Schwannoma of the Hypoglossal Nerve Mimicking Carotid Body Paraganglioma

Carotid body paragangliomas (CBPs) clinically present as highly vascularized cervical masses with a pathognomonic localization at the carotid artery bifurcation. Following ultrasonography and MRI/CT imaging, surgical resection with optional preoperative embolization is considered as the treatment of choice in most cases. We herein present the case of a 60-year-old female with characteristic clinical signs and imaging findings of a right-sided CBP who finally went to surgical treatment. Intraoperatively, the tumor showed an adherent growth to the hypoglossal nerve that had to be partially resected, resulting in a postoperative nerve palsy. Histological examination of the resected tumor revealed the unexpected diagnosis of a hypoglossal nerve schwannoma. To the best of our knowledge, we herein present the third case reported in the literature of a unilateral hypoglossal schwannoma located at the carotid bifurcation mimicking clinical symptoms, imaging and intraoperative findings of a CBP

Complete remission of an early-stage laryngeal cancer under combined pembrolizumab and chemotherapy treatment of a synchronous lung adenocarcinoma

Background: Anti-PD1-Checkpoint inhibition (CI) is an established treatment of recurrent and/or metastatic head and neck cancer. A potential beneft from CI in early-stage disease that is usually treated by radiation or surgery has not been investigated so far and is currently not addressed in clinical trials. Case presentation: A 58-year-old man was diagnosed with a cT2 supraglottic laryngeal cancer and a synchronous metastasized adenocarcinoma of the lung. As the patient refused any treatment of his laryngeal cancer, he received combined immune-chemotherapy according to the KEYNOTE-189 protocol. After 4 cycles of pembrolizumab/carboplatin/pemetrexed, the patient showed a complete remission of his laryngeal cancer with a clear shrinkage of the mediastinal and hilar lung cancer metastases. After 21 cycles of maintenance therapy, the lung adenocarcinoma shows a stable disease status with no signs of any residual or recurrent laryngeal cancer. Conclusions: Anti-PD1-CI may be a treatment option also for early-stage HNSCC with excellent functional outcome when established therapies are not available

Influence of Chloride and Nitrate Anions on Copper Electrodeposition onto Au(111) from Deep Eutectic Solvents

Copper electrodeposition on Au(111) from deep eutectic solvents (DESs) type III was investigated employing cyclic voltammetry as well as chronoamperometry. It was further examined on Au(poly) using the electrochemical quartz crystal microbalance (EQCM). The employed DESs are mixtures of choline chloride (ChCl) or choline nitrate (ChNO$_{3}$) with ethylene glycol (EG) as hydrogen bond donor (HBD), each in a molar ratio of 1 : 2. CuCl, CuCl$_{2}$, or Cu(NO$_{3}$)$_{2}$ ⋅ 3H$_{2}$O were added as copper sources. Underpotential deposition (UPD) of Cu precedes bulk deposition in chloride as well as nitrate electrolytes. Cu deposition from Cu$^{+}$ in chloride media is observed as a one-electron reaction, whereas deposition from Cu$^{2+}$ occurs in two steps since Cu$^{+}$ is strongly stabilized by chloride. Cu$^{+}$ is less stabilized by nitrate and the beginning of bulk deposition in the nitrate-containing DES with Cu$^{2+}$ is shifted by several hundred mV to more positive potentials compared to the chloride DES. A diffusion-controlled, three-dimensional nucleation and growth mechanism is found by chronoamperometric measurements and analysis based on the model of Scharifker and Mostany

Differential nasal swab cytology represents a valuable tool for therapy monitoring but not prediction of therapy response in chronic rhinosinusitis with nasal polyps treated with Dupilumab

Introduction: Chronic Rhinosinusitis with nasal polyps (CRSwNP) is a common chronic disease with a high impact on patients’ quality of life. If conservative and surgical guideline treatment cannot sufficiently control disease burden, biologicals can be considered as a comparably new treatment option that has revolutionized CRSwNP therapy since the first approval of Dupilumab in 2019. With the aim to select patients who benefit from this new treatment and to find a marker for therapy monitoring, we investigated the cellular composition of nasal mucous membranes and inflammatory cells of patients suffering from CRSwNP and undergoing Dupilumab therapy using non-invasive nasal swab cytology. Methods: Twenty CRSwNP patients with the indication for Dupilumab therapy have been included in this prospective clinical study. In total, five study visits were conducted with ambulatory nasal differential cytology using nasal swabs starting with the beginning of therapy and followed by visits every 3 months for 12 months. First, these cytology samples were stained with the May-GrunwaldGiemsa method (MGG) and the percentage of ciliated cells, mucinous cells, eosinophil cells, neutrophil cells, and lymphocytes was analyzed. Secondly, an immunocytochemical (ICC) ECP-staining was performed to detect eosinophil granulocytes. Additionally, during each study visit the nasal polyp score, SNOT20 questionnaire, olfactometry, the total IgE concentration in peripheral blood as well as the eosinophil cell count in peripheral blood were recorded. The change of parameters was evaluated over one year and the correlation between clinical effectiveness and nasal differential cytology was analyzed. Results: In both MGG (p<0.0001) and ICC analysis (p<0.001) a significant decrease of eosinophils was seen under Dupilumab treatment. When patients were divided into a Eo-low- (<21%) and Eo-high- (≥21%) group according to the percentage eosinophils in nasal swab catology in the first study visit, the Eo-highgroup showed a greater change of eosinophils over time (D17.82) compared to the Eo-low-group (D10.67) but, however, no better response to therapy. The polyp score, SNOT20 questionnaire, and total IgE concentration in peripheral blood showed a significant decrease during the observation period (p<0.0001). Discussion: Nasal swab cytology as an easy-to-apply diagnostic method allows detection and quantification of the different cell populations within the nasal mucosa at a given time. The nasal differential cytology showed a significant decrease of eosinophils during Dupilumab therapy and can therefore be used as non-invasvive method for monitoring therapy success of this cost intensive therapy and potentially can allow an optimized individual therapy planning and management for CRSwNP patients. Since the validity of initial nasal swab eosinophil cell count as a predictive biomarker for therapy response was limited in our study, additional studies including larger number of participants will be necessary to further evaluate the potential benefits for clinical practice of this new diagnostic method

Expression of 3q oncogene SEC62 in atypical fibroxanthoma-immunohistochemical analysis of 41 cases and correlation with clinical, viral and histopathologic features

Atypical fibroxanthoma (AFX) is a rare mesenchymal tumor with predominance in older male patients located mainly in chronically UV-exposed skin. Differentiation from clinically more aggressive pleomorphic dermal sarcoma (PDS) is still under debate and immunohistochemical markers are not available yet. An immunohistochemical study, including 41 cases of AFX was conducted to investigate the expression of 3q encoded oncogene SEC62 in AFX and determine the associations with histomorphologic, clinical and viral parameters. Our cohort displayed a mean of 79.9 years at the onset of the disease. In total, 90.2% (37/41) AFXs were located in the head and neck area, whereas, four were located at the extremities (9.7%). Tumor diameter ranged between 0.06 and 40 cm2 with a mean of 5.7 cm2. SEC62 expression was markedly increased in lesional tissue compared with the adjacent healthy squamous epithelium. We found significantly higher expression of SEC62 in cases of AFX with tumor necrosis. Tendency of higher Sec62-IRS-scores were found for tumors with higher Clark levels and a tumor size >5 cm2. Sec62 is involved in endoplasmic reticulum stress tolerance and cell migration, and has been identified as a novel prognostic marker for non-small cell lung cancer as well as head and neck squamous cell carcinoma. For the first time, to the best of our knowledge, we suggest a role of 3q oncogene SEC62 in AFX and discuss a potential prognostic relevance in cases of disputable AFX with unfavorable histomorphologic features and may initiate a discussion on Sec62 serving as discriminating marker between AFX and PDS

Expression of SEC62 Oncogene in Benign, Malignant and Borderline Melanocytic Tumors—Unmasking the Wolf in Sheep’s Clothing?

SEC62 oncogene located at chromosomal region 3q26 encodes for a transmembrane protein of the endoplasmic reticulum (ER) and is expressed at high levels in numerous human malignancies. SEC62 overexpression has been associated with worse prognosis and high risk for lymphatic and distant metastases in head and neck cancer, cervical cancer, hepatocellular cancer, and lung cancer. However, its role in the development and tumor biology of melanocytic lesions has not been investigated so far. An immunohistochemical study including 209 patients with melanocytic lesions (malignant melanoma (MM), n = 93; melanoma metastases (MET), n = 28; Spitz nevi (SN), n = 29; blue nevi (BN), n = 21; congenital nevi (CN), n = 38) was conducted and SEC62 expression was correlated with clinical data including patient survival and histopathological characteristics. SN showed the highest SEC62 expression levels followed by MET, MM, CN, and BN. High SEC62 expression correlated with a shorter overall and progression-free survival in MM patients. Additionally, high Sec62 levels correlated significantly with higher tumor size (T stage), the presence of tumor ulceration, and the presence of lymph node as well as distant metastases. Strikingly, SEC62 expression showed a strong correlation with Clark level. Taken together, these data demonstrate that SEC62 is a promising prognostic marker in MM and has the potential to predict biological behavior and clinical aggressiveness of melanocytic lesions

Antagonizing Sec62 function in intracellular Ca2+ homeostasis represents a novel therapeutic strategy for head and neck cancer

Various cancer types including head and neck squamous cell carcinomas (HNSCC) show a frequent amplification of chromosomal region 3q26 that encodes, among others, for the SEC62 gene. Located in the ER membrane, this translocation protein is known to play a critical role as a potential driver oncogene in cancer development. High SEC62 expression levels were observed in various cancer entities and were associated with a poor outcome and increased metastatic burden. Because of its intracellular localization the SEC62 protein is poorly accessible for therapeutic antibodies, therefore a functional SEC62 knockdown represents the most promising mechanism of a potential antineoplastic targeted therapy. By stimulating the Ca2+ efflux from the ER lumen and thereby increasing cellular stress levels, a functional inhibition of SEC62 bears the potential to limit tumor growth and metastasis formation. In this study, two potential anti-metastatic and -proliferative agents that counteract SEC62 function were investigated in functional in vitro assays by utilizing an immortalized human hypopharyngeal cancer cell line as well as a newly established orthotopic murine in vivo model. Additionally, a CRISPR/ Cas9 based SEC62 knockout HNSCC cell line was generated and functionally characterized for its relevance in HNSCC cell proliferation and migration as well as sensitivity to SEC62 targeted therapy in vitro

Comparison of In Vitro and In Vivo Results Using the GastroDuo and the Salivary Tracer Technique: Immediate Release Dosage Forms under Fasting Conditions

The fasted state administration of immediate release (IR) dosage forms is often regarded as uncritical since physiological aspects seem to play a minor role for disintegration and drug release. However, recent in vivo studies in humans have highlighted that fasted state conditions are in fact highly dynamic. It was therefore the aim of this study to investigate the disintegration and drug release behavior of four different IR formulations of the probe drug caffeine under physiologically relevant conditions with the aid of the GastroDuo. One film-coated tablet and three different capsule formulations based on capsule shells either made from hard gelatin or hydroxypropylmethyl cellulose (HPMC) were tested in six different test programs. To evaluate the relevance of the data generated, the four IR formulations were also studied in a four-way cross-over study in 14 healthy volunteers by using the salivary tracer technique (STT). It could be shown that the IR formulations behaved differently in the in vitro test programs. Thereby, the simulated parameters affected the disintegration and dissolution behavior of the four IR formulations in different ways. Whereas drug release from the tablet started early and was barely affected by temperature, pH or motility, the different capsule formulations showed a longer lag time and were sensitive to specific parameters. However, once drug release was initiated, it typically progressed with a higher rate for the capsules compared to the tablet. Interestingly, the results obtained with the STT were not always in line with the in vitro data. This observation was due to the fact that the probability of the different test programs was not equal and that certain scenarios were rather unlikely to occur under the controlled and standardized conditions of clinical studies. Nonetheless, the in vitro data are still valuable as they allowed to discriminate between different formulations