[Increasing incidence of mastoidectomies in children : Result of reduced antibiotic therapy or late COVID-19 sequela?] / Steigende Inzidenzen bei Mastoidektomien im Kindesalter : Folge geringeren Antibiotikaeinsatzes oder eine COVID-19-Spätfolge?

BACKGROUND: An increasing number of pediatric patients with mastoiditis and a consequent increase in mastoidectomy rates was noted in 2022 and 2023. OBJECTIVE: This study aimed to analyze the increase in the number of children presenting with mastoiditis and subsequent mastoidectomy, to assess correlations with prior antibiotic treatment or COVID-19 infection, and to provide an overview of involved pathogens, treatment, and disease course. MATERIALS AND METHODS: A retrospective analysis of all patients with mastoidectomy since 2012 was conducted. Data collected comprised type and duration symptoms, prior antibiotic therapy, diagnostic tests and disease course, causal pathogens, length of hospitalization, and complications. RESULTS: A highly significant increase in mastoidectomies in children could be demonstrated from 2022. Neither the pathogens involved nor the course of disease or complications showed differences. An increase in the number of patients with prior outpatient antibiotic therapy could be shown. About a half of the patients becoming ill after fall 2022 had a positive history of COVID. Hyperplasia of adenoid tissue was a far less frequent causal mechanism than in the years before COVID. CONCLUSION: No clear correlation with reduced outpatient antibiotic therapy could be found. Whether there exists an association with prior COVID infection cannot be judged at this time, due to the high number of asymptomatic and therefore unknown COVID infections.

[Diagnosis and therapy of sinonasal mucosal melanoma]. / Diagnostik und Therapie von Schleimhautmelanomen der Nase/Nasennebenhöhlen.

Sinonasal mucosal melanoma (SNMM) is a rare and aggressive disease representing only 4% of all sinonasal malignancies and 1.4% of all melanomas. With an incidence of approximately 0.2 to 2 cases per million, the disease represents a very rare cancer type. As a result, there is a lack of data and most of the evidence for this highly aggressive disease is based on retrospective observations and analyses. The standard of care is radical tumor resection followed by an adjuvant radiotherapy. Nevertheless, the rate of local recurrence is high, up to 50%. In addition, the majority of patients (up to 70%) develop distant metastases during the course of their disease. Both contribute to the extremely poor prognosis of the disease. Mucosal melanomas (SM) and cutaneous melanomas (CM) behave differently with respect to biology, clinic presentation and prognosis. Compared to CM, survival rates are significantly lower for SM. The 5-year survival rate is around 25% in SNMM but 39-97% in cutaneous melanoma. Similar to CM, immune checkpoint inhibitors achieve promising results in SM. However, response rates are lower in SM compared to CM. The goal of this CME article is to provide an overview on biology, diagnosis, therapy, and prognosis of SNMM.

Comparison of three different image enhancement systems for detection of laryngeal lesions.

OBJECTIVE: Image enhancement systems are important diagnostic tools in the detection of laryngeal pathologies. This study aimed to compare three different image enhancement systems: professional image enhancement technology, Image1 S and narrow-band imaging. METHOD: Using the three systems, 100 patients with laryngeal lesions were investigated using a flexible and a 30° rigid endoscope. The lesions were diagnosed by three experts and classified using the Ni classification. The findings were compared. RESULTS: Lesions classified as 'benign' were histopathologically confirmed in 50 per cent of patients, malignant lesions were confirmed in 41 per cent and recurrent respiratory papillomatosis were confirmed in 9 per cent. There was no significant difference between the experts' assessments of each image enhancement system. CONCLUSION: The three systems give comparable results in the detection of laryngeal lesions. With two additional systems, more users can perform image-enhanced endoscopy, resulting in a broadly available tool that can help to improve oncological assessment.

[18F]FDG PET/CT can trigger relevant oncological management changes leading to favorable outcome in iodine-negative thyroid cancer patients.

BACKGROUND: In patients with iodine-negative thyroid cancer (TC), current guidelines endorse an [18F]FDG PET/CT to identify dedifferentiated sites of disease. We aimed to determine the rate of oncological management changes triggered by such a molecular imaging approach, along with the impact on outcome. METHODS: 42 consecutive patients with negative findings on [131I] whole body scan were scheduled for [18F]FDG PET/CT and treatment based on PET results were initiated. To determine the impact on oncological management, we compared the therapeutic plan prior to and after molecular imaging. Based on imaging follow-up, the rate of controlled disease (CD, defined as stable disease, complete or partial response) was also recorded, thereby allowing to assess whether [18F]FDG-triggered management changes can also lead to favorable outcome. RESULTS: We observed no alterations of the treatment plan in 9/42 (21.4%) subjects (active surveillance in 9/9 [100%]). Oncological management was changed in the remaining 33/42 (78.6%; systemic treatment in 9/33 [27.3%] and non-systemic treatment in 24/33 [72.7%]). Among patients receiving non-systemic therapy, the following changes were noted: surgery in 20/24 (83.3%) and radiation therapy in 4/24 (16.7%). In the systemic group, tyrosine kinase inhibitor (TKI) was prescribed in 8/9 (88.9%), while radioiodine therapy based on a TKI-mediated redifferentiation approach was conducted in 1/9 (11.1%). In 26 subjects with available follow-up, rate of CD was 22/26 (84.6%) and among those, 15/22 (68.1%) had experienced previous management changes based on PET/CT findings. CONCLUSIONS: In subjects with iodine-negative TC, [18F]FDG PET/CT triggered relevant management changes along with disease control in the vast majority of patients. As such, in dedifferentiated TC, [18F]FDG PET/CT may serve as a relevant management tool and therapeutic decision-aid in the clinic.

Diagnostic efficacy of C-X-C motif chemokine receptor 4-directed PET/CT in newly diagnosed head and neck squamous cell carcinoma - a head-to-head comparison with [18F]FDG.

BACKGROUND: The aim of this study was to determine the read-out capabilities of the novel C-X-C motif chemokine receptor 4 (CXCR4)-targeting radiotracer [68Ga]Ga-PentixaFor compared to the reference radiotracer [18F]FDG in untreated individuals with head and neck squamous cell carcinoma (HNSCC). MATERIAL AND METHODS: 12 patients with histologically confirmed HNSCC were scheduled for [18F]FDG and [68Ga]Ga-PentixaFor PET/CT. Maximum standardized uptake values (SUVmax) and target-to-background ratios (TBR) were applied with vena cava superior serving as reference. In addition, we compared [68Ga]Ga-PentixaFor-PET findings with immunohistochemical (IHC) results of CXCR4 expression. RESULTS: On visual assessment, [18F]FDG identified more sites of disease, with increased detection rates for both the primary tumor ([18F]FDG, 12/12 [100%] vs. [68Ga]Ga-PentixaFor, 10/12 [83%]) and LN metastases ([18F]FDG, 9/12 [75%] vs. [68Ga]Ga-PentixaFor, 8/12 [67%]). Indicative for improved image contrast using [18F]FDG, quantification showed a higher TBR for the latter radiotracer, when compared to [68Ga]Ga-PentixaFor for all lesions ([18F]FDG, 11.7 ± 8.5 vs. [68Ga]Ga-PentixaFor, 4.3 ± 1.3; P=0.03), primary tumors ([18F]FDG, 13.6 ± 8.7 vs. [68Ga]Ga-PentixaFor, 4.4 ± 1.4; P<0.01), and LN lesions ([18F]FDG, 9.3 ± 10.6 vs. [68Ga]Ga-PentixaFor, 4.7 ± 1.5; P=0.3). IHC showed variable CXCR4 expression in the primary and LN, along with no associations between ex-vivo CXCR4 upregulation and [68Ga]Ga-PentixaFor-based TBR (R=0.33, P=0.39) or SUVmax (R=0.44, P=0.2). Of note, IHC also revealed heterogeneous expression of CXCR4 in immune cells in the tumor microenvironment and in germinal centers, indicative for inflammatory reactions. CONCLUSIONS: In HNSCC, [18F]FDG demonstrated superior diagnostic performance relative to [68Ga]Ga-PentixaFor, in particular for assessment of the primary. Based on the IHC analyses, these findings may be explained by CXCR4 upregulation not only by tumor but also by immune cells in the tumor microenvironment.

Establishing safe high hydrostatic pressure devitalization thresholds for autologous head and neck cancer vaccination and reconstruction.

High hydrostatic pressure specifically devitalizes cells and tissues without major changes in their molecular structure. Hence, high hydrostatic pressure may enhance the development of whole-cell anti-tumor vaccines, representing tumor heterogeneity and thus (neo-) antigen diversity. Moreover, safe devitalization of tumor-infiltrated supporting tissue may facilitate reimplantation for functional reconstruction. However, precise high hydrostatic pressure thresholds for safe cancer cell killing are unknown. Here, we show that high hydrostatic pressure of at least 450 MPa is necessary to safely devitalize head and neck squamous cell cancer. A pressure of 300 MPa, which has been used frequently in cancer vaccine preparation, resulted in partial devitalization with 27% live cells in flow cytometry and 4% remaining autofluorescence in cell culture after one week. The remaining cells could form vital tumors in the chorioallantoic membrane assay. In contrast, 450 MPa killed all cells in vitro and prevented tumor outgrowth in ovo. The effectiveness of 450 MPa was attributed to the induction of DNA double-strand breaks, independent of apoptosis, autophagy, or methuosis. Furthermore, 450 MPa continued to induce immunogenic cell death. Our results demonstrate that 450 MPa of high hydrostatic pressure induces safe and sustained devitalization of head and neck cancer cells and tissues. Because of the heterogeneity in pressure resistance, we propose our approach as a starting point for determining the precise thresholds for other cancer entities. Further studies on head and neck cancer should focus on immunological co-cultures, combinations of immune checkpoint inhibition, and accurate anatomical reconstruction with pressure-treated autografts.

Discontinuation of anti­programmed cell death protein 1 immune checkpoint inhibition after complete remission in head and neck squamous cell carcinoma: A case report and literature review.

Programmed cell death protein 1 (PD-1) inhibition plays a central role in the current treatment of recurrent or metastatic head and neck squamous cell carcinoma (R/M-HNSCC). Some patients achieve a durable response, and even complete remission (CR) is possible, though it occurs rarely. In cases of durable CR, there are no guidelines regarding a possible discontinuation of immunotherapy. Since clinical experience on this issue is limited, the present study reported on a case of a durable CR following discontinuation of PD-1 inhibition in R/M-HNSCC and additionally presented an overview on the current literature. The present study reported on a case of CR of recurrent oropharyngeal cancer after four cycles of PD-1 monotherapy with Nivolumab. The therapy was discontinued after overall 46 cycles. Even after 3 more years of follow-up, there was no sign of tumor recurrence. Overall, according to reports from the literature, CR seems to be an indicator for durable disease control after therapy discontinuation. Since data on therapy termination is rare, decisions about when to stop successful immunotherapy in R/M-HNSCC have to be made individually for each patient.

Somatostatin Receptor-Directed PET/CT Can Differentiate Between Different Subtypes of Head and Neck Paragangliomas.

BACKGROUND: Given their neuroendocrine origin, head and neck paragangliomas (HNPGLs) can be imaged with somatostatin receptor (SSTR)-directed PET/CT. We aimed to determine whether the in vivo PET signal can differentiate between varying HNPGL subtypes. PATIENTS AND METHODS: Fourteen patients with HNPGL received pretherapeutic SSTR-PET/CTs using 68 Ga-DOTATOC. Six (42.9%) patients had a jugular paraganglioma (PGL-J), 5 (35.7%) were diagnosed with carotid paraganglioma (PGL-Cs), and the remaining 3 patients (21.4%) had PGL-C with pathogenic SDHx germline variants (PGL-C-SDH). A visual and quantitative assessment of the primary tumor on SSTR-PET was performed, including SUV max and target-to-background ratio (TBR). Quantitative values were then compared between subgroups of patients affected with different HNPGL entities. RESULTS: On visual assessment, all primary HNPGLs could be identified on SSTR-PET/CT. Quantification of HNPGL revealed substantially elevated SUV max in PGL-J (101.7 ± 58.5) when compared with PGL-C-SDH (13.4 ± 5.6, P < 0.05), but not when compared with PGL-C (66.7 ± 27.3, P = 0.4; PGL-C vs PGL-C-SDH, P = 0.2). TBR of PGL-J (202.9 ± 82.2), however, further differentiated between PGL-C (95.7 ± 45.4, P < 0.05) and PGL-C-SDH (20.4 ± 12.2, P < 0.01; PGL-C vs PGL-C-SDH, P = 0.3). Moreover, whole-body readout revealed metastases in 2/3 (66.7%) of PGL-C-SDH patients, with a single SSTR-expressing skeletal lesion in one subject and bipulmonary lesions in the other patient. CONCLUSIONS: In patients with HNPGL, SSTR-PET/CT identified the primary and metastatic disease and provides substantially elevated TBR, indicating excellent image contrast. PET-based quantification can also differentiate between varying HNPGL subtypes.

Multimodal treatment and immune checkpoint inhibition in sinonasal mucosal melanoma: real-world data of a retrospective, single-center study.

PURPOSE: Local failure and distant metastases occur frequently in sinonasal mucosal melanoma (SNMM). Response rates to chemotherapy are low and targetable mutations are rarely detected. However, there is increasing data indicating efficacy of immune checkpoint inhibition (ICI). The aim of this retrospective monocenter study was to assess the mutational landscape and to evaluate the outcome of surgical treatment and ICI in SNMM in a real-world setting. METHODS: Thirty-eight SNMM patients being treated between 1999 and 2020 at our institution were retrospectively reviewed. Survival curves were generated according to Kaplan-Meier and compared by the log-rank test. RESULTS: Local failure was seen in 60% of patients treated in a curative intent. Overall, 24% of all patients suffered from regional and 66% from distant metastases. Next generation sequencing revealed mutations of BRAF, NRAS and KRAS. One out of three patients treated with a primary ICI showed a complete response (CR) and two showed progressive disease. Eleven patients received ICI as a palliative treatment. CR could be observed in three patients and stable disease in one patient. In the whole study population, the 5-year overall survival rate (OS) was 26%. OS was better for patients who received ICI during the course of disease. CONCLUSIONS: Recurrences and distant metastases are frequent in SNMM. Durable CR could be observed after primary and palliative ICI. Therefore, ICI in a palliative, adjuvant or even neoadjuvant setting might play a promising role in SNMM therapy while targetable mutations are rarely detected.

Evaluation of the cytotoxic and genotoxic potential of printer toner particles in a 3D air-liquid interface, primary cell-based nasal tissue model.

Printer toner particles (TPs) are a common, potentially hazardous substance, with an unclear toxicological impact on the respiratory mucosa. Most of the airways surface is covered by a ciliated respiratory mucosa, therefore appropriate tissue models of the respiratory epithelium with a high in vivo correlation are necessary for in vitro evaluation of airborne pollutants toxicology and the impact on the functional integrity. The aim of this study is the evaluation of TPs toxicology in a human primary cell-based air-liquid-interface (ALI) model of respiratory mucosa. The TPs were analyzed and characterized by scanning electron microscopy, pyrolysis and X-ray fluorescence spectrometry. ALI models of 10 patients were created using the epithelial cells and fibroblasts derived from nasal mucosa samples. TPs were applied to the ALI models via a modified Vitrocell® cloud and submerged in the dosing 0.89 - 892.96 µg/ cm2. Particle exposure and intracellular distribution were evaluated by electron microscopy. The MTT assay and the comet assay were used to investigate cytotoxicity and genotoxicity, respectively. The used TPs showed an average particle size of 3 - 8 µm. Mainly carbon, hydrogen, silicon, nitrogen, tin, benzene and benzene derivates were detected as chemical ingredients. By histomorphology and electron microscopy we observed the development of a highly functional, pseudostratified epithelium with a continuous layer of cilia. Using electron microscopy, TPs could be detected on the cilia surface and also intracellularly. Cytotoxicity was detected from 9 µg/ cm2 and higher, but no genotoxicity after ALI and submerged exposure. The ALI with primary nasal cells represents a highly functional model of the respiratory epithelium in terms of histomorphology and mucociliary differentiation. The toxicological results indicate a weak TP-concentration-dependent cytotoxicity. AVAILABILITY OF DATA AND MATERIALS: The datasets used and analysed during the current study are available from the corresponding author on reasonable request.

[COVID-19: Collateral damage in head and neck oncology and preventive measures for future pandemics]. / COVID-19: Kollateralschäden in der Kopf-Hals-Onkologie und Präventivmaßnahmen für künftige Pandemien.

The start of the COVID-19 pandemic led to enormous challenges for global healthcare, as capacities and resources had to be made available quickly for the treatment of COVID-19 patients. As a result, restrictions had to be accepted, especially in the care of oncological patients. The collateral damage of these limitations inevitably also affects patients with head and neck cancer. This review article summarizes the development of tumor incidences during the pandemic, internationally developed guidelines for the care of patients with head and neck cancer and studies on the delay in oncological therapies and mortality. In addition, the effects on the mental health of the patients, the psychosocial consequences and ethical issues are examined. In perspective, preventive measures for such negative collateral effects in future pandemics are discussed using the example of a concept for application software (app)-based digital care for patients with head and neck cancer.

Aspergillus fumigatus-Specific T Cells in Patients with Chronic Rhinosinusitis.

INTRODUCTION: Aspergillus fumigatus belongs to the saprophytic fungi, and its spores form a significant part of the daily load of fungal spores inhaled as particles in aerosols. A. fumigatus is a possible T-cell activator. Its contribution to the pathogenesis of chronic rhinosinusitis (CRS) is controversially discussed. The aim of this study was to detect and characterize A. fumigatus-specific CD4+ and CD8+ T cells in patients with CRS with (CRSwNP) and without (CRSsNP) nasal polyps. METHODS: Tissue and blood samples were collected from patients who underwent paranasal sinus surgery due to CRSwNP or CRSsNP. Afterward, purified CD4+ and CD8+ cells were cultured together with antigen-presenting cells. A peptide mix derived from A. fumigatus antigen was added to the cultures. After 6 days, multicolor flow cytometry was performed, and proliferation was measured using the marker Ki-67. Cytokine secretion was quantified from the supernatant of the cell culture. RESULTS: Significant differences in the proliferation of nasal CD4+ T cells to A. fumigatus antigen were observed for cells from patients with CRSwNP in comparison to CRSsNP, while no differences were found between nasal and peripheral blood T cells. The activation of tissue-derived CD4+ T cells was associated with significantly higher concentrations of IL-4, IL-5, and IL-17a in the cell culture from patients with CRSwNP in comparison to CRSsNP and/or healthy controls. CONCLUSION: Our findings indicate that patients with CRSwNP harbor a higher proportion of A. fumigatus-reactive CD4+ T cells in the nasal mucosa than patients with CRSsNP. A. fumigatus-reactive CD4+ T cells of CRSwNP patients secreted TH2 cytokines and IL-17. Our findings suggest a role for A. fumigatus in the pathogenesis of CRSwNP and provide a rationale for targeted therapies.

The Impact of Tissue Preparation on Salivary Gland Tumors Investigated by Fourier-Transform Infrared Microspectroscopy.

Due to the wide variety of benign and malignant salivary gland tumors, classification and malignant behavior determination based on histomorphological criteria can be difficult and sometimes impossible. Spectroscopical procedures can acquire molecular biological information without destroying the tissue within the measurement processes. Since several tissue preparation procedures exist, our study investigated the impact of these preparations on the chemical composition of healthy and tumorous salivary gland tissue by Fourier-transform infrared (FTIR) microspectroscopy. Sequential tissue cross-sections were prepared from native, formalin-fixed and formalin-fixed paraffin-embedded (FFPE) tissue and analyzed. The FFPE cross-sections were dewaxed and remeasured. By using principal component analysis (PCA) combined with a discriminant analysis (DA), robust models for the distinction of sample preparations were built individually for each parotid tissue type. As a result, the PCA-DA model evaluation showed a high similarity between native and formalin-fixed tissues based on their chemical composition. Thus, formalin-fixed tissues are highly representative of the native samples and facilitate a transfer from scientific laboratory analysis into the clinical routine due to their robust nature. Furthermore, the dewaxing of the cross-sections entails the loss of molecular information. Our study successfully demonstrated how FTIR microspectroscopy can be used as a powerful tool within existing clinical workflows.

Surgical management of lateral neck abscesses in children: a retrospective analysis of 100 cases.

Cervical abscesses are relatively common infections in pediatric patients. There is an ongoing debate about the necessity and time point of surgical drainage. The identification of a focus of infection might play an important role in facilitating a therapeutic decision. In a retrospective study, 100 pediatric patients aged 1-18 years who underwent incision and drainage of a lateral cervical abscess at our institution were analyzed. Patients were divided into two groups based on whether a focus of infection could be identified or not. Data collection included patient characteristics, microbiological results, antibiotic regimen, and clinical course. A focus of infection was found in 29% (29/100) of the patients, most frequently in the tonsils. A causative microorganism was found in 75% (75/100) of all patients, with Staphylococcus aureus and Streptococcus pyogenes being the most common pathogens. All patients received an empiric antibiotic therapy in addition to surgery. Antibiotic medication was changed in 31% in both groups (9/29 with a focus of infection and 22/71 without a focus of infection) during therapy. Children without an identified focus of infection generally were younger and had more comorbidities reducing immune response while also showing differences in the pathogens involved. There were no complications associated to surgery or antibiotic therapy in any of the patients involved. CONCLUSION: Children with an identified focus of infection show several differences compared to those with isolated lateral abscesses, especially regarding the microorganisms involved. But the focus of infection seems not to have an impact on patient's outcome. WHAT IS KNOWN: • Neck abscesses are a relatively common disease in the pediatric population and may cause serious complications. • Therapy in general consists of intravenous antibiotics with or without surgery. WHAT IS NEW: • The focus identification has no impact on patient's outcome. • Children with an identified focus of infection show several differences compared to those with isolated lateral abscesses, especially regarding their medical history, age, and the microorganisms involved.

Influence of Wound Fluid on the Transdifferentiation of Human Mesenchymal Bone Marrow Stem Cells into Cancer-Associated Fibroblasts.

Cancer-associated fibroblasts (CAF) in the tumor microenvironment have a decisive influence on tumor growth and metastatic behavior. The cellular origins as well as the stimuli leading to CAF formation are heterogenous, impeding a precise characterization. Aim of this study was to analyze the influence of cytokines secreted in the process of wound healing, tumor cell-associated paracrine-secreted factors, and direct cell-cell contact on the expression of the CAF-associated markers fibroblast activation protein (FAP), α-smooth muscle actin (α-SMA), thrombospondin-1 (THBS1), and tenascin-c (TNC) by RT-PCR in mesenchymal stem cells (MSC). Cells developed different morphological characteristics after incubation with wound fluid (WF). Moreover, expression of FAP and α-SMA in MSC was significantly reduced after WF compared to tumor-conditioned medium and in co-culture with tumor cells; THBS1 and TNC were not significantly altered after any of the different incubation methods. There were no alterations of expression patterns of FAP and α-SMA in the immunohistochemical analysis. Differ-ences in the cytokine composition of the media were found in the dot blot. The heterogeneity of the results emphasizes the complexity of the interactions of tumor cells and cells of the microenvironment, particularly through the addition of human-derived WF.

Differentiation of Salivary Gland and Salivary Gland Tumor Tissue via Raman Imaging Combined with Multivariate Data Analysis.

Salivary gland tumors (SGTs) are a relevant, highly diverse subgroup of head and neck tumors whose entity determination can be difficult. Confocal Raman imaging in combination with multivariate data analysis may possibly support their correct classification. For the analysis of the translational potential of Raman imaging in SGT determination, a multi-stage evaluation process is necessary. By measuring a sample set of Warthin tumor, pleomorphic adenoma and non-tumor salivary gland tissue, Raman data were obtained and a thorough Raman band analysis was performed. This evaluation revealed highly overlapping Raman patterns with only minor spectral differences. Consequently, a principal component analysis (PCA) was calculated and further combined with a discriminant analysis (DA) to enable the best possible distinction. The PCA-DA model was characterized by accuracy, sensitivity, selectivity and precision values above 90% and validated by predicting model-unknown Raman spectra, of which 93% were classified correctly. Thus, we state our PCA-DA to be suitable for parotid tumor and non-salivary salivary gland tissue discrimination and prediction. For evaluation of the translational potential, further validation steps are necessary.

Head and neck squamous cancer cells enhance the differentiation of human mesenchymal stem cells to adipogenic and osteogenic linages in vitro.

Human mesenchymal stem cells (hMSC) are multipotent cells with the ability to differentiate into a range of different cell types, including fat, bone, cartilage or muscle. A pro-tumorigenic effect of hMSC has been previously reported as part of the tumor stroma. In addition, studies have previously revealed the influence of hematopoietic and lymphoid tumors on hMSC differentiation to support their own growth. However, this possible phenomenon has not been explored in solid malignancies. Therefore, the aim of the present study was to investigate the effects of head and neck squamous cell carcinoma (HNSCC) lines Cal27 and HLaC78 on the induction of osteogenic and adipogenic differentiation in hMSCs. Native hMSCs were co-cultured with Cal27 and HLaC78 cells for 3 weeks. Subsequently, hMSC differentiation was assessed using reverse transcription-PCR and using Oil Red O and von Kossa staining. Furthermore, the effects of differentiated hMSCs on Cal27 and HLaC78 were examined. For this purpose, hMSCs differentiated into the adipogenic (adipo-hMSC) and osteogenic (osteo-hMSC) lineages were co-cultured with Cal27 and HLaC78. Cell viability, cytokine secretion and activation of STAT3 signaling were measured by cell counting, dot blot assay (42 cytokines with focus on IL-6) and western blotting (STAT3, phosphorylated STAT3, ß-actin), respectively. Co-culturing hMSCs with Cal27 and HLaC78 cells resulted in both adipogenic and osteogenic differentiation. In addition, the viability of Cal27 and HLaC78 cells was found to be increased after co-cultivation with adipo-hMSCs, compared with that of cells co-cultured with osteo-hMSC. According to western blotting results, Cal27 cells incubated with adipo-hMSCs exhibited increased STAT3 activation, compared with that in cells co-cultured with native hMSCs and osteo-hMSCs. IL-6 concentration in the media of Cal27 and HLaC78 after co-cultivation with respectively incubation with conditioned media of hMSCs, adipo-hMSCs and osteo-hMSCs were also found to be increased compared with that in the media of Cal27 and HLaC78 cells incubated with DMEM. To conclude, HNSCC cell lines Cal27 and HLaC78 induced hMSC differentiation towards the adipogenic and osteogenic lineages in vitro. Furthermore, a proliferative effect of adipo-hMSCs on Cal27 and HLaC78 cells was revealed with STAT3 activation as a possible mechanism. These results warrant further investigation of the interaction between HNSCC cells and hMSCs, with focus on the mechanism underlying the differentiation of hMSCs.

Surgical management of tympanojugular paragangliomas using the flexible CO2 laser.

PURPOSE: Surgery is a standard therapy for tympanojugular paragangliomas (TJP). Maintaining the quality of life (QoL) requires functional preservation. The flexible CO2 laser allows contact-free tumor removal. This retrospective study compares the postoperative functional outcomes of TJP surgery with and without the flexible CO2 laser. METHODS: Between 2005 and 2019, 51 patients with TJP were surgically treated at a tertiary hospital. Until 2012, 17 patients received conventional surgery. Thereafter, the flexible laser was used in 34 patients. Tumor extend, pre- and postoperative cranial nerve function, and complications were compared between the groups. RESULTS: The cohort consisted of 33 class A and B tumors and 18 class C and D tumors. Preoperative embolization was performed in 17 cases. Class C/D TJP were usually removed via an infratemporal fossa type A approach. Gross total tumor removal was achieved in 14/18 class C/D tumors. 3/51 patients suffered from long-term partial or complete facial palsy. No differences in post-therapeutic cranial nerve function or complications were noted between the conventional and laser group. One recurrence was observed after complete tumor resection. CONCLUSION: The flexible CO2 laser was shown to be a safe and effective alternative to conventional bipolar cauterization, which is appreciated by the surgeon in these highly vascularized tumors. Both techniques allowed a high tumor control rate and good long-term results also from a functional point of view.

Deep neck infections with and without mediastinal involvement: treatment and outcome in 218 patients.

PURPOSE: Infections of the deep neck, although becoming scarcer due to the widespread use of antibiotics, still represent a dangerous and possibly deadly disease, especially when descending into the mediastinum. Due to the different specialities involved in the treatment and the heterogenous presentation of the disease, therapeutic standard is still controversial. This study analyzes treatment and outcome in these patients based on a large retrospective review and proposes a therapeutic algorithm. METHODS: The cases of 218 adult patients treated with deep neck abscesses over a 10-year period at a tertiary university hospital were analyzed retrospectively. Clinical, radiological, microbiological and laboratory findings were compared between patients with and without mediastinal involvement. RESULTS: Forty-five patients (20.64%) presented with abscess formation descending into the mediastinum. Those patients had significantly (all items p < 0.0001) higher rates of surgical interventions (4.27 vs. 1.11) and tracheotomies (82% vs. 3.4%), higher markers of inflammation (CRP 26.09 vs. 10.41 mg/dl), required more CT-scans (3.58 vs. 0.85), longer hospitalization (39.78 vs 9.79 days) and more frequently needed a change in antibiotic therapy (44.44% vs. 6.40%). Multi-resistant pathogens were found in 6.67% vs. 1.16%. Overall mortality rate was low with 1.83%. CONCLUSION: Despite of the high percentage of mediastinal involvement in the present patient collective, the proposed therapeutic algorithm resulted in a low mortality rate. Frequent CT-scans, regular planned surgical revisions with local drainage and lavage, as well as an early tracheotomy seem to be most beneficial regarding the outcome.

Pilot study on the value of Raman spectroscopy in the entity assignment of salivary gland tumors.

BACKGROUND: The entity assignment of salivary gland tumors (SGT) based on histomorphology can be challenging. Raman spectroscopy has been applied to analyze differences in the molecular composition of tissues. The aim of this study was to evaluate the suitability of RS for entity assignment in SGT. METHODS: Raman data were collected in deparaffinized sections of pleomorphic adenomas (PA) and adenoid cystic carcinomas (ACC). Multivariate data and chemometric analysis were completed using the Unscrambler software. RESULTS: The Raman spectra detected in ACC samples were mostly assigned to nucleic acids, lipids, and amides. In a principal component-based linear discriminant analysis (LDA) 18 of 20 tumor samples were classified correctly. CONCLUSION: In this proof of concept study, we show that a reliable SGT diagnosis based on LDA algorithm appears possible, despite variations in the entity-specific mean spectra. However, a standardized workflow for tissue sample preparation, measurement setup, and chemometric algorithms is essential to get reliable results.