Preoperative percutaneous Onyx embolization of carotid body paragangliomas with balloon test occlusion.

Objectives: The study aims to analyze our first experience with direct percutaneous embolization of carotid body tumors (CBTs) using ethylene-vinyl alcohol copolymer (Onyx) along with balloon test occlusion (BTO). Methods: A retrospective preliminary single-center study was conducted at the Otorhinolaryngology and Head and Neck Surgery Department and the Medical Imaging Department of the University Teaching Hospital. A consecutive series of three patients with CBTs was treated at the local institution between October 2018 and June 2019. All three patients underwent preoperative percutaneous embolization using ethylene-vinyl alcohol copolymer (Onyx 18) with the addition of BTO. Outcome measures were the percentage of tumor devascularization, intraoperative blood losses, and operation times. BTO was evaluated by clinical neurological examination and neurosonological transcranial Doppler examination of the middle cerebral artery (MCA). Results: Devascularization of all three tumors was complete or near complete. All three tumors were surgically extirpated with excellent surgical outcomes. The blood losses were minimal, and the average operation time was 2 h and 8 min. BTO was positive in one patient, which was valuable additional information on carotid branches ligation limitations. The other two patients showed negative BTOs with the result of safety of eventual carotid arteries ligations. Conclusion: Preoperative direct percutaneous embolization of CBT with Onyx is a highly effective procedure that significantly facilitates surgery. BTO provides valuable additional information on the most appropriate and safe surgical approach.

Prevalence of Fabry disease in men with tinnitus and sensorineural hearing loss.

Fabry disease (FD) is a lysosomal storage disorder caused by pathogenic mutations in the alpha-galactosidase A (AGALA) encoding gene region. This rare disease affects several organs including the cochlea-vestibular system. Tinnitus and sensorineural hearing loss (SNHL) are reported among otoneurological symptoms. Early and correct diagnosis of FD is important with a view to available therapy. The aim of the study was to screen for alpha-galactosidase deficiency in men with tinnitus/SNHL. A prospective multicentric study including consecutive patients with SNHL confirmed by tone audiometry or tinnitus evaluated (10/2016-8/2019). The diagnosis of AGALA deficiency was done by dry blood spot method using a threshold of 1.2 µmol/l/h. Only men aged 18-60 were included. 181 patients were subject to evaluation. SNHL was reported in 126 (70%) patients, 50 (28%) patients had unilateral, 76 (42%) patients had bilateral SNHL. Tinnitus was found in 161 (89%) patients, unilateral in 96 (53%) and bilateral in 65 (36%) patients. Suspected FD was not detected in any patient; alpha-galactosidase The AGALA values ranged 1.5-8.8 µmol/l/h, an average of 3.4 µmol/l/h. None of the 181 patients participating in the study had AGALA levels below the threshold 1.2 µmol/l/h. The occurrence of tinnitus and sensorineural hearing loss in men appears to be an irrelevant clinical sign for FD systematic screening.

Gene Mutations in Circulating Tumour DNA as a Diagnostic and Prognostic Marker in Head and Neck Cancer-A Systematic Review.

(1) Background: Head and Neck Squamous Cell Carcinoma (HNSCC) is one of the most common malignancies globally. An early diagnosis of this disease is crucial, and the detection of gene mutations in circulating tumour DNA (ctDNA) through a liquid biopsy is a promising non-invasive diagnostic method. This review aims to provide an overview of ctDNA mutations in HNSCC patients and discuss the potential use of this tool in diagnosis and prognosis. (2) Methods: A systematic search for articles published in the English language between January 2000 and April 2021 in the Medline and Scopus databases was conducted. (3) Results: A total of 10 studies published in nine publications were selected and analysed. Altogether, 390 samples were obtained from HNSCC patients, and 79 control samples were evaluated. The most often explored gene mutation in ctDNA was TP53. (4) Conclusions: The examination of a larger group of gene mutations and the use of a combination of multiple detection methods contribute to a higher detection rate of mutated ctDNA. More studies are necessary to verify these conclusions and to translate them into clinical practice.

Salivary microRNAs identified by small RNA sequencing as potential predictors of response to intensity-modulated radiotherapy in head and neck cancer patients.

PURPOSE: Progress in radiation therapy of head and neck squamous cell carcinomas (HNSCCs) is logically linked to the development of molecular predictors that would help to enhance individually tailored treatment. MicroRNA (miRNA) expression profiles in tumors have repeatedly been tested to optimize the molecular diagnostics of HNSCC. In addition to tumor tissues, miRNAs are stably present in body fluids, including saliva, and can thus be collected non-invasively. The aim of our current study was to evaluate whether salivary miRNAs have potential as response predictors in HNSCC patients treated with intensity modulated radiation therapy (IMRT). METHODS: In total 48 HNSCC patients treated by definitive IMRT were enrolled in our prospective study. To identify predictive salivary miRNAs, we used small RNA sequencing in 14 saliva samples of HNSCC patients and qRT-PCR validation of selected miRNA candidates in an independent set of 34 patients. RESULTS: We found that salivary miR-15a-5p and miR-15b-5p exhibited differential levels between patients with and without complete remission (p = 0.025 and p = 0.028, respectively). Subsequent Kaplan-Meier analysis confirmed that patients with higher levels of miR-15a-5p reached a significantly longer locoregional progression-free survival (LPFS) than those with low levels (p = 0.024). Finally, multivariate Cox regression analysis revealed that miR-15a-5p may serve as an independent predictive biomarker of LPFS in HNSCC patients treated with IMRT (HR 0.104; 95% CI 0.004-0.911; p = 0.04). CONCLUSIONS: We conclude that salivary miR-15a-5p may represent a potential biomarker for individualized treatment decision-making in HNSCC patients.

Biomarkers - a possibility for monitoring of obstructive sleep apnea syndrome.

OBJECTIVES: Sleep apnea syndrome affects approximately 4% of adult males and 2% of adult females. It is associated with significant cardio-, cerebrovascular, metabolic and hormonal comorbidities and ranks among the more expensive medical specialties due to the requirement of high-quality technical diagnostic and therapeutic equipment as well as well-educated and experienced personnel. The aim of this study is to detect the relationship between C-reactive protein (CRP), pentraxin-3 (PTX-3), interleukin 6 (IL6), high-sensitivity troponin I (hsTnI), brain natriuretic protein (BNP) and galectin-3 serum levels and obstru-ctive sleep apnea syndrome. DESIGN: Prospective cohort study. MATERIAL AND METHODS: A group of 146 patients with middle to severe obstructive sleep apnea syndrome (OSAS) were monitored, and the results were compared with the results from a control group of healthy individuals. RESULTS: We assessed serum levels of the following biomarkers: CRP, PTX-3, IL6, hsTnI, BNP, and galectin-3. PTX-3 serum levels were statistically significantly higher (p<0.0001) in patients with OSAS, compared to controls. Statistical results related to the other biomarkers did not suggest any clinical value. ROC analysis showed that PTX-3 might be able to distinguish patients with OSAS from healthy individuals (AUC=7438). CONCLUSION: The elevation of PTX-3 serum levels is significantly associated with middle to severe obstructive sleep apnea syndrome. The PTX-3 biomarker appears to be a promising alternative method for sleep apnea syndrome investigations.

MicroRNA-15b-5p Predicts Locoregional Relapse in Head and Neck Carcinoma Patients Treated With Intensity-modulated Radiotherapy.

BACKGROUND/AIM: Head and neck cancers are a heterogenous group of epithelial tumors represented mainly by squamous cell carcinomas (HNSCC), which are the sixth most common type of cancer worldwide. Surgery together with radiotherapy (RT) is among the basic treatment modalities for most HNSCC patients. Various biomarkers aiming to predict patients' response to RT are currently investigated. The reason behind this effort is, on one hand, to distinguish radioresistant patients that show weak benefit from RT and, on the other hand, reduce the ionizing radiation dose in less aggressive radiosensitive HNSCC with possibly less acute or late toxicity. MATERIALS AND METHODS: A total of 94 HNSCC patients treated by definitive intensity-modulated radiotherapy were included in our retrospective study. We used a global expression analysis of microRNAs (miRNAs) in 43 tumor samples and validated a series of selected miRNAs in an independent set of 51 tumors. RESULTS: We identified miR-15b-5p to be differentially expressed between patients with short and long time of locoregional control (LRC). Kaplan-Meier analysis confirmed that HNSCC patients with higher expression of miR-15b-5p reach a significantly longer locoregional relapse-free survival compared to patients expressing low levels. Finally, multivariable Cox regression analysis revealed that miR-15b-5p is an independent predictive biomarker of LRC in HNSCC patients (HR=0.25; 95% CI=0.05-0.78; p<0.016). CONCLUSION: miR-15b-5p represents a potentially helpful biomarker for individualized treatment decisions concerning the management of HNSCC patients.

Improved prediction of CPAP failure using T90, age and gender.

Sleep apnea syndrome is associated with increased risk of cardiovascular disease. In treating older patients, there is a special emphasis put on minimally invasive and conservative procedures and a simple method for predicting the potential for treatment success is essential. Continuous positive airway pressure (CPAP) is the first choice for treatment, however, it is not always successful. In cases where CPAP was unsuccessful, treatment with bilevel positive airway pressure (BiPAP) is the next treatment option. In this study, we examine commonly evaluated respiratory parameters, obesity, and age relative to their ability to predict CPAP failure. We also tried to find differences in the predictive ability of these parameters in older and younger patients. The predictive ability, relative to CPAP failure, was examined for each individual parameter as well as for combinations of parameters. All variables had a statistical association with CPAP failure; failure prediction reliability ranged from poor to moderate. Combining T90, age, and gender can be used to find patients who will benefit from BiPAP as the first choice for treatment. An initial BiPAP indication can produce relevant reductions in treatment cost.

Implantable bone conduction hearing systems.

Implantable bone conduction hearing systems are intended for patients with a conductive or mixed hearing loss, in whom other treatment options do not provide sufficient benefits or are contraindicated. In general, they are called BAHDs (bone-anchored hearing devices) and they transform acoustic energy into vibrations transferred by a titanium implant through cranial bones to cochlea and fluids of the inner ear. The implantable bone conduction hearing systems are classified as passive and active based on the location of the vibration unit. The review describes the basic types of passive systems, their advantages and disadvantages. Special attention is paid to the Bonebridge active bone conduction system which represents a state-of-the-art, efficient and patient-friendly treatment method that removes the disadvantages of passive implantable systems.

Diagnostics of retrocochlear hearing loss.

Diagnosis of retrocochlear lesions is a relatively frequent issue of otolaryngological practice, the omission of which may have serious consequences for the patient. Properly set clinical guidelines and diagnostic protocols are thus one of the key aspects of good clinical practice. There are two methods available: the first is an audiological diagnosis with ABR as the primary tool to determine a group of patients with a possible tumour with subsequent MRI; the second is to examine the MRI in each patient with a clinical suspicion of a CPA tumour. The sensitivity of both diagnostic methods in relation to cost-effectiveness is discussed.

Diagnosis of retrocochlear lesions with emphasis on expansion of the cerebellopontine angle.

The correct diagnosis of CPA tumours is a relatively common issue in both neurological and ENT practice, the omission of which can have serious consequences for the patient. Properly set clinical guidelines and diagnostic protocols are key aspects of good clinical practice. In the case of CPA tumours, two options are available: the first is diagnosis with the help of an ABR as the primary tool for determining the group of patients with a possible tumour; the second is an MRI scan of the posterior cranial fossa. With an appropriately set diagnostic protocol in place, and despite the 40% chance of failure of the ABR to detect tumours less than or equal to 1 cm, similar treatment results can be achieved with much higher cost efficacy in case of primary ABR testing.

Prognostic value of c-MET in head and neck cancer: A systematic review and meta-analysis of aggregate data.

OBJECTIVES: The hepatocyte growth factor (HGF)/mesenchymal-epithelial transition factor (c-MET) ligand/receptor axis has been implicated in pathogenesis of malignant diseases including squamous cell carcinoma of the head and neck (SCCHN). Overexpression of c-MET has been reported as a common molecular abnormality in SCCHN, although its prognostic and predictive value remains to be validated. METHODS: We systematically searched literature for studies evaluating c-MET expression on immunohistochemistry in newly diagnosed, non-metastatic SCCHN. The c-MET expressing cases were classified into three categories according to predefined cut-off values for positivity. Our aim was to assess the prevalence of c-MET expression and its relationship with selected clinicopathological variables. RESULTS: Twenty-eight studies with 2019 cases were included. Relative frequencies of c-MET expression above cut-off levels I, II, and III were 81.8%, 63.8%, and 46.2%, respectively. Differences between these three values were statistically significant (p<1.0×10-6). Above cut-off level II, c-MET positivity was associated with worse overall survival (p=4.0×10-6), positive nodal status (p=1.0×10-4), higher disease stage (p=7.0×10-4), older age (p=2.1×10-3), disease recurrence (p=2.0×10-2), and primary tumour localization in the oral cavity (p=2.3×10-2). Above cut-off level III, c-MET positivity was associated with worse disease-free or progression-free survival (p=9.0×10-6), p16 negativity (p=2.4×10-4), worse overall survival (p=4.0×10-4), positive epidermal growth factor receptor (EGFR) status (p=7.2×10-4), and larger primary tumours (p=4.6×10-3). CONCLUSION: In SCCHN, immunohistochemical overexpression of c-MET above cut-off levels III and particularly II was associated with inferior survival outcomes and advanced disease. Moreover, it represents a promising predictive biomarker for c-MET targeting, yet the optimal scoring method remains to be defined.

Distinctive behaviour of live biopsy-derived carcinoma cells unveiled using coherence-controlled holographic microscopy.

Head and neck squamous cell carcinoma is one of the most aggressive tumours and is typically diagnosed too late. Late diagnosis requires an urgent decision on an effective therapy. An individualized test of chemosensitivity should quickly indicate the suitability of chemotherapy and radiotherapy. No ex vivo chemosensitivity assessment developed thus far has become a part of general clinical practice. Therefore, we attempted to explore the new technique of coherence-controlled holographic microscopy to investigate the motility and growth of live cells from a head and neck squamous cell carcinoma biopsy. We expected to reveal behavioural patterns characteristic for malignant cells that can be used to imrove future predictive evaluation of chemotherapy. We managed to cultivate primary SACR2 carcinoma cells from head and neck squamous cell carcinoma biopsy verified through histopathology. The cells grew as a cohesive sheet of suspected carcinoma origin, and western blots showed positivity for the tumour marker p63 confirming cancerous origin. Unlike the roundish colonies of the established FaDu carcinoma cell line, the SACR2 cells formed irregularly shaped colonies, eliciting the impression of the collective invasion of carcinoma cells. Time-lapse recordings of the cohesive sheet activity revealed the rapid migration and high plasticity of these epithelial-like cells. Individual cells frequently abandoned the swiftly migrating crowd by moving aside and crawling faster. The increasing mass of fast migrating epithelial-like cells before and after mitosis confirmed the continuation of the cell cycle. In immunofluorescence, analogously shaped cells expressed the p63 tumour marker, considered proof of their origin from a carcinoma. These behavioural traits indicate the feasible identification of carcinoma cells in culture according to the proposed concept of the carcinoma cell dynamic phenotype. If further developed, this approach could later serve in a new functional online analysis of reactions of carcinoma cells to therapy. Such efforts conform to current trends in precision medicine.

[Can fish oil improve wound healing in surgery?]. / Dokáze rybí olej zlepsit hojení ran v chirurgii?

UNLABELLED: A surgical insult induces both local and systemic inflammatory responses which, if inappropriate, could impair wound healing. According to many studies ω-3 polyunsaturated fatty acids from fish oil improve the process of wound healing by their immunomodulatory effect. In contrast to current anti-inflammatory drugs, which could alter immune defence and impair the resolution of inflammation, ω-3 fatty acids have a simultaneous anti-inflammatory pro-resolution effect which is not immunosuppressive. Besides that they improve cicatrix quality. With regard to this effect they prevent excessive or prolonged inflammation and wound complications. KEY WORDS: anti-inflammatory agent - cicatrix - fish oil - macrophage - ω-3 fatty acid - resolution of inflammation - Toll-like receptor - wound healing.

[Importance of taste in maintaining homeostasis and pathological impact of orosensory reflexes distraction in relation to sweet taste after non-caloric sweeteners consumption]. / Význam chuti v udrzení homeostázy organizmu a patologický dopad vyrusení orocefalických reflexu ve vazbe na sladkou chut v následku konzumace nekalorických sladidel.

Taste signals and their reflexes have important signalling function in nature. They protect organism against toxic substances in food with help of taste aversion, they help to cope nutrition deficiencies through taste preferences, on the other hand, they act in many postprandial reflexes to maintain energy homeostasis. It is well-known that sweet taste is important oro-sensory stimulus for mammals. It acts as predictor of caloric food intake even before its entry into stomach and circulation. Taste and other oro-sensory signals from oral cavity affect not only the intake regulation, but also influence hormonal, neural and metabolic pathways to maintain homeostasis. The aim is to utilize effectively food energy and prevent energy instability of organism. Oro-sensory reflexes mediated by taste cells develop naturally from the first contact with sweet breast milk in infancy. It has been proven that the attenuation of reflexes due to the use of artificial sweeteners that don´t bring any caloric value to human body leads to hormonal and energetic dysregulation of organism and may contribute to metabolic syndrome.

Elevated malondialdehyde correlates with the extent of primary tumor and predicts poor prognosis of oropharyngeal cancer.

The aim of the study was to investigate the relationship between plasma levels of malondialdehyde (MDA), a routinely used marker of oxidative stress, and squamous cell carcinoma of the oral cavity and oropharynx (OSCC). The prospective cohort study comprised a total of 67 patients who underwent surgery for OSCC. MDA was assessed using high performance liquid chromatography. The MDA levels in the pooled T1-2 patients were lower than in the patients with T3-4 tumors. A negative correlation of MDA and tumor grade was shown. Seventeen patients who manifested recurrence during the 49.6 months follow-up had significantly increased MDA compared to those staying in complete remission. Kaplan-Meier analysis revealed that the median disease-free interval and overall survival in the group with MDA > median was 19.3 and 22.5 months respectively, in contrast to 31.5 and 31.6 months respectively, in patients with MDA < or = median. The prognostic value and low cost of MDA measurement could make it a versatile and useful prognostic tool for the identification of OSCC patients with a high risk of recurrence.