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Andrzej Sieśkiewicz,1 Bartosz Piszczatowski,1 Joanna Reszeć,2 Michał Sieśkiewicz,3 Zuzanna Micun,3 Joanna Konopińska4 1Department of Otolaryngology, Medical University of Bialystok, Białystok, Poland; 2Department of Medical Pathomorphology, Medical University of Bialystok, Bialystok, Poland; 3Faculty of Medicine, Medical University of Białystok, Bialystok, Poland; 4Department of Ophthalmology, Medical University of Bialystok, Białystok, PolandCorrespondence: Joanna Konopińska, Department of Ophthalmology, Medical University of Bialystok, M. Sklodowska-Curie 24A Street, Białystok, 15-276, Poland, Tel/Fax +48 600471666, Email joannakonopinska@o2.plPurpose: The main challenge in maintaining long-term success of endoscopic dacryocystorhinostomy is preventing fibrosis and scarring at the anastomosis site. Despite numerous studies on surgical techniques, research on histological factors linked to postoperative scarring is limited. This study evaluated long-term (range, 12– 18 months) outcomes and systematically examined clinical and histopathological factors that may contribute to restenosis.Patients and Methods: This retrospective study included 47 patients who underwent a unilateral surgery intervention for primary acquired lacrimal duct obstruction. The following clinical and histopathological variables were considered to assess the risk factors for the development of restenosis: sex, age, duration of disease, clinical manifestation of disease, clinical features of the lacrimal sac perceived intraoperatively, fibrosis, and mononuclear cell infiltrates.Results: Statistical analysis showed that only patient sex (Pearson’s chi-squared test, p = 0.007) and severity of intraoperative adhesions in the lacrimal sac (Pearson’s chi-square test, p = 0.029) were significantly linked to restenosis. However, the skewed male-to-female ratio, few surgical failures make the conclusion that sex is a risk factor speculative. Thus, only adhesion intensity can be considered a risk factor. Additionally, fibrosis assessed using trichrome staining and T-cell lymphocytic infiltration showed potential negative prognostic value in a larger cohort.Conclusion: Our findings indicate that patients with significant lacrimal sac adhesions, identified during endoscopic dacryocystorhinostomy, are particularly prone to postoperative restenosis. Although histological and immunohistochemical studies did not reveal a correlation between the analyzed data and restenosis, a larger patient cohort might show that fibrosis and T-cell lymphocytic infiltration could potentially have a negative prognostic value. The poorer treatment outcomes in women, seen in our study as well as in other investigations, may be due to anatomical and physiological traits of the female lacrimal drainage system that predispose them to stenosis. This hypothesis requires further study in a larger cohort.Keywords: fibrosis, lacrimal sac, restenosis, tearing

Mateusz Cieśluk,1 Katarzyna Pogoda,2 Piotr Deptuła,1 Paulina Werel,3 Alina Kułakowska,3 Jan Kochanowicz,3 Zenon Mariak,4 Tomasz Łysoń,4 Joanna Reszeć,5 Robert Bucki1 1Department of Medical Microbiology and Nanobiomedical Engineering, Medical University of Bialystok, Bialystok PL-15222, Poland; 2Institute of Nuclear Physics, Polish Academy of Sciences, Krakow PL-31342, Poland; 3Department of Neurology, Medical University of Bialystok, Bialystok PL-15276, Poland; 4Department of Neurosurgery, Medical University of Bialystok, Bialystok PL-15276, Poland; 5Department of Pathology, Medical University of Bialystok, Bialystok PL-15269, PolandCorrespondence: Robert BuckiDepartment of Medical Microbiology and Nanobiomedical Engineering, Medical University of Bialystok, Mickiewicza 2C, Bialystok 15-222, PolandTel +48 85 784 5483Email buckirobert@gmail.comBackground: The tissue-mechanics environment plays a crucial role in human brain physiological development and the pathogenesis of different diseases, especially cancer. Assessment of alterations in brain mechanical properties during cancer progression might provide important information about possible tissue abnormalities with clinical relevance.Methods: With atomic force microscopy (AFM), the stiffness of freshly removed human brain tumor tissue was determined on various regions of the sample and compared to the stiffness of healthy human brain tissue that was removed during neurosurgery to gain access to tumor mass. An advantage of indentation measurement using AFM is the small volume of tissue required and high resolution at the single-cell level.Results: Our results showed great heterogeneity of stiffness within metastatic cancer or primary high-grade gliomas compared to healthy tissue. That effect was not clearly visible in lower-grade tumors like meningioma.Conclusion: Collected data indicate that AFM might serve as a diagnostic tool in the assessment of human brain tissue stiffness in the process of recognizing tumors.Keywords: AFM, brain tumors, human tissue rheology, mechanomarkers, glioblastoma

This paper presents a review on retinal gliosis illustrated by series of three cases of patients (a 39-year-old man and a 35-year-old woman with massive retinal gliosis (MRG) and a 51-year-old man with truly focal nodular gliosis of retina) with intraocular tumor-like masses and loss of vision, who recently suffered from painful inflammation of eyeball and who classically had a history of remote ocular trauma, onset of blindness early in lifetime or gradual but progressive loss of sight. The diagnosis of this pathological entity is given for the lesions that are composed of GFAP strongly positive, elongated, fusiform cells consistent with fibrillary astrocytes. As illustrated in cases from our pathological practice, PAS gave positive patchy disseminated reaction in form of cellular densely purplish granules in minority of cells representing glycogen storing. This feature could be consistent with PAS-positive Müller cells that also constitute retinal gliosis as one of cellular components of normal retina that is induced to reactive proliferation. Thus, the paper presents histological background and differential diagnosis of the entity.

Papillomas and squamous cell carcinomas are the most common conjunctival and eyelid lesions. The etiology is still unclear and recently human papillomavirus infection and p53 gene mutation have been taken into consideration. The aim of our study was the evaluation of HPV DNApresence and p53 gene mutation in 45 benign and 38 malignant squamous lesions of the conjunctiva and eyelid. For HPV detection PCR-RFLP and immunohistochemical reaction were used; for p53 gene mutation PCR-SSCP was used. Only 8.8% papillomas, 9.1% squamous cell cancers and 3.7% basal cell cancers (using PCR-RFLP method) and 26.6% papillomas, 7.4% squamous cell cancers and 9.1% basal cell cancers (using immunohisto-chemical reaction) were HPV positive. p53 gene mutation was evaluated in 24.4% papillomas, 54.5% squamous cell cancers and 22.2% basal cell cancers; most commonly in 6 and 7 exon. Human papillomavirus infection, opposite to p53 gene mutation, is not a significant etiological factor of the benign and malignant conjunctival and eyelid lesions development.

Papillomas and squamous cell carcinomas are the most common conjunctival and eyelid lesions. The etiology isstill unclear and recently human papillomavirus infection and p53 gene mutation have been taken into consideration. Theaim of our study was the evaluation of HPV DNApresence and p53 gene mutation in 45 benign and 38 malignant squamouslesions of the conjunctiva and eyelid. For HPV detection PCR-RFLP and immunohistochemical reaction were used; for p53gene mutation PCR-SSCP was used. Only 8.8% papillomas, 9.1% squamous cell cancers and 3.7% basal cell cancers (usingPCR-RFLP method) and 26.6% papillomas, 7.4% squamous cell cancers and 9.1% basal cell cancers (using immunohistochemicalreaction) were HPV positive. p53 gene mutation was evaluated in 24.4% papillomas, 54.5% squamous cell cancersand 22.2% basal cell cancers; most commonly in 6 and 7 exon. Human papillomavirus infection, opposite to p53 genemutation, is not a significant etiological factor of the benign and malignant conjunctival and eyelid lesions development.

Acute lymphoblastic leukemia (ALL) and glioma are some of the most common malignancies, with ALL most often affecting children and glioma affecting adult men. Proangiogenic cytokines and growth factors play an important role in the development of both of these tumors. Glioma is characterized by an extremely extensive network of blood vessels, which continues to expand mainly in the process of neoangiogenesis, the direct inducers of which are cytokines from the family of vascular endothelial growth factors, i.e., vascular endothelial growth factor (VEGF-A) and its receptor vascular endothelial growth factor receptor 2 (VEGF-R2), as well as a cytokine from the fibroblast growth factor family, fibroblast growth factor 2 (FGF-2 or bFGF). Growth factors are known primarily for their involvement in the progression and development of solid tumors, but there is evidence that local bone marrow angiogenesis and increased blood vessel density are also present in hematological malignancies, including leukemias. The aim of this study was to examine changes in the concentrations of VEGF-A, VEGF-R2, and FGF-2 (with a molecular weight of 17 kDa) in a group of patients divided into specific grades of malignancy (glioma) and a control group; changes of VEGF-A and FGF-2 concentrations in childhood acute lymphoblastic leukemia and a control group; and to determine correlations between the individual proteins as well as the influence of the patient's age, diet, and other conditions that may place the patient in the risk group. During the statistical analysis, significant differences in concentrations were found between the patient and control groups in samples from people with diagnosed glioma and from children with acute lymphoblastic leukemia, but in general, there are no significant differences in the concentrations of VEGF-A, VEGF-R2, and FGF-2 between different grades of glioma malignancy. Among individuals treated for glioma, there was no significant impact from the patient's gender and age, consumption of food from plastic packaging, frequency of eating vegetables and fruit, smoking of tobacco products, the intensity of physical exercise, or the general condition of the body (Karnofsky score) on the concentrations of the determined cytokines and receptor. The listed factors do not bring about an actual increase in the risk of developing brain glioma.

Proline metabolism has been identified as a significant player in several neoplasms, but knowledge of its role in gliomas is limited despite it providing a promising line of pursuit. Data on proline metabolism in the brain are somewhat historical. This study aims to investigate alterations of proline metabolism in gliomas of WHO grade 4 (GG4) in the context of the brain. A total of 20 pairs of samples were studied, consisting of excised tumor and unaffected brain tissue, obtained when partial brain resection was required to reach deep-seated lesions. Levels of proline oxidase/proline dehydrogenase (POX/PRODH), Δ 1 -pyrroline-5-carboxylate reductases (PYCR1/2/3), prolidase (PEPD), and metalloproteinases (MMP-2, MMP-9) were assessed, along with the concentration of proline and proline-related metabolites. In comparison to normal brain tissue, POX/PRODH expression in GG4 was found to be suppressed, while PYCR1 expression and activity of PEPD, MMP-2, and -9 were upregulated. The GG4 proline concentration was 358% higher. Hence, rewiring of the proline metabolism in GG4 was confirmed for the first time, with a low-POX/PRODH/high-PYCR profile. High PEPD and MMPs activity is in keeping with GG4-increased collagen turnover and local aggressiveness. Further studies on the mechanisms of the interplay between altered proline metabolism and the GG4 microenvironment are warranted.

Background: Morbid obesity co-exists with non-alcoholic fatty liver disease in up to 90% of cases. Laparoscopic sleeve gastrectomy leads to a reduction in body mass and thus may improve the course of non-alcoholic fatty liver disease. The aim of this study was to evaluate the effect of laparoscopic sleeve gastrectomy on the resolution of non-alcoholic fatty liver disease., Methods: The study included 55 patients with non-alcoholic fatty liver disease who underwent laparoscopic sleeve gastrectomy at a tertiary institution. The analysis consisted of preoperative liver biopsy, abdominal ultrasound, weight loss parameters, Non-Alcoholic Fatty Liver Fibrosis Score and selected laboratory parameters., Results: Before the surgery, 6 patients were diagnosed with grade 1 liver steatosis, 33 patients with grade 2 and 16 patients with grade 3. One year after the surgery, only 21 patients had features of liver steatosis at ultrasound. All weight loss parameters showed statistically significant changes during the observation; the median percentage of total weight loss was 31.0% (IQR: 27.5; 34.5) with p = 0.0003, the median percentage of excess weight loss was 61.8% (IQR: 52.4; 72.3) with p = 0.0013 and the median percentage of excess body mass index loss was 71.0% (IQR: 61.3; 86.9) with p = 0.0036 12 months after laparoscopic sleeve gastrectomy. The median Non-Alcoholic Fatty Liver Fibrosis Score at baseline was 0.2 (IQR: -0.8; 1.0) and decreased to -1.6 (IQR: -2.4; -0.4) ( p < 0.0001). Moderate negative correlations between Non-Alcoholic Fatty Liver Fibrosis Score and percentage of total weight loss (r = -0.434, p < 0.0001), percentage of excess weight loss (r = -0.456, p < 0.0001) and percentage of excess body mass index loss (r = -0.512, p < 0.0001) were found., Conclusions: The study supports the thesis that laparoscopic sleeve gastrectomy is an effective method for treatment of non-alcoholic fatty liver disease in patients with morbid obesity.

Purpose: From April to September 2020, Poland was minimally affected by COVID-19 compared to other EU countries. We aimed to investigate the risks of false reverse transcription polymerase chain reaction (RT-PCR) results during the first wave (compared to later waves), that rises when cycle threshold (Ct) of positive result is close to limit of detection (LOD)., Materials/methods: We analyzed Ct values of SARS-CoV-2 positive RT-PCR results of 7726 patients in Poland from April-September 2020. SARS-CoV-2 positive RT-PCR results of 14,534 patients in the 2nd-3rd wave and 10,861 patients in the 4th-5th pandemic waves were used. Statistical analysis was based on one-way analysis of variance. To verify, 95% confidence intervals with Bonferroni correction were computed. Incidence of SARS-CoV-2 variants in Poland was analyzed using Whole Genome Sequencing from 923 (3.6%) patients., Results: The mean Ct of RT-PCR positive test results analyzed ranged between 22.89 and 26.71 depending on the month of the results collection. The differences between months were significant (p ​< ​0.001). Differences in Ct were observed between age groups, with younger patients displaying higher Ct values, however, major trends over time were paralleled between age groups., Conclusions: The mean Ct of the tested RT-PCR positive test results was lower than 35 which is considered an upper borderline for reliable positive results of the assay. Therefore, most COVID-19 cases recorded in Poland from April to September 2020 were detected with minor risks of inaccuracy. Data from a single center exhibited greater consistency for both virus Ct level and SARS-CoV-2 virus variant identification., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2022 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.)

The incidence of papillary thyroid cancer (PTC) has increased in recent years. To improve the diagnostic management of PTC, we propose the use of microRNAs (miRNAs) as a biomarker. Our aim in this study was to evaluate the miRNA expression pattern in PTC using NanoString technology. We identified ten miRNAs deregulated in PTC compared with reference tissue: miR-146b-5p, miR-221-3p, miR-221-5p, miR-34-5p, miR-551b-3p, miR-152-3p, miR-15a-5p, miR-31-5p, and miR-7-5p (FDR < 0.05; |fold change (FC)| ≥ 1.5). The gene ontology (GO) analysis of differentially expressed miRNA (DEM) target genes identified the predominant involvement of epidermal growth factor receptor (EGFR), tyrosine kinase inhibitor resistance, and pathways in cancer in PTC. The highest area under the receiver operating characteristic (ROC) curve (AUC) for DEMs was found for miR-146-5p (AUC = 0.770) expression, indicating possible clinical applicability in PTC diagnosis. The combination of four miRNAs (miR-152-3p, miR-221-3p, miR-551b-3p, and miR-7-5p) showed an AUC of 0.841. Validation by real-time quantitative polymerase chain reactions (qRT-PCRs) confirmed our findings. The introduction of an miRNA diagnostic panel based on the results of our study may help to improve therapeutic decision making for questionable cases. The use of miRNAs as biomarkers of PTC may become an aspect of personalized medicine.

Lung cancer is responsible for the most cancer-related mortality worldwide and the mechanism of its development is poorly understood. Proteomics has become a powerful tool offering vital knowledge related to cancer development. Using a two-dimensional difference gel electrophoresis (2D-DIGE) approach, we sought to compare tissue samples from non-small-cell lung cancer (NSCLC) patients taken from the tumor center and tumor margin. Two subtypes of NSCLC, adenocarcinoma (ADC) and squamous cell carcinoma (SCC) were compared. Data are available via ProteomeXchange with identifier PXD032736 and PXD032962 for ADC and SCC, respectively. For ADC proteins, 26 significant canonical pathways were identified, including Rho signaling pathways, a semaphorin neuronal repulsive signaling pathway, and epithelial adherens junction signaling. For SCC proteins, nine significant canonical pathways were identified, including hypoxia-inducible factor-1α signaling, thyroid hormone biosynthesis, and phagosome maturation. Proteins differentiating the tumor center and tumor margin were linked to cancer invasion and progression, including cell migration, adhesion and invasion, cytoskeletal structure, protein folding, anaerobic metabolism, tumor angiogenesis, EMC transition, epithelial adherens junctions, and inflammatory responses. In conclusion, we identified several proteins that are important for the better characterization of tumor development and molecular specificity of both lung cancer subtypes. We also identified proteins that may be important as biomarkers and/or targets for anticancer therapy., Competing Interests: The authors have declared that no competing interests exist.

Infection of human cells by pathogens, including SARS-CoV-2, typically proceeds by cell surface binding to a crucial receptor. The primary receptor for SARS-CoV-2 is the angiotensin-converting enzyme 2 (ACE2), yet new studies reveal the importance of additional extracellular co-receptors that mediate binding and host cell invasion by SARS-CoV-2. Vimentin is an intermediate filament protein that is increasingly recognized as being present on the extracellular surface of a subset of cell types, where it can bind to and facilitate pathogens' cellular uptake. Biophysical and cell infection studies are done to determine whether vimentin might bind SARS-CoV-2 and facilitate its uptake. Dynamic light scattering shows that vimentin binds to pseudovirus coated with the SARS-CoV-2 spike protein, and antibodies against vimentin block in vitro SARS-CoV-2 pseudovirus infection of ACE2-expressing cells. The results are consistent with a model in which extracellular vimentin acts as a co-receptor for SARS-CoV-2 spike protein with a binding affinity less than that of the spike protein with ACE2. Extracellular vimentin may thus serve as a critical component of the SARS-CoV-2 spike protein-ACE2 complex in mediating SARS-CoV-2 cell entry, and vimentin-targeting agents may yield new therapeutic strategies for preventing and slowing SARS-CoV-2 infection., (© 2021 Wiley-VCH GmbH.)

Gliomatosis peritonei (GP) is a rare clinical condition characterized by presence of mature glial cells in the peritoneum. Growing teratoma syndrome (GTS) is described as an uncommon phenomenon that could be related to the incidence of non-seminomatous germ cell tumors. We report a case of a patient treated for immature ovarian teratoma, in whom both GP and GTS were observed, an association to date scarcely described in literature. A 15-year-old girl presented to the emergency department with severe pain in her lower abdomen and right lumbar region. Upon admission, concentration of α-fetoprotein (AFP) was 1500 ng/mL and β-human chorionic gonadotropin (β-hCG) less than 2 ng/mL. A computed tomography (CT) scan of the abdominal cavity and pelvis confirmed the presence of an anomalous mass in the abdominal cavity and pelvis. Initial surgery was performed. Histopathology revealed the presence of immature teratoma with epithelial elements. Normalization of AFP was achieved within 8 weeks. Five months after surgery, a progressive increase in AFP was noted. Magnetic resonance imaging (MRI) and CT scans of the pelvis minor showed local relapse. Evaluation of the remission after 2 blocks of preoperative chemotherapy revealed the presence of a large tumor mass in the pelvis minor, despite normalization of the AFP concentration. After opening the abdominal walls, numerous abnormal white nodules were observed in the peritoneum. Histopathology revealed the presence of mature glial tissue (gliomatosis peritonei). The remaining tumor mass was removed, and histopathology confirmed existence of mature teratoma (growing teratoma syndrome). Postoperative chemotherapy was continued. To date, the patient remains under clinical and laboratory remission. Concomitant incidence of GP and GTS, although rare, should always be taken into consideration in pediatric patients with diagnosis of either condition., (Copyright © 2021 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.)

Introduction: Taking into account the possibility of myelin-associated proteins having a role in brain tumour development, the study aimed to evaluate the diagnostic usefulness of myelin-associated proteins (Nogo-A, MAG, OMgp) released into extracellular space in patients with brain tumours., Patients and Methods: Protein concentration in primary brain tumour ( n  = 49) and non-tumoural subjects ( n  = 24) was measured in cerebrospinal fluid (CSF) and serum by means of ELISA. Immunohistochemistry for IDH1-R132H was done on 5-μm thick formalin-fixed, paraffin-embedded tumour sections with the use of an antibody specific for the mutant IDH1-R132H protein., Results: The receiver operator characteristic curve analysis showed that CSF Nogo-A and serum MAG were useful in differentiating patients with primary brain tumour from non-tumoural individuals. This was also true in the case of the separate analysis of the astrocytic tumour versus non-tumoural groups and the meningeal tumour versus non-tumoural groups. Neither Nogo-A nor MAG or OMgp concentrations were significantly different, in serum or CSF, between IDH1 wild-type astrocytic brain tumour patients compared to IDH1 mutant patients., Conclusions: Our results indicated the potential usefulness of CSF Nogo-A and serum MAG evaluation as circulating biomarkers of primary brain tumours. Because blood is relatively easy to obtain, future research should be conducted to explicitly indicate the value of serum MAG concentration evaluation as a brain tumour biomarker.Key messagesMyelin-associated proteins may be circulating brain tumour biomarkers.Nogo-A and MAG proteins seem to be the most useful in brain tumour diagnosis.Decreased CSF Nogo-A concentration is an adverse prognostic factor for patients' survival.

Purpose: We analyzed the SARS-CoV-2 genome using our integrated genome analysis system and present the concept of a comprehensive approach to monitoring and surveillance of emerging variants., Material/methods: A total of 69 SARS-CoV-2 positive samples (with Ct value ​≤ ​28) were tested. Samples included in this study were selected from 7 areas of eastern Poland. All samples were sequenced on an Illumina MiSeq platform using a 300-cycle MiSeq Reagent Kit v2. BWA was used for reads mapping on the reference SARS-CoV-2 sequence. SAMTools were used for post-processing of reads to genome assembly. Pango lineage and Nexstrain were used to identify variants and amino acid mutations. Statistical analysis was performed with R 4.0.2., Results: This study shows the first confirmed case of SARS-CoV-2 in Poland with the lineage B.1.351 (known as 501Y.V2 South African variant), as well as another 18 cases with epidemiologically relevant lineage B.1.1.7, known as British variant. Supplementary analysis of SARS-CoV-2 sequences deposited in GISAID shows that the share of a new variant can change rapidly within one month. In addition, we show a complete, integrated concept of a networked system for analyzing the variability of the SARS-CoV-2 genome, which, used in the present study, generated data and a variant report within 6 days., Conclusion: The analyzed viral genomes showed considerable variability with simultaneous clear distinction of local clusters of genomes showing high similarity. Implementing real-time monitoring of new SARS-CoV-2 variants in Poland is urgently needed, and our developed system is available to be implemented on a large scale., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2021 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.)

Identification of the NSCLC subtype at an early stage is still quite sophisticated. Metabolomics analysis of tissue and plasma of NSCLC patients may indicate new, and yet unknown, metabolic pathways active in the NSCLC. Our research characterized the metabolomics profile of tissue and plasma of patients with early and advanced NSCLC stage. Samples were subjected to thorough metabolomics analyses using liquid chromatography-mass spectrometry (LC-MS) technique. Tissue and/or plasma samples from 137 NSCLC patients were analyzed. Based on the early stage tissue analysis, more than 200 metabolites differentiating adenocarcinoma (ADC) and squamous cell lung carcinoma (SCC) subtypes as well as normal tissue, were identified. Most of the identified metabolites were amino acids, fatty acids, carnitines, lysoglycerophospholipids, sphingomyelins, plasmalogens and glycerophospholipids. Moreover, metabolites related to N-acyl ethanolamine (NAE) biosynthesis, namely glycerophospho (N-acyl) ethanolamines (GP-NAE), which discriminated early-stage SCC from ADC, have also been identified. On the other hand, the analysis of plasma of chronic obstructive pulmonary disease (COPD) and NSCLC patients allowed exclusion of the metabolites related to the inflammatory state in lungs and the identification of compounds (lysoglycerophospholipids, glycerophospholipids and sphingomyelins) truly characteristic to cancer. Our results, among already known, showed novel, thus far not described, metabolites discriminating NSCLC subtypes, especially in the early stage of cancer. Moreover, the presented results also indicated the activity of new metabolic pathways in NSCLC. Further investigations on the role of NAE biosynthesis pathways in the early stage of NSCLC may reveal new prognostic and diagnostic targets.

Oral leukoplakia is a clinical term relating to various morphological lesions, including squamous cell hyperplasia, dysplasia and carcinoma. Leukoplakia morphologically manifested as hyperplasia with epithelial dysplasia is clinically treated as precancerous condition. Nevertheless, there is a lack of good markers indicating the transformation of premalignancies towards cancer. A better understanding of the mechanical environment within the tissues where tumors grow might be beneficial for the development of prevention, diagnostic, and treatment methods in cancer management. Atomic force microscopy (AFM) and immunohistology techniques were used to assess changes in the stiffness and morphology of oral mucosa and leukoplakia samples at different stages of their progression towards cancer. The Young's moduli of the tested leukoplakia samples were significantly higher than those of the surrounding mucus. Robust inhomogeneity of stiffness within leukoplakia samples, reflecting an increase in regeneration and collagen accumulation (increasing density) in the extracellular matrix (ECM), was observed. Within the histologically confirmed cancer samples, Young's moduli were significantly lower than those within the precancerous ones. Inhomogeneous stiffness within leukoplakia might act as "a mechanoagonist" that promotes oncogenesis. In contrast, cancer growth might require the reorganization of tissue structure to create a microenvironment with lower and homogenous stiffness. The immunohistology data collected here indicates that changes in tissue stiffness are achieved by increasing cell/ECM density. The recognition of new markers of premalignancy will aid in the development of new therapies and will expand the diagnostic methods., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier Inc.)

Infection of human cells by pathogens, including SARS-CoV-2, typically proceeds by cell surface binding to a crucial receptor. In the case of SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2) has been identified as a necessary receptor, but not all ACE2-expressing cells are equally infected, suggesting that other extracellular factors are involved in host cell invasion by SARS-CoV-2. Vimentin is an intermediate filament protein that is increasingly recognized as being present on the extracellular surface of a subset of cell types, where it can bind to and facilitate pathogens' cellular uptake. Here, we present evidence that extracellular vimentin might act as a critical component of the SARS-CoV-2 spike protein-ACE2 complex in mediating SARS-CoV-2 cell entry. We demonstrate direct binding between vimentin and SARS-CoV-2 pseudovirus coated with the SARS-CoV-2 spike protein and show that antibodies against vimentin block in vitro SARS-CoV-2 pseudovirus infection of ACE2-expressing cells. Our results suggest new therapeutic strategies for preventing and slowing SARS-CoV-2 infection, focusing on targeting cell host surface vimentin., Competing Interests: Competing Interests: The authors declare no competing interests.

Introduction: Fibrosis is one of the factors contributing to the development of primary acquired lacrimal duct obstruction (LDO). LIGHT (homologous to lymphotoxins, exhibiting inducible expression and competing with herpes simplex virus glycoprotein D for herpes virus entry mediator [HVEM]), a receptor expressed by T lymphocytes, has recently emerged as a new regulator of connective tissue remodeling and fibrotic response. The purpose of this study was to evaluate the role of LIGHT in the pathogenesis of LDO through: (1) assessment of expression of LIGHT and its two receptors, HVEM and LTβR (lymphotoxin β receptor), and (2) investigation of potential relationships between expression of LIGHT and its receptors and clinical and histopathologic features., Methods: Lacrimal sacs of 30 patients undergoing endoscopic dacryocystorhinostomy because of LDO were assessed intraoperatively and histopathologically with respect to inflammation and fibrosis. Expression of LIGHT, HVEM and LTβR was assessed by immunohistochemistry using specific antibodies and evaluated semiquantitatively using a four-grade scoring system., Results: All investigated molecules, LIGHT/TNFSF14, HVEM and LTβR, were expressed in biopsies from all patients. The most prominent expression was seen within inflammatory infiltrates. Expression of LIGH, HVEM and LTβR correlated significantly with the intensity of fibrosis and duration of the disease. In multivariate analysis only LIGHT showed a significant relationship with fibrosis (β coefficient = 0.759, p = 0.02). There was no significant correlation between expression of any molecule and other demographic or clinical features., Conclusion: We assume that LIGHT along with its receptors may be a factor contributing to fibrosis and synechiae formation in the lacrimal sac. This assumption needs to be proven in a future study in a group of patients who fail to improve after the first operation.

Introduction: Recent studies have revealed the presence of zinc and the expression of zinc transporter (ZnT) family members in most endocrine cell types. It was demonstrated that ZnT family plays an important role in the synthesis and secretion of many hormones. Moreover, recently ZnT8 was described as a newly islet autoantigen in type 1 diabetes., Materials and Methods: We studied the expression of ZnT8 transporter in thyroid tissues from patients with immune and non-immune thyroid diseases. The study was performed in thyroid tissues after thyroidectomy from patients with thyroid non-toxic nodular goitre (NTNG; n  = 17, mean age 15.8 ± 2.2 years) and cases with Graves' disease ( n  = 20, mean age 15.6 ± 2.8). In our study we investigated the expression of ZnT8 in human thyroid tissues from patients with immune and non-immune thyroid diseases using immunohistochemistry, Western Blot as well as immunofluorescence analyses. To the best of our knowledge, this is the first investigation which identified ZnT8 protein expression in human thyroid tissues, moreover, confirmed by three different laboratory techniques. Results and Conclusions Expression of ZnT8 transporter was identified by immunohistochemistry in the thyroid tissues from paediatric patients with Graves' disease (on +++) and non-toxic nodular goitre (on ++). ZnT8 transporter expression was found both in thyroid follicular cells (within the cytoplasm and cytoplasmic membrane in follicular cells) and C cells (membrane-cytoplasmic reaction) in fluorescence. Predominant expression of ZnT8 in band 41 kDa in immune than in non-immune thyroid disorders may suggest potential role of ZnT8 as a new thyroid autoanitgen but it requires further study on a larger cohort.

Introduction: In cancer treatment an attempt has been made to pharmacologically regulate the proteasome functions, thus the aim was to test whether 20S proteasome chymotrypsin-like (ChT-L) activity has a role in glial brain tumors. Furthermore, we analyzed the correlation between proteasome activity and IL-8, CCL2, NF-κB1 and NF-κB2 concentrations, which impact on brain tumors has already been indicated., Methods: Plasma 20S proteasome ChT-L activity was assayed using the fluorogenic peptide substrate Suc-Leu-Leu-Val-Tyr-AMC in the presence of SDS. IL-8, CCL2, NF-κB1 and NF-κB2 concentration was analyzed with the use of ELISA method. Immunohistochemistry for IDH1-R132H was done on 5-microns-thick formalin-fixed, paraffin-embedded tumor sections with the use of antibody specific for the mutant IDH1-R132H protein. Labelled streptavidin biotin kit was used as a detection system., Results: Brain tumor patients had statistically higher 20S proteasome ChT-L activity (0.649 U/mg) compared to non-tumoral individuals (0.430 U/mg). IDH1 wild-type patients had statistically higher 20S proteasome ChT-L activity (1.025 U/mg) compared to IDH1 mutants (0.549 U/mg). 20S proteasome ChT-L activity in brain tumor patients who died as the consequence of a tumor (0.649) in the following 2 years was statistically higher compared to brain tumor patients who lived (0.430 U/mg). In brain tumor patients the 20S proteasome ChT-L activity positively correlated with IL-8 concentration., Conclusions: Elevated 20S proteasome ChT-L activity was related to the increased risk of death in glial brain tumor patients. A positive correlation between 20S proteasome ChT-L activity and IL-8 concentration may indicate the molecular mechanisms regulating glial tumor biology. Thus research on proteasomes may be important and should be carried out to verify if this protein complexes may represent a potential therapeutic target to limit brain tumor invasion., Competing Interests: The authors have declared that no competing interests exist.

Plasma gelsolin (pGSN) is a highly conserved abundant circulating protein, characterized by diverse immunomodulatory activities including macrophage activation and the ability to neutralize pro-inflammatory molecules produced by the host and pathogen. Using a murine model of Gram-negative sepsis initiated by the peritoneal instillation of Pseudomonas aeruginosa Xen 5, we observed a decrease in the tissue uptake of IRDye ® 800CW 2-deoxyglucose, an indicator of inflammation, and a decrease in bacterial growth from ascitic fluid in mice treated with intravenous recombinant human plasma gelsolin (pGSN) compared to the control vehicle. Pretreatment of the murine macrophage line RAW264.7 with pGSN, followed by addition of Pseudomonas aeruginosa Xen 5, resulted in a dose-dependent increase in the proportion of macrophages with internalized bacteria. This increased uptake was less pronounced when cells were pretreated with pGSN and then centrifuged to remove unbound pGSN before addition of bacteria to macrophages. These observations suggest that recombinant plasma gelsolin can modulate the inflammatory response while at the same time augmenting host antibacterial activity.

Summary: Papillary thyroid gland carcinoma is the most common type of malignancy of the endocrine system. Metastases to the pituitary gland have been described as a complication of papillary thyroid cancer in few reported cases since 1965. We report the case of a 68-year-old female patient with a well-differentiated form of thyroid gland cancer. Despite it being the most common malignant cancer of the endocrine system, with its papillary form being one of the two most frequently diagnosed thyroid cancers, the case we present is extremely rare. Sudden cardiac arrest during ventricular fibrillation occurred during hospitalization. Autopsy of the patient revealed papillary carcinoma of the thyroid, follicular variant, with metastasis to the sella turcica, and concomitant sarcoidosis of heart, lung, and mediastinal and hilar lymph nodes. Not only does atypical metastasis make our patient's case most remarkable, but also the postmortem diagnosis of sarcoidosis makes her case particularly unusual., Learning Points: The goal of presenting this case is to raise awareness of the clinical heterogeneity of papillary cancer and promote early diagnosis of unexpected metastasis and coexisting diseases to improve clinical outcomes. Clinicians must be skeptical. They should not fall into the trap of diagnostic momentum or accept diagnostic labels at face value. Regardless of the potential mechanisms, clinicians should be aware of the possibility of the coexistence of thyroid cancer and sarcoidosis as a differential diagnosis of lymphadenopathy. This case highlights the importance of the diagnostic and therapeutic planning process and raises awareness of the fact that one uncommon disease could be masked by another extremely rare disorder.

Background : Oral squamous cell carcinoma remains a significant worldwide public health challenge, associated with high morbidity and mortality. Treatment of this type of cancer lacks effective medication. Moreover, there are very few specific biomarkers that are useful in early diagnosis or treatment optimisation. Proline metabolism may prove to be of importance in the search for new treatment modalities. Methods : To evaluate the significance of proline metabolism in the development of oral cancer, proline concentration was assessed in oral cancer tissue and normal oral mucosa. The results were compared to the clinical stage and histological grade of the tumours. Moreover, the expression of proteins involved in proline metabolism via proline dehydrogenase/oxidase (PRODH/POX, PPARγ, HIF1-α) was determined. In the next stage of the study, conducted on cell lines of tongue cancer treated with celecoxib, the aforementioned factors involved in proline metabolism were evaluated. Cellular viability and cell proliferation, as well as apoptosis, were also assessed. Results : Our research results indicate that a high intracellular proline concentration and expression of factors involved in its metabolism correlate with the clinical stage and histological grade of oral cancer. Moreover, we are the first researchers to demonstrate that celecoxib can affect proline metabolism, causing an increase in pro-apoptotic factors (PRODH/POX, PPARγ), reducing the expression of HIF-1α and activating apoptosis. Conclusions : Proline metabolism, due to its involvement in the process of apoptosis, can be of great importance in anticancer therapy. It appears that celecoxib, which influences the PRODH/POX pathway, may be a promising therapeutic compound in oral cancer treatment.

Introduction Sleep is a physiological state essential for proper functioning of the body. One of the reasons for sleep disorders is obstructive sleep apnea syndrome (OSAS)., Aim: The aim of this research is histological evaluation of the mucous membrane of the soft palate in patients affected by various forms of OSAS., Material and Method: The studied group consisted of patients with sleep-related breathing disorder in the form of primary snoring or OSAS. People with chronic tonsillitis, without a history of sleep-related breathing disorders, were included in the comparative group. Fragments of the mucous membrane of the uvula (study group) and the glossopalatine arch (comparative group) were taken for histological examination during surgery. Using histological, histochemical and immunohistochemical methods, we assessed the presence and severity of inflammation (CD3, CD20, CD68), the structure of nerve fibers (S-100) and the size of blood vessels (CD34) in the examined tissue., Results: Patients with OSAS developed a local inflammatory process in the oropharyngeal tissues (stronger expression of CD3, CD20, CD68 in people with OSAS). The exacerbation of the immunohistochemical reaction with CD3 correlated with the phase of OSAS. We found a higher degree of fibrosis and a higher expression of CD34 and S-100 receptors in subjects with OSAS compared to snoring patients and patients from the comparative group., Discussion: Due to chronic tissue vibration, snoring most likely leads to damage to the nerve fibers in the soft palate, which can intensify episodes of shallow breathing during sleep and increase the occurrences of apnea.

Background: Despite the previously suggested role of Neudesin in tumorigenesis and its potential as a novel target for the treatment of cancers, its prognostic value has never been examined. Thus, the aim of the study was to evaluate Neudesin concentrations in primary brain tumor patients and make a comparison with non-tumoral individuals., Methods: Cerebrospinal fluid (CSF) and serum Neudesin concentration was evaluated by means of the ELISA method., Results: The total group of brain tumor patients had statistically lower serum Neudesin concentrations compared to the non-tumoral group (P = 0.037). The meningeal tumor subgroup also had statistically lower serum Neudesin concentrations compared to the non-tumoral group (P = 0.012). The Astrocytic brain tumor subgroup had significantly higher CSF Neudesin concentrations compared to the non-tumoral group (P = 0.046). Neudesin Quotient (CSF concentration divided by serum concentration) in the astrocytic brain tumor subgroup was statistically higher compared to the non-tumoral group (P = 0.023). Males had statistically lower concentrations of the serum Neudesin compared to females (P = 0.047). Univariate linear regression analysis revealed that for women the serum Neudesin concentration was 1.53 times higher than for men. In the model of multivariate linear regression analysis, predictor variables influencing serum Neudesin concentrations included CSF Neudesin concentration and the Neudesin Quotient, if other model parameters are fixed. The developed model explains 82% of the variance in serum Neudesin concentration. Both linear regression models, univariate and multivariate, pointed to fewer factors with a potential to influence the Neudesin Quotient compared to serum Neudesin concentration., Conclusions: In astrocytic brain tumor patients Neudesin concentrations within the cerebrospinal fluid are higher compared with non-tumoral individuals. Serum Neudesin concentration strongly correlates with its CSF level. In primary brain tumor patients serum Neudesin concentration is clearly gender-dependent. Linear regression models pointed to fewer factors that may influence the Neudesin Quotient value, which suggests it is a better biomarker of astrocytic brain tumors than serum and CSF Neudesin concentrations alone.

Obesity is a new risk factor, to which more and more research is devoted, related to the development of cancer. Many studies of recent years have drawn attention to the role of adipose tissue as an important internal endocrine organ. In the adipose tissue proteins are produced, referred to by the common name as adipokines. In the case of obesity, the neoplasm cells are constantly stimulated by pro-inflammatory cytokines and adipokines, among which leptin dominates. The studies show that leptin can affect the cancer cells through numerous phenomena, e.g. inflammation, cell proliferation, suppression of apoptosis and angiogenesis. In this literature review we examined the role of leptin in the development of the individual cancers: breast cancer, colorectal cancer, prostate cancer, ovarian cancer, endometrial cancer and brain neoplasms: glioma and meningioma. However, leptin has very complicated mechanisms of action which require better understanding in certain types of cancer., Competing Interests: The authors declare no conflict of interest.

Cysteinyl leukotrienes (CysLTs) have been implicated in the pathogenesis of chronic rhinosinusitis (CRS). This study was undertaken to better understand the role of CysLTs in the development of CRS through 1). assessment of the pattern of expression of CysLT1 receptor in nasal polyps from patients with CRS and 2). correlation of expression of CysLT1 receptor with clinical features. Expression of CysLT1 receptor was evaluated immunohistochemically in nasal polyps from 20 patients with CRS and nasal mucosa from 10 control subject undergoing plastic surgery of the nose. Patients with CRS showed significantly higher expression of CysLT1 receptor as compared with the control group (p&lt;0.05). The expression of CysLT1 receptor in sub-epithelial inflammatory infiltrates tended to be higher in patients with CRS and allergy as compared with patients with CRS but without allergy (p=0.07). In particular, the expression of CysLT1 receptor in sub-epithelial inflammatory infiltrates was significantly greater in 3 patients with CRS and drug allergy as compared with patients with CRS but without drug allergy (p=0.03). Increased expression of CysLT1 receptor in inflamed mucosa of nasal polyps in patients with allergy might suggest particular role of CysLTs in the pathogenesis of nasal polyps in this group of patients.

Objective: To analyze the expression of β-catenin and N-cadherin in large series of meningioma cases and to investigate their correlation with peritumoral brain edema (PTBE)., Materials and Methods: Study group consists of 154 patients diagnosed with intracranial meningioma divided into: low-grade (G1) and high-grade (G2 or G3) group. PTBE was graded into four groups (0, I, II, III) using Steinhoff classification. The expression of N-cadherin, β-catenin was analyzed and graded based on the positive ratio of immunoreactivity. The results were analyzed statistically., Results: 104 cases were low-grade and 50 high-grade meningiomas. PTBE was observed in 103(66.8 %) cases: 57 grade I, 44 grade II and 2 grade III. Positive N-cadherin expression was found only in the membrane of the neoplastic cells in 50(48.1%) cases of low-grade, and in 34(68%) of high-grade group. In low-grade meningioma, β-catenin expression was observed within the cytoplasm and nucleus in 54(51.9%) cases. In high-grade meningiomas, β-catenin expression was observed in 33(66%) tumors only within the nucleus. N-cadherin expression was observed in 36 cases with PTBE grade I, 28 with grade II and 2 with grade III. β-catenin expression was observed in 40 cases with PTBE grade I, 24 with grade II and 2 with grade III. The results were statistically significant., Conclusions: Significant N-cadherin expression especially in high-grade meningioma group was found. β-catenin expression was the most evident in the nucleus rather than in cytoplasm. The degree of PTBE correlated with the N-cadherin and β-catenin expression and was the most prominent in high-grade meningioma group.

Introduction: Due to the lack of highly specific and sensitive methods for diagnosing ovarian cancer at advanced stages (according to the International Federation of Gynecology and Obstetrics (FIGO) classification stage III-IV), new noninvasive biomarkers are urgently needed. This study aims to investigate how the levels of plasma bioactive sphingolipids (ceramides, sphingosine-1-phosphate, sphingosine and sphinganine) are altered in serum, erythrocytes and platelets of patients with advanced serous ovarian cancer., Material and Methods: A total of 135 patients with advanced serous ovarian cancer and 159 women with normal ovarian morphology were enrolled. Plasma levels of sphingosine, sphingosine-1-phosphate, sphinganine, ceramide C14:0-Cer, C16:0-Cer, C18:1-Cer, C18:0-Cer, C20:0-Cer, C22:0-Cer, C24:1-Cer and C24:0-Cer were assessed by LC/MS/MS., Results: Plasma concentrations of C16-Cer, C18:1-Cer and C18-Cer were significantly higher in the advanced ovarian cancer group than in the control group (1.5-fold, p = 0.021; 1.8-fold, p = 0.036 and 1.5-fold, p = 0.031, respectively). Plasma concentration of C18:1-Cer was significantly higher in erythrocytes of women with advanced serous cancer compared to the control group ( p = 0.027). Plasma C16-Cer and C18:1-Cer levels and erythrocyte C18:1-Cer levels were able to distinguish patients with moderate/severe serous ovarian cancer from patients with mild ovarian cancer (AUC: 0.86, 0.898, 0.795, respectively). Plasma concentrations of C16, C18.1 and C18 significantly correlated with FIGO staging ( p = 0.001, p = 0.024 and p = 0.005), and grading ( p = 0.021, p = 0.021 and p = 0.033)., Conclusions: Plasma concentrations of C16, C18.1 and C18 correlated with the progression of ovarian cancer (FIGO staging and grading). Plasma levels of C16-Cer and C18:1-Cer and erythrocyte C18:1-Cer levels could be used to distinguish patients with advanced serous ovarian cancer., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2018 Termedia & Banach.)

The article describes epidemiology, clinical features and treatment strategy of chondrosarcoma with special regard to diagnostic and therapeutic difficulties in low grade chondrosarcomas. Chondrosarcomas account for 3.5-9% of primary bone tumors and approximately 30% of primary bone malignancies. They occur in the 4th to 7th decade of life, slightly more commonly in men. The most common locations are the pelvis, ribs, proximal femur and proximal humerus. Gradually increasing pain is the most common presenting symptom. Diagnosis must be based on clinical, radiological (conventional radiology, computed tomography, magnetic resonance imaging) and histopathological features. Treatment of the tumor is based on complete removal according to the principles of oncological asepsis. Lung metastases may develop and are associated with a markedly poorer prognosis.

Revision of the fourth edition of the World Health Organisation (WHO) Classification of Haematopoietic and Lymphatic Tissues, which was published in 2017, introduced important changes updating the biology, pathology, genetics, and clinical presentation of aggressive B-cell lymphomas. High grade B-cell lymphomas (HGBLs) replaced B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma, the new provisional entity Burkitt-like lymphoma with 11q aberration was identified, and some categories were upgraded, e.g. EBV-positive diffuse large B-cell lymphoma, not otherwise specified. Still the histopathological diagnostics is based on morphology and immunoprofile, but to define the HGBLs evaluation of MYC, BCL2, and BCL6 gene statuses is required. According to the presented WHO criteria, in the comprehensive histopathological diagnostics of aggressive B-cell lymphomas a highly specialised diagnostic team including a pathologist, a molecular biologist, a geneticist, a haematologist, and immunophenotyping technicians is needed.

We present the case of a 43-year-old patient with a radionegative tumor of the distal third of the femur. Work-up following a knee injury without any abnormalities on x-ray was extended to include an MRI study, which revealed an osteolytic lesion in the distal third of the femur. Extended work-up including an open biopsy identified a low-grade chondrosarcoma. Considering the patient's clinical status and the diagnostic findings, tumour resection and placement of a resection knee endoprosthesis appeared to be the best solution. The clinical outcome was good.

Meningiomas (MGs) are the frequent benign intracranial tumors. Their complete removal does not always guarantee relapse-free survival. Recurrence-associated chromosomal anomalies in MGs haves been proposed as prognostic factors in addition to the World Health Organisation (WHO) grading, tumor size and resection rate. The aim of this study was to evaluate the frequency of deletions on chromosomes in sporadic MGs and to correlate them with the clinical findings and tumor behaviour. Along with survival, the tumor recurrence was the main endpoint. Chromosomal loss of heterozygosity (LOH) was studied. 46 benign MGs were subjected to the analysis, complete tumor resection was intended and no early mortalities were observed. Incomplete removal was related to parasagittal location and psammomatous hisptopathology (p<0.01). Chromosomal alterations were present in 82.6% of cases; LOH at 22q (67.4%) and 1p (34.8%) were the most frequent and associated with male sex (p=0.04). Molecular findings were not specific for any of the histopathologic grade. Tumor recurrence (14 of 46) correlated with tumor size (≥35mm), LOH at 1p, 14q, coexistence of LOH at 1p/14q, 10q/14q, 'complex karyotype' status (≥2 LOHs excluding 22q), patient age (younger <35), and Simpson grading of resection rate (≥3 of worse prognosis). The last 3 variables were independent significant prognostic factors in multivariate analysis and of the same importance in recurrence prediction (Receiver Operating Characteristic curves comparison p>0.05). Among the cases of recurrence, tumor progression was observed in 3 of 14. In 2 cases, LOH on 1p and/or coexistence of LOH 1p/14q correlated with anaplastic transformation., (Copyright © 2016 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)

Haemangiopericytoma (HPC) is an uncommon, vascular tumor derived from Zimmerman pericytes surrounding blood vessels. HPC constitute around 1% of all tumors of vascular origin and may appear anywhere, 5% of them can be situated in nasal cavity. Tumor location within the head and neck predispose to its benign character and improves prognosis. This case report presents the case of 33-year-old patient with haemangiopericytoma-like tumor of the nasal cavity, presented symptoms of impaired nasal breathing and recurrent epistaxis. Tumor was excised with 0 degree endoscope. The follow-up recurrence-free period was 2 year 6 months and shows this is effective way of treatment. Described in the literature late recurrences and metastases reminds that regular, life-long observation is mandatory.

Purpose: Gliomas are the most common primary brain tumors. The etiology is still unclear and the progression from low to high-grade gliomas is frequent. The molecular mechanisms are quite established, however the heterogeneity of glioblastomas force the scientist to look for the new therapeutic targets. The aim of the study was to evaluate the caspase-3 and survivin expression in correlation with MIB-1 expression in gliomas of various grade to assess the apoptosis in gliomas and to determinate new possible targets for the future therapy., Material and Methods: We identified 131 patients with a histopathological diagnosis of astrocytic tumors (diffuse astrocytoma, anaplastic astrocytoma and glioblastoma). The evaluation of caspase-3, survivin and MIB-1 expression was done using immunohistochemical methods., Results: Caspase-3 and survivin expression was observed both in low- and high-grade astrocytomas. The differences in expression were the most evident in glioblastoma group. All primary glioblastomas (31 cases) expressed caspase-3. In secondary glioblastoma group only 17 out of 30 specimens were positive for caspase-3. Survivin expression was observed in 80.6% primary glioblastomas and in all examined secondary glioblastomas and the staining was strong and diffuse in all cases. MIB-1 expression was low in diffuse astrocytomas (DA) and ranged between 1 and 5%. In anaplastic astrocytoma group it was ranged between 5 and 10% and the highest percentage of the positive cells was observed in glioblastoma cases and ranged from 10% even to 30%. The most evident MIB-1 expression was observed in the cells surrounding the pathological blood vessels and necrosis., Conclusions: The high incidence of survivin and caspase-3 expression in diffuse and anaplastic astrocytoma cases may suggest, that the regulation between pro- and antiapoptotic proteins may play an important role in tumor growth and progression. The overexpression of survivin and MIB-1 expression in glioblastoma cases also may confirm the theory about the important role of anti-apoptotic and proliferation processes in glioblastoma progression and as such may be potential therapeutic targets., (Copyright © 2016 Medical University of Bialystok. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)

Olfactory neuroblastoma (ONB) is a rare neoplasm of the sinonasal area with neuroendocrine differentiation. ISL-1, TTF-1 and PAX5 are transcription factors that are frequently upregulated in tumors showing neuroendocrine differentiation. The aim of our study was to evaluate these markers in a group of ONBs. We included 11 ONBs from 4 large university hospitals. Immunohistochemical expression of TTF-1, PAX5 and ISL-1 was evaluated. TTF-1, ISL-1 and PAX5 were expressed in 3/11 cases (27.27%, h-score: 3-45), 7/11 cases (63.64%, h-score: 23-200), and in 3/11 cases (27.77%, h-score 3-85), respectively. The patient with the strongest PAX5 reactivity exhibited an aggressive clinical course with rapid dissemination to the spine and death shortly after the diagnosis. No significant correlation in the expression of PAX5 and TTF-1 ( = 0.43; p = 0.18) was observed. ISL-1 is widely expressed in tumors with neuroendocrine differentiation and therefore of limited value in their differential diagnosis. TTF-1 positivity does not exclude the diagnosis of primary ONB, although usually only a small percentage of cells are positive. PAX5 expression is infrequent (27.27%) in ONB; however, if present it can be associated with a very aggressive clinical course.

Background: Osteoid osteoma is a primary, benign bone tumour. The characteristic clinical symptom is nocturnal pain at the tumour site that decreases or resolves completely with salicylates and non-steroidal antiinflammatory drugs (NSAIDs). The typical radiological features include a radiolucent area with an osteosclerotic rim. An unusual location or absence of visible abnormalities on conventional radiographs may pose a diagnostic challenge., Material and Methods: We report our clinical experience with osteoid osteoma in 15 patients, with special regard to diagnostic and therapeutic difficulties in two cases., Results: All patients reported the characteristic pattern of nocturnal pain that was reduced or resolved after administration of aspirin or NSAIDs. A typical radiological appearance of osteoid osteoma was observed in 13 patients, with radiological studies showing no changes in two patients, who required extended imaging workup to establish the diagnosis., Conclusions: 1. Osteoid osteoma may be a diagnostic and therapeutic problem. 2. Lack of visible abnormalities on conventional radiographs in the presence of typical clinical symptoms does not rule out osteoid osteoma. 3. Bone scintigraphy and magnetic resonance imaging are helpful methods in the imaging of radiologically silent pathological lesions.

Myxomas are the most common non-invasive but life-threatening cardiac neoplasms due to obstruction of heart chambers and risk of embolism in a manner resembling thromboembolism as well. They can occasionally disseminate via their detached fragments into the bloodstream to seed and grow as secondary still benign tumors. In this study we evaluated morphological and clinical aspects of 14 ancient, degenerated left or right-sided cardiac atrial myxomas with expression of CD9 and CD63, which are found to contribute to platelet activation, aggregation and, as a result, intratumoral thrombosis or fragmentation. The appearance of tumors varied from sessile to polypoid revealing that a higher rate of endocardial thrombosis was associated with sessile compared to polypoid myxomas and left-sided tumors compared to right-sided ones in our study. In the general aspect of ancient calcifications, amorphous calcification with intra-tumor thrombosis was noted more frequently in sessile tumors, while well-formed osseous metaplasia was usually a feature of polypoid tumors. In our material osseous metaplasia did not coexist with massive thrombosis and was found in polypoid, pedunculated myxomas. Most importantly, CD9 overexpression was recorded in every studied myxoma and CD63 gave a weak reaction in myxoma cells.

Purpose: Glaucoma is one of the most important reason causes of the blindness, associated with retinal ganglion cells (RGC) death. This process is not fully understood, however apoptosis due to hypoxia is one of the most important processes leading to RGC death. Glaucomatous optic neuropathy is characterized by remodeling of the extracellular matrix due to metalloproteinase activation, which leads to loss of RGC and axons at the optic nerve head. The aim of the study was to evaluate metalloproteinase 9 (MMP-9) and tissue metalloproteinase inhibitor-1 (TIMP-1) expression in the retinal ganglion cells and optic nerve axons in 33 eyes with absolute primary glaucoma., Material/methods: To evaluate MMP-9 and TIMP-1 expression primary polyclonal goat antibodies against MMP-9 and TIMP-1 were used. The control group was composed of 8 cases of eyes enucleated and fixed in the first day after trauma., Results: MMP-9 expression was observed in retinal ganglion cells and in the inner nuclear layer of the retina in all the examined cases. In 28 out of 33 glaucomatous eyes, MMP-9 expression was observed in the proliferating glial cells surrounding the optic nerve axons. TIMP-1 expression was observed in 10 out of 33 glaucomatous eyes, only in retinal ganglion cells. None of the examined injured eyes showed MMP-9 and TIMP-1 expression., Conclusions: MMP-9 activation rather than TIMP-1 may by associated with the pathomechanism of retinal ganglion cell and optic nerve damage in absolute glaucoma., (Copyright © 2015 Medical University of Bialystok. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)

Objectives: The present study was performed to investigate the expression of hepatocyte (HGF), epidermal (EGF) and vascular endothelial (VEGF) growth factors in the course of healing of experimental tympanic membrane (TM) perforations in rats. The goal was to explain the role of these growth factors in the healing process of TM and to assess the possibility of their future application as healing promoters., Methods: Seventy rats were used, of which 10 served as controls and the others had their TM perforated. The experimental animals were divided into six subgroups on the basis of time points (01, 03, 05, 07, 09, 15 day after injury). Videootoscopy and histology were employed to assess the morphology of the healing process. The expressions of HGF, EGF and VEGF were evaluated using Western blot analysis. Tissue localization of HGF was determined by the immunofluorescence method., Results: HGF was hardly detectable in normal TM; however, a significant increase was noted in its expression starting from the third day after injury throughout the follow-up period, with the highest level on day 05. The analysis of HGF tissue localization with immunofluorescence revealed diffuse staining in the cytoplasm of proliferating epithelial cells. The expression of EGF was elevated on the first day after injury, not reaching statistical significance, and then returned to the level observed in the control TM. No significant differences were noted in the expression of VEGF., Conclusion: High expression of HGF during the healing process of acute TM perforations makes it a promising candidate for further studies oriented towards its possible use in augmentation of TM healing., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Tympanic membrane (TM) perforations are commonly seen in clinical practice as a result of trauma or in the course of otitis media. The TM is a unique structure suspended in air which makes its healing processes different than in the skin wounds. The aim of the study was otoscopical and histological evaluation of the rat's TM healing process., Material and Methods: 56 male Wistar rats were used for the study. Fifty of them had TMs perforated bilaterally using CO2 laser, additional 6 served as a controls. The animals were sacrificed on either day 1, 2, 3, 6 and 10 post injury. Process of healing was assessed otoscopicaly, subsequently TM were dissected and processed for histological evaluation., Results: At day 6 after perforation half and on day 10 all of TM were healed. On the first day, in histological evaluation, focal thickening of the epithelial layer was observed at some distance from the edge of perforation, on the side of annulus. On the following day proliferation of epithelium covering outer surface of TM on the side of the malleus handle and annulus was clearly visible. An eosinophilic mass containing macrophages and granulocytes was seen in front of the migrating epithelium. On day 3-6 migrating epithelium reached the edge of perforation. Proliferation of the connective tissue layer followed the epithelium., Conclusions: The present results indicate that the squamous epithelium covering the outer surface of TM constitutes the first layer which restores continuity of TM. The proliferation of the connective tissue occurs in the direct vicinity of the proliferating and migrating epithelium., (Copyright © 2014 Polish Otorhinolaryngology - Head and Neck Surgery Society. Published by Elsevier Urban & Partner Sp. z.o.o. All rights reserved.)

Purpose: To evaluate the correlation between quality of the surgical field, intraoperative bleeding during endoscopic sinus surgery (ESS) and the density of microvasculature of the nasal mucosa., Material/methods: Nasal mucosa of 30 patients, operated for chronic rhinosinusitis, was biopsied to assess expression of CD34 antigen on vascular endothelium. Quality of surgical field was evaluated with Fromm-Boezaart scale at mean arterial pressure (MAP) of 70-80 mmHg. If at this MAP surgical field quality was not satisfactory further reduction of hemodynamic parameters was performed until 'bloodless surgical field' (grade 2 or lower) was achieved. The rate of intraoperative bleeding was calculated from the ratio of total blood loss and the operative time. The extent of the disease was assessed according to computed tomography findings using Lund-Mackay staging system., Results: Significant positive correlation (Spearman correlation test; p<0.05) was found between CD34 antigen expression and quality of surgical field at MAP between 70 and 80 mmHg as well as the rate of intraoperative bleeding. More intense reduction of MAP was necessary to achieve 'bloodless surgical field' in patients with high CD34 expression than in those with moderate and low expression. Lund-Mackay score correlated with quality of surgical field but not with the rate of intraoperative bleeding., Conclusion: During ESS, it is microvascular density of the nasal mucosa rather than the extent of the disease that contributes to the intensity of intraoperative bleeding, although both factors negatively influence the quality of surgical field., (Copyright © 2014 Medical University of Bialystok. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)