Publications by authors named "Vaclav Mandys"

40 Publications

Secondary central nervous system lymphoma: spectrum of morphological MRI appearances.

Neuropsychiatr Dis Treat 2018 12;14:733-740. Epub 2018 Mar 12.

Radiology Department, Third Faculty of Medicine, Faculty Hospital Kralovske Vinohrady, Charles University, Prague, Czech Republic.

Background: Secondary central nervous system lymphoma (SCNSL) is a rare and aggressive disease, which is defined as secondary central nervous system (CNS) involvement in patients with systemic lymphoma. According to previous reports, SCNSL presents mostly with leptomeningeal spread; however, our experience differs. In the present study, we demonstrate the diversity of magnetic resonance imaging (MRI) patterns in SCNSL.

Patients And Methods: Initial morphological MRI findings in 21 patients (10 women and 11 men with mean age 62.3±16.2 years) with SCNSL were retrospectively evaluated. All patients suffered from neurological symptoms and underwent MRI, and all cases were histologically verified. Twelve patients were treated by corticosteroids at the time of the initial MRI.

Results: Parenchymal lesions were present in 18 of 21 cases (85.7%), solitary meningeal infiltration was present in 1 patient (4.8%), leptomeningeal infiltration in combination with hypophyseal involvement in 1 patient (4.8%), and solitary involvement of the sixth cranial nerve (CN) was found in 1 patient (4.8%). Multiple lesions were present in 11 of 21 cases (52.4%). Diffusion restriction in all or part of the lesion was detected in 14 of 18 cases (77.8%). All parenchymal lesions had an infiltrative appearance and most enhanced homogenously (11 of 17 cases; 64.7%). A combination of parenchymal and meningeal involvement was found in 10 of 21 cases (47.6%). Infiltration of the CNs, basal ganglia, corpus callosum, and ependyma was present in 8 of 21 cases (38.1%) for each of the abovementioned structures; hypothalamic-hypophyseal axis was affected in 7 of 21 cases (33.3%).

Conclusion: In contrast to previous reports, SCNSL presented as parenchymal disease. MRI is not sufficient for differentiation between primary and secondary CNS lymphoma.
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http://dx.doi.org/10.2147/NDT.S157959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5856045PMC
March 2018

[Isolated infectious endocarditis of the pulmonary valve: a case report].

Cesk Patol Fall 2017;53(3):129-133

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.
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April 2019

Detection of carotid artery stenosis using histological specimens: a comparison of CT angiography, magnetic resonance angiography, digital subtraction angiography and Doppler ultrasonography.

Acta Neurochir (Wien) 2016 08 2;158(8):1505-14. Epub 2016 Jun 2.

Department of Neurosurgery, 1st Faculty of Medicine, Central Military Hospital, Charles University, U vojenské nemocnice 1200, 169 02, Prague 6, Czech Republic.

Background: Carotid endarterectomy (CEA) is accepted as a primary modality to treat carotid stenosis. The accuracy of measuring carotid stenosis is important for indication of the CEA procedure. Different diagnostic tools have been developed and used in the past 2 decades for the diagnosis of carotid stenosis. Only a few studies, however, have focused on the comparison of different diagnostic tools to histological findings of carotid plaque.

Method: Patients with internal carotid artery (ICA) stenosis were investigated primarily by computed tomography angiography (CTA). Digital subtraction angiography (DSA), Doppler ultrasonography (DUS) and magnetic resonance angiography (MRA) were performed as well. Atherosclerotic plaque specimens were transversally cut into smaller segments and histologically processed. The slides were scanned and specimens showing maximal stenosis were determined; the minimal diameter and the diameter of the whole plaque were measured. High quality histological specimen and histological measurement was considered to be the prerequisite for inclusion into the analysis. The preoperative findings were compared with histological measurement. CTA and histological measurements were obtained from 152 patients. DSA measurements were available in 138 of these cases, MRA in 107 and DUS in 88. A comparison between preoperative and histological findings was performed. In addition, correlation coefficients were computed and tested.

Results: A significant correlation was found for each of the diagnostic procedures. The strongest correlation coefficient and the best allocation of stenosis into clinical significant groups (<50 %, 50-69 %, ≥70 %) was observed for CTA. Mean differences in the whole cohort between preoperative and histological measurements were as follows: CTA underestimated histological measurement by 2.4 % (based on European Carotid Surgery Trial [ECST] methodology) and 11.9 % (based on North American Symptomatic Carotid Endarterectomy Trial [NASCET] methodology). DSA underestimated the histological measurement by 7 % (ECST) and 12.2 % (NASCET). MRA overestimated the histological measurement by 2.6 % (ECST) and underestimated by 0.6 % (NASCET). DUS overestimated the stenosis by 1.8 %.

Conclusions: CTA yields the best accuracy in detection of carotid stenosis, provided that all axial slices of the stenosis are checked and carefully analysed. DSA underestimates moderate and mild ICA stenosis, whereas DUS overestimates high-grade ICA stenosis. For MRA, a relatively low correlation coefficient was observed with histological findings. We conclude that CTA-ecst technique is the most reliable technique for carotid stenosis measurement.
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http://dx.doi.org/10.1007/s00701-016-2842-0DOI Listing
August 2016

HPV Involvement in Head and Neck Cancers: Comprehensive Assessment of Biomarkers in 3680 Patients.

J Natl Cancer Inst 2016 Jun 28;108(6):djv403. Epub 2016 Jan 28.

Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), IDIBELL, L'Hospitalet de Llobregat, Catalonia, Spain (XC, LAle, BQ, ST, OC, MM, IGB, SdS, FXB); CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain (XC, LAle, SdS); Hospital Sant Pau, Barcelona, Spain (MQ, XL); German Cancer Research Center (DKFZ), Heidelberg, Germany (GHale, DH, MPa); Hospital Clínic, University of Barcelona, Spain (LAlò); Department of Pathology, University Hospital Tuebingen, Tuebingen, Germany (TB); Department of Otorhinolaryngology, Faculty of Medicine and Dentistry, Warsaw Medical University, Czerniakowski Hospital, Warsaw, Poland (TS); Hospital General de l'Hospitalet, L'Hospitalet de Llobregat, Barcelona, Spain (MA); Instituto Nacional de Cancerología, Bogotá, Colombia (ECa, NM); Universidad Nacional de Colombia, Bogotá, Colombia (ECa); Insituto Oncológico del Oriente Boliviano (IOOB), Laboratorio Privado de Patología Oncos, Santa Cruz, Bolivia (ECl); Manchester Royal Infirmary, Manchester, UK (GHall); The Fingerland Department of Pathology, Charles University Faculty of Medicine and University Hospital, Hradec Kralove, Czech Republic (JL); University of Ljubljana, Faculty of Medicine, Institute of Microbiology and Immunology, Ljubljana, Slovenia (MPo); Regina Elena National Cancer Institute, Rome, Italy (MB); Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asunción, Asunción, Paraguay (EK); Institute of Head and Neck Studies and Education, University of Birmingham, Birmingham, UK (HMe); Department of Social and Preventive Medicine, Université de Montréal, Montreal, Canada (CN); DDL Diagnostic Laboratory, Rijswijk, the Netherlands (NG, WQ); Pathology Department, Hospital del Mar IMIM, Universitat Pompeu Fabra, Barcelona, Spain (BL); Laboratorio Clínico y Molecular, Hospital SOLCA, Guayaquil, Ecuador (JCRC); Hospital de Oncología Centro Médico Nacional Siglo XXI, IMSS Mexico, D.F., Mexico (IAC); Yeouido St. Mary's

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.
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http://dx.doi.org/10.1093/jnci/djv403DOI Listing
June 2016

Role of Human Papillomavirus in Penile Carcinomas Worldwide.

Eur Urol 2016 05 5;69(5):953-61. Epub 2016 Jan 5.

Institut Català d'Oncologia, Barcelona, Spain; CIBER en Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.

Background: Invasive penile cancer is a rare disease with an approximately 22 000 cases per year. The incidence is higher in less developed countries, where penile cancer can account for up to 10% of cancers among men in some parts of Africa, South America, and Asia.

Objective: To describe the human papillomavirus (HPV) DNA prevalence, HPV type distribution, and detection of markers of viral activity (ie, E6*I mRNA and p16(INK4a)) in a series of invasive penile cancers and penile high-grade squamous intraepithelial lesions (HGSILs) from 25 countries. A total of 85 penile HGSILs and 1010 penile invasive cancers diagnosed from 1983 to 2011 were included.

Design, Setting, And Participants: After histopathologic evaluation of formalin-fixed paraffin-embedded samples, HPV DNA detection and genotyping were performed using the SPF-10/DEIA/LiPA25 system, v.1 (Laboratory Biomedical Products, Rijswijk, The Netherlands). HPV DNA-positive cases were additionally tested for oncogene E6*I mRNA and all cases for p16(INK4a) expression, a surrogate marker of oncogenic HPV activity.

Outcome Measurements And Statistical Analysis: HPV DNA prevalence and type distributions were estimated.

Results And Limitations: HPV DNA was detected in 33.1% of penile cancers (95% confidence interval [CI], 30.2-36.1) and in 87.1% of HGSILs (95% CI, 78.0-93.4). The warty-basaloid histologic subtype showed the highest HPV DNA prevalence. Among cancers, statistically significant differences in prevalence were observed only by geographic region and not by period or by age at diagnosis. HPV16 was the most frequent HPV type detected in both HPV-positive cancers (68.7%) and HGSILs (79.6%). HPV6 was the second most common type in invasive cancers (3.7%). The p16(INK4a) upregulation and mRNA detection in addition to HPV DNA positivity were observed in 69.3% of HGSILs, and at least one of these HPV activity markers was detected in 85.3% of cases. In penile cancers, these figures were 22.0% and 27.1%, respectively.

Conclusions: About a third to a fourth of penile cancers were related to HPV when considering HPV DNA detection alone or adding an HPV activity marker, respectively. The observed HPV type distribution reinforces the potential benefit of current and new HPV vaccines in the reduction of HPV-related penile neoplastic lesions.

Patient Summary: About one-third to one-quarter of penile cancers were related to human papillomavirus (HPV). The observed HPV type distribution reinforces the potential benefit of current and new HPV vaccines to prevent HPV-related penile neoplastic lesions.
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http://dx.doi.org/10.1016/j.eururo.2015.12.007DOI Listing
May 2016

Small nucleolar RNA U91 is a new internal control for accurate microRNAs quantification in pancreatic cancer.

BMC Cancer 2015 Oct 24;15:774. Epub 2015 Oct 24.

Department of Pathology, Third Faculty of Medicine, Charles University in Prague and University Hospital Kralovske Vinohrady, Srobarova 50, 100 00, Prague 10, Czech Republic.

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.
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http://dx.doi.org/10.1186/s12885-015-1785-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4619559PMC
October 2015

[Factors causing damage and destruction of beta-cells of the islets of Langerhans in the pancreas].

Vnitr Lek 2014 Sep;60(9):684-90

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.
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September 2014

Epithelial cell morphology and adhesion on diamond films deposited and chemically modified by plasma processes.

Biointerphases 2014 Sep;9(3):031012

Department of Pathology, Third Faculty of Medicine, Charles University in Prague, Ruská 87, 10000 Praha 10, Czech Republic.

The authors show that nanocrystalline diamond (NCD) thin films prepared by microwave plasma enhanced chemical vapor deposition apparatus with a linear antenna delivery system are well compatible with epithelial cells (5637 human bladder carcinoma) and significantly improve the cell adhesion compared to reference glass substrates. This is attributed to better adhesion of adsorbed layers to diamond as observed by atomic force microscopy (AFM) beneath the cells. Moreover, the cell morphology can be adjusted by appropriate surface treatment of diamond by using hydrogen and oxygen plasma. Cell bodies, cytoplasmic rims, and filopodia were characterized by Peakforce AFM. Oxidized NCD films perform better than other substrates under all conditions (96% of cells adhered well). A thin adsorbed layer formed from culture medium and supplemented with fetal bovine serum (FBS) covered the diamond surface and played an important role in the cell adhesion. Nevertheless, 50-100 nm large aggregates formed from the RPMI medium without FBS facilitated cell adhesion also on hydrophobic hydrogenated NCD (increase from 23% to 61%). The authors discuss applicability for biomedical uses.
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http://dx.doi.org/10.1116/1.4890471DOI Listing
September 2014

Synchronous gastric and sebaceous cancers, a rare manifestation of MLH1-related Muir-Torre syndrome.

Int J Clin Exp Pathol 2014 15;7(8):5196-202. Epub 2014 Jul 15.

Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic Prague.

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.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4152087PMC
June 2015

Human papillomavirus DNA prevalence and type distribution in anal carcinomas worldwide.

Int J Cancer 2015 Jan 30;136(1):98-107. Epub 2014 May 30.

Unit of Infections and Cancer, Cancer Epidemiology Research Program, Institut Català d'Oncologia, Barcelona, Spain; CIBER en Epidemiología y Salud Pública (CIBERESP), Spain.

Knowledge about human papillomaviruses (HPV) types involved in anal cancers in some world regions is scanty. Here, we describe the HPV DNA prevalence and type distribution in a series of invasive anal cancers and anal intraepithelial neoplasias (AIN) grades 2/3 from 24 countries. We analyzed 43 AIN 2/3 cases and 496 anal cancers diagnosed from 1986 to 2011. After histopathological evaluation of formalin-fixed paraffin-embedded samples, HPV DNA detection and genotyping was performed using SPF-10/DEIA/LiPA25 system (version 1). A subset of 116 cancers was further tested for p16(INK4a) expression, a cellular surrogate marker for HPV-associated transformation. Prevalence ratios were estimated using multivariate Poisson regression with robust variance in the anal cancer data set. HPV DNA was detected in 88.3% of anal cancers (95% confidence interval [CI]: 85.1-91.0%) and in 95.3% of AIN 2/3 (95% CI: 84.2-99.4%). Among cancers, the highest prevalence was observed in warty-basaloid subtype of squamous cell carcinomas, in younger patients and in North American geographical region. There were no statistically significant differences in prevalence by gender. HPV16 was the most frequent HPV type detected in both cancers (80.7%) and AIN 2/3 lesions (75.4%). HPV18 was the second most common type in invasive cancers (3.6%). p16(INK4a) overexpression was found in 95% of HPV DNA-positive anal cancers. In view of the results of HPV DNA and high proportion of p16(INK4a) overexpression, infection by HPV is most likely to be a necessary cause for anal cancers in both men and women. The large contribution of HPV16 reinforces the potential impact of HPV vaccines in the prevention of these lesions.
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http://dx.doi.org/10.1002/ijc.28963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4270372PMC
January 2015

Granulomatous pancreatitis in a patient with acute manifested insulin-dependent diabetes mellitus.

Case Rep Pathol 2014 5;2014:615426. Epub 2014 Mar 5.

Second Department of Internal Medicine, Third Faculty of Medicine, Charles University in Prague, 100 00 Prague, Czech Republic.

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 postmortem examination. 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.
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http://dx.doi.org/10.1155/2014/615426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3965917PMC
April 2014

Spectrum of Gastroenteropancreatic NENs in Routine Histological Examinations of Bioptic and Surgical Specimen: A Study of 161 Cases Collected from 17 Departments of Pathology in the Czech Republic.

Gastroenterol Res Pract 2014 18;2014:373828. Epub 2014 Feb 18.

Department of Pathology, Third Faculty of Medicine, Charles University and University Hospital King's Vineyards, Srobarova 50, 100 34 Prague 10, Czech Republic.

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.
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http://dx.doi.org/10.1155/2014/373828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3948195PMC
April 2014

Expression of selected proteins in breast cancer brain metastases.

Folia Histochem Cytobiol 2013 ;51(3):213-8

Department of Gynaecology and Obstetrics, Department of Pathology, FNKV and Charles University in Prague, Third Faculty of Medicine, Ruská 87,100 00 Prague 10, Czech Republic.

The aim of the study was to assess the immunohistochemical (IHC) profiles of SRC3, Pax2, ER, PgR, Her2, EGFR, CK5/6, and Ki67 proteins in breast-cancer brain metastasis. The study utilized tumor samples from 30 metastatic patients and calculated correlations between all IHC variables. In fourteen cases, primary breast cancers paired with secondary deposits were analyzed. We evaluated the association between IHC status in the primary and secondary deposits, grade, and histotype of the tumors. The examination of the metastatic deposits in all 30 patients resulted in positive detection in the following cases: SRC3 in 20 cases (66.6%), Pax2 in 22 (73.3%), ER in 22 (73.3%), PgR in 25 (83.3%), Her2 in 10 (33.3%), EGFR in 12 (40%), CK5/6 in 7 (23.3%), and Ki67 in 23 (76.6%). Grade 2 was found in 13.3% of all patients, and grade 3 in 86.7%. SRC3 and Pax2 were positive in both G2 and G3. Invasive lobular carcinoma and invasive ductal carcinoma were diagnosed in 23.3% and 76.7% of cases, respectively. There were no differences between the IHC expression of the studied proteins in either grading or histotype of the tumors. In the IHC profiles, which included SRC3, Pax2, ER, PgR, Her2, CK5/6, Ki67, and EGFR, we found no statistically significant differences between the primary cancer and the brain metastasis. In our study of metastatic breast carcinoma deposits, there was no correlation between SRC3, Pax2 status and histotype, and tumor grade. The IHC status of the paired primary and metastatic deposits did not differ in a statistically significant manner.
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http://dx.doi.org/10.5603/FHC.2013.0030DOI Listing
June 2014

Expression of 11β-hydroxysteroid dehydrogenase type 2 is deregulated in colon carcinoma.

Histol Histopathol 2014 Apr 5;29(4):489-96. Epub 2013 Nov 5.

Institute of Physiology, Academy of Sciences of the Czech Republic, and Department of Physiology, Faculty of Science, Charles University, Prague, Czech Republic.

Although the effects of glucocorticoids on proliferation, differentiation and apoptosis are well known, and steroid hormones have been identified to play a role in pathogenesis and the development of various cancers, limited data are available regarding the relationship between the local metabolism of glucocorticoids and colorectal adenocarcinoma (CRC) formation. Glucocorticoid metabolism is determined by 11β-hydroxysteroid dehydrogenases type 1 and 2 (11HSD1, 11HSD2), which increase the local concentration of cortisol due to the reduction of cortisone, or decrease this concentration due to the oxidation of cortisol. The objective of this study was to evaluate the extent of 11HSD1 and 11HSD2 mRNA in pre-malignant colorectal polyps and in CRC. The specimens were retrieved from patients by endoscopic or surgical resection and the expression of 11HSD1 and 11HSD2 was measured by real-time PCR. The polyps were of the following histological types: hyperplastic polyps and adenomas with low- or high-grade dysplasia. The neoplastic tissue of CRC obtained during tumor surgery was also studied. It was found that 11HSD2 was not only downregulated in CRC but already in the early stages of neoplastic transformation (adenoma with low-grade dysplasia). In contrast, the level of 11HSD1 was significantly increased in CRC but not in pre-malignant polyps. The results demonstrate that the downregulation of 11HSD2 gene expression is a typical feature of the development of colorectal polypous lesions and their transformation into CRC.
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http://dx.doi.org/10.14670/HH-29.10.489DOI Listing
April 2014

Worldwide human papillomavirus genotype attribution in over 2000 cases of intraepithelial and invasive lesions of the vulva.

Eur J Cancer 2013 Nov 22;49(16):3450-61. Epub 2013 Jul 22.

Unit of Infections and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology, IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain; CIBER en Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain. Electronic address:

Background: Human papillomavirus (HPV) contribution in vulvar intraepithelial lesions (VIN) and invasive vulvar cancer (IVC) is not clearly established. This study provides novel data on HPV markers in a large series of VIN and IVC lesions.

Methods: Histologically confirmed VIN and IVC from 39 countries were assembled at the Catalan Institute of Oncology (ICO). HPV-DNA detection was done by polymerase chain reaction using SPF-10 broad-spectrum primers and genotyping by reverse hybridisation line probe assay (LiPA25) (version 1). IVC cases were tested for p16(INK4a) by immunohistochemistry (CINtec histology kit, ROCHE). An IVC was considered HPV driven if both HPV-DNA and p16(INK4a) overexpression were observed simultaneously. Data analyses included algorithms allocating multiple infections to calculate type-specific contribution and logistic regression models to estimate adjusted prevalence (AP) and its 95% confidence intervals (CI).

Results: Of 2296 cases, 587 were VIN and 1709 IVC. HPV-DNA was detected in 86.7% and 28.6% of the cases respectively. Amongst IVC cases, 25.1% were both HPV-DNA and p16(INK4a) positive. IVC cases were largely keratinising squamous cell carcinoma (KSCC) (N=1234). Overall prevalence of HPV related IVC cases was highest in younger women for any histological subtype. SCC with warty or basaloid features (SCC_WB) (N=326) were more likely to be HPV and p16(INK4a) positive (AP=69.5%, CI=63.6-74.8) versus KSCC (AP=11.5%, CI=9.7-13.5). HPV 16 was the commonest type (72.5%) followed by HPV 33 (6.5%) and HPV 18 (4.6%). Enrichment from VIN to IVC was significantly high for HPV 45 (8.5-fold).

Conclusion: Combined data from HPV-DNA and p16(INK4a) testing are likely to represent a closer estimate of the real fraction of IVC induced by HPV. Our results indicate that HPV contribution in invasive vulvar cancer has probably been overestimated. HPV 16 remains the major player worldwide.
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http://dx.doi.org/10.1016/j.ejca.2013.06.033DOI Listing
November 2013

[Microscopic colitis].

Cas Lek Cesk 2013 ;152(2):59-66

Interni Klinika 1. LF UK a VFN, Praha.

Microscopic colitis is characterized by chronic or intermittent watery diarrhoea. Microscopic colitis is a common cause of chronic diarrhoea in predominantly older adults. The underlying mechanism in the pathogenesis of microscopic colitis remains unspecified. Microscopic colitis including colitis collagenous, lymphocytic, microscopic colitis with incomplete findings, minimal change colitis, eosinophilic colitis, Brainerd´s diarrhoea, graft-versus-host disease, mastocytic enterocolitis and postinfectious irritable bowel syndrome. Careful consideration of the clinical features and colonic mucosal biopsies usually lead to correct diagnosis. Treatments of microscopic colitis were based primarily on case reports and personal experience. Many medications have been proposed that either offer symptomatic relief (loperamide, cholestyramine) or had anti-inflammatory or immunosuppressive properties (aminosalicylates, steroids, adalimumab, azathioprine).
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October 2015

Multiple adenomatous duodenal polyposis.

Case Rep Gastrointest Med 2013 31;2013:181704. Epub 2013 Mar 31.

2nd Department of Internal Medicine,Third Faculty of Medicine, Charles University in Prague, Šrobárova 50 100 34, Prague 10, Czech Republic.

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.
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http://dx.doi.org/10.1155/2013/181704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3626175PMC
April 2013

Human keratinocyte growth and differentiation on acellular porcine dermal matrix in relation to wound healing potential.

ScientificWorldJournal 2012 3;2012:727352. Epub 2012 May 3.

Prague Burn Centre, 3rd Faculty of Medicine, Charles University in Prague, 100 00 Prague 10, Czech Republic.

A number of implantable biomaterials derived from animal tissues are now used in modern surgery. Xe-Derma is a dry, sterile, acellular porcine dermis. It has a remarkable healing effect on burns and other wounds. Our hypothesis was that the natural biological structure of Xe-Derma plays an important role in keratinocyte proliferation and formation of epidermal architecture in vitro as well as in vivo. The bioactivity of Xe-Derma was studied by a cell culture assay. We analyzed growth and differentiation of human keratinocytes cultured in vitro on Xe-Derma, and we compared the results with formation of neoepidermis in the deep dermal wounds treated with Xe-Derma. Keratinocytes cultured on Xe-Derma submerged in the culture medium achieved confluence in 7-10 days. After lifting the cultures to the air-liquid interface, the keratinocytes were stratified and differentiated within one week, forming an epidermis with basal, spinous, granular, and stratum corneum layers. Immunohistochemical detection of high-molecular weight cytokeratins (HMW CKs), CD29, p63, and involucrin confirmed the similarity of organization and differentiation of the cultured epidermal cells to the normal epidermis. The results suggest that the firm natural structure of Xe-Derma stimulates proliferation and differentiation of human primary keratinocytes and by this way improves wound healing.
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http://dx.doi.org/10.1100/2012/727352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3354742PMC
October 2012

Properties of bcr-abl-transformed mouse 12B1 cells secreting interleukin-2 and granulocyte-macrophage colony stimulating factor (GM-CSF): II. Adverse effects of GM-CSF.

Int J Oncol 2012 Jun 22;40(6):1915-22. Epub 2012 Mar 22.

Department of Experimental Virology, Institute of Hematology and Blood Transfusion, Prague, Czech Republic.

Granulocyte-macrophage colony stimulating factor (GM-CSF) is considered to be the most effective immunostimulating factor for the construction of gene-engineered anti-cancer vaccines. In some tumour cells, this type of genetic modification has resulted in the loss of the oncogenic potential. This was not the case with bcr-abl-transformed mouse 12B1 cells. A cell line, designated 12B1/GM-CSF/cl-5 producing more than 100 ng/106 cells/24 h, displayed higher pathogenicity than the parental, non-transduced cells. Although the tumours induced by the parental 12B1 cells and 12B1/GM-CSF/cl-5 cells appeared nearly at the same time and then grew at an approximately equal rate, the latter mice were in a much poorer clinical condition. In these animals the growth of the tumours was associated with gradually increasing blood levels of GM-CSF. In both groups of animals splenomegaly was observed; it was much more pronounced in the case of 12B1/GM-CSF/cl-5-inoculated animals. While in the case of animals inoculated with the parental cells the splenomegaly was probably mainly due to infiltration with tumour cells, in the animals inoculated with the GM-CSF-secreting cells splenomegaly and derangement of parenchymal organs, such as lungs, liver and kidneys, were more complex, including congestion and infiltration with hemopoietic cells, predominantly immature cells of myeloid lineage. The most conspicuous of these changes was the hyperaemia of the lungs. No such alterations were seen in animals inoculated with the parental cells. On the other hand, the contents of T regulatory cells were comparable in both groups and they increased in parallel at the end of the observation period. When GM-CSF neutralizing antibody was administered to animals inoculated with the 12B1/GM-CSF/cl-5 cells, the pathological changes observed within the organs were suppressed, this proving that the overproduced GM-CSF and not any other substance, played the key role in their induction.
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http://dx.doi.org/10.3892/ijo.2012.1410DOI Listing
June 2012

Magnetic resonance angiography, digital subtraction angiography and Doppler ultrasonography in detection of carotid artery stenosis: a comparison with findings from histological specimens.

Acta Neurochir (Wien) 2010 Jul 22;152(7):1215-21. Epub 2010 Apr 22.

Department of Neurosurgery, First Faculty of Medicine, Central Military Hospital, U Vojenské Nemocnice 1200, 169 02, Prague 6, Czech Republic.

Background: Patients' life expectancy, clinical symptomatology and the extent of carotid stenosis are the most important factors when deciding whether to perform carotid endarterectomy (CEA) in patients with carotid stenosis. Therefore, the accuracy of measuring carotid stenosis is of utmost importance.

Methods: Patients with internal carotid artery (ICA) stenosis were investigated by digital subtraction angiography (DSA), Doppler ultrasonography (DUS) and magnetic resonance angiography (MRA). Atherosclerotic plaque specimens were transversally cut into smaller segments and histologically processed. The slides were scanned and specimens showing maximal stenosis were determined; the minimal diameter and the diameter of the whole plaque were measured. DSA, DUS and MRA measurements were obtained in 103 patients. A comparison between preoperative and histological findings was performed. In addition, correlation coefficients were computed and tested.

Results: Results show a significant correlation for each of the diagnostic procedures. Mean differences in the whole cohort between preoperative measurements and the histological measurements are as follows: angiographic measurement of carotid stenosis underestimated histological measurement by 14.5% and MRA by 0.7%, but DUS overestimated by 6.6%. The results in severe stenosis (> or =70%) are as follows: angiographic measurement underestimated the histological measurements by 2.3%, but MRA overestimated by 12.1% and DUS by 11.3%. The results in moderate stenosis (50-69%): angiographic measurement underestimated the histological measurements by 12.3%, but MRA overestimated by 0.2% and DUS by 7.2%. The results in mild stenosis (30-49%): angiographic measurement underestimated the histological measurements by 24.7% and MRA by 7.6%, but DUS overestimated by 3.3%.

Conclusions: Our study confirms that DSA underestimates moderate and mild ICA stenosis. DUS slightly overestimated moderate ICA stenosis and highly overestimated high-grade ICA stenosis. MRA proved to be accurate in detecting moderate ICA stenosis, but slightly underestimated mild stenosis and overestimated high-grade stenosis. The surgeon should be aware of these discrepancies when deciding whether to perform CEA in patients with ICA stenosis.
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http://dx.doi.org/10.1007/s00701-010-0645-2DOI Listing
July 2010

Comparison of morphological, immunohistochemical, and molecular genetic features of inflammatory fibroid polyps (Vanek's tumors).

Virchows Arch 2010 May;456(5):491-7

Department of Pathology, Medical Faculty Hospital,, Charles University in Prague, Medical Faculty in Plzen, Edvarda Benese 13, Plzen, Czech Republic.

Vanek's tumor (inflammatory fibroid polyp) is a rare benign lesion occurring throughout the digestive tract. Histologically, two patterns can be recognized. Classical Vanek's tumor contains concentric formations of proliferating spindle cells which are CD34 positive. Atypical, inflammatory pseudotumor-like Vanek's tumor lacks concentric formations and is CD34 negative. Recently, mutations in platelet-derived growth factor receptor alpha (PDGFRA) were reported in gastric and small intestinal Vanek's tumors. In this study, KIT exons 9, 11, 13, and 17, PDGFRA exons 12, 14, and 18, and a part of exon 15 BRAF for point mutation V600E were screened in 23 cases of Vanek's tumor, both classical (n = 16) and inflammatory pseudotumor-like (n = 7). No mutations in all analyzed exons of KIT and BRAF and in exon 14 of PDGFRA were detected. Six Vanek's tumors harbored activating mutations in PDGFRA exons 12 (n = 5) and 18 (n = 1) respectively: S566_E571delinsK (n = 1), S566_E571delinsR (n = 4), and D842 del (n = 1). The mutations were detected in the classical (n = 5), as well as inflammatory pseudotumor-like (n = 1) Vanek's tumors. The results of this study suggest that the two morphological patterns of Vanek's tumor more probably represent only variants of one type of tumor than two different lesions. Furthermore, BRAF mutations were not shown to drive growth of PDGFRA wild-type Vanek's tumors.
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http://dx.doi.org/10.1007/s00428-010-0914-8DOI Listing
May 2010

Expression profiles of proliferative and antiapoptotic genes in sporadic and colitis-related mouse colon cancer models.

Int J Exp Pathol 2010 Feb;91(1):44-53

Second Department of Internal Medicine, Third Faculty of Medicine, Charles University, Prague, Czech Republic.

Elevated levels of survivin, telomerase catalytic subunit (TERT), integrin-linked kinase (ILK), cyclooxygenase 2 (COX-2), inducible nitric oxide synthase (iNOS) and the regulatory factors c-MYB and Tcf-4 are often found in human cancers including colorectal cancer (CRC) and have been implicated in the development and progression of tumorigenesis. The aim of this study was to determine the expression of these genes in mouse models of sporadic and colitis-associated CRC. To address these issues, we used qRT-PCR approach to determine changes in gene expression patterns of neoplastic cells (high-grade dysplasia/intramucosal carcinoma) and surrounding normal epithelial cells in A/J and ICR mouse strains using laser microdissection. Both strains were injected with azoxymethane and ICR mice were also given drinking water that contained 2% dextran sodium sulphate. In both sporadic (A/J mice) and colitis-associated (ICR mice) models of CRC, the levels of TERT mRNA, COX-2 mRNA and Tcf-4 mRNA were higher in neoplastic cells than in surrounding normal epithelial cells. In contrast, survivin mRNA was upregulated only in neoplastic cells from A/J mice and ILK mRNA was upregulated only in neoplastic cells from ICR mice. However, the expression of iNOS mRNA was similar in normal and neoplastic cells in both models and c-MYB mRNA was actually downregulated in neoplastic cells compared with normal cells in both models. These findings suggest that the genetic background and/or the molecular mechanisms of tumorigenesis associated with genotoxic insults and colonic inflammation influence the gene expression of mTERT, COX-2, Tcf-4, c-MYB, ILK and survivin in colon epithelial neoplasia.
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http://dx.doi.org/10.1111/j.1365-2613.2009.00698.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2812727PMC
February 2010

Enhanced expression of proproliferative and antiapoptotic genes in ulcerative colitis-associated neoplasia.

Inflamm Bowel Dis 2010 Jul;16(7):1127-37

Second Department of Internal Medicine, Third Faculty of Medicine, Charles University, Prague, Czech Republic.

Background: Inflammatory bowel diseases including long-standing ulcerative colitis (UC) have an increased risk of evolving into colorectal cancer (CRC). The overexpression of some proproliferative and antiapoptotic genes, such as survivin, telomerase catalytic subunit (hTERT), integrin-linked kinase (ILK), and regulatory factors c-MYB and Tcf-4, has been implicated in the development and progression of several human malignancies including CRC.

Methods: In this study we analyzed the expression alterations of these markers and proinflammatory enzymes cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) during the transition of colonic mucosa from chronic inflammation to epithelial neoplasia in biopsies of UC patients using quantitative real-time polymerase chain reaction and immunohistochemistry; additionally, we compared the expression profiles of this gene panel in samples of patients with CRC after tumor resection and in human tumor xenografts of SW620 malignant colonic cells.

Results: The transcript levels of survivin, c-MYB, COX-2, iNOS, and Tcf-4 showed a statistically significant increase during neoplastic transformation of UC patient colonic mucosa, whereas hTERT and ILK were not elevated. In contrast, the specimens of CRC showed upregulated expression of not only survivin, c-MYB, Tcf-4, COX-2, and iNOS but also hTERT. A similar expression profile was observed in human tumor xenografts in which all transcripts with the exception of c-MYB were upregulated.

Conclusions: These results suggest that telomerase and ILK activation occurs during the later stages of carcinoma progression, whereas upregulation of survivin, c-MYB, and Tcf-4 is a feature of the early stage of development of neoplasia, and thus, they might serve as early indicators for UC-associated colorectal carcinogenesis.
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http://dx.doi.org/10.1002/ibd.21178DOI Listing
July 2010

Cytokeratins 8 and 18 in adult human corneal endothelium.

Exp Eye Res 2009 Sep 4;89(3):426-31. Epub 2009 May 4.

Laboratory of the Biology and Pathology of the Eye, Institute of Inherited Metabolic Disorders, General Teaching Hospital and First Faculty of Medicine, Charles University, Prague, Czech Republic.

The aim of this study was to determine if cytokeratins (CKs) 8 and 18--typical epithelial cell markers--are constitutively expressed in adult human corneal endothelium. Cryosections, paraffin-embedded sections and corneal endothelial imprints obtained from eleven adult human corneal discs not suitable for transplantation were used. Different fixative solutions were applied before indirect immunofluorescent or enzymatic staining was performed with antibodies against CK8 (Chemicon), CK18 (Dako and Sigma) and CK8/18 (Novocastra). Semi-quantitative RT-PCR and Western blotting (mRNA or proteins were isolated from Millicell membranes) were used to determine cytokeratin mRNA and protein levels. Approximately 50% of the corneal endothelial cells were positive for CK8 (Chemicon), CK18 (Sigma) and the CK pair 8/18 (Novocastra) in the endothelium when acetone was used for fixation. Four and 52% CK18-positive cells were observed using immunofluorescent and enzymatic immunohistochemistry, respectively, when the CK18 antibody from Dako was used. No signal was detected when 4% formalin or 10% paraformaldehyde was used as a fixative, irrespective of the antibody used. CK8 and CK18 proteins and mRNAs were detected in the endothelium of all tested corneas by Western blotting or semi-quantitative RT-PCR, respectively. We detected both CK8 and CK18 in the endothelium of all specimens at both the protein and mRNA levels. These results clearly demonstrate that cells of the corneal endothelium express CKs 8 and 18 and share some features with simple epithelia.
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http://dx.doi.org/10.1016/j.exer.2009.04.009DOI Listing
September 2009

Clinical anatomy of the calcaneal tuberosity.

Ann Anat 2008 4;190(3):284-91. Epub 2008 Mar 4.

Department of Anatomy, Third Faculty of Medicine, Charles University in Prague, Ruska 87, 100 00 Prague 10, Czech Republic.

The aim of the study was a qualitative anatomical analysis of the macroscopic features of the surface of the calcaneal tuberosity, of the architecture of its cancellous bone and histological structure of the whole region. Dry human bones and pathological dissection material 24-36 h post mortem were used in the study. On the tuberosity, the variability of its surface relief and the two borders between the superior, middle and inferior facets were studied. More frequent medial declination of the inferior line, corresponding to the distal circumference of the Achilles tendon attachment, was found. Two systems of expressive condensation of cancellous bone just below the surface of the calcaneal tuberosity were described. In the histological part of the study, the distribution and different thickness of the fibrous cartilage layer covering the attachment region of Achilles tendon, the bottom of retro-calcaneal bursa and the whole surface of the calcaneal tuberosity were described. The functional and clinical relevance of results obtained are evaluated from the point of view of disciplines dealing with the pathology and surgery of the heel region. The relationships of official anatomical terms and a wide spectrum of clinical synonyms designating this region are discussed.
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http://dx.doi.org/10.1016/j.aanat.2008.02.001DOI Listing
August 2008

Expression of CD44s and CD44v6 in transitional cell carcinomas of the urinary bladder: comparison with tumour grade, proliferative activity and p53 immunoreactivity of tumour cells.

APMIS 2007 Nov;115(11):1194-205

Department of Urology, 3rd Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.

Alterations of CD44 glycoproteins have been shown to play an important role in progression of various malignancies, including urothelial cancer. We investigated expression patterns of CD44s and CD44v6 in transitional cell carcinoma (TCC) of the urinary bladder in relation to tumour grade, proliferative activity, and immunoreactivity for p53. The selected markers were detected immunohistochemically in 122 samples of TCC. We found a close relationship between CD44s and CD44v6 expression and tumour grade. The extension of positive staining for CD44s and CD44v6 towards the luminal surface was a predominant feature of differentiated carcinomas (grades 1 and 2), suggesting deranged maturation of cancer cells related to their neoplastic transformation. Heterogeneous expression of CD44s and CD44v6 predominated in poorly differentiated tumours (G3-4). However, areas of squamous differentiation within the high-grade tumours displayed strong immunoreactivity for both CD44s and CD44v6. The proliferative activity and p53 overexpression increased with the dedifferentiation of the tumour. The results of this study are discussed in relation to the significance of CD44 expression in TCC and to the explanation for controversial results reported in previous studies on the relationship between CD44 expression and the biological behaviour of urothelial cells.
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http://dx.doi.org/10.1111/j.1600-0643.2007.00602.xDOI Listing
November 2007

Poorly differentiated endocrine carcinoma and intraductal papillary-mucinous neoplasm of the pancreas: Description of an unusual case.

Pathol Res Pract 2007 23;203(12):879-84. Epub 2007 Oct 23.

Clinic of General Surgery, 3rd Faculty of Medicine, Charles University, Srobarova 50, 10034 Prague, Czech Republic.

Neuroendocrine tumors and intraductal papillary-mucinous neoplasms constitute histologically distinctive but relatively rare entities among pancreatic tumors. Collision of these tumors is extremely rare and causes several diagnostic problems regarding the histopathologic differential diagnosis of other pancreatic epithelial tumors. The question of whether the neoplastic populations originate from common progenitor cell or whether they represent only a fortuitous association has not been sufficiently explained. Here, we describe a new case of poorly differentiated endocrine carcinoma combined with an intraductal papillary-mucinous neoplasm. To disclose the relationship between the two histologic components, neuroendocrine differentiation was studied by confocal laser scanning microscopy using double immunofluorescence labeling with chromogranin-A and CD57 antibodies. Our results revealed a co-localization of both antigens in neuroendocrine cells of the intraductal papillary-mucinous neoplasm. The finding has previously been described in non-neoplastic neuroendocrine cells. Cells forming poorly differentiated endocrine carcinoma showed a wide heterogeneity in immunoreactions. Our results do not indicate a potential histogenetic similarity between these two neoplasms, which are dissimilar histologically, and underline the previous thesis that cells in intraductal papillary-mucinous neoplasm revealing neuroendocrine differentiation represent only a non-neoplastic cell admixture.
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http://dx.doi.org/10.1016/j.prp.2007.08.012DOI Listing
February 2008

Expression of class III beta-tubulin in malignant epithelial tumours: an immunohistochemical study using TU-20 and TuJ-1 antibodies.

Folia Histochem Cytobiol 2007 ;45(1):41-5

Department of Pathology, 3rd Faculty of Medicine, Charles University, Prague, Czech Republic.

Class III beta-tubulin has been discovered as a marker of early phases of neuronal differentiation in developmental conditions, as well as in different tumours of neuronal origin. More recently, the expression of class III beta-tubulin molecule has been described as a marker of different types of malignant epithelial tumours. This study attempts to compare the immunostaining features of two different mouse monoclonal antibodies TU-20 and TuJ-1, both detecting class III beta-tubulin, in a group of twenty bioptically evaluated carcinomas of various sites. The proposal that class III beta-tubulin expression can correlate with the degree of tumour differentiation and thus could be potentially used as predictive marker of prognosis has been previously done; one of aims of our study was to confirm this hypothesis. Our results showed that both TuJ- 1 and TU-20 antibodies displayed similar immunostaining profile and pattern within individual tumours. Surprisingly, we discovered that only 50% of tumours included in our group showed expression of class III beta-tubulin, however, positive immunoreaction did not correspond with the degree of differentiation of individual tumours. In our group of carcinomas, the class III beta-tubulin positivity was not related to the tumour site, histologic type of tumour or its grade.
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May 2007

Tissue and serum levels of principal androgens in benign prostatic hyperplasia and prostate cancer.

Steroids 2007 Apr 13;72(4):375-80. Epub 2007 Feb 13.

Department of Urology, 3rd Faculty of Medicine, Charles University in Prague, Ruska 87, 10000 Prague 10, Czech Republic.

Androgens are considered to play a substantial role in pathogenesis of both benign prostatic hyperplasia (BPH) and prostate cancer. The importance of determination of androgen levels in tissue and serum for cancer progression and prognosis has been poorly understood. The aim of study was to find out hormonal differences in both diseases, their correlations between intraprostatic and serum levels and predicted value of their investigation. Testosterone, dihydrotestosterone, androstenedione and also epitestosterone were determined in prostate tissue from 57 patients who underwent transvesical prostatectomy for BPH and 121 patients after radical prostatectomy for prostate cancer. In 75 subjects with cancer and 51 with BPH the serum samples were analyzed for testosterone, dihydrotestosterone and SHBG. Significantly higher intraprostatic androgen concentrations, i.e. 8.85+/-6.77 versus 6.44+/-6.43 pmol/g, p<0.01 for dihydrotestosterone, and 4.61+/-7.02 versus 3.44+/-4.53 pmol/g, p<0.05 for testosterone, respectively, were found in patients with prostate cancer than in BPH. Higher levels in cancer tissue were found also for epitestosterone. However, no differences were found in serum levels. Highly significant correlations occurred between all pairs of intraprostatic androgens and also epitestosterone as well as between serum testosterone and dihydrotestosterone (p<0.001) in both BPH and cancer groups. Correlation was not found between corresponding tissue and serum testosterone and dihydrotestosterone, either in benign or cancer samples. The results point to importance of intraprostatic hormone levels for evaluation of androgen status of patients, contrasting to a low value of serum hormone measurement.
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http://dx.doi.org/10.1016/j.steroids.2007.01.004DOI Listing
April 2007

Mastoiditis complicated with Gradenigo syndrome and a hypertrophic pachymeningitis with consequent communicating hydrocephalus.

Acta Otolaryngol 2007 Jan;127(1):93-7

Department of Neurology, Charles University, 3rd Medical Faculty and Faculty Hospital Královské Vinohrady, Prague, Czech Republic.

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.
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http://dx.doi.org/10.1080/00016480500475583DOI Listing
January 2007