81. Completely resected stage III melanoma controversy : 15 years of national tertiary centre experienceBarbara Perić, Sara Milićević, Andraž Perhavec, Marko Hočevar, Janez Žgajnar, 2021, izvirni znanstveni članek Povzetek: Background Two prospective randomized studies analysing cutaneous melanoma (CM) patients with sentinel lymph node (SLN) metastases and rapid development of systemic adjuvant therapy have changed our approach to stage III CM treatment. The aim of this study was to compare results of retrospective survival analysis of stage III CM patients% treatment from Slovenian national CM register to leading international clinical guidelines. Patients and methods Since 2000, all Slovenian CM patients with primary tumour % TIb are treated at the Institute of Oncology Ljubljana and data are prospectively collected into a national CM registry. A retrospective analysis of 2426 sentinel lymph node (SLN) biopsies and 789 lymphadenectomies performed until 2015 was conducted using Kaplan-Meier survival curves and log-rank tests. Results Positive SLN was found in 519/2426 (21.4%) of patients and completion dissection (CLND) was performed in 455 patients. The 5-year overall survival (OS) of CLND group was 58% vs. 47% of metachronous metastases group (MLNM) (p = 0.003). The 5-year OS of patients with lymph node (LN) metastases and unknown primary site (UPM) was 45% vs. 21% of patients with synchronous LN metastasis. Patients with SLN tumour burden < 0.3 mm had 5-year OS similar to SLN negative patients (86% vs. 85%; p = 0.926). The 5-year OS of patients with burden > 1.0 mm was similar to the MLNM group (49% vs. 47%; p = 0.280). Conclusions Stage III melanoma patients is a heterogeneous group with significant OS differences. CLND after positive SLNB might still remain a method of treatment for selected patients with stage III.
Ključne besede: cutaneous melanoma, surgery treatment, sentinel node biopsy
Objavljeno v DiRROS: 17.07.2024; Ogledov: 229; Prenosov: 104
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82. Infiltrating natural killer cells bind, lyse and increase chemotherapy efficacy in glioblastoma stem-like tumorospheresBarbara Breznik, Meng-Wei Ko, Christopher Tse, Po-Chun Chen, Emanuela Senjor, Bernarda Majc, Anamarija Habič, Nicolas Angelillis, Metka Novak, Vera Župunski, Jernej Mlakar, David Nathanson, Anahid Jewett, 2022, izvirni znanstveni članek Povzetek: Glioblastomas remain the most lethal primary brain tumors. Natural killer (NK) cell-based therapy is a promising immunotherapeutic strategy in the treatment of glioblastomas, since these cells can select and lyse therapy-resistant glioblastoma stem-like cells (GSLCs). Immunotherapy with super-charged NK cells has a potential as antitumor approach since we found their efficiency to kill patient-derived GSLCs in 2D and 3D models, potentially reversing the immunosuppression also seen in the patients. In addition to their potent cytotoxicity, NK cells secrete IFN-γ, upregulate GSLC surface expression of CD54 and MHC class I and increase sensitivity of GSLCs to chemotherapeutic drugs. Moreover, NK cell localization in peri-vascular regions in glioblastoma tissues and their close contact with GSLCs in tumorospheres suggests their ability to infiltrate glioblastoma tumors and target GSLCs. Due to GSLC heterogeneity and plasticity in regards to their stage of differentiation personalized immunotherapeutic strategies should be designed to effectively target glioblastomas.
Ključne besede: glioblastoma, natural killer cells, translational oncology
Objavljeno v DiRROS: 16.07.2024; Ogledov: 238; Prenosov: 208
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83. Upregulation of cathepsin X in glioblastoma : interplay with γ-enolase and the effects of selective cathepsin X inhibitorsBernarda Majc, Anamarija Habič, Metka Novak, Ana Rotter, Andrej Porčnik, Jernej Mlakar, Vera Župunski, Urša Pečar Fonović, Damijan Knez, Nace Zidar, Stanislav Gobec, Janko Kos, Tamara Lah Turnšek, Anja Pišlar, Barbara Breznik, 2022, izvirni znanstveni članek Ključne besede: glioblastoma, cathepsin X, γ-enolase, tumor microenvironment, glioblastoma stem cells, cathepsin X inhibitors
Objavljeno v DiRROS: 16.07.2024; Ogledov: 213; Prenosov: 162
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84. The prevalence of occult ovarian cancer in the series of 155 consequently operated high risk asymptomatic patients : Slovenian population based studyAndreja Gornjec, Sebastjan Merlo, Srdjan Novaković, Vida Stegel, Barbara Gazić, Andraž Perhavec, Ana Blatnik, Mateja Krajc, 2020, izvirni znanstveni članek Povzetek: We assessed the prevalence, localization, type and outcome of occult cancer at risk-reducing salpingo-oophorectomy or salpingectomy (RRSO) in asymptomatic carriers of pathogenic or likely pathogenic BRCA1/2 variants and high-risk BRCA1/2 negative women. Patients and methods. A retrospective analysis of all consecutive gynaecologic preventive surgeries from January 2009 to December 2015 was performed. Participants underwent genetic counselling and BRCA1/2 testing before the procedure. Data on clinical parameters, adjuvant treatment and follow-up were collected and analysed. Results. One hundred and fifty-five RRSO were performed in 110 BRCA1, 35 BRCA2 carriers of pathogenic or likely pathogenic variants and 10 high-risk BRCA1/2 negative women, at the mean age of 48.3 years. Nine occult cancers (9/155, 5.8%) were identified; eight in BRCA1 positive women and one in high-risk BRCA1/2 negative woman. We identified four non-invasive serous intraepithelial tubal carcinomas (3 in BRCA1 carriers and 1 in a high-risk BRCA1/2 negative woman) and five invasive tubo-ovarian high grade serous cancers (all detected in BRCA1 carriers). Only one out of nine patients (11.1%) with occult cancer had a slightly elevated CA-125 value preoperatively. Conclusions. A 5.8% prevalence of occult invasive and noninvasive tubo-ovarian serous cancer after RRSO was found in high risk asymptomatic and screen negative women. We conclude that RRSO should be performed in BRCA1/2 carriers and in high-risk BRCA1/2 negative women. Age of preventive gynaecologic surgery should be carefully planned, taking into account the completion of childbearing age and type of mutation. The results favour the tubal hypothesis of tubal origin of high grade serous ovarian and peritoneal cancer. Cytology result of peritoneal cavity washing was important for the decision making process in determining treatment. Cytology examination should be performed in all cases of RRSO. CA-125 assay did not prove to be an effective screening tool for early cancer detection in our patients.
Ključne besede: risk-reducing salpingo-oophorectomy, occult serous cancer, serous tubal intraepithelial cancer, BRCA1/2 pathogenic or likely pathogenic variant
Objavljeno v DiRROS: 12.07.2024; Ogledov: 193; Prenosov: 74
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85. Dietary iodine intake, therapy with radioiodine, and anaplastic thyroid carcinomaNikola Bešić, Barbara Gazić, 2020, izvirni znanstveni članek Povzetek: Anaplastic thyroid cancer (ATC) is one of the most aggressive tumors. The aim of the study was to determine the correlation between a higher dietary intake of iodine, frequency of ATC and the characteristics of ATC, and to find out how often patients with ATC had a history of radioiodine (RAI) therapy. Patients and methods. This retrospective study included 220 patients (152 females, 68 males; mean age 68 years) with ATC who were treated in our country from 1972 to 2017. The salt was iodinated with 10 mg of potassium iodide/ kg before 1999, and with 25 mg of potassium iodide/kg thereafter. The patients were assorted into 15-year periods: 1972%1986, 1987%2001, and 2002%2017. Results. The incidence of ATC decreased after a higher iodination of salt (p = 0.04). Patients are nowadays older (p = 0.013) and have less frequent lymph node metastases (p = 0.012). The frequency of distant metastases did not change over time. The median survival of patients in the first, second, and third periods was 3, 4, and 3 months, respectively (p < 0.05). The history of RAI therapy was present in 7.7% of patients. Conclusions. The number of patients with a history of RAI therapy did not change statistically over time. The incidence of ATC in Slovenia decreased probably because of higher salt iodination.
Ključne besede: anaplastic thyroid carcinoma, iodination of salt, treatment, survival
Objavljeno v DiRROS: 12.07.2024; Ogledov: 170; Prenosov: 101
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86. Does regular quality control improve the quality of surgery in Slovenian breast cancer screening program?Andraž Perhavec, Sara Milićević, Barbara Perić, Janez Žgajnar, 2020, izvirni znanstveni članek Povzetek: The aim of our study was to evaluate the quality of surgery of Slovenian breast cancer screening program (DORA) using the requested EU standards. Furthermore, we investigated whether regular quality control over the 3-year period improved the quality of surgical management. Patients and methods. Patients who required surgical management within DORA between January 1st, 2016 and December 31st, 2018 were included in the retrospective study. Quality indicators (QIs) were adjusted mainly according to European Society of Breast Cancer Specialists (EUSOMA) and European Breast Cancer Network (EBCN) recommendations. Five QIs for therapeutic and two for diagnostic surgeries were selected. Additionally, variability in achieving the requested QIs among surgeons was analysed. Results. Between 2016 and 2018, 14 surgeons performed 1421 breast procedures in 1398 women. There were 1197 therapeutical (for proven breast cancer) and 224 diagnostic surgical interventions respectively. Overall, the minimal standard was met in two QIs for therapeutic and none for diagnostic procedures. A statistically significant improvement in three QIs for therapeutic and in one QI for diagnostic procedures was observed however, indicating that regular quality control improves the quality of surgery. A high variability in achieving the requested QIs was observed among surgeons, which remained high throughout the study period. Conclusions. Adherence to all selected surgical QIs in patients from screening program is difficult to achieve, especially to those specifically defined for screen-detected lesions. Regular quality control may improve results over time. Reducing the number of surgeons dedicated to breast pathology may reduce variability of management inside the institution.
Ključne besede: breast surgery, mammography, screening program, quality control
Objavljeno v DiRROS: 12.07.2024; Ogledov: 186; Prenosov: 69
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87. Significance of nuclear factor - kappa beta activation on prostate needle biopsy samples in the evaluation of Gleason score 6 prostatic carcinoma indolenceMarko Zupančič, Boris Pospihalj, Snežana Cerović, Barbara Gazić, Primož Drev, Marko Hočevar, Andraž Perhavec, 2020, izvirni znanstveni članek Povzetek: The goal of our study was to find out whether the immunohistochemical expression of nuclear factor-kappa beta (NF-%B) p65 in biopsy samples with Gleason score 3 + 3 = 6 (GS 6) can be a negative predictive factor for Prostate cancer (PCa) indolence. Patients and methods Study was conducted on a retrospective cohort of 123 PCa patients with initial total PSA % 10 ng/ml, number of needle biopsy specimens % 8, GS 6 on biopsy and T1/T2 estimated clinical stage who underwent laparoscopic radical prostatectomy and whose archived formalin-fixed and paraffin-embedded (FFPE) prostate needle biopsy specimens were used for additional immunohistochemistry staining for detection of NF-%B p65. Both cytoplasmic and nuclear NF-%B p65 expression in biopsy cores with PCa were correlated with postoperative pathological stage, positive surgical margins, GS and biochemical progression of disease. Results After follow-up of 66 months, biochemical progression (PSA % 0.2 ng/ml) occurred in 6 (5.1%) patients, 3 (50%) with GS 6 and 3 (50%) with GS 7 after radical prostatectomy. Both cytoplasmic and nuclear NF-%B p65 expressions were not significantly associated with pathological stage, positive surgical margin and postoperative GS. Patients with positive cytoplasmic NF-kB reaction had significantly more frequent biochemical progression than those with negative cytoplasmic NF-kB reaction with PSA 0.2 ng/ml as cutoff point (p = 0.015) and a trend towards more biochemical progression with PSA % 0.05 ng/ml as cutoff point (p = 0.068). Conclusions Cytoplasmic expression of NF-%B is associated with more biochemical progression and might be an independent prognostic factor for recurrence-free survival (RFS), but further studies including larger patient cohorts are needed to confirm these initial results.
Ključne besede: prostate cancer, needle biopsy, nuclear factor-kappa beta, Gleason
Objavljeno v DiRROS: 12.07.2024; Ogledov: 209; Prenosov: 113
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88. Anti-vimentin nanobody decreases glioblastoma cell invasion in vitro and in vivoAlja Zottel, Metka Novak, Neja Šamec, Bernarda Majc, Sara Colja, Mojca Katrašnik, Miloš Vittori, Barbara Hrastar, Ana Rotter, Andrej Porčnik, Tamara Lah Turnšek, Radovan Komel, Barbara Breznik, Ivana Jovchevska, 2023, izvirni znanstveni članek Povzetek: Purpose: Glioblastoma (GBM) is the most common primary brain tumour and one of the deadliest cancers. In addition to late diagnosis and inadequate treatment, the extremely low survival rate is also due to the lack of appropriate therapeutic biomarkers and corresponding therapeutic agents. One of the potential therapeutic biomarkers is the intermediate filament vimentin, which is associated with epithelial-mesenchymal transition (EMT). The purpose of this study was to analyse the effect of the anti-vimentin nanobody Nb79 on cell invasion in vitro and in vivo. To further our understanding of the mechanism of action, we investigated the association between Nb79 and EMT in GBM and GBM stem cells by analysing the expression levels of key EMT-related proteins. Methods: The expression of vimentin in glioma tissues and cells was determined by RT-qPCR. An invasion assay was performed on differentiated glioblastoma cell line U-87 MG and stem cell line NCH421k in vitro as well as in vivo in zebrafish embryos. The effect of Nb79 on expression of EMT biomarkers beta-catenin, vimentin, ZEB-1 and ZO1 was determined by Western blot and immunocytochemistry. Results: Our study shows that vimentin is upregulated in glioblastoma tissue compared to lower grade glioma and non-tumour brain tissue. We demonstrated that treatment with Nb79 reduced glioblastoma cell invasion by up to 64% in vitro and up to 21% in vivo. In addition, we found that the tight junction protein ZO-1 had higher expression on the cell membrane, when treated with inhibitory anti-vimentin Nb79 compared to control. Conclusion: In conclusion, our results suggest that anti-vimentin nanobody Nb79 is a promising tool to target glioblastoma cell invasion.
Ključne besede: glioblastoma, vimentin, nanobody
Objavljeno v DiRROS: 12.07.2024; Ogledov: 203; Prenosov: 158
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89. Advances in the management of craniopharyngioma in children and adultsMojca Jensterle Sever, Sončka Jazbinšek, Roman Bošnjak, Mara Popović, Lorna Zadravec-Zaletel, Tina Vipotnik-Vesnaver, Barbara Faganel Kotnik, Primož Kotnik, 2019, pregledni znanstveni članek Povzetek: Childhood and adult-onset craniopharyngioma is a rare embryogenic tumor of the sellar, suprasellar, and parasellar region. Survival rates are high; however, tumor location and treatment sequalae including endocrine deficits, visual impairment, metabolic complications, cognitive and psychosocial deficits can significantly impair patient%s quality of life. There is considerable controversy regarding the optimal management of craniopharyngiomas. Subtotal resection of the tumor followed by targeted irradiation to avoid further hypothalamic damage is currently indicated. Novel insights in the tumor%s molecular pathology present the possibility for targeted therapy possibly decreasing the rate and severity of treatment-associated morbidity. Conclusions. Craniopharyngioma should be seen as a chronic disease. To achieve optimal outcomes a multidisciplinary team of specialized neurosurgeons, neuro-radiologists, neuro-oncologists, pathologists and endocrinologists should be involved in the diagnosis, planning of the surgery, irradiation and long-term follow-up.
Ključne besede: craniopharyngioma, hypopituitarism, metabolic syndrome
Objavljeno v DiRROS: 09.07.2024; Ogledov: 237; Prenosov: 127
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90. Diagnostic accuracy of haemophilia early arthropathy detection with ultrasound (HEAD-US) : a comparative magnetic resonance imaging (MRI) studyDomen Plut, Barbara Faganel Kotnik, Irena Preložnik Zupan, Damjana Ključevšek, Gaj Vidmar, Žiga Snoj, Carlo Martinoli, Vladka Salapura, 2019, izvirni znanstveni članek Ključne besede: haemophilia, haemophilic arthropathy, magnetic resonance imaging
Objavljeno v DiRROS: 09.07.2024; Ogledov: 220; Prenosov: 88
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