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Povzetek: Rak neznanega izvora (RNI) je opredeljen kot karcinom ali nediferencirana neoplazma, pri kateri z naborom standardnih diagnostičnih postopkov ni mogoče odkriti izvornega mesta bolezni. Tradicionalno RNI delimo v dve podskupini, pri čemer le približno 15 % primerov predstavlja prognostično ugodno skupino. Velika večina bolnikov spada v prognostično neugodno skupino in ima ob prvi prezentaciji obsežno breme bolezni. Možnosti zdravljenja so omejene, izidi bolnikov, zdravljenih z empirično kemoterapijo (KT) s platino ali taksani, pa so še vedno slabi, srednje celokupno preživetje je manj kot 10 mesecev. Za mnoge bolnike ostaja optimalna izbira najboljše možno podporno zdravljenje. Novi pristopi k obravnavi teh bolnikov se zdijo obetavni in so temeljit premik v paradigmi zdravljenja RNI; od zdravljenja, specifičnega za organ/tkivo, k zdravljenju, usmerjenemu na posameznega bolnika, ki temelji na genomskih spremembah njegovega tumorja. Prispevek povzema trenutne dokaze o uporabi vsakega od teh pristopov. Predstavljeno je tudi zdravljenje treh bolnikov z neugodnim RNI.
Ključne besede: rak neznanega izvora, molekularne značilnosti, biološki označevalci
Objavljeno v DiRROS: 26.07.2024; Ogledov: 18; Prenosov: 4
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Povzetek: The aim of the study was to evaluate the independent prognostic role of PIK3CA activating mutationsand an association between PIK3CA activating mutations and efficacy of adjuvant endocrine therapy (ET) in patientswith operable invasive lobular carcinoma (ILC).Patients and methods.A single institution study of patients with early-stage ILC treated between 2003 and 2008 wasperformed. Clinicopathological parameters, systemic therapy exposure and outcomes (distant metastasis-free sur-vival [DMFS] and overall survival [OS]) were collected based on presence or absence of PIK3CA activating mutationin the primary tumor determined using a quantitative polymerase chain reaction (PCR)-based assay. An associationbetween PIK3CA mutation status and prognosis in all patient cohort was analyzed by Kaplan-Meier survival analysis,whereas an association between PIK3CA mutation and ET was analyzed in estrogen receptors (ER) and/or progester-one receptors (PR)-positive group of our patients by the Cox proportional hazards model.Results. Median age at diagnosis of all patients was 62.8 years and median follow-up time was 10.8 years. Among365 patients, PIK3CA activating mutations were identified in 45%. PIK3CA activating mutations were not associatedwith differential DMFS and OS (p = 0.36 and p = 0.42, respectively). In patients with PIK3CA mutation each year oftamoxifen (TAM) or aromatase inhibitor (AI) decreased the risk of death by 27% and 21% in comparison to no ET, re-spectively. The type and duration of ET did not have significant impact on DMFS, however longer duration of ET hada favourable impact on OS.Conclusions. PIK3CA activating mutations are not associated with an impact on DMFS and OS in early-stage ILC.Patients with PIK3CA mutation had a statistically significantly decreased risk of death irrespective of whether theyreceived TAM or an AI.
Ključne besede: invasive lobular carcinoma, PIK3CA mutation, endocrine therapy
Objavljeno v DiRROS: 25.07.2024; Ogledov: 22; Prenosov: 4
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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: 63; Prenosov: 20
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Povzetek: BRAF, NRAS and c-KIT mutations are characteristics of tumour tissues that influence on treatment decisions in metastatic melanoma patients. Mutation frequency and their correlation with histological characteristics in Slovenian population have not been investigated yet. Patients and methods. In our retrospective analysis we analysed mutational status of BRAF, NRAS and c-KIT in 230 pathological samples of patients who were intended to be treated with systemic therapy due to metastatic disease at the Institute of Oncology Ljubljana between 2013 and 2016. We collected also histological characteristics of primary tumours and clinical data of patients and correlated them with mutational status of tumour samples. Results. The study population consisted of 230 patients with a mean age 59 years (range 25%85). 141 (61.3%) were males and 89 (38.7%) females. BRAF mutations were identified in 129 (56.1%), NRAS in 31 (13.5%) and c-KIT in 3 (1.3%) tissue samples. Among the 129 patients with BRAF mutations, 114 (88.4%) patients had V600E mutation and 15 (11.6%) had V600K mutation. Patients with BRAF mutations tended to be younger at diagnosis (52 vs. 59 years, p < 0.05), patients with NRAS mutations older (61 vs. 55 years, p < 0.05). Number of c-KIT mutations were too low for any statistical correlation, but there was one out of 3 melanoma located in mucus membranes. Conclusions. The analysis detected high rate of BRAF mutations, low NRAS mutations and low c-KIT mutations compared to previously published studies in Europe and North America. One of the main reasons for this observation is specific characteristics of study population.
Ključne besede: BRAF, NRAS, c-KIT, melanoma
Objavljeno v DiRROS: 10.06.2024; Ogledov: 123; Prenosov: 62
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Povzetek: Background. Clonality determination in patients with lymphoproliferative disorders can improve the final diagnosis.The aim of our study was to evaluate the applicative value of standardized BIOMED-2 gene clonality assay protocolsfor the analysis of clonality of lymphocytes in a group of different lymphoid proliferations.Materials and methods. With this purpose, 121 specimens from 91 patients with suspected lymphoproliferationssubmitted for routine diagnostics from January to December 2011 were retrospectively analyzed. According to thefinal diagnosis, our series comprised 32 cases of B-cell lymphomas, 38 cases of non-Hodgkins T-cell lymphomas and51 cases of reactive lymphoid proliferations. Clonality testing was performed using the BIOMED-2 clonality assays.Results. The determined sensitivity of the TCR assay was 91.9%, while the sensitivity of the IGH assay was 74.2%. Thedetermined specificity of the IGH assay was 73.3% in the group of lymphomas and 87.2% in the group of reactivelesions. The determined specificity of the TCR assay was 62.5% in the group of lymphomas and 54.3% in the group ofreactive lesions.Conclusions. In the present study, we confirmed the utility of standardized BIOMED-2 clonality assays for the detectionof clonality in a routine diagnostical setting of non-Hodgkins lymphomas. Reactions for the detection of thecomplete IGH rearrangements and reactions for the detection of the TCR rearrangements are a good choice forclonality testing of a wide range of lymphoid proliferations and specimen types while the reactions for the detectionof incomplete IGH rearrangements have not shown any additional diagnostic value.
Ključne besede: Biomed-2, clonality analysis, lymphomas, IGH rearrangement, TCR rearrangement
Objavljeno v DiRROS: 11.04.2024; Ogledov: 263; Prenosov: 72
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