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Povzetek: Asbestos exposure has been proposed as a risk factor for shorter telomere length. The aim of our study was to investigate whether telomere length in leukocytes and hTERT genetic polymorphisms may serve as potential biomarkers for the risk of developing asbestos-related diseases and as biomarkers of progression and chemotherapy response rate in malignant mesothelioma (MM). Subjects and methods. We conducted two retrospective studies. In the first study, a case-control study, telomere length and hTERT polymorphisms were determined in patients with MM, subjects with pleural plaques and controls without the asbestos related disease, who were occupationally exposed to asbestos. In the second study, a longitudinal observational study, telomere length was also determined in samples from MM patients before and after chemotherapy. Telomere length was determined by monochromatic multiplex quantitative polymerase chain reaction (PCR), while competitive allele-specific PCR was used to genotype hTERT rs10069690, rs2736100 and rs2736098. Logistic regression and survival analysis were used in statistical analysis. Results. Patients with MM had shorter telomere length than subjects with pleural plaques (p < 0.001). After adjustment for age, rs2736098 CT, and rs10069690 TT and CT+TT genotypes were significantly associated with a higher risk of MM (padj = 0.023; padj = 0.026 and padj = 0.017), while rs2736100 AA and CA+AA genotypes conferred to a lower risk for MM compared to all other subjects (padj = 0.017, and padj = 0.026). Telomere length was not associated with a response to chemotherapy (p > 0.05) or time to disease progression (p > 0.05). Carriers of one or two polymorphic rs10069690 T alleles had a good response to chemotherapy (p = 0.039, and p = 0.048), these associations remained statistically significant after adjustment for age (padj = 0.019; padj = 0.017). Carriers of two polymorphic rs2736100 A alleles had a longer time to disease progression (p = 0.038). Conclusions. Shorter telomere length and hTERT polymorphisms may serve as a biomarker for the risk of developing MM. Additionally, rs10069690 and rs2736100 polymorphisms, but not telomere length, were associated with a chemotherapy response or MM progression.
Ključne besede: malignant mesothelioma, asbestos, telomere length
Objavljeno v DiRROS: 26.06.2026; Ogledov: 114; Prenosov: 60
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Povzetek: Fatigue after breast cancer treatment is a common burden that is challenging to treat. The aim of this study was to explore if such integrated rehabilitation program reduces the prevalence of chronic fatigue compared to simple, non-integrated rehabilitation. Patients and methods The subjects of our prospective study were 600 female breast cancer patients (29–65 [mean 52 years] of age), who participated in the pilot study on the individualized integrated rehabilitation of breast cancer patients in 2019–2021 and were monitored for one year. The control group included 301 patients and the intervention group numbered 299 patients. The patients completed three questionnaires (EORTC QLQ-C30, -BR23 and NCCN): before cancer treatment, and then six and twelve months after the beginning of cancer treatment. The control group obtained the standard rehabilitation program, while the intervention group was part of the early, individualized multidisciplinary and integrated approach of rehabilitation. The rehabilitation coordinator referred patients for additional interventions (e.g., psychologist, gynecologist, pain management team, physiotherapy, clinical nutrition team, kinesiologist-guided online training, vocational rehabilitation, general practitioner). Data on the patients’ demographics, disease extent, cancer treatment and complaints reported in questionnaires were collected and analyzed. Results There were no differences between the control and the intervention group of patients in terms of age, education, disease extent, surgical procedures, systemic cancer treatment, or radiotherapy, and also no differences in the fatigue before the beginning of treatment. However, patients from the control group had a greater level of constant fatigue than patients from the intervention group half a year (p = 0.018) and a year (p = 0.001) after the beginning of treatment. Furthermore, a greater proportion of patients from the control group experienced significant interference with their usual activities from fatigue than from the intervention group, half a year (p = 0.042) and a year (p = 0.001) after the beginning of treatment. A multivariate logistic regression showed that one year after the beginning of treatment, the only independent factor correlated to fatigue was inclusion into the intervention group (p = 0.044). Inclusion in the intervention group was beneficial—patients from the control group were 1.5 times more likely to be fatigued. Conclusions Early individualized integrated rehabilitation is associated with a lower prevalence of chronic fatigue or fatigue interfering with usual activities in breast cancer patients in comparison to the control group of patients.
Ključne besede: breast cancer, early integrated rehabilitation, fatigue
Objavljeno v DiRROS: 26.06.2026; Ogledov: 113; Prenosov: 59
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Povzetek: Transarterial chemoembolisation with irinotecan-loaded drug-eluting beads (DEBIRI TACE) can be considered in patients with unresectable colorectal cancer liver metastases (CRLM) who progress after all approved standard therapies or in patients unsuitable for systemic therapy. Patients and methods Between September 2010 and March 2020, thirty patients (22 men and 8 women; mean age 66.8 ± 13.2) were included in this retrospective study. DEBIRI TACE was conducted in 43% of patients unsuitable for systemic therapy as a first-line treatment and 57% as salvage therapy after the progression of systemic therapy. All the patients had liver-limited disease. In the case of unilobar disease, two treatments were performed at four-week intervals, and in the case of bilobar disease, four treatments were performed at two-week intervals. All patients were premedicated and monitored after the procedure. Adverse events were graded according to the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) classification system for complications. Results The median overall survival (OS) from the beginning of DEBIRI TACE in the salvage group was 17.4 months; in the group without prior systemic therapy, it was 21.6 months. The median overall survival of all patients was 17.4 months (95% confidence interval [CI]: 10.0–24.7 months), and progression-free survival (PFS) was 4.2 months (95% CI: 0.9–7.4 months). The one-year survival rate after the procedure was 61%, and the two-year rate was 25%. Univariate analysis showed better survival of patients with four or fewer liver metastases (p = 0.002). There were no treatment-related deaths or grade 4 and 5 adverse events. Nonserious adverse events (Grades 1 and 2) were present in 53% of patients, and Grade 3 adverse events were present in 6% of the patients. Conclusions DEBIRI TACE is a well-tolerated treatment option for patients with liver metastases of colorectal cancer. Patients with four or fewer liver metastases correlated with better survival.
Ključne besede: colorectal cancer, liver metastases, irinotecan
Objavljeno v DiRROS: 26.06.2026; Ogledov: 86; Prenosov: 48
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Povzetek: Flow cytometry plays is important in the diagnosis of acute lymphoblastic leukaemia (ALL) and when antigen-specific immunotherapy is indicated. We have investigated the effects of prednisolone, vincristine, daunorubicin, asparaginase and methotrexate on the antigen expression on blast cells that could influence the planning of antigen-specific therapy as well as risk-based treatment assignment. Patients and methods. Patients aged ≤ 17 years with de novo B-cell ALL (B-ALL) were enrolled in the study. Blast cells were isolated and exposed in vitro to 5 individual cytotoxic drugs in logarithmically increasing concentrations. Then, the expression of CD10, CD19, CD20, CD27, CD34, CD45, CD58, CD66c and CD137 antigens was determined by quantitative flow cytometry. Results. Cytotoxic drugs caused dose-dependent or dose-independent modulation of antigen expression. Daunorubicin caused a dose-dependent down-modulation of CD10, CD19, CD34, CD45 and CD58 and an up-modulation of CD137. Vincristine caused a dose-dependent down-modulation of CD19 and CD58 and an up-modulation of CD45. Daunorubicin also caused dose-independent down-modulation of CD27 and prednisolone down-modulation of CD10, CD19, CD27, CD34 and CD58. Down-modulation of CD20 was detected only in relation to the specific dose of daunorubicin. Conclusions. The results of the study have shown that cytotoxic drugs can alter the expression of antigens that are important for immunotherapy. Importantly, daunorubicin, prednisolone and vincristine caused down-modulation of CD19 and CD58, suggesting that these drugs are better avoided during bridging therapy prior to bispecific antibodies or CAR-T cell therapy. In addition, immunophenotypic changes on blast cells induced by different drugs could also influence risk-based treatment assignment.
Ključne besede: immunophenotypic changes, chemotherapy, immunotherapy
Objavljeno v DiRROS: 26.06.2026; Ogledov: 103; Prenosov: 53
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Povzetek: Background: Multiparametric magnetic resonance imaging (mpMRI) is a prerequisite for targeted prostate biopsy. The aim of our study was to evaluate the performance and learning curve of the mpMRI-transrectal ultrasound (TRUS) software image fusion (MRI-TRUS fusion) biopsy (BX) process in the first year after its introduction in our urology department. Patients and methods: MRI-TRUS fusion BX was performed in 293 patients with at least one Prostate Imaging-Reporting and Data System (PIRADS) ≥3 lesion. The proportion of patients and lesions with positive histopathologic result for prostate cancer (PCa) was analyzed. The learning curve for MRI-TRUS fusion BX was assessed at institutional and individual level. Positive BX lesions were further analyzed by PIRADS and Gleason scores. Results: The proportion of patients with positive histopathologic results for targeted BX, systematic BX, and combined BX was 53.9%, 47.9%, and 63.5%, respectively. The chi-square test for the proportion of PCa positive patients showed no significant difference between the time-based patient groups at the institutional level and no significant difference between individual urologists. PIRADS score (p < 0.001), total PSA concentration (p = 0.05), prostate volume (p < 0.001) and number of cores per lesion (p = 0.034) were significant predictors of a positive histopathologic result in a lesion-based analysis. Clinically significant PCa (csPCa) was confirmed in 34.7% of the 412 BX lesions and 76.4% of the 187 positive PCa lesions. Conclusions: MRI-TRUS fusion targeted BX significantly improves the overall rate of PCa detection compared with systematic BX alone. No steep learning curve was observed in our urologists. The proportion of lesions with clinically insignificant PCa was low, limiting overdiagnosis of PCa.
Ključne besede: complications, learning curve, prostate cancer, targeted prostate biopsy
Objavljeno v DiRROS: 26.06.2026; Ogledov: 116; Prenosov: 84
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