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Martin Lovecek,1,* Marketa Janatova,2,* Pavel Skalicky,1 Tomas Zemanek,3 Roman Havlik,1 Jiri Ehrmann,4 Ondrej Strouhal,3 Petra Zemankova,2 Klara Lhotova,2 Marianna Borecka,2 Jana Soukupova,2 Hana Svebisova,3 Pavel Soucek,5 Viktor Hlavac,5 Zdenek Kleibl,2 Cestmir Neoral,1 Bohuslav Melichar,3 Beatrice Mohelnikova-Duchonova3 1Department of Surgery I, Faculty of Medicine and Dentistry, Palacky University Olomouc, University Hospital Olomouc, Olomouc, Czech Republic; 2Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, Prague, Czech Republic; 3Department of Oncology, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic; 4Department of Clinical and Molecular Pathology, Faculty of Medicine and Dentistry, Palacky University Olomouc, University Hospital Olomouc, Olomouc, Czech Republic; 5Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen Czech Republic *These authors contributed equally to this work Background: The principal aim of this report was to study second primary malignant neoplasms (SMNs) in long-term survivors of pancreatic ductal adenocarcinoma (PDAC) with regard to the germline genetic background.Patients and methods: A total of 118 PDAC patients after a curative-intent surgery who were treated between 2006 and 2011 were analyzed. Of the 22 patients surviving for >5 years, six went on to develop SMNs. A genetic analysis of 219 hereditary cancer-predisposition and candidate genes was performed by targeted next-generation sequencing in germline DNA from 20 of these patients.Results: Of all the radically resected PDAC patients, six patients went on to subsequently develop SMNs, which accounted for 27% of the long-term survivors. The median time to diagnosis of SMNs, which included two cases of rectal cancer, and one case each of prostate cancer, malignant melanoma, breast cancer, and urinary bladder cancer, was 52.5 months. At the time of analysis, none of these patients had died as a result of PDAC progression. We identified four carriers of germline pathogenic mutations in 20 analyzed long-term survivors. One carrier of the CHEK2 mutation was found among four analyzed patients who developed SMNs. Of the remaining 16 long-term PDAC survivors, 3 patients (19%) carried germline mutation(s) in the MLH1+ ATM, CHEK2, and RAD51D gene, respectively.Conclusion: This retrospective analysis indicates that SMNs in PDAC survivors are an important clinical problem and may be more common than has been acknowledged to be the case. In patients with good performance status, surgical therapy should be considered, as the SMNs often have a favorable prognosis. Keywords: pancreatic ductal adenocarcinoma, second primary neoplasms, subsequent malignant neoplasm, hereditary cancer genes, long-term survivors, surgical treatment

Copyright of Transfusiology & Haematology Today / Transfuze a Hematologie Dnes is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Revision & Assessment Medicine / Revizní a Posudkové Lékařství is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This case report demonstrates a series of small deviations from the routine diabetes care which resulted in a fatal outcome with forensic consequences. A 75-year old man with type 2 diabetes was referred to a hospital due to acute pain in his right hip. The omitting of insulin prescription resulted in a fatal outcome. The experts concluded, various mishaps and such a critical medical error may occure in any healthcare institution at any time. The purpose of this report is reduce the risk of such pitfalls in the future. [ABSTRACT FROM AUTHOR]

The glomus tumour is mostly a benign growth that most frequently occurs in the subungual area or within the pulp of the distal phalanx of the fingers. Its incidence is very rare. Glomus tumour is clinically characterized by -- pain, -- tenderness, and -- cold sensitivity. Despite this typical manifestation, the correct diagnosis is mostly determined after several months or years, and patient is often repeatedly examined by physicians of various specializations. The glomus tumour can cause the blue discoloration of the nail or form a palpable nodule within the pulp. X-ray examination does not show the tumour directly but it can expose the bony defect in the distal phalanx. By contrast, MR Imaging can demonstrate well-bordered formation, thus helping to locate the tumour and select the appropriate surgical approach. MRI can also indentify the rare occurrence of multiple glomus tumours. Surgical extirpation of the tumour under local or general anaesthesia is the treatment of choice. [ABSTRACT FROM AUTHOR]

The aim of our study was to correlate apoptosis, assessed by means of lamin B degradation, with grade of tumour and immunohistochemical expression of p27Kip1 and retinoblastoma protein (pRB) in a series of 32 low-grade astrocytomas (LGA) and 43 high-grade astrocytomas (HGA). Determination and analysis of lamin B expression was achieved stereologically with the use of computerised interactive image analysis. The average stereological surface density of the lamin-positive nuclear surface of cells showing evidence of lamin degradation cells was 13.80 mm2/mm3 in LGA and 21.02 mm2/mm3 in HGA. The average range of immunopositivity of p27 and pRB expression was 2.85 and 2.10, respectively, in LGA and 1.80 and 0.88, respectively, in HGA. The rate of apoptosis indirectly correlated with the expression of both p27 and pRB but was not fully significant (P < or = 0.09). Our findings suggest that there may be a loss of function of main cell-cycle regulators and increased uncontrolled cell death in addition to increased cell proliferation in high-grade astrocytomas. Moreover, we believe that the detection of lamin B degradation in astroglial tumours can be an alternative, precise and convenient assay for the detection of a defined set of apoptotic cells. However, before being applied more generally, comparative research should be done on different methods of quantifying apoptosis, with the intent of finding the difference between biologically different methods. Such studies would also be able to find the method associated with the strongest prognostic power. [ABSTRACT FROM AUTHOR]

Abstract Background Barrett's esophagus (BE) is a disease with a rising prevalence in western countries probably due to the unhealthy lifestyle. In significant number of cases it develops to esophageal adenocarcinoma. Two decades ago, important gene regulators (microRNAs) were discovered and their attendance in the process of malignant transformation was demonstrated (e.g. miR-192, 196a, 203). Our aim was to select the patients with the increased risk of malignant transformation before the cancer develops. Methods 71 patients with BE disease were selected, slides from FFPE blocks were prepared, the lesions were microdissected and a qPCR relative expression analysis for selected microRNAs (generally known to be connected with malignant transformation process) was carried out. Results We demonstrated unequivocal statistically significant upregulation of two microRNAs (miR-192, 196a) and downregulation of miR-203 and positive miR-196a correlation with progression from intestinal metaplasia to adenocarcinoma compared to normal individuals. Conclusions We hypothetize that there do exist changes of selected microRNAs which can undoubtedly distinguish the patients with BE from normal healthy individuals.

Abstract Background Invasive ductal and lobular carcinomas (IDC and ILC) are the most common histological types of breast cancer. Clinical follow-up data and metastatic patterns suggest that the development and progression of these tumors are different. The aim of our study was to identify gene expression profiles of IDC and ILC in relation to normal breast epithelial cells. Methods We examined 30 samples (normal ductal and lobular cells from 10 patients, IDC cells from 5 patients, ILC cells from 5 patients) microdissected from cryosections of ten mastectomy specimens from postmenopausal patients. Fifty nanograms of total RNA were amplified and labeled by PCR and in vitro transcription. Samples were analysed upon Affymetrix U133 Plus 2.0 Arrays. The expression of seven differentially expressed genes (CDH1, EMP1, DDR1, DVL1, KRT5, KRT6, KRT17) was verified by immunohistochemistry on tissue microarrays. Expression of ASPN mRNA was validated by in situ hybridization on frozen sections, and CTHRC1, ASPN and COL3A1 were tested by PCR. Results Using GCOS pairwise comparison algorithm and rank products we have identified 84 named genes common to ILC versus normal cell types, 74 named genes common to IDC versus normal cell types, 78 named genes differentially expressed between normal ductal and lobular cells, and 28 named genes between IDC and ILC. Genes distinguishing between IDC and ILC are involved in epithelial-mesenchymal transition, TGF-beta and Wnt signaling. These changes were present in both tumor types but appeared to be more prominent in ILC. Immunohistochemistry for several novel markers (EMP1, DVL1, DDR1) distinguished large sets of IDC from ILC. Conclusion IDC and ILC can be differentiated both at the gene and protein levels. In this study we report two candidate genes, asporin (ASPN) and collagen triple helix repeat containing 1 (CTHRC1) which might be significant in breast carcinogenesis. Besides E-cadherin, the proteins validated on tissue microarrays (EMP1, DVL1, DDR1) may represent novel immunohistochemical markers helpful in distinguishing between IDC and ILC. Further studies with larger sets of patients are needed to verify the gene expression profiles of various histological types of breast cancer in order to determine molecular subclassifications, prognosis and the optimum treatment strategies.