were 5.8%, 29.3%, 20.0%, and 44.1%, respectively. Significant risk factors for facial palsy included multiple and larger lesions as well as surgery duration and extension. CONCLUSIONS: Postoperative facial palsy remains a common complication after parotidectomy for BN and is associated with the extent of parotidectomy, presence of multiple neoplasms, and operative duration. The results of this study showed that ECD could be a safe technique for avoiding facial palsy. Level of Evidence: 2.

Paraparesis after low dose administration of fluorescein for endoscopic resection of an encephalocele: a case report.

The main causes for cerebrospinal fluid (CSF) leaks are known to be traumatic, iatrogenic, neoplastic, a meningoencephalocele, congenital bone defects, and spontaneous. Off-label intrathecal administration of fluorescein is widely used to localize a CSF leak. Complications are rare and low dose administration is described to be safe. In this case report, we present a case of a patient, who showed a CSF leak due to an encephalocele. Low dose fluorescein was applied intrathecally via lumbar catheter, the CSF leaks could be identified, and multilayered closure was performed. Postoperatively, the patient presented with motor and sensory deficits in the lower limbs which regressed only partially within 2 months. A possible explanation may be an increased local concentration of fluorescein, possibly on the basis of a preexisting lumbar spinal canal stenosis. To our knowledge, this is the first case in which a dose as low as 20 mg of fluorescein (2% saline mixture) led to persisting paraplegia. Therefore, the potential benefits and risks of the intrathecal fluorescein use in the detection of a CSF leak have to be discussed comprehensively prior to surgery.

Interest in, willingness-to-pay for and willingness-to-recommend genetic testing for prostate cancer among affected men after radical prostatectomy.

Knowledge about interest in genetic testing and willingness-to-pay for a genetic test among men affected from prostate cancer (PCa) is limited. This study aimed to gain insight into men's attitudes in genetic testing for PCa. 4699 men with PCa from the German multicenter prospective database "Familial Prostate Cancer" were included. Interest in, Willingness-to-pay for and Willingness-to-recommend a genetic test for PCa were quantified. Associations with several sociodemographic and psychosocial variables were evaluated by logistic regression. 76.8% of the affected men with a median follow-up of 12.9 years were interested in a genetic test for PCa. Newly identified variables significantly associated with interest were having sons (OR 1.66, p < 0.001) and a high perceived severity of the PCa (OR 1.40, p < 0.001). 19% of men were willing to pay more than 500 € for a genetic test. Men with higher education, men with a better self-reported economic situation and men with a lethal PCa in their family were more likely to be willing to pay a larger sum for a test. 84.9% of men were willing to recommend a test to their relatives. Interest in genetic testing for PCa among affected men was generally high with most men willing to recommend a test to their relatives. Various characteristics associated with interest and willingness-to-pay larger sums for genetic testing were uncovered and need to be addressed when designing both future educational material and genetic tests for PCa.

Evidence base and practice variation in acute care processes for knee and hip arthroplasty surgeries.

BACKGROUND: Lack of evidence contributes to unnecessary variation in treatment costs and outcomes. This study aimed to identify from interventions historically used for total knee or hip arthroplasty (TKA, THA): i) if routine use is supported by high-level evidence; ii) whether surgeon use aligns with the evidence. METHODS: Part 1: Systematic search of electronic library databases for systematic reviews and practice guidelines concerning seven acute-care interventions. Intervention-specific recommendations concerning routine use were extracted by assessors. Part 2: Prospective medical record audit of the acute-care received by 1900 patients involving 120 orthopaedic surgeons. Surgeon use per intervention was summarized using caterpillar plots. Surgeon-specific routine and non-routine use was defined as use in ≥ 90% and ≤ 10% of patients, respectively. Primary analysis included only surgeons contributing ≥ 10 patients. RESULTS: Continuous passive motion (TKA): Routine use not recommended; 85.7% of surgeons did not use it routinely. Tranexamic Acid: Routine use recommended; 26.9% of surgeons used it routinely. Cryotherapy: Routine use not recommended; 45.7% of surgeons used it routinely for TKA; 31.8% used it routinely for THA. Intra-articular drainage: Routine use not recommended for TKA, but possible benefits for THA; 5.7% of surgeons used it routinely for TKA, 0.0% used it routinely for THA. Antibiotic loaded bone cement: Routine use for TKA not supported, recommendations for use for THA are inconsistent; 90.0% of surgeons used it routinely for TKA, 100.0% used it routinely for THA. Patella resurfacing (TKA): No recommendation could be made; 57.1% of surgeons routinely resurfaced the patella. Indwelling urinary catheterisation: Routine use recommended; 59.6% of surgeons used it routinely. CONCLUSION: Recommendations for routine use or not exist for some of the acute-care interventions examined. Surgeon practices vary widely even in the presence of high-level recommendations. It is unclear whether further evidence alone would lessen unwarranted practice variation.

Operative treatment of 2-part surgical neck fractures of the proximal humerus (AO 11-A3) in the elderly: Cement augmented locking plate Philos™ vs. proximal humerus nail MultiLoc®.

BACKGROUND: Proximal humeral fractures are with an incidence of 4-5 % the third most common fractures in the elderly. In 20 % of humeral fractures there is an indication for surgical treatment according to the modified Neer-Criteria. A secondary varus dislocation of the head fragment and cutting-out are the most common complications of angle stable locking plates in AO11-A3 fractures of the elderly. One possibility to increase the stability of the screw-bone-interface is the cement augmentation of the screw tips. A second is the use of a multiplanar angle stablentramedullary nail that might provide better biomechanical properties after fixation of 2-part-fractures. A comparison of these two treatment options augmented locking plate versus multiplanar angle stable locking nail in 2-part surgical neck fractures of the proximal humerus has not been carried out up to now. METHODS/DESIGN: Forty patients (female/male, ≥60 years or female postmenopausal) with a 2-part-fracture of the proximal humerus (AO type 11-A3) will be randomized to either to augmented plate fixation group (PhilosAugment) or to multiplanar intramedullary nail group (MultiLoc). Outcome parameters are Disabilities of the Shoulder, Arm and Hand-Score (DASH) Constant Score (CS), American Shoulder and Elbow Score (ASES), Oxford Shoulder Score (OSS), Range of motion (ROM) and Short Form 36 (SF-36) after 3 weeks, 6 weeks, 3 months, 6 months, 12 and 24 months. DISCUSSION: Because of the lack of clinical studies that compare cement augmented locking plates with multiplanar humeral nail systems after 2-part surgical neck fractures of the proximal humerus, the decision of surgical method currently depends only on surgeons preference. Because only a randomized clinical trial (RCT) can sufficiently answer the question if one treatment option provides advantages compared to the other method we are planning to perform a RCT. TRIAL REGISTRATION: Clinical Trial ( NCT02609906 ), November 18, 2015, registered retrospectively.

Multilayer Fresnel zone plates for high energy radiation resolve 21 nm features at 1.2 keV.

X-ray microscopy is a successful technique with applications in several key fields. Fresnel zone plates (FZPs) have been the optical elements driving its success, especially in the soft X-ray range. However, focusing of hard X-rays via FZPs remains a challenge. It is demonstrated here, that two multilayer type FZPs, delivered from the same multilayer deposit, focus both hard and soft X-rays with high fidelity. The results prove that these lenses can achieve at least 21 nm half-pitch resolution at 1.2 keV demonstrated by direct imaging, and sub-30 nm FWHM (full-pitch) resolution at 7.9 keV, deduced from autocorrelation analysis. Reported FZPs had more than 10% diffraction efficiency near 1.5 keV.

Efficient focusing of 8 keV X-rays with multilayer Fresnel zone plates fabricated by atomic layer deposition and focused ion beam milling.

Fresnel zone plates (FZPs) recently showed significant improvement by focusing soft X-rays down to ~10 nm. In contrast to soft X-rays, generally a very high aspect ratio FZP is needed for efficient focusing of hard X-rays. Therefore, FZPs had limited success in the hard X-ray range owing to difficulties of manufacturing high-aspect-ratio zone plates using conventional techniques. Here, employing a method of fabrication based on atomic layer deposition (ALD) and focused ion beam (FIB) milling, FZPs with very high aspect ratios were prepared. Such multilayer FZPs with outermost zone widths of 10 and 35 nm and aspect ratios of up to 243 were tested for their focusing properties at 8 keV and shown to focus hard X-rays efficiently. This success was enabled by the outstanding layer quality thanks to ALD. Via the use of FIB for slicing the multilayer structures, desired aspect ratios could be obtained by precisely controlling the thickness. Experimental diffraction efficiencies of multilayer FZPs fabricated via this combination reached up to 15.58% at 8 keV. In addition, scanning transmission X-ray microscopy experiments at 1.5 keV were carried out using one of the multilayer FZPs and resolved a 60 nm feature size. Finally, the prospective of different material combinations with various outermost zone widths at 8 and 17 keV is discussed in the light of the coupled wave theory and the thin-grating approximation. Al2O3/Ir is outlined as a promising future material candidate for extremely high resolution with a theoretical efficiency of more than 20% for as small an outermost zone width as 10 nm at 17 keV.

Cognitively automated assembly processes: a simulation based evaluation of performance.

The numerical control of an experimental assembly cell with two robots--termed a cognitive control unit (CCU)--is able to simulate human information processing at a rule-based level of cognitive control. To enable the CCU to work on a large range of assembly tasks expected of a human operator, the cognitive architecture SOAR is used. The CCU can plan assembly processes autonomously and react to ad-hoc changes in assembly sequences effectively. Extensive simulation studies have shown that cognitive automation based on SOAR is especially suitable for random parts supply, which reduces planning effort in logistics. Conversely, a disproportional increase in processing time was observed for deterministic parts supply, especially for assemblies containing large numbers of identical parts. In this contribution, the effect of phase-shifts in deterministic part supply is investigated for assemblies containing maximal different parts. It can be shown that the concept of cognitive automation is as well suitable for these planning problems.