RNAs in tumour-derived extracellular vesicles and their significance in the tumour microenvironment.

Small extracellular vesicles (sEVs) secreted by various types of cells serve as crucial mediators of intercellular communication within the complex tumour microenvironment (TME). Tumour-derived small extracellular vesicles (TDEs) are massively produced and released by tumour cells, recapitulating the specificity of their cell of origin. TDEs encapsulate a variety of RNA species, especially messenger RNAs, microRNAs, long non-coding RNAs, and circular RNAs, which release to the TME plays multifaced roles in cancer progression through mediating cell proliferation, invasion, angiogenesis, and immune evasion. sEVs act as natural delivery vehicles of RNAs and can serve as useful targets for cancer therapy. This review article provides an overview of recent studies on TDEs and their RNA cargo, with emphasis on the role of these RNAs in carcinogenesis.

Preservation of orbit in tumor invasion through the periorbita in sinonasal malignancy.

OBJECTIVE: One of the possible risks of sinonasal malignancy is its possible spread in the orbit. However, there is no clear consensus among the different departments as to whether it is necessary to exenterate the orbit in limited tumorous infiltration of periorbital fat. The purpose of the study was to demonstrate that periorbital infiltration and periorbital fat invasion without involvement of deeper orbital tissues are not the indication of orbital exenteration. MATERIALS AND METHODS: Retrospective analysis was performed over a 17-year period of patients undergoing surgical treatment for sinonasal malignancy with histologically verified periorbital infiltration or deeper invasion into the orbit. A total of 32 patients were included in the study. For each group, the following data were analysed: sex, age, preoperative imaging studies, histological findings, site of origin, stage, surgical reconstruction, oncological treatment, survival, cause of death, number of recurrences in the orbit and functional status of preserved eyes. RESULTS: Based on our criteria for orbital exenteration, orbital preservation was feasible in 18 patients. Orbital exenteration was performed in 14 patients with deeper tumor infiltration. There was a statistically insignificant difference in survival between the two groups. The 5-year overall survival (OS) was 44% for the orbital preservation group (only 2 patients died from local tumor recurrence) and 34% for the orbital exenteration group. The groups did not differ in other observed factors other than the extent of orbital infiltration. In 11 (61.1%) patients, vision was without significant change after radiation therapy. In 2 (11.1%) patients, visual function was impaired due to diplopia. 5 (27.8%) patients had severely impaired vision due to optic nerve atrophy after radiation therapy. CONCLUSIONS: Our results show a relatively high survival rate in the group of patients with orbital preservation with a high chance of vision preservation, which justifies our approach to orbital preservation even in some tumors with periorbital infiltration.

C-reactive protein as an early marker of postoperative leakage in patients after endoscopic laser assisted Zenker's diverticulotomy.

BACKGROUND AND AIM: Minimally invasive endoscopic techniques are the treatment of choice for Zenker's diverticulum (ZD). Our objective was to evaluate the results and efficacy of endoscopic and open approaches, to determine whether postoperative C-reactive protein (CRP) serum levels can be used as a marker to exclude the presence of esophageal leakage, and to identify risk factors for development of postoperative leakage and complications. MATERIALS AND METHODS: Patients who underwent transcervical myotomy and diverticulotomy (TMD) or endoscopic cricopharyngeal myotomy (ECM) with CO2 laser for ZD in years 2008-2021 at our department were included in this retrospective study. RESULTS: Of the 101 patients enrolled, 83 patients underwent ECM and 18 TMD. The procedure time of the endoscopic technique was significantly shorter compared to that of transcervical method (p < 0.001). The median time to oral intake was 6 days for ECM and 10.5 days in the TMD group (p < 0.001). There was a 13% (n = 11) and 16.7% (n = 3) symptomatic recurrence rate and 3.6% (n = 3) and 16.7% (n = 3) major complications rate for ECM and TMD groups, respectively. The incidence of contrast leak (CL) evaluated by postoperative swallow study was 8.9% (9 from 83 patients in the ECM group only). In patients with CL, a significant increase in CRP levels on postoperative day (POD) 2 and 3 was detected when compared to patients without CL. CONCLUSIONS: Endoscopic diverticulotomy with CO2 laser represents a safe and efficient treatment of ZD. Elevation of postoperative CRP serum levels over 123.8 mg/L on POD2 and 98.8 mg/L on POD3 may indicate presence of an esophageal leakage.

The importance of preoperative and perioperative Narrow Band Imaging endoscopy in the diagnosis of pre-tumor and tumor lesions of the larynx.

INTRODUCTION: Narrow band imaging (NBI) is an endoscopic imaging method intended for the diagnosis of mucosal lesions of the larynx that are not visible in white-light endoscopy, but are typical of pre-tumor and tumor lesions of the larynx. THE PURPOSE OF THE STUDY: To compare preoperative/perioperative white light endoscopy and NBI endoscopy with the results of histopathological examinations in pre-tumor and tumor lesions of the larynx. METHODS: A prospective study, over a period of five years (5/2018-5/2023), included 87 patients with laryngeal lesions aged 24-80 years. We evaluated preoperative/ perioperative white light and NBI endoscopy, established a working prehistological diagnosis, and compared this with the definitive histopathological results of laryngeal biopsies. RESULTS: In relation to the definitive histology score, a statistically significant correlation was found between the evaluation of the finding and the definitive histology for preoperative and perioperative white light endoscopy and NBI endoscopy (p < 0.001). Both methods showed higher precision when used perioperatively. CONCLUSION: NBI endoscopy is an optical method that allows us to improve the diagnosis of laryngeal lesions, perform a controlled perioperative biopsy, and refine the surgical scope. The NBI endoscopy is a suitable method for the diagnosis of early cancerous lesions of the larynx. The use of preoperative/perioperative NBI endoscopy allowed us to achieve a high level of agreement correlation (p < 0.001) between the prehistological working diagnosis and the final histopathological result. The NBI method proves its application in the diagnosis of pre-tumor and tumor lesions of the larynx.

Olfactory event-related potentials (OERPs) and trigeminal event-related potentials (TERPs) - a pilot study in Czech participants with normal sense of smell.

INTRODUCTION: In recent years, the evaluation of potential events related to olfactory events (OERPs) and trigeminal events (TERPs) has become increasingly important in the diagnosis of olfactory disorders. This technique is increasingly used in basic research and clinical practice to evaluate people suffering from olfactory disorders. PURPOSE OF THE STUDY: In a pilot project of the first investigations of OERPs and TERPs in the Czech Republic, we analyse the event-related potentials of the data of normosmic participants. METHODS: In the prospective study, 21 normosmic participants were enrolled for a 2-year period (5/2021-5/2023). OERPs/TERPs were recorded at the scalp vertex (electrode Pz/Cz). Odourants 2-phenylethanol/CO2 were used to selectively activate Nervus olfactorius/ Nervus trigeminus. Brain responses to olfactory/trigeminal stimuli (EEG) were recorded in 21/18 normosmic subjects. RESULTS: In the statistical analysis of the olfactory interval N1-P2 (age, gender), we found no statistically significant differences. In the statistical analysis of the trigeminal interval N1-P2 (age, gender) we found statistically significant differences in amplitude by gender (male amplitudes were higher than female amplitudes, p = 0.006). CONCLUSION: Our pilot data can function very well as an internal guide for ongoing and future olfactory research studies. Evaluation of the presence of OERPs appears to be an important parameter for the evaluation of olfactory disorders. The absence of OERPs is a strong indicator of the presence of olfactory dysfunction.

The expression profiles of CD47 in the tumor microenvironment of salivary gland cancers: a next step in histology-driven immunotherapy.

BACKGROUND: Salivary gland carcinomas (SGC) are extremely rare malignancies with only limited treatment options for the metastatic phase of the disease. Treatment with anti-CD47 antibodies could represent a potent therapy for SGCs by promoting the phagocytic clearance of tumor cells through various mechanisms. However, the efficacy of anti-CD47 therapy is largely dependent on the expression of CD47 within the tumor microenvironment (TME). MATERIALS AND METHODS: In 43 patients with SGC, we were the first to investigate the CD47 expression in both tumor cells and tumor-infiltrating immune cells (TIIC) in the center and periphery of primary tumors. We also correlated the data with the clinicopathological variables of the patients and offered novel insights into the potential effectiveness of anti-CD47 therapy in SGCs. RESULTS: We observed that the CD47+ tumor cells are outnumbered by CD47+ TIICs in mucoepidermoid carcinoma. In the tumor center, the proportion of CD47+ tumor cells was comparable to the proportion of CD47+ TIICs in most histological subtypes. In low-grade tumors, significantly higher expression of CD47 was observed in TIICs in the periphery of the tumor as compared to the center of the tumor. CONCLUSION: The reason for a high expression of 'don't eat me' signals in TIICs in the tumor periphery is unclear. However, we hypothesize that in the tumor periphery, upregulation of CD47 in TIICs could be a mechanism to protect newly recruited leukocytes from macrophage-mediated phagocytosis, while also allowing the removal of old or exhausted leukocytes in the tumor center.

Experience with follow-up strategy in selected patients with Warthin tumour diagnosed by ultrasound-guided fine-needle aspiration biopsy (FNAB).

PURPOSE: Warthin tumour (WT) management options comprise surgery or follow-up. The purpose of this study was to asses our experience with the follow-up strategy in selected patients with an ultrasound-guided fine-needle aspiration biopsy (FNAB) showing WT. METHODS: We performed a retrospective analysis of patients diagnosed with WT using FNAB between 1.1.2006 and 31.12.2019. Patients were divided into three groups according to the therapeutic approach-immediate surgery, follow-up or surgery and follow-up. RESULTS: 323 patients were diagnosed with WT and met the study's inclusion criteria (154 women, 47.7% and 169 men, 52.3%). 192 patients were operated right after the diagnosis, 109 patients were observed with their first detected tumour and 22 patients had parotid WT surgery and were in the wait-and-scan protocol with a contralateral tumour, recurrence or both. The growth rate (GR) of observed WT was highly variable (mean GR 1.0 mm/year (5%), median GR 0.8 mm (9%), range - 19.7 to +20.0 mm/year). From 131 patients in the follow-up group, 19 patients underwent surgery and definitive histology revealed 17 WTs and 2 adenocarcinomas. However, these 2 patients had changes in sonographic findings at their next control. The mean observation time was 44.7 months (range 12-138 months) in patients followed exclusively at our institution and 50.9 months (range 12-110 months) in patients observed in cooperation with an otorhinolaryngologist at the patients' place of residence. CONCLUSION: Ultrasound-guided FNAB is an accurate and simple method in WT diagnosis and based on its result a follow-up strategy can be chosen for selected patients with WT.

Oncocytic papillary cystadenoma of the larynx: comparative study of ten cases and review of the literature.

OBJECTIVE: Oncocytic papillary cystadenomas (OPCs) of the larynx are rare benign cystic lesions that usually present as supraglottic masses arising from the laryngeal ventricles. OPCs are found in patients older than 60 years, with a female predominance. Symptoms vary from asymptomatic to hoarseness, dyspnea, and dysphagia; often, they mimic a laryngocele. The treatment is surgical. Diagnosis is based on histopathologic examination. MATERIALS AND METHODS: Surgical records for laryngeal masses diagnosed between 2005 and 2020 were searched retrospectively. RESULTS: Ten patients were identified and included in the study. OPCs predominantly occurred in women (9/10), and the mean age at presentation was 73 years. Most patients (8/10) presented with hoarseness and were smokers. OPCs were localized in the ventricle in eight out of ten patients. Surgical treatment was performed in all cases, mostly using transoral endolaryngeal approach (9/10). Histopathologic examination revealed oncocytic cyst or oncocytic papillary cystadenoma (the former term being the older synonym for OPC). CONCLUSION: OPCs present a separate clinicopathologic entity, distinct from other cystic laryngeal lesions. They have a characteristic location, age and sex group, microscopic appearance, and potential for local recurrence.

Sensitivity to Cisplatin in Head and Neck Cancer Cells Is Significantly Affected by Patient-Derived Cancer-Associated Fibroblasts.

Cancer-associated fibroblasts (CAFs) are one of the most abundant and critical components of the tumor stroma. CAFs can impact many important steps of cancerogenesis and may also influence treatment resistance. Some of these effects need the direct contact of CAFs and cancer cells, while some involve paracrine signals. In this study, we investigated the ability of head and neck squamous cell carcinomas (HNSCC) patient-derived CAFs to promote or inhibit the colony-forming ability of HNSCC cells. The effect of cisplatin on this promoting or inhibiting influence was also studied. The subsequent analysis focused on changes in the expression of genes associated with cancer progression. We found that cisplatin response in model HNSCC cancer cells was modified by coculture with CAFs, was CAF-specific, and different patient-derived CAFs had a different "sensitizing ratio". Increased expression of VEGFA, PGE2S, COX2, EGFR, and NANOG in cancer cells was characteristic for the increase of resistance. On the other hand, CCL2 expression was associated with sensitizing effect. Significantly higher amounts of cisplatin were found in CAFs derived from patients who subsequently experienced a recurrence. In conclusion, our results showed that CAFs could promote and/or inhibit colony-forming capability and cisplatin resistance in HNSCC cells via paracrine effects and subsequent changes in gene expression of cancer-associated genes in cancer cells.

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.

The role of fine-needle aspiration biopsy (FNAB) in the diagnostic management of parotid gland masses with emphasis on potential pitfalls.

PURPOSE: The treatment strategy of parotid gland tumours depends mainly on the histopathological type of the lesion. Fine-needle aspiration biopsy (FNAB) is recommended in preoperative diagnostics. The aim of the study was to evaluate the FNAB standing in the diagnostic algorithm of parotid gland lesions and to correlate FNAB results in relation to the definitive histopathological diagnosis. MATERIAL AND METHODS: The retrospective analyses of 651 examined and consequently surgically treated parotid gland lesions at the Department of Otorhinolaryngology and Head and Neck Surgery, 1st Faculty of Medicine, Charles University in Prague between 2006 and 2016 were used. Preoperative cytological results were consequently evaluated in relation to the definitive histopathological diagnosis. RESULTS: The cohort consisted of 367 women and 284 men (average age 58 years). FNAB was diagnostic in 604 (92.8%) patients and non-diagnostic in 47 (7.2%) patients. The result of FNAB was positive (suspicious for malignant tumour) in 89 (14.7%) patients and negative (benign) in 515 (85.3%) patients. Sensitivity of the examination was 80.00%, specificity was 93.82%, PPV 62.92%, NPV 97.28%, and LR + and LR- were 12.95 and 0.21, respectively, with an accuracy of 92.22%. CONCLUSION: Our results confirm the significant role of FNAB in the diagnostic algorithm of parotid gland lesions.

The role of fine-needle aspiration biopsy (FNAB) in Warthin tumour diagnosis and management.

PURPOSE: Warthin tumour (WT) is the second most common benign tumour of the parotid gland. The aim of this study was to assess the value of the FNAB in the diagnosis and treatment decision in patients with WT. MATERIALS AND METHODS: We performed a retrospective study of patients treated for parotid gland mass between 2006 and 2016. Patients who underwent the surgery with preoperative FNAB were considered. The first group was comprised of patients with preoperative FNAB showing WT and the second group was formed by patients with definitive histology of WT. RESULTS: 216 patients had FNAB with the result of WT and underwent surgery (98 women-45.4% and 118 men-54.6%). The definitive histology corresponded with the preoperative diagnosis in 201 cases (93.1%). The other way round, 222 patients were operated with definitive histology showing WT and we correlated this finding with preoperative FNAB. The result of FNAB corresponded with definitive histology of WT in 201 cases (90.5%). Counted sensitivity and specificity of the ultrasound-guided FNAB for the diagnosis of WT were, respectively: 96.63% (CI 93.19-98.64%) and 96.21 (CI 93.83-97.86%). The accuracy of this method was 96.36% (CI 94.54-97.70%). CONCLUSION: Ultrasound-guided FNAB is a safe, accurate and important method in WT diagnosis. The therapeutic approach can be chosen based on FNAB results correlated with other clinical findings. We propose that when WT is suspected, follow-up or enucleation of the tumour are appropriate treatments. Patient preferences should be also considered.

Detection of Cervical Lymph Node Micrometastases in Patients with Squamous Cell Carcinoma of the Oral Cavity, Pharynx and Larynx.

BACKGROUND: The goal of this prospective study was to determine the frequency of micrometastases in patients with squamous cell carcinoma (SCC) of the oral cavity, pharynx and larynx in whom elective neck dissection was indicated (cN0). PATIENTS AND METHODS: A total of 12 patients (10 males and 2 females) were enrolled in the study. The age ranged 42-73 years (median 62 years). Elective neck dissection was performed in all patients (8 ipsilateral, 4 bilateral) and a total of 256 lymph nodes were removed and sent for microscopic examination. RESULTS: The presence of tumor cells in cervical lymph nodes was found in 5/12 (42%) patients. Micrometastases of SCC were found in two patients and isolated tumor cells (ITC) in two other patients. In the remaining one patient with oropharyngeal SCC, a micrometastasis of papillary thyroid carcinoma (PTC) was detected. Positive lymph nodes were localized in level II in three patients with SCC of larynx, hypopharynx and tongue base, respectively, in level I in one patient with SCC of oral tongue and in level III in one patient with PTC. CONCLUSION: Our results indicate that SCC of head and neck has a high potential for creating micrometastases which frequency is higher compared to clinically detected macrometastases. Therefore, elective neck dissection or radiotherapy of the neck should be considered in patients with high risk of occult metastases or micrometastases.

Histological Changes of the Middle Ear Ossicles Harvested during Cholesteatoma Surgery.

BACKGROUND: In the cholesteatoma surgery ossicles can be replaced to reconstruct middle ear function. It is important that these ossicles are free of squamous epithelium, to prevent residual disease. This study focuses on the histological findings of the malleus and incus harvested during cholesteatoma surgery. MATERIALS AND METHODS: Eighty middle ears ossicles were examined in vivo and histologically to consider the relationship of cholesteatoma to ossicles, grade of bone destruction and invasion of cholesteatoma to deeper layers of bone. RESULTS: Serious ossicular destruction was observed more frequently in incus compared to malleus (p=0.0065). Difference of ossicles destruction between children and adults was not significant (p=0.3032). Deep invasion of cholesteatoma into the vascular spaces or inner core of the bone was not observed. CONCLUSIONS: Autograft ossicles from cholesteatomatous ears should not necessarily be rejected for reconstruction of the ossicular chain. Regarding the histological finding, the authors suggest mechanical cleaning of the ossicle surface to eliminate residual disease.

Deep neck infections: risk factors for mediastinal extension.

The goal of the study was to find out the risk factors for the development of mediastinitis in patients with deep neck infections (DNI) and describe the differences in symptoms and clinical image between uncomplicated DNI and infections with mediastinal spread. Our study represents the retrospective analysis of 634 patients with DNI. The file was divided into two groups. There were 619 patients (97.6%) in the first group who had an uncomplicated course of DNI without spread of infection into mediastinum (DNI group). The second group included 15 patients (2.4%) with descending mediastinitis as a complication of DNI (mediastinitis group). The most frequent comorbidities were cardiac and pulmonary diseases, which were more frequent in the mediastinitis group comparing to DNI group. Dental origin of the infection was more frequent in DNI group than in the mediastinitis group. On the other hand, tonsillar origin of the infection was more frequent in the mediastinitis group than in DNI group. In both mediastinitis and DNI groups, the typical presenting symptoms were pain, oedema and dysphagia. Furthermore, dysphagia, dyspnoea, dysphonia and restriction of neck movements were more significant in the mediastinitis group than in DNI group. The incidence of airway obstruction, sepsis, pneumonia and death was significantly higher in the mediastinitis group than in DNI group. Due to our results, the predisposing factors for mediastinal extension of DNI are cardiovascular and pulmonary diseases. Mediastinitis is associated with higher morbidity and mortality than DNI. The most common complications are airway obstruction, pneumonia and sepsis.

LOW-GRADE MYOFIBROBLASTIC SARCOMA OF THE LARYNX: CASE REPORT AND REVIEW OF LITERATURE.

Low-grade myofibroblastic sarcoma (LGMS) is a very rare, atypical myofibroblastic tumor with fibromatosis-like features with predilection mostly in head and neck region. LGMS occurs primarily in adult patients with a slight male predominance. Only few cases of LGMS affecting the larynx have been reported in literature to this date. We describe a case of low-grade myofibroblastic sarcoma of the larynx in a 40-year-old male patient. The clinicopathological characteristics, immunohistochemical findings and treatment are discussed.

[Vitamin D in relation to head and neck cancer]. / Vitamin D ve vztahu ke karcinomu hlavy a krku.

Vitamin D was lately introduced as the important anti-cancer agent with therapeutic potential to be used in prevention and therapy of malignant tumors. Head and neck squamous cell cancer (HNSCC) is the sixth most common cancer in the world. Prognosis of this cancer is in most patients poor. In attempts to improve therapy of this cancer, contemporary research is focused on extension of the etiological and pathobiological aspects of cancerogenesis of HNSCC. This fact provoked us to summarize present scientific knowledge about etiopathological, chemopreventive and therapeutic role of vitamin D in head and neck squamous cancer and outline the direction of further research in this interesting and from clinical point of view important field. Key words: head and neck squamous cell carcinoma - anti-tumor effect - vitamin D.

How the Milan System for Reporting Salivary Gland Cytopathology works in cytopathology practice: Meta-analysis of prospective studies and comparison with retrospective studies.

BACKGROUND: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) is widely accepted and endorsed by professional societies. Although several studies focusing on the MSRSGC have been published, few have been prospective studies. The objective of this study was to evaluate the effectiveness of the MSRSGC in cytopathology practice. METHODS: A comprehensive literature search was conducted to identify all prospective studies on the MSRSGC. The risk of malignancy (ROM), risk of neoplasm, and diagnostic accuracy for each diagnostic category were calculated. Data were tabulated in Microsoft Excel, and analyses were performed with the Open Meta-Analyst program. RESULTS: Seven prospective and seven retrospective studies were identified. The total number of fine-needle aspirations (FNAs) was 1587 in the prospective studies and 1764 in the retrospective studies. The ROM values for the nondiagnostic, nonneoplastic, atypia of undetermined significance, benign neoplasm, salivary gland neoplasm of uncertain malignant potential, suspicious for malignancy, and malignant categories in prospective versus retrospective studies were 21.0% versus 26.6%, 9.4% versus 8.1%, 34.9% versus 39.6%, 2.4% versus 2.1%, 36.6% versus 31.2%, 86.0% versus 66.0%, and 97.0% versus 96.7%, respectively. Sensitivities, specificities, and diagnostic odds ratios were 83.1% (95% confidence interval [CI], 71.1%-90.8%) versus 89.1% (95% CI, 83.6%-92.9%), 98.4% (95% CI, 96.6%-99.3%) versus 94.9% (95% CI, 91.9%-96.9%), and 310.7 (95% CI, 121.2-796.6) versus 218.8 (95% CI, 107.3-438.1). CONCLUSIONS: This meta-analysis indicated that the MSRSGC works well in FNA cytopathology practice and improves diagnostic accuracy in all diagnostic categories. The ROMs of prospective studies were in concordance with the MSRSGC reference values.