Background: Hürthle cell thyroid carcinoma (HCTC) is a rare disease. It is believed that it is more aggressive than follicular thyroid carcinoma. The aim of our study was to identify factors associated with disease-specific and disease-free survival. Methods: Altogether, 108 patients with HCTC (26 male, 82 female; median age 62 years; range 19%87 years) treated at our Institute from 1972 to 2011 were included in the present retrospective study. Data on age, clinical and histopathological factors, tumor stage, recurrence, disease-free and disease-specific survival were collected. Univariate analysis was used to identify factors associated with disease-specific survival. Cox%s multivariate regression model was used to identify independent prognostic factors for disease-specific survival. Results: The follow-up period was 1 to 337 (median 105) months. Of 108 patients, 12 (11%) had distant and 8 (7%) had locoregional metastases before primary treatment. Recurrence was diagnosed in 26 cases (24%): locoregional, distant, and both locoregional and distant in 12, 11, and 3 cases, respectively. The 5-year, 10-year, and 20-year disease-specific survival were 96%, 88%, and 67%, respectively. Independent prognostic factors for disease-specific survival were: age of patients at diagnosis, distant metastases and residual tumor after surgery. Conclusion: Long disease-specific survival was found in patients with HCTC younger than 45 years of age without distant metastases and without residual tumor after surgery.
COBISS.SI-ID: 1899643
BACKGROUND: Sentinel node biopsy (SNB) is the "gold standard" in axillary staging in clinically node-negative breast cancer patients. However, axillary treatment is undergoing a paradigm shift and studies are being conducted on whether SNB may be omitted in low-risk patients. The purpose of this study was to evaluate the risk factors for axillary metastases in breast cancer patients with negative preoperative axillary ultrasound. METHODS: A total of 1,395 consecutive patients with invasive breast cancer and SNB formed the original patient series. A univariate analysis was conducted to assess risk factors for axillary metastases. Binary logistic regression analysis was conducted to form a predictive model based on the risk factors. The predictive model was first validated internally in a patient series of 566 further patients and then externally in a patient series of 2,463 patients from four other centers. All statistical tests were two-sided. RESULTS: A total of 426 of the 1,395 (30.5 %) patients in the original patient series had axillary lymph node metastases. Histological size (P ( 0.001), multifocality (P ( 0.001), lymphovascular invasion (P ( 0.001), and palpability of the primary tumor (P ( 0.001) were included in the predictive model. Internal validation of the model produced an area under the receiver operating characteristics curve (AUC) of 0.731 and external validation an AUC of 0.79. CONCLUSIONS: We present a predictive model to assess the patient-specific probability of axillary lymph node metastases in patients with clinically node-negative breast cancer. The model performs well in internal and external validation. The model needs to be validated in each center before application to clinical use.
COBISS.SI-ID: 1937531
Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is the most common undifferentiated ovarian malignancy in women under 40 years of age. We sequenced the exomes of six individuals from three families with SCCOHT. After discovering segregating deleterious germline mutations in SMARCA4 in all three families, we tested DNA from a fourth affected family, which also carried a segregating SMARCA4 germline mutation. All the familial tumors sequenced harbored either a somatic mutation or loss of the wild-type allele. Immunohistochemical analysis of these cases and additional familial and non-familial cases showed loss of SMARCA4 (BRG1) protein in 38 of 40 tumors overall. Sequencing of cases with available DNA identified at least one germline or somatic deleterious SMARCA4 mutation in 30 of 32 cases. Additionally, the SCCOHT cell line BIN-67 had biallelic deleterious mutations in SMARCA4. Our findings identify alterations in SMARCA4 as the major cause of SCCOHT, which could lead to improvements in genetic counseling and new treatment approaches.
COBISS.SI-ID: 1744251
Eight predictive models assessing the risk of nonsentinel nodes (nonSN) involvement in patients with breast cancer sentinel node (SN) metastasis were tested in a multiinstitutional setting. Data of 200 consecutive patients with metastatic SNs and axillary lymph node dissection from each of the 5 participating centres were entered into the selected nonSN metastasis predictive tools. There were significant differences between centres in the distribution of most parameters used in the predictive models. There were also significant differences in the proportion of cases classified as having low risk of nonSN metastasis. Each predictive tool used in clinical practice for patient and physician decision on further axillary treatment of SN positive patients may require individual institutional validation; such validation may reveal different predictive tools to be the best in different institutions.
COBISS.SI-ID: 1467003
Background: Despite surgical treatment, chemotherapy, and/or radiotherapy, the vast majority of patients with anaplastic thyroid carcinoma (ATC) have a dismal prognosis. Better knowledge of the frequency of metastases to different sites might help us to perform the appropriate diagnostic tests before treatment and during the course of the disease. The aim of this study was to determine the frequency of metastases from ATC in different sites as found at autopsy. Methods: Altogether, 205 patients were treated for ATC at our institute during the years 19722008. Autopsy was performed in 45 cases (30 females, 15 males; median age 66 years). The relative frequencies of metastases in different sites were analyzed using descriptive statistics. Results: Altogether, 41 cases (91%) had metastases at autopsy. The most common sites of metastases were the lungs (78%), intrathoracic lymph nodes (58%), neck lymph nodes (51%), pleura (29%), adrenal glands (24%), liver (20%), brain (18%), heart (18%), and retroperitoneal lymph nodes (18%). Less common sites of distant metastases were the pericardium (13%), bones (13%), kidneys (13%), mesentery or peritoneum (13%), skin (9%), pancreas (4%), stomach (4%), diaphragm (4%), pituitary gland (2%), ovary (2%), jejunum (2%), axillary lymph nodes (2%), and gingival mucosa (2%). Both distant and regional metastases were present in 23 cases, while only distant metastases were present in 18 cases. An extensive local infiltration of the primary tumor was found in 76% of the cases. The total number of the involved organs and lymph node basins were 123 and 58, respectively. The mean number of metastatic sites was 4.022.75. Lung metastases were present in 34 of 38 (89%) of our patients who had distant metastases found at autopsy. Of these 34 patients, 27 were known to have lung metastases when they were alive.
COBISS.SI-ID: 1507195
The combined efficacy analysis of the TEXT and SOFT trials showed a significant disease-free survival benefit with exemestane plus ovarian function suppression (OFS) compared with tamoxifen plus OFS. We present patient-reported outcomes from these trials. METHODS: Between Nov 7, 2003, and April 7, 2011, 4717 premenopausal women with hormone-receptor positive breast cancer were enrolled in TEXT or SOFT to receive unmasked adjuvant treatment with 5 years of exemestane plus OFS or tamoxifen plus OFS. Gonadotropin-releasing hormone analogue triptorelin, bilateral oophorectomy, or bilateral ovarian irradiation were used to achieve OFS. Chemotherapy use was optional. Randomisation with permuted blocks was done with the International Breast Cancer Study Group's internet-based system and was stratified by chemotherapy use and status of lymph nodes. Patients completed a quality of life (QoL) form comprising several global and symptom indicators at baseline, every 6 months for 24 months, and then every year during years 3 to 6. Differences in the change of QoL from baseline between the two treatments were tested at 6 months, 24 months, and 60 months with mixed-models for repeated measures for each trial with and without chemotherapy and overall. The analysis was by intention to treat. At the time of analysis, the median follow-up was 5%7 years (IQR 3%7-6%9); treatment and follow-up of patients continue. The trials are registered with ClinicalTrials.gov, as NCT00066703 (TEXT) and NCT00066690 (SOFT). FINDINGS: Patients on tamoxifen plus OFS were more affected by hot flushes and sweats over 5 years than were those on exemestane plus OFS, although these symptoms improved. Patients on exemestane plus OFS reported more vaginal dryness, greater loss of sexual interest, and difficulties becoming aroused than did patients on tamoxifen plus OFS; these differences persisted over time. An increase in bone or joint pain was more pronounced, particularly in the short term, in patients on exemestane plus OFS than patients on tamoxifen plus OFS. Changes in global QoL indicators from baseline were small and similar between treatments over the 5 years. INTERPRETATION: Overall, from a QoL perspective, there is no strong indication to favour either exemestane plus OFS or tamoxifen plus OFS. The distinct effects of the two treatments on the burden of endocrine symptoms need to be addressed with patients individually.
COBISS.SI-ID: 2063483
Serial quantification of BCR–ABL1 mRNA is an important therapeutic indicator in chronic myeloid leukaemia, but there is a substantial variation in results reported by different laboratories. To improve comparability, an internationally accepted plasmid certified reference material (CRM) was developed according to ISO Guide 34:2009. Fragments of BCR–ABL1 (e14a2 mRNA fusion), BCR and GUSB transcripts were amplified and cloned into pUC18 to yield plasmid pIRMM0099. Six different linearised plasmid solutions were produced with the following copy number concentrations, assigned by digital PCR, and expanded uncertainties: 1.08±0.13 × 106, 1.08±0.11 × 105, 1.03±0.10 × 104, 1.02±0.09 × 103, 1.04±0.10 × 102 and 10.0±1.5 copies/µl. Two suitability studies performed by 63 BCR–ABL1 testing laboratories demonstrated that this set of 6 plasmid CRMs can help to standardise a number of measured transcripts of e14a2 BCR–ABL1 and three control genes (ABL1, BCR and GUSB). The set of six plasmid CRMs is distributed worldwide by the Institute for Reference Materials and Measurements (Belgium) and its authorised distributors https://ec.europa.eu/jrc/en/referencematerials/catalogue/; CRM code ERM-AD623a-f).
COBISS.SI-ID: 31742169
In the monograph on the classification of tumors of endocrine organs of the World Health Organization, Janez Lamovec co-authored the chapter on angiosarkoma. This book allows for proper classification of tumors in diagnosis and is used by all pathologists in the world.
COBISS.SI-ID: 2728827
We collaborated in the population based registry about the treatment regimen and the effect of treatment of adult patients with Philadelphia chromosomal BCR-ABL1 + chronic leukemia. Patients were followed from 12-60 months. Imatinib was the first treatment agent in 80% of patients, and tyrosine kinase inhibitor was used in 17% of patients. The annual, 24-month and 30-month survival of patients was 97%, 94% and 92%. The results of this study will be the basis for comparing the effectiveness of future therapies.
COBISS.SI-ID: 4142764
One of the editors of the atlas for diagnosis of tumors in the pediatric population from small bioptic samples is Živa Pohar-Marinšek. Atlas is an important diagnostic tool for cytologists and pathologists in the appropriate classification of patients with this pathology.
COBISS.SI-ID: 2843259