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Abstract: Glioblastoma is the most common primary brain tumour. It has a poor prognosis despite some advances in treatment that have been achieved over the last ten years. In Slovenia, 50 to 60 glioblastoma patients are diagnosed each year. In order to establish whether the current treatment options have any influence on the survival of the Slovenian glioblastoma patients, their data in the period from the beginning of the year 1997 to the end of the year 2008 have been analysed. Patients and methods. All patients treated at the Institute of Oncology Ljubljana from 1997 to 2008 were included in the retrospective study. Demographics, treatment details, and survival time after the diagnosis were collected and statistically analysed for the group as a whole and for subgroups. Results. From 1997 to 2008, 527 adult patients were diagnosed with glioblastoma and referred to the Institute of Oncology for further treatment. Their median age was 59 years (from 20 to 85) and all but one had the diagnosis confirmed by a pathologist. Gross total resection was reported by surgeons in 261 (49.5%) patients; good functional status (WHO 0 or 1) after surgery was observed in 336 (63.7%) patients, radiotherapy was performed in 422 (80.1%) patients, in 317 (75.1%) of them with radical intent, and 198 (62.5 %) of those received some form of systemic treatment (usually temozolomide). The median survival of all patients amounted to 9.7 months. There was no difference in median survival of all patients or of all treated patients before or after the chemo-radiotherapy era. However, the overall survival of patients treated with radical intent was significantly better (11.4 months; p < 0.05). A better survival was also noticed in radically treated patients who received additional temozolomide therapy (11.4 vs. 13.1 months; p = 0.014). The longer survival was associated with a younger age and a good performance status as well as with a more extensive tumour resection. In patients treated with radical intent, having a good performance status, and receiving radiotherapy and additional temozolomide therapy, the survival was significantly longer, based on multivariate analysis.
Keywords: glioblastoma, treatment, survival, surgery, radiotherapy, termozolomide
Published in DiRROS: 11.04.2024; Views: 67; Downloads: 32
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Abstract: Multi-material components, also known as functionally graded materials (FGMs), are innovative materials that possess unique properties due to their composition and have many potential applications in engineering and science. The effect of the heat treatment (HT) of functionally graded materials 15–5 precipitation-hardened (PH) martensitic steel and SAF 2507 duplex stainless steel (and the opposite order of deposition, i.e. SAF 2507 first followed by 15–5 PH stainless steel) on the interface microstructures was systematically investigated in the presented research. The choice of HT followed the trend of optimum post-processing for the individual alloys. A significant modification in the interface microstructure, characterized in the microstructural transition zone (MTZ) formed above the fusion line. Mechanical properties by miniaturized testing method including hardness measurement characterized both types of interfaces. The sequence of the materials’ application did not have a significant effect on their final mechanical tensile properties in the heat-treated states. Nevertheless, the microstructural change at the MTZ led to drop in the hardness at the interface. The research presents heat-treated FGMs in a horizontal configuration to form a high-quality metallurgical joint between heterogeneous materials manufactured by powder-based directed energy deposition method.
Keywords: heat treatment, additive manufacturing, martensitic stainless steel, duplex steel, microstructure, mechanical properties
Published in DiRROS: 04.04.2024; Views: 53; Downloads: 11
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Abstract: Background. Etoposide is a chemotherapeutic agent, widely used for the treatment of various malignancies, including small cell lung cancer (SCLC), an aggressive disease with poor prognosis. Oral etoposide administration exhibits advantages for the quality of life of the patient as well as economic benefits. However, widespread use of oral etoposide is limited by incomplete and variable bioavailability. Variability in bioavailability was observed both within and between patients. This suggests that some patients may experience suboptimal tumor cytotoxicity, whereas other patients may be atrisk for excess toxicity. Conclusions. The article highlights dilemmas as well as solutions regarding oral treatment with etoposide by presenting and analyzing relevant literature data. Numerous studies have shown that bioavailability of etoposide is influenced by genetic, physiological and environmental factors. Several strategies were explored to improve bioavailability and to reduce pharmacokinetic variability of oral etoposide, including desired and undesired drug interactions (e.g. with ketoconazole), development of suitable drug delivery systems, use of more water-soluble prodrug of etoposide, and influence on gastric emptying. In addition to genotype-based dose administration, etoposide is suitable for pharmacokinetically guided dosing, which enables dose adjustments in individual patient. Further, it is established that oral and intravenous schedules of etoposide in SCLC patients do not result in significant differences in treatment outcome, while results of toxicity are inconclusive. To conclude, the main message of the article is that better prediction of the pharmacokinetics of oral etoposide may encourage its wider use in routine clinical practice.
Keywords: oral etoposide, bioavailability, pharmacokinetic variability, small cell lung cancer, treatment
Published in DiRROS: 22.03.2024; Views: 65; Downloads: 25
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Abstract: Background. Due to superior results observed with the addition of rituximab into treatment of patients with the diffuse large B-cell lymphoma (DLBCL),the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) regimen and its variants became the standard initial treatment of these patients. However, the treatment recommendations are based on resultsof clinical studies while the conditions of routine treatment are far different from the ones in clinical studies. The aim of this retrospective study was therefore to compare the treatment results of routinelz treated patients with the DLBCL to results reported by some larger studies. Patients and methods. Two hundred and ninety five patients with the DLBCL were treated between 2004 and 2008 according to the then protocol with R-CHOP or R-CHOP-like regimens at the Institute of Oncology Ljubljana. Treatment response was evaluated according to Chesonʼs criteria and the disease-free andoverall survival by means of Kaplan Meier survival curves. Results. Response to treatment in our evaluation diverged from the reported one predominately in the low risk group (international prognostic index [IPI] categorisation) and in the very good prognosis group (revised international prognostic index (R-IPI) categorisation). The determined complete response (CR) rates in other IPI and R-IPI groups were generally within expectations. Also in the disease-free survival the largest discrepancy occurred in the low-risk patient group (3 year disease-free survival rate of 75%) and in the very good prognosis group (4 year disease-free survival rate of 59%). In all other IPI risk groups, the disease-free survival at 3 zears (low intermediate risk 76%, high intermediate risk group 57%, and high risk group 53%) agreed verz well with the quoted ones. Slightly worse was the compliance of the 4 year disease-free survival rates (72% in the good prognosis and 51% in the poor prognosis group) with the results from the literature. The 3 year overall survival rates (low risk patients 87%, high intermediate risk 61% and high risk patients 51%) were somewhat worse than the reported ones in all IPI subgroups except in the low intermediate risk group (82%). On the other hand, the 4 year overall survival rates of the R-IPI categories (94% in the very good prognosis group, 80% in the good prognosis group, 56% in the poor prognosis group) were much better correlated with the data from the literature. Conclusions. In total, the treatment outcomes of routinely treatedpatient with the DLBCL at our institute are quite encouraging when compared to results of some larger studies. There are probably no dilemmas about how to treat young good prognosis patients and patients aged over 60 years at present. However, the 5 year overall survival rate of 76% for the young poor prognosis group is unsatisfying and needs to be improved. At present, quite a few studies are underway to clarify which of the regimens will perform best in this population.
Keywords: diffuse large B-cell lymphoma, R-CHOP, treatment result, routine treatments
Published in DiRROS: 21.03.2024; Views: 73; Downloads: 29
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Abstract: Background. Various electrofusion parameters have to be adjusted to obtain theoptimal electrofusion efficiency. Based on published data, good electrofusion conditions can be achieved with the hypotonic treatment. However, the duration of the hypotonic treatment before electroporation and buffer hypoosmolarity have to be adjusted in order to cause cell swelling, to avoid regulatory volume decrease and to preserve cell viability. The aims of our study were to determine cell size dynamics and viability of four different cell lines in hypotonic buffer and to study the influence of the electroporation on the selected cell line in hypotonic buffer. Materials and methods. Cell size dynamics of different cell lines exposed to hypotonic buffer and electroporation were analyzed by time-resolvedcell size measurements. The viability of hypotonically treated oržand electroporated cells was determined 24 h after the experiment by a modified crystal violet (CV) viability assay. Results. In our experimental conditions the hypotonic treatment at 100 mOsm was efficient for CHO, V79 and B16-F1 cell lines. The optimal duration of the treatment was between two and five minutes. On the other hand the same hypotonic treatment did not cause cell swelling of NS1 cells. Cell swelling was also observed after electroporation of B16-F1 in isotonic buffer and it was amplified when hypotonic buffer was used. In addition, the regulatory volume decrease was successfully inhibited with electroporation. Conclusions. Cell size dynamicsin hypotonic conditions should be studied for each cell line since they differ in their sensitivity to the hypotonic treatment. The inhibition of cell regulatory volume decrease by electroporation may be beneficial in achieving higher electrofusion efficiency. (Abstract truncated at 2000 characters)
Keywords: hypotonic treatment, cell swelling, regulatory volume decrease, cell size measurements, viability, electrofusion, electroporation
Published in DiRROS: 08.03.2024; Views: 98; Downloads: 32
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