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Objective: The survival benefit of a complete resection of the contrast-enhancing malignant glioma tissue has clearly been demonstrated. Recently, molecular pattern, mainly MGMT promotor methylation and IDH1 mutation gained more importance within the decision-making process of the therapy. As prognostic[for full text, please go to the a.m. URL], 68. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), 7. Joint Meeting mit der Society of British Neurological Surgeons (SBNS)

PURPOSE OF THE STUDY A consensual classification of the periprosthetic interface membrane obtained at revision total joint arthroplasty was published by Morawietz et al. in 2006. Based on histomorphological criteria, four types of periprosthetic membrane were proposed: type I, aseptic failure; type II, septic failure; type III, combined type (carrying signs of both type I and II); and type IV, indeterminate type. The aim of this study was to find out whether and to what extent the Morawietz system would be suitable for use at an independent institution involved in the evaluation of periprosthetic membranes for a long time. Should it appear that the institution achieved an equally good or even better agreement between the clinical diagnosis and the histopathological finding, this consensus classification could be recommended for routine use. MATERIAL AND METHODS The samples of periprosthetic tissue evaluated in this study were obtained during surgery from the following groups of patients: 66 patients with aseptic loosening of total hip (THA) or knee arthroplasty, 15 patients with infection of THA, 16 patients with THA without any signs of aseptic loosening, osteolysis or infection; 8 patients with hip osteoarthritis and 8 patients with knee osteoarthritis. Sample collection and processing (for purposes of histomorphological evaluation and immunohistochemical staining) was performed according to the established protocol. The tissue samples evaluation was made by an experienced pathologist hand in hand with the method described in the original paper by Morawietz et al. For a more detailed tissue analysis, selected antibodies (CD4, CD8, CD20, IFN-γ and Hsp-60) were visualized by immunohistochemistry. RESULTS The majority of samples from aseptic reoperations were classified as membranes of the type I (79%) and III (16%). Specimens retrieved from septic cases were mostly classified as membranes of type II and III (60% together). The septic membranes showed a significantly higher expression of CD20 protein when compared with both the aseptic (p0.0001) and control THA samples (p = 0.003). The membranes retrieved from the surroundings of a stable THA without osteolysis and infection had lower expression levels of Hsp60 and IFN-γ, when compared with those from both aseptic and septic loosening. Finally, Hsp-60 expression was significantly higher in osteoarthritic tissue than in samples from stable THA (p = 0.041). DISCUSSION Morawietz et al. proposed a standardized classification system for evaluation of periprosthetic tissue. As any attempt at generalization of a complex issue, this proposal has certain shortcomings. One of these is poor detection of chronic and low-grade infections. A method that would improve the conventional counting of polymorphonuclear leukocytes is still being sought. In this connection, immunostaining for CD20 combined with an assessment of antimicrobial peptides may be a promising option. The supplementary specimen staining showed that pseudosynovial tissue is much more active in patients carrying infection and the least active in samples from stable THA in which certain tolerance and thus tissue homeostasis might be expected. CONCLUSIONS 1. In this study the distribution of findings classified according to the Morawietz system was similar to the results published in the original study from 2006. 2. The definition of an aseptic membrane (type I) in the Morawietz system meets the requirements of clinical practice (agreement, about 80%). 3. An increased sensitivity for infectious membrane detection can be achieved by using supplementary immunohistochemical staining effective particularly in chronic and low-grade infections. 4. Painless and stable THAs typically have very low expression levels of CD4, CD20 and Hsp-60 proteins, and interferon- -gamma (IFN-γ) as well. Key words: total hip arthroplasty, total knee arthroplasty, aseptic loosening, prosthetic joint infection, tissue analysis, membranes, CD receptors, Hsp-60 protein, IFN-γ.

Targeted therapy has become an integral part of treatment procedures of malignant tumors. Colorectal carcinomas are frequently targeted with monoclonal anti-EGFR antibodies (cetuximab and panitumumab). Activating somatic mutations in codons 12 and 13 of the exon 2 of KRAS gene are considered negative predictive factors of response to anti-EGFR therapy in patients with metastatic colorectal cancer. In the Czech Republic, evaluation of mutational status of KRAS gene is performed in several referral laboratories. In 2009, these laboratories performed 2580 tests of the KRAS mutational status--out of these, 60.2% cases reported non-mutated, wild-type KRAS. In one of the referral laboratories, we demonstrate the logistics of KRAS testing procedure. Stratification of patients with metastatic colorectal tumors based on their KRAS mutational status has evolved to a standard procedure. Laboratories performing these methods shall therefore adhere to the recommendations of the professional and accredited societies.

The expression of Bcl-2, Bcl-X, Mcl-1, and Bax was examined by immunohistochemical methods in 93 tumors of nervous system origin, including 49 gliomas (30 astrocytomas and 19 glioblastoma multiforme (GMs)), 16 medulloblastomas (MBs), 19 neuroblastomas (NBs; 9 undifferentiated and 10 differentiated), and 9 miscellaneous neuroectodermal neoplasms. Among the 49 gliomas, immunopositivity (defined as > or = 10%) was observed for Bcl-2 in 45 (92%), Bcl-X in 48 (98%), Mcl-1 in 49 (100%), and Bax in 48 (98%) of 49 specimens. In 11 (37%) of 30 astrocytomas (WHO grades I to III), the tumor specimens were composed predominantly of malignant cells with strong-intensity Bcl-2 immunostaining, whereas none of the 19 GMs (WHO grade IV) exhibited strong-intensity Bcl-2 immunoreactivity (P = 0.001). Similarly, Mcl-1 immunointensity was strong in 15 (50%) of 30 astrocytomas, compared with only 2 (11%) of 19 GMs (P = 0.005). The percentage of Mcl-1-immunopositive tumor cells was also higher in astrocytomas than GMs (P < 0.002). Thus, contrary to a priori expectations, the expression of the anti-apoptotic proteins Bcl-2 and Mcl-1 was significantly higher in astrocytomas than in GMs. Of the 16 MBs, immunopositivity was found for Bcl-2 in 4 (25%), Bcl-X in 9 (56%), Mcl-1 in 8 (50%), and Bax in 16 (100%) of the cases. The intensity of immunostaining was strong for Bcl-2 in only 1 (6%) specimen, for Bcl-X in 3 (19%), and for Mcl-1 in 2 (12.5%), in contrast to Bax immunostaining, which was strong in 12 (75%) tumors. Significantly higher percentages of Bax-immunopositive tumor cells were also found in MBs, compared with Bcl-2, Bcl-X, and Mcl-1 (P < 0.0001). All 19 NBs were immunopositive for Bcl-2, Bcl-X, Mcl-1, and Bax. Higher percentages of Bcl-X- and Mcl-1-immunopositive tumor cells were observed in well differentiated tumors (P = 0.04 and 0.004, respectively). The intensity of Mcl-1 immunostaining was also generally higher in differentiated than undifferentiated NBs (strong immunointensity in 7 of 10 versus 0 of 9; P = 0.002). Conversely, strong-intensity Bax immunostaining was associated with undifferentiated histology (5 of 9 (56%) versus 1 of 10 (10%); P = 0.03). Taken together, these findings begin to delineate trends in the regulation of the relative levels of the Bcl-2 family proteins, Bcl-2, Bcl-X, Mcl-1, and Bax in gliomas, MBs, NBs, and some of their histological subtypes. The suggestion that expression of some of these Bcl-2 family genes may be differentially regulated in association with tumor progression and differentiation provides insights into the diverse biology and clinical behavior of these tumors of nervous system origin.

The nuclear receptors PPARs (peroxisome proliferator-activated receptors) are transcription factors activated by specific ligands. PPARs play an important role in carcinogenesis, inflammation, atherosclerosis, lipid metabolism and diabetes. There is evidence that activation of PPARs by specific ligands is able to suppress the growth of different types of human cancer by mechanisms including the growth arrest, apoptosis and induction of differentiation, although the detailed signalling pathways have not been completely elucidated to date. The aim of our study was to determine whether synthetic ligands of PPARalpha and PPARgamma could affect the viability, proliferation, differentiation, apoptosis and expression of some cell cycle related proteins in glial tumor cell lines. The study was performed on human glioblastoma cell lines U-87 MG, T98G, A172 and U-118 MG. Cell lines were treated by ligands of PPARalpha (bezafibrate, gemfibrozil) and PPARgamma (ciglitazone). MTT, flow cytometry, TUNEL assay and immunoblotting were used for detection of changes in cell viability, proliferation, differentiation and apoptosis. Bezafibrate, ciglitazone and gemfibrozil inhibited viability of glioblastoma cell lines. The synthetic ligands significantly reduced or induced the expression of cyclins, p27Kip1, p21Waf1/Cip1, MDM-2, Bcl-2, Bax, PARP, Caspase 3, androgen receptors, etc. and did not affect the expression of the differentiation marker GFAP. Flow cytometry confirmed arrest of the cell cycle although the detection of apoptosis was controversial. Apart from hypolipidemic and hypoglycaemic effects, PPAR ligands may also have significant cytostatic effects of potential use in anticancer treatment.