[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.

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.

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.

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.

Investigation of Cellular Function and DNA Integrity during 2D in vitro Culture of Human Salivary Gland Epithelial Cells.

In vitro culture of human salivary gland epithelial cells (SGEC) is still a challenge. A high quantity and quality of cells are needed for the cultivation of 3D matrices. Furthermore, it is known that DNA damage is supposed to be an important factor involved in carcinogenesis. This study investigates cellular function and DNA integrity of human SGEC during 3 passage steps in 2 groups (group 1: n = 10; group 2: n = 9). Cellular function was analyzed by immunofluorescence, transmission electron microscopy (TEM), and quantitative real-time polymerase chain reaction (qPCR). DNA integrity was tested via the comet assay. Immunohistochemistry and qPCR results showed stable α-amylase and pan-cytokeratin levels; TEM revealed functional cells; and no significant DNA damage could be detected in the comet assay during 3 culture steps. The study shows that not only at cellular but also at DNA level human SGEC can be safely quantified over 3 passages for preclinical tissue engineering without loss of differentiation and function.

[Laserhemorrhoidoplasty with 1470 nm Diode Laser in the Treatment of Second to Fourth Degree Hemorrhoidal Disease - a Cohort Study with 497 Patients]. / Laserhämorrhoidoplastie mit dem 1470-nm-Diodenlaser in der Behandlung des zweit- bis viertgradigen Hämorrhoidalleidens ­ eine Kohortenstudie mit 497 Fällen.

BACKGROUND: Laser haemorrhoidoplasty (LHP) with the 1470 nm diode laser in minimally invasive surgery for advanced haemorrhoid disease has been studied with respect to clinical variables, such as pain and complications, and intraoperative characteristics such as mucopexia, number of treated knots and energy consumed per patient. The study also included patient satisfaction, symptom relevance and cost effectiveness. PATIENTS AND METHODS: Between November 2010 and November 2016, 497 patients (age 55 ± 14 years) were submitted to laser haemorrhoidoplasty with a 1470 nm diode laser in the centre for minimally invasive proctology in Siegen District Hospital. All operated patients were included in the study. Perioperative clinical and technical data up to 6 weeks and follow-up data up to 6 months were analysed prospectively. RESULTS: The mean duration of operation was 14 min (± 5.2). A mean of 2.7 knots of 2.7 size were treated per patient. The mean postoperative pain was 2.5/10 (VAS). Long-term symptom relevance was 86%, and patient satisfaction 91%. Complications occurred in 49 patients (9.9%): bleeding 1.8%, infection 1%, urine retention 1.8%, oedema/thrombosis/prolapse 6.6%. 8.8% of patients suffered a relapse within 6 months. There were significant differences in pain on the day of the operation, and the parameters mucopexia, 3 treated segments and energy level > 500 J (p < 0.05). Complications were more common when mucopexia was performed, with 3 treated knots and energy consumed per patient > 500 J. The only significant difference was for energy level > 500 J (p < 0.05). CONCLUSION: LHP is a safe, low pain and minimally invasive surgical procedure with long-term good patient acceptance and satisfaction and is suited for routine work. The energy applied should be reduced to a minimum. Complication rates are largely comparable with those of other minimally invasive conventional methods. Additional prospective studies must be performed, particularly in comparison to the Parks method, which gives similar functional results. With circular confluent findings, LHP cannot replace stapler hemorrhoidopexia.

[Mesenchymal stem cells: Cancer promoting effects or tumor suppression - A current overview]. / Mesenchymale Stammzellen: Tumorfördernde oder -hemmende Eigenschaften ­ Ein aktueller Überblick.

The multimodal treatment of cancer deals with cancer cells as well as with the cancer surrounding stroma. This stroma contains non-malignant cells like fibroblasts, immune cells as well as mesenchymal stem cells (MSC). MSC have the ability to migrate towards cancer tissue. In the current literature the impact of MSC on cancer cells is discussed divergently. The majority of the current publications reveal an induction of cancer progression by MSC. Four main processes namely the secretion of soluble factors and cell-cell contact, the transdifferentiation of MSC into carcinoma associated fibroblasts, the improvement of neoangiogenesis and the induction of immune suppression are responsible for cancer progression. This publication gives an overview on the current literature.

Perioperative changes in osteopontin and TGFß1 plasma levels and their prognostic impact for radiotherapy in head and neck cancer.

BACKGROUND: In head and neck cancer little is known about the kinetics of osteopontin (OPN) expression after tumor resection. In this study we evaluated the time course of OPN plasma levels before and after surgery. METHODS: Between 2011 and 2013 41 consecutive head and neck cancer patients were enrolled in a prospective study (group A). At different time points plasma samples were collected: T0) before, T1) 1 day, T2) 1 week and T3) 4 weeks after surgery. Osteopontin and TGFß1 plasma concentrations were measured with a commercial ELISA system. Data were compared to 131 head and neck cancer patients treated with primary (n = 42) or postoperative radiotherapy (n = 89; group B1 and B2). RESULTS: A significant OPN increase was seen as early as 1 day after surgery (T0 to T1, p < 0.01). OPN levels decreased to base line 3-4 weeks after surgery. OPN values were correlated with postoperative TGFß1 expression suggesting a relation to wound healing. Survival analysis showed a significant benefit for patients with lower OPN levels both in the primary and postoperative radiotherapy group (B1: 33 vs 11.5 months, p = 0.017, B2: median not reached vs 33.4, p = 0.031). TGFß1 was also of prognostic significance in group B1 (33.0 vs 10.7 months, p = 0.003). CONCLUSIONS: Patients with head and neck cancer showed an increase in osteopontin plasma levels directly after surgery. Four weeks later OPN concentration decreased to pre-surgery levels. This long lasting increase was presumably associated to wound healing. Both pretherapeutic osteopontin and TGFß1 had prognostic impact.

Vascularization of engineered cartilage constructs in a mouse model.

Tissue engineering of cartilage tissue offers a promising method for reconstructing ear, nose, larynx and trachea defects. However, a lack of sufficient nutrient supply to cartilage constructs limits this procedure. Only a few animal models exist to vascularize the seeded scaffolds. In this study, polycaprolactone (PCL)-based polyurethane scaffolds are seeded with 1 × 10(6) human cartilage cells and implanted in the right hind leg of a nude mouse using an arteriovenous flow-through vessel loop for angiogenesis for the first 3 weeks. Equally seeded scaffolds but without access to a vessel loop served as controls. After 3 weeks, a transposition of the vascularized scaffolds into the groin of the nude mouse was performed. Constructs (verum and controls) were explanted 1 and 6 weeks after transposition. Constructs with implanted vessels were well vascularized. The amount of cells increased in vascularized constructs compared to the controls but at the same time noticeably less extracellular matrix was produced. This mouse model provides critical answers to important questions concerning the vascularization of engineered tissue, which offers a viable option for repairing defects, especially when the desired amount of autologous cartilage or other tissues is not available and the nutritive situation at the implantation site is poor.

Feasibility of Optical Biopsy During Endoscopic Sinus Surgery With Confocal Laser Endomicroscopy: A Pilot Study.

OBJECTIVE: Confocal laser endomicroscopy (CLE) is an optical imaging technique that allows in vivo, real-time, microscope-like assessment of superficial lesions. Although there is substantial data on CLE use in the upper GI tract, there is limited information regarding its application in the nasal cavity and paranasal sinuses. This study aims to assess the feasibility and diagnostic metrics of CLE in the nasal cavity and paranasal sinuses regarding differentiation between healthy/benign and malignant tissue. These structures show, however, a wider variety of frequent and concomitant benign and malignant pathologies, which could pose an increased challenge for optical biopsy by CLE. METHODS: We performed CLE on a case series of six patients with various findings in the nose (three chronic rhinosinusitis, adenocarcinoma, meningoenzephalozele, esthesionneuroblastoma). Forty-two sequences (3792 images) from various structures in the nasal cavity and/or paranasal sinuses were acquired. Biopsies were taken at corresponding locations and analyzed in hematoxylin and eosin staining as a standard of reference. Three independent examiners blinded to the histopathology assessed the sequences. RESULTS: Healthy and inflamed mucosa could be distinguished from malignant lesions with an accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of 84.1%, 85.4%, 83.1%, 72.5%, and 92.1%, respectively, with a substantial agreement between raters (Fleiss κ = 0.62). CONCLUSION: This technique shows, despite its limitations, potential as an adjunctive imaging technique during sinus surgery; however, the creation of a scoring system based on reproducible and defined characteristics in a larger more diverse population should be the focus of further research to improve its diagnostic value and clinical utility. LEVEL OF EVIDENCE: NA Laryngoscope, 2024.

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.

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.

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.

Mental Health and Health-Related Quality of Life in German Adolescents after the Third Wave of the COVID-19 Pandemic.

Evaluations after the first and second waves of the COVID-19 pandemic in Germany showed an increase in mental health problems and a reduction in health-related quality of life (HRQoL). The aim of the study was to assess those aspects after the third wave of COVID-19 in adolescents who decided to receive a vaccination. In students aged 12-17 years recruited from schools in one German region, mental health (by the strengths and difficulties questionnaire, SDQ) and HRQoL (by KIDSCREEN-10) were assessed by both a self- and parental report. Data from 1412 adolescents (mean age 14.3 years, SD = 1.64) and 908 parents were collected. The mean self-reported HRQoL was T = 53.7 (SD = 11.2), significantly higher in boys than in girls and higher in younger (12-14 years) than in older (15-17 years) adolescents. In total, 18.7% of adolescents reported clinically relevant psychological symptoms, especially peer problems (23.5%), emotional problems (17.4%), and hyperactivity (17.1%). Comparing the present data to evaluations after the first and second waves of COVID-19, adolescents rated a higher HRQoL and reported less mental health problems after the third wave. After 1.5 years of living with the pandemic, adolescents have adapted to the changes in everyday life. Further, the relaxation of restrictions, better school organization, and the prospect of the vaccination may have increased optimism, wellbeing, and contentment, leading to declining but still alarming rates of psychological symptoms.

Problematic Internet Use among Adolescents 18 Months after the Onset of the COVID-19 Pandemic.

Studies in recent years and especially since the beginning of the COVID-19 pandemic have shown a significant increase in the problematic use of computer games and social media. Adolescents having difficulties in regulating their unpleasant emotions are especially prone to Problematic Internet Use (PIU), which is why emotion dysregulation has been considered a risk factor for PIU. The aim of the present study was to assess problematic internet use (PIU) in adolescents after the third wave (nearly 1.5 years after the onset in Europe) of the COVID-19 pandemic. In the German region of Siegen-Wittgenstein, all students 12 years and older from secondary-level schools, vocational schools and universities were offered a prioritized vaccination in August 2021 with an approved vaccine against COVID-19. In this context, the participants filled out the Short Compulsive Internet Use Scale (SCIUS) and two additional items to capture a possible change in digital media usage time and regulation of negative affect due to the COVID-19 pandemic. A multiple regression analysis was performed to identify predictors of PIU. The original sample consisted of 1477 participants, and after excluding invalid cases the final sample size amounted to 1268 adolescents aged 12-17 (x = 14.37 years, SD = 1.64). The average prevalence of PIU was 43.69%. Gender, age, digital media usage time and the intensity of negative emotions during the COVID-19 pandemic were all found to be significant predictors of PIU: female gender, increasing age, longer digital media usage time and higher intensity of negative emotions during the COVID-19 pandemic were associated with higher SCIUS total scores. This study found a very high prevalence of PIU among 12- to 17-year-olds for the period after the third wave of the COVID-19 pandemic, which has increased significantly compared to pre-pandemic prevalence rates. PIU is emerging as a serious problem among young people in the pandemic. Besides gender and age, pandemic-associated time of digital media use and emotion regulation have an impact on PIU, which provides starting points for preventive interventions.

Tuberculosis in the Head and Neck: Changing Trends and Age-Related Patterns.

OBJECTIVE: To evaluate changing trends in patient collectives, age-related patterns of manifestation, and diagnostic pathways of patients with extrapulmonary head and neck tuberculosis (TB), and to provide strategies to fasten diagnosis in these patients. STUDY DESIGN: Case control study. METHODS: A 10-year retrospective analysis of 35 patients diagnosed with extrapulmonary TB in the head and neck at a tertiary university institution from 2009 to 2019, with special focus on the influence of the patient's age on consideration of TB and clinical patterns. RESULTS: The vast majority of patients younger than 40 years had their origin in countries with high TB burden (P = .0003), and TB was considered very early as a differential diagnosis (P = .0068), while most patients older than 40 years were domestic citizens initially suspected for a malignancy, who more often had an underlying immunosuppressive condition (0.0472). Most frequent manifestations in both groups were the lymph nodes, larynx, and oropharynx. Surprisingly, no differences in the rates of open TB or history of TB infection in the family anamnesis were found. CONCLUSION: The two groups of patients found most often are younger patients migrating from regions with high TB burden and elderly domestic patients suffering from immunosuppressive conditions, with the latter often being misdiagnosed as malignancies. TB remains an important but difficult differential diagnosis, due to the initially unspecific symptoms and the great variety in the presentation of manifestations in the head and neck. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2701-2705, 2021.

Effect of Hypoxia on Proliferation and the Expression of the Genes HIF-1α and JMJD1A in Head and Neck Squamous Cell Carcinoma Cell Lines.

BACKGROUND/AIM: The aim of the study was to investigate the effects of hypoxia on proliferation and the expression of HIF-1α (hypoxia-inducible factor 1 alpha) and JMJD1A (jumonji domain 1A) in head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: FaDu and HLaC78 cells were incubated for 1-24 h in hypoxia and normoxia. Cell proliferation, mRNA and protein levels of HIF-1α and JMJD1A were quantified by counting, PCR and western blot. RESULTS: Hypoxia led to a constant decrease in cell proliferation. Short hypoxia resulted in an increase in HIF-1α mRNA levels. This effect was reversed after longer incubation. The western blot for HIF-1α showed a maximum accumulation after 3-6 h of hypoxia. In FaDu cells, the concentration of JMJD1A reached a peak after 6 h and decreased thereafter, whereas in HLaC78 cells, it presented a second peak after 48 h. CONCLUSION: The transcription factors HIF-1α and JMJDA1 were confirmed as relevant hypoxia-dependent regulators of carcinogenesis in HNSCC.

Interaction of head and neck squamous cell carcinoma cells and mesenchymal stem cells under hypoxia and normoxia.

Mesenchymal stem cells (MSCs) exhibit strong tropism towards tumor tissue. While MSCs generally surround tumors, they can also infiltrate tumors and thereby influence their proliferation. Interactions between MSCs and tumor cells are usually tested under normoxia, but the majority of solid tumors, including head and neck squamous cell carcinoma (HNSCC), are also characterized by hypoxic areas. Hence, the present study aimed to assess the interaction between MSCs and tumor cells under hypoxic conditions. MSCs were cultivated under normoxia and hypoxia, and conditioned media were used to cultivate the HNSCC cell line FaDu. The cell cycle distribution and viability of MSCs and the proliferation of FaDu cells were analyzed under normoxia and hypoxia, and changes in cytokine levels in the conditioned media were evaluated. No cell cycle changes were observed for MSCs after 24 h of cultivation under hypoxia, but the cell viability had declined. Hypoxia also led to a decrease in the proliferation of FaDu cells; however, FaDu cells proliferated faster after 48 h under hypoxia compared with normoxic conditions. This effect was reversed after incubation under normoxia for 72 h and hypoxia for 72 h. While these changes constituted a trend, these differences were not statistically significant. A cytokine assay showed an increase in interleukin (IL)-6 in the hypoxic medium. Overall, the results indicated that there was an interaction between MSCs and tumor cells. The presence or absence of oxygen seemed to influence the functionality of MSCs and their protumorigenic properties, in which IL-6 was identified as a potential mediator. Since MSCs are a component of the tumor stroma, further in vitro and in vivo studies are needed to investigate this interaction in order to develop novel approaches for tumor therapy.

Laryngeal mask versus intubation for adenoidectomies in children: Analysis of 1,500 operations.

OBJECTIVES/HYPOTHESIS: To evaluate whether endotracheal intubations are superior to the use of laryngeal masks in the airway management for adenoidectomies in pediatric patients in terms of safety and duration of surgery. STUDY DESIGN: Retrospective case series. METHODS: A retrospective analysis of 1,500 adenoidectomies in children using laryngeal mask or endotracheal intubation for intraoperative ventilation between 2009 and 2017. Data collected included complications, duration of surgery, and duration of induction and emergence from anesthesia. RESULTS: The use of laryngeal masks did not accelerate the time needed for induction and emergence of anesthesia although significantly increasing the duration of surgery itself. There also were significantly more complications during and after anesthesia when using a laryngeal mask. In 10% of the children, the laryngeal mask had to be replaced by an endotracheal tube intraoperatively. CONCLUSIONS: There is no reason to recommend the use of a laryngeal mask as the first choice of airway management regarding adenoidectomies in children. LEVEL OF EVIDENCE: 3 Laryngoscope, 129:E383-E388, 2019.

Wound fluid enhances cancer cell proliferation via activation of STAT3 signal pathway in vitro.

Wound healing begins immediately after surgery with a modification of the microenvironment via a well­orchestrated interaction between cells, cytokines and growth factors. Some of these growth factors and cytokines have mitogenic effects on cancer cells, which may lead to enhanced cancer cell proliferation and early metastatic events. The present study aimed to investigate the effects of wound fluid (WF) on the head and neck squamous carcinoma cell lines FaDu and HLaC78 in vitro. WF was harvested from 7 patients who had undergone a planned neck dissection. The presence of cytokines and growth factors was evaluated with the dot blot assay. Proliferation and cell viability were investigated via MTT assay and Ki-67 staining. Cell invasion was measured via tree­dimensional invasion assay. Western blotting was used to investigate STAT 3 activation. WF contained several cytokines and growth factors responsible for pro­ and anti­inflammation, chemotaxis, proliferation and angiogenesis. The proliferation effect of WF on FaDu and HLaC78 was concentration dependent. Media with 40% WF resulted in the highest proliferation effect. FaDu and HLaC78 exhibited enhanced motility after cultivation with 40% WF compared with cultivation with expansion medium. Cultivating cancer cells with WF had no advantageous effect on cell viability after the paclitaxel treatment. Western blot analysis revealed enhanced activation of the STAT3 signaling pathway by WF in both FaDu and HLaC78. In conclusion, surgery leads to excessive release of mitogenic factors. The contact of non­resected cancer cells and these factors may have a negative impact on patient outcome. Future investigations should specifically focus on the inhibition of mitogenic factors following cancer surgery in order to prevent early metastasis and cancer recurrence.