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Background/Aim: Adenoid cystic carcinoma (AdCC) is a rare malignant tumor that primarily affects the salivary glands but can also occur in other organs. Low incidence and unpredictable clinical behavior make AdCC one of the most difficult head and neck tumors to treat. Case Report: We present the case of a 54-year-old woman with AdCC localized at the base of the tongue, following radical surgical and oncological therapy. Due to advances in palliative oncological treatment, there is a more than fiveyear survival period before the progression of metastatic disease. Considering the rare occurrence of this disease, a literature search was also conducted, and therapy options are discussed. Ensuring a sufficient extent of the surgical procedure is still a challenge, and most specialists agree that subsequent postoperative radiotherapy reduces the risk of local recurrence. The effective dose of radiotherapy to the area of the primary tumor and lymph nodes is not clearly defined. Conclusion: The distinct biological behavior of AdCC results in varying sensitivity to chemotherapy or radiotherapy compared to treatments commonly used for head and neck squamous cell carcinomas. Treatment recommendations for these rarer tumors are based mainly on case reports and small clinical trials. The acquired therapeutic experience can contribute to prolonging the survival period of patients and improving their prognosis and quality of life. [ABSTRACT FROM AUTHOR]

Undifferentiated carcinoma with osteoclast-like giant cells (UCOGC) of the pancreas represents a rare subtype of pancreatic ductal adenocarcinoma (PDAC). Despite a distinct morphology and specific clinical behavior, UCOGCs exhibit unexpected similarities in regard to DNA mutational profiles with conventional PDAC. Treating pancreatic ductal adenocarcinoma is particularly challenging, with limited prospects for cure. As with many other malignant neoplasms, the exploration of microRNAs (miRNAs, miRs) in regulating the biological characteristics of pancreatic cancer is undergoing extensive investigation to enhance tumor diagnostics and unveil the therapeutic possibilities. Herein, we evaluated the expression of miR-21, -96, -148a, -155, -196a, -210, and -217 in UCOGCs and poorly differentiated (grade 3, G3) PDACs. The expression of miR-21, miR-155, and miR-210 in both UCOGCs and G3 PDACs was significantly upregulated compared to the levels in normal tissue, while the levels of miR-148a and miR-217 were downregulated. We did not find any significant differences between cancerous and normal tissues for the expression of miR-96 and miR-196a in G3 PDACs, whereas miR-196a was slightly, but significantly, downregulated in UCOGCs. On the other hand, we have not observed significant differences in the expression of the majority of miRNAs between UCOGC and G3 PDAC, with the exception of miR-155. UCOGC samples demonstrated lower mean levels of miR-155 in comparison with those in G3 PDACs. [ABSTRACT FROM AUTHOR]

Therapy for pancreatic ductal adenocarcinoma remains challenging, and the chances of a complete cure are very limited. As in other types of cancer, the expression and role of miRNAs in controlling the biological properties of this type of tumor have been extensively studied. A better insight into miRNA biology seems critical to refining diagnostics and improving their therapeutic potential. In this study, we focused on the expression of miR-21, -96, -196a, -210, and -217 in normal fibroblasts, cancer-associated fibroblasts prepared from a ductal adenocarcinoma of the pancreas, and pancreatic carcinoma cell lines. We compared these data with miRNAs in homogenates of paraffin-embedded sections from normal pancreatic tissues. In cancer-associated fibroblasts and cancer cell lines, miRNAs differed significantly from the normal tissue. In detail, miR-21 and -210 were significantly upregulated, while miR-217 was downregulated. Similar transcription profiles were earlier reported in cancer-associated fibroblasts exposed to hypoxia. However, the cells in our study were cultured under normoxic conditions. We also noted a relation to IL-6 production. In conclusion, cultured cancer-associated fibroblasts and carcinoma cells reflect miR-21 and -210 expression similarly to the cancer tissue samples harvested from the patients. [ABSTRACT FROM AUTHOR]

Background: Predicting stroke risk in patients with carotid artery stenosis (CS) remains challenging. Circulating biomarkers seem to provide improvements with respect to risk stratification. Methods: Study patients who underwent carotid endarterectomy were categorized into four groups according to symptomatology and compared as follows: symptomatic with asymptomatic patients; and asymptomatic patients including amaurosis fugax (AF) (asymptomatic + AF group) with patients with a transient ischemic attack (TIA) or brain stroke (BS) (hemispheric brain stroke group). Carotid specimens were histologically analyzed and classified based on the American Heart Classification (AHA) standard. As a marker of OS, the plasma levels of malondialdehyde (MDA) were measured. Comparisons of MDA plasma levels between groups were analyzed. Results: In total, 35 patients were included in the study. There were 22 (63%) patients in the asymptomatic group and 13 (37%) in the symptomatic group. Atheromatous plaque (p = 0.03) and old hemorrhage (p = 0.05), fibrous plaque (p = 0.04), myxoid changes (p = 0.02), plaques without hemorrhage (p = 0.04), significant neovascularization (p = 0.04) and AHA classification (p = 0.006) had significant correlations with clinical presentation. There were 26 (74%) patients in the asymptomatic group and 9 (26%) in the hemispheric brain stroke group. Atheromatous plaque (p = 0.02), old hemorrhage (p = 0.05) and plaques without neovascularization (p = 0.02), fibrous plaque (p = 0.03), plaques without hemorrhage (p = 0.02) and AHA classification (p = 0.01) had significant correlations with clinical presentation. There was no significant difference between symptomatic and asymptomatic groups with respect to MDA plasma levels (p = 0.232). A significant difference was observed when MDA plasma levels were compared to asymptomatic + AF and the hemispheric stroke group (p = 0.002). Conclusions: MDA plasma level correlates with the risk of hemispheric stroke (TIA or BS) and is a reliable marker of plaque vulnerability in carotid artery stenosis. [ABSTRACT FROM AUTHOR]

Background: RT-qPCR quantification of miRNAs expression may play an essential role in pancreatic ductal adenocarcinoma (PDAC) diagnostics. RT-qPCR-based experiments require endogenous controls for the result normalization and reliability. However, expression instability of reference genes in tumors may introduce bias when determining miRNA levels.Methods: We investigated expression of 6 miRNAs, isolated from FFPE samples of pancreatic adenocarcinomas. Four internal controls were utilized for RT-qPCR result normalization: artificial miR-39 from C. elegans, U6 snRNA, miR-16 and snoRNA U91.Results: We found miR-21, miR-155 or miR-217 expression values in tumors may differ up to several times, depending on selected internal controls. Moreover, different internal controls can produce controversial results for miR-96, miR-148a or miR-196a quantification. Also, expression of our endogenous controls varied significantly in tumors. U6 demonstrated variation from -1.03 to 8.12-fold, miR-16 from -2.94 up to 7.38-fold and the U91 from -3.05 to 4.36-fold respectively. On the other hand, the most stable gene, determined by NormFinder algorithm, was U91. Each miRNA normalized relatively to the spike or U91, demonstrated similar expression values. Thus, statistically significant and insignificant differences between tumors and normal tissues for miRNAs were equal for the spike and the U91. Also, the differences between the spike and U91 were statistically insignificant for all of miRs except miR-217. Among three endogenous controls, U91 had the lowest average expression values and standard deviation in cancer tissues.Conclusions: We recommend U91 as a new normalizer for miRNA quantification in PDACs. [ABSTRACT FROM AUTHOR]

Objective. To characterize GEP-NENs in routine biopsies and surgical specimen in the Czech Republic and to evaluate how WHO Classification (2010) is acceptable in diagnostic practice. Methods. Paraffin-embedded blocks and bioptic reports were collected from 17 departments of pathology. Histologic slides were stained with H&E and immunohistologically for CgA, synaptophysin, and Ki-67. Results. Out of 28 gastric NENs, there were 22 NETs, G1, 5 NETs, G2, and 1 NEC. Ten duodenal NENs were NETs, G1. Among 27 NENs of jejunum and ileum, 23 were NETs, G1, 2 NETs, G2, and 1 NEC and 1 mixed adenoneuroendocrine carcinoma (MANEC). Among 42 appendiceal "incidentalomas", 39 were NETs G1, 2 goblet cell carcinoids, and 1 MANEC. Out of 34 large intestinal NENs, 30 were NETs, G1, 3 NETs, G2, and 1 NEC. One small intestinal and 6 large bowel neoplasms were reclassified as poorly differentiated adenocarcinomas. In 12 pancreatic NENs, there were 7 NETs, G1, 3 NETs, G2, and 2 NECs. Conclusions. Our study demonstrates differences in GEP-NENs frequency in sites of origin in our region, comparing to other countries. Regarding routine bioptic diagnostics, we gave evidence that the WHO 2010 classification of NENs is fully acceptable for exact categorisation of tumours. [ABSTRACT FROM AUTHOR]

Isolated granulomatous noncaseating pancreatitis is a rare condition exceptionally described in human population. We demonstrate a case of the a 71-years-old female patient suffering from recent diabetes mellitus, generalized atherosclerosis and hypertension who died due to pulmonary embolism and terminal bronchopneumonia. Lipomatosis of pancreatic tissue was observed during the postmortemexamination. Histological examination of pancreatic tissue discovered multiple small noncaseating epithelioid cell and giant cell granulomas, partly replacing the islets of Langerhans. To our knowledge, our case represents the first description of noninfectious granulomatous pancreatitis associated with acute manifested insulin-dependent diabetes mellitus. [ABSTRACT FROM AUTHOR]

We present the clinical, radiological and pathological features of a case of a cranial hypertrophic pachymeningitis that developed in the course of mastoiditis and petrous apex inflammation and responded to immunosuppressive therapy only. Documented by the development of clinical findings, magnetic resonance imaging, cerebrospinal fluid changes, histopathology findings, by otosurgical intervention and finally by the insertion of a ventriculo-peritoneal shunt, the case illustrates a gradual development of pachymeningitis with consequent hydrocephalus and intracranial hypertension. We consider this disease development an example of immune-induced proliferative fibrotic changes in meninges. [ABSTRACT FROM AUTHOR]

The case of an 11-year-old boy with recurrent abdominal pain is presented. Physiological findings were found normal during a clinical investigation, as well as many laboratory tests, ultrasonography and CT of abdomen. Only a high level of sedimentation rate and the focus of increased activity in the sacral region on scintigraphy using 99mTc-HMPAO (hexamethypropyleneaminooxime) labelled leukocytes were found. The other findings on bone scintigraphy, X-ray and MRI led to a deflection of the correct diagnosis. The real culprit proved to be an ingested foreign body (a piece of a wooden skewer) that the patient failed to reveal. [ABSTRACT FROM AUTHOR]

Simple Summary: Heat shock proteins (HSPs) are cytoprotective chaperones occurring in virtually all living organisms including various types of cancer cells to repair proteotoxic damage. Some of HSPs influence tumor prognosis and represent promising therapeutic targets. To clarify prognostic significance of HSPs 27, 70, and 110 in colorectal carcinoma, we retrospectively performed HSP immunohistochemistry on tissue microarrays from archive tumor tissue from 297 patients. Survival analysis revealed significantly shorter overall survival (OS) and borderline insignificantly shorter cancer specific survival (CSS) in patients with HSP70+ tumors. In HSP27+, both OS and CSS were insignificantly shorter. HSP110 showed no influence on survival. We found an association of HSP27 and HSP70 expression with advanced cancer stage. In multivariate analysis, only advanced stage and right sided localization were independent predictors of worse survival, whereas all three examined HSPs were insignificant. In conclusion, from all three HSPs examined in our study, only HSP70 had an impact on colorectal cancer prognosis, although it is stage-dependent. Heat shock proteins (HSPs) are evolutionarily conserved chaperones occurring in virtually all living organisms playing a key role in the maintenance of cellular homeostasis. They are constitutively expressed to prevent and repair protein damage following various physiological and environmental stressors. HSPs are overexpressed in various types of cancers to provide cytoprotective function, and they have been described to influence prognosis and response to therapy. Moreover, they have been used as a tumor marker in blood serum biochemistry and they represent a potentially promising therapeutic target. To clarify prognostic significance of two canonical HSPs (27 and 70) and less known HSP110 (previously known as HSP105) in colorectal carcinoma (CRC), we retrospectively performed HSP immunohistochemistry on tissue microarrays from formalin-fixed paraffin-embedded tumor tissue from 297 patients with known follow-up. Survival analysis (univariate Kaplan–Meier analysis with the log-rank test and multivariate Cox regression) revealed significantly shorter overall survival (OS, mean 5.54 vs. 7.07, p = 0.033) and borderline insignificantly shorter cancer specific survival (CSS, mean 6.3 vs. 7.87 years, p = 0.066) in patients with HSP70+ tumors. In the case of HSP27+ tumors, there was an insignificantly shorter OS (mean 6.36 vs. 7.13 years, p = 0.2) and CSS (mean 7.17 vs. 7.95 years, p = 0.2). HSP110 showed no significant impact on survival. Using Pearson's chi-squared test, there was a significant association of HSP27 and HSP70 expression with advanced cancer stage. HSP27+ tumors were more frequently mismatch-repair proficient and vice versa (p = 0.014), and they occurred more often in female patients and vice versa (p = 0.015). There was an enrichment of left sided tumors with HSP110+ compared to the right sided (p = 0.022). In multivariate Cox regression adjusted on the UICC stage, grade and right/left side; both HSPs 27 and 70 were not independent survival predictors (p = 0.616 & p = 0.586). In multivariate analysis, only advanced UICC stage (p = 0) and right sided localization (p = 0.04) were independent predictors of worse CSS. In conclusion, from all three HSPs examined in our study, only HSP70 expression worsened CRC prognosis, although stage-dependent. The contribution of this article may be seen as a large survival analysis of HSPs 27 and 70 and the largest analysis of HSP110 described in CRC. [ABSTRACT FROM AUTHOR]

Multiple duodenal polyps are a relatively rare finding, usually co-occurrent with familial adenomatous polyposis (FAP).We report a patient with multiple duodenal adenomas and a negative examination for FAP: multiple flat polyps were detected endoscopically in a 37-year-old male patient, extending from the apex of the bulb to the end of the descending part of the duodenum. In terms of histology, they were tubular adenomas with moderate dysplasia. Colonoscopy and enteroclysis were normal. Both push and capsule enteroscopy only showed multiple polyps in the area of the descending duodenum. DNA analysis of the APC gene was as follows: DGGE, exon 1-15, deletion at codons 1309 and 1061 by means of PCR for attenuated APC were negative. Afterwards we screened the patient for germline MYH mutations using the denaturing high-performance liquid chromatography (DHPLC) in combination with sequencing. No novel pathogenic mutation has been identified. Large polyps were removed by means of endoscopic polypectomy and mucosectomy, while small polyps were removed by means of argon plasma coagulation.We conduct yearly checkups, removing only sporadic polyps. The rare finding of duodenal polyposis not co-occurrent with FAP proves that multiple adenomas in the digestive tube need not necessarily co-occur with FAP. [ABSTRACT FROM AUTHOR]

Background Nanofiber wound dressings remain the domain of in vitro studies. The purpose of our study was to verify the benefits of chitosan (CTS) and polylactide (PLA)-based nanofiber wound dressings on a porcine model of a naturally contaminated standardized wound and compare them with the conventional dressings, i.e. gauze and Inadine. Material and Methods The study group included 32 pigs randomized into four homogeneous groups according to the wound dressing type. Standardized wounds were created on their backs, and wound dressings were regularly changed. We evaluated difficulty of handling individual dressing materials and macroscopic appearance of the wounds. Wound swabs were taken for bacteriological examination. Blood samples were obtained to determine blood count values and serum levels of acute phase proteins (serum amyloid A, C-reactive protein, and haptoglobin). The crucial point of the study was histological analysis. Microscopic evaluation was focused on the defect depth and tissue reactions, including formation of the fibrin exudate with neutrophil granulocytes, the layer of granulation and cellular connective tissue, and the reepithelialization. Statistical analysis was performed by using SPSS software. The analysis was based on the Kruskal–Wallis H test and Mann–Whitney U test followed by Bonferroni correction. Significance was set at P  < .05. Results Macroscopic examination did not show any difference in wound healing among the groups. However, evaluation of histological findings demonstrated that PLA-based nanofiber dressing accelerated the proliferative (P  = .025) and reepithelialization (P  < .001) healing phases, while chitosan-based nanofiber dressing potentiated and accelerated the inflammatory phase (P  = .006). No statistically significant changes were observed in the blood count or acute inflammatory phase proteins during the trial. Different dynamics were noted in serum amyloid A values in the group treated with PLA-based nanofiber dressing (P  = .006). Conclusion Based on the microscopic examination, we have documented a positive effect of nanofiber wound dressings on acceleration of individual phases of the healing process. Nanofiber wound dressings have a potential to become in future part of the common wound care practice. [ABSTRACT FROM AUTHOR]

The aim was to construct a composite structure for bone tissue substitute on the basis of a degradable composite of an organic nanofiber carrier and an inorganic matrix in 3D, and to achieve subsequent colonisation by differentiated human mesenchymal stem cells (hMSC) towards osteocytes. We developed an active bone tissue substitute using nanofiber technology for a polycaprolactone (PCL) scaffold with the addition of hydroxyapatite and the colonisation of both components with hMSC with the ability of differentiation towards osteocytes. The constructed composition included the components necessary for bone healing (inorganic and cellular) and it also forms a spatially-oriented 3D structure. We used polycaprolactone Mw 70,000 with electrostatic spinning for the formation of nanofibers using a modified Nanospider™ method. For the inorganic component we used orthophosphate-calcium silicate with a crystal size of 1-2 mm which the nanofiber membrane was coated with. Both components were connected together with a tissue adhesive based of fibrin glue. Cultivated hMSC cells at a concentration of 1.2 × 104 /cm2 were multiplied in vitro and then cultivated in the expansion medium. HMSC overgrew both the PCL membrane and the Si-CaP crystals. After colonisation with cultivated cells, this composite 3D structure can serve as a three-dimensional bone tissue replacement. [ABSTRACT FROM AUTHOR]

In a brief review is presented a summary of news in the classification of neuroendocrine neoplasms of the digestive system, as they were introduced in the 5th edition of the WHO Classification of Digestive System Tumors published in summer 2019.

Isolated infectious endocarditis of the pulmonary valve is a rare condition and represents 1,5-2% of all cases of infectious endocarditis. We present a case of a 37year-old woman without any relevant medical history. The woman was hospitalized with hallmarks of severe sepsis and bilateral pneumonia; she died several hours after admission with progressive multiorgan failure and disseminated intravascular coagulopathy. Microbiologic examination approved Staphylococcus aureus as the etiological agent. The autopsy showed isolated endocarditis of the pulmonary valve, without any known predisposing factor. Literary data refer single cases or small groups of patients with isolated pulmonary infectious endocarditis. The clinical suspicion of this rare disease in differential diagnosis of febrile conditions is an essential factor in prognosis of afflicted persons. The crucial diagnostic methods for infectious endocarditis are echocardiography and CT examination.

Background: We conducted a large international study to estimate fractions of head and neck cancers (HNCs) attributable to human papillomavirus (HPV-AFs) using six HPV-related biomarkers of viral detection, transcription, and cellular transformation., Methods: Formalin-fixed, paraffin-embedded cancer tissues of the oral cavity (OC), pharynx, and larynx were collected from pathology archives in 29 countries. All samples were subject to histopathological evaluation, DNA quality control, and HPV-DNA detection. Samples containing HPV-DNA were further subject to HPV E6*I mRNA detection and to p16(INK4a), pRb, p53, and Cyclin D1 immunohistochemistry. Final estimates of HPV-AFs were based on HPV-DNA, HPV E6*I mRNA, and/or p16(INK4a) results., Results: A total of 3680 samples yielded valid results: 1374 pharyngeal, 1264 OC, and 1042 laryngeal cancers. HPV-AF estimates based on positivity for HPV-DNA, and for either HPV E6*I mRNA or p16(INK4a), were 22.4%, 4.4%, and 3.5% for cancers of the oropharynx, OC, and larynx, respectively, and 18.5%, 3.0%, and 1.5% when requiring simultaneous positivity for all three markers. HPV16 was largely the most common type. Estimates of HPV-AF in the oropharynx were highest in South America, Central and Eastern Europe, and Northern Europe, and lowest in Southern Europe. Women showed higher HPV-AFs than men for cancers of the oropharynx in Europe and for the larynx in Central-South America., Conclusions: HPV contribution to HNCs is substantial but highly heterogeneous by cancer site, region, and sex. This study, the largest exploring HPV attribution in HNCs, confirms the important role of HPVs in oropharyngeal cancer and drastically downplays the previously reported involvement of HPVs in the other HNCs., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Insulin secretion in patients with manifested diabetes mellitus tends to disappear months to decades after the diagnosis, which is a clear sign of a gradual loss of pancreatic islet beta-cells. In our sample of 30 type 2 diabetic patients, whose disease manifested between 30 and 45 years of age, about a half have retained or even increased insulin secretion 30 years later, while the other half exhibit a much diminished or lost insulin secretion. Factors that can damage or destroy beta-cells can be divided into the following groups: Metabolic factors: hyperglycemia and glucotoxicity, lipotoxicity, hypoxia, reactive oxygen species; Pharmacological factors: antimicrobial medication pentamidine, SSRI antidepressants; Factors related to impaired insulin secretion: MODY type diabetes; Environmental toxic factors: rat poison Vacor, streptozotocin, polychlorinated and polybrominated hydrocarbons; Disorders of the exocrine pancreas: tumor infiltration, fibrous infiltration, chronic pancreatitis, cystic fibrosis; Infections, inflammation, autoimmunity, viral factors: Coxsackie viruses, H1N1 influenza, enteroviruses. We are currently working on finding other factors leading to beta-cell damage, studying their effect on apoptosis and necrosis and looking for possible protective factors to prevent this damage. We our increasing knowledge about the mechanisms of beta-cell damage and destruction we come ever closer to suggest measures for their prevention. In this review we offer a brief and simplified summary of some of the findings related to this area.Key words: pancreatic islet beta-cells of Langerhans - factors damaging or destroying beta-cells - insulin secretion.

Muir-Torre syndrome (MTS), a rare variant of the hereditary non polyposis colorectal cancer syndrome, is an autosomal dominant genodermatosis characterised by coincidence of sebaceous gland neoplasms (sebaceous adenoma, epithelioma, or carcinoma) and at least one internal malignancy. The underlying cause of MTS is a germline mutation in DNA mismatch repair genes MSH2, MLH1 and MSH6. We report the case of a 52-year-old caucasian woman with the development of metachronous colon cancer at the age of 38 years, uterine cancer at the age of 43 years, and unique occurrence of synchronous gastric and sebaceous carcinomas related to germline point mutation c. 2194A>T in the last exon of MLH1 gene, resulting in truncated protein in C-terminal region p. Lys732X due to premature stop codon. This mutation, not previously reported in MTS, disrupts the function of MutL complexes presumably by preventing the interaction with PMS1/PMS2 and impairing the endonuclease active site. This case points out the importance of sebaceous neoplasia, especially sebaceous adenocarcinoma, as cutaneous markers of MTS for timely implementation of cancer screening programs.