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Szolnok, Hungary

Pritchard K.I.,University of Toronto | Burris III H.A.,Sarah Cannon Research Institute | Ito Y.,Cancer Institute Hospital | Rugo H.S.,University of California at San Francisco | And 16 more authors.
Clinical Breast Cancer | Year: 2013

Background Postmenopausal women with hormone receptor-positive (HR +) breast cancer in whom disease progresses or there is recurrence while taking a nonsteroidal aromatase inhibitor (NSAI) are usually treated with exemestane (EXE), but no single standard of care exists in this setting. The BOLERO-2 trial demonstrated that adding everolimus (EVE) to EXE improved progression-free survival (PFS) while maintaining quality of life when compared with EXE alone. Because many women with HR+ advanced breast cancer are elderly, the tolerability profile of EVE plus EXE in this population is of interest. Patients and Methods BOLERO-2, a phase III randomized trial, compared EVE (10 mg/d) and placebo (PBO), both plus EXE (25 mg/d), in 724 postmenopausal women with HR+ advanced breast cancer recurring/progressing after treatment with NSAIs. Safety and efficacy data in elderly patients are reported at 18-month median follow-up. Results Baseline disease characteristics and treatment histories among the elderly subsets (≥ 65 years, n = 275; ≥ 70 years, n = 164) were generally comparable with younger patients. The addition of EVE to EXE improved PFS regardless of age (hazard ratio, 0.59 [≥ 65 years] and 0.45 [≥ 70 years]). Adverse events (AEs) of special interest (all grades) that occurred more frequently with EVE than with PBO included stomatitis, infections, rash, pneumonitis, and hyperglycemia. Elderly EVE-treated patients had similar incidences of these AEs as did younger patients but had more on-treatment deaths. Conclusion Adding EVE to EXE offers substantially improved PFS over EXE and was generally well tolerated in elderly patients with HR + advanced breast cancer. Careful monitoring and appropriate dose reductions or interruptions for AE management are recommended during treatment with EVE in this patient population. © 2013 Elsevier Inc. All rights reserved.

Ferenci P.,Medical University of Vienna | Aires R.,Federal University of Goais | Beavers K.L.,NC Associates | Curescu M.,Victor Babes University of Medicine and Pharmacy Timisoara | And 12 more authors.
Hepatology International | Year: 2014

Purpose: Advanced liver fibrosis is a negative predictor of virologic response in genotype 1 chronic hepatitis C (CHC) patients. Biopsy, however, is invasive, costly, and carries some risk of complications. Methods: Using data from the prospective, international cohort study PROPHESYS, we assessed two alternative noninvasive measures of fibrosis, the FIB-4 and AST-to-platelet ratio index (APRI), to predict virologic response in CHC patients. Results: CHC genotype 1, monoinfected, treatment-naive patients prescribed peginterferon alfa-2a (40 KD)/ribavirin in accordance with country-specific legal and regulatory requirements and who had baseline METAVIR, FIB-4, and APRI scores (N = 1,592) were included in this analysis. Patients were stratified according to the baseline METAVIR, FIB-4, or APRI score to assess virologic response [hepatitis C virus (HCV) RNA <50 IU/mL] by week 4 of treatment (rapid virologic response) and 24 weeks after untreated follow-up ]sustained virologic response (SVR)]. Baseline predictors of SVR were explored by multiple logistic regression, and the strength of the association between each fibrosis measure and SVR was evaluated. Both FIB-4 and APRI scores increased with increasing levels of biopsy-assessed fibrosis. The association between FIB-4 and SVR (p < 0.1 × 10-30) was stronger than that between METAVIR (p = 3.86 × 10-13) or APRI (p = 5.48 × 10-6) and SVR. Baseline factors significantly associated with SVR included male gender, lower HCV RNA, lower FIB-4 score, no steatosis, and higher alanine aminotransferase ratio. Conclusion: The FIB-4 index provides a valuable, noninvasive measure of fibrosis and can be used to predict virologic response in patients treated with peginterferon alfa-2a (40 KD)/ribavirin. © 2013 Asian Pacific Association for the Study of the Liver.

Kiss O.,Semmelweis University | Tokes A.-M.,Progression | Spisak S.,Semmelweis University | Szilagyi A.,Szent Gyorgy Hospital | And 4 more authors.
Pathology and Oncology Research | Year: 2014

Adenoid cystic carcinoma (ACC) is a malignant tumor of the salivary glands but identical tumors can also arise from the breast. Despite their similar histomorphological appearance the salivary gland- and the breast-derived forms differ in their clinical features: while ACC of the salivary glands (sACC) have an agressive clinical course, the breast-derived form (bACC) shows a very favourable clinical outcome. To date no exact molecular alterations have yet been identified which would explain the diverse clinical features of the ACCs of different origin. In our pilot experiment we investigated the post-transcriptional features of ACC cases by performing microRNA-profiling on 2-2 bACC and sACC tissues and on 1-1 normal breast and salivary gland tissue. By comparing the microRNA-profiles of the investigated samples we identified microRNAs which were expressed differently in bACC and sACC cases according to their normal controls: 7 microRNAs were overexpressed in sACC cases and downexpressed in bACC tumors (let-7b, let-7c, miR-17, miR-20a, miR-24, miR-195, miR-768-3) while 9 microRNAs were downexpressed in sACC cases and overexpressed in bACC tissues (let-7e, miR-23b, miR-27b, miR-193b, miR-320a, miR-320c, miR-768-5p, miR-1280 and miR-1826) relative to their controls. We also identified 8 microRNAs which were only expressed in sACCs and one microRNA (miR-1234) which was only absent in sACC cases. By target predictor online databases potential targets of the these microRNAs were detected to identify genes that may play central role in the diverse cinical outcome of bACC and sACC cases. © 2014, Arányi Lajos Foundation.

Antalfi B.,Diosgyori Vasgyari Hospital | Pongracz E.,Hetenyi Geza Hospital | Csiki Z.,Debrecen University | Mezei Z.A.,Debrecen University | And 2 more authors.
International Journal of Laboratory Hematology | Year: 2013

Blood coagulation factor XIII (FXIII) plays a key role in the protection of fibrin clot against fibrinolysis, in the cross-linking of fibrin and its mechanical strength. The role of the FXIII-A subunit Val34Leu polymorphism with fatal primary intracerebral hemorrhages (PICH) has not been studied. We evaluated retrospectively the prevalence of this polymorphism in stroke patients with fatal PICH and population control matched for age and gender. The prevalence of this polymorphism was determined for patients with fatal PICH (n = 98, female/male: 41/57) and controls. DNA was obtained from peripheral white blood cells in case of controls and from paraffin-embedded tissue sections in case of fatal PICH. The odds for increasing the risk of PICH against the control group were 5.429, 3.286, and 7.661 for total, female, and male patients, respectively. The Leu34Leu homozygous variant of the FXIII Val34Leu polymorphism significantly increased the risk of fatal PICH stroke in men. © 2012 Blackwell Publishing Ltd.

Csiszko A.,Debrecen University | Herr G.,Hetenyi Geza Hospital | Sz. Kiss S.,Debrecen University | Hallay J.,Debrecen University | And 2 more authors.
Journal of Minimal Access Surgery | Year: 2013

Lymphangioleiomyomatosis with tuberous sclerosis complex is a rare disease. One of the most frequent complications of lymphangioleiomyomatosis is pleural effusion (chylothorax) wich can be treated with the use of VATS. Authors report a case of pulmonary lymphangioleiomyomatosis in a 56-year-old female patient with tuberous sclerosis complex with an 8-week history of recurrent chylothorax, dyspnea and debilitating weakness. By CT scan a flat tissue proliferation was seen in the site of the thoracic duct and it was supposed to be the reason for the pleural effusion. A VATS resection of this laesion and ligation of the thoracic duct was performed successfully. Chylothorax is often associated with pulmonary lymphangioleiomyomatosis. Lymphangioleiomyomatosis combined with tuberous sclerosis complex is extremely rare. In case of chylothorax VATS treatment is successful and may be the first choice. Copyright © Journal of Minimal Access Surgery 2013.

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