Elona Juozaityte

Lack of association between gene polymorphisms of Angiotensin converting enzyme, Nod-like receptor 1, Toll-like receptor 4, FAS/FASL and the presence of Helicobacter pylori-induced premalignant gastric lesions and gastric cancer in Caucasians

BackgroundSeveral polymorphisms of genes involved in the immunological recognition of Helicobacter pylori and regulating apoptosis and proliferation have been linked to gastric carcinogenesis, however reported data are partially conflicting. The aim of our study was to evaluate potential associations between the presence of gastric cancer (GC) and high risk atrophic gastritis (HRAG) and polymorphisms of genes encoding Angiotensin converting enzyme (ACE), Nod-like receptor 1 (NOD1), Toll-like receptor 4 (TLR4) and FAS/FASL.MethodsGene polymorphisms were analyzed in 574 subjects (GC: n = 114; HRAG: n = 222, controls: n = 238) of Caucasian origin. ACE I/D (rs4646994), NOD1 796G>A (rs5743336), TLR4 3725G>C (rs11536889), FAS 1377G>A (rs2234767), FAS 670A>G (rs1800682) and FASL 844T>C (rs763110) were genotyped by different PCR approaches and restriction fragment length polymorphism analysis.ResultsFrequencies of genotypes in our study are similar to the data reported on subjects of Caucasian ethnicity. There was a tendency for NOD1 796G/G genotype to be associated with increased risk of HRAG (62.4% vs. 54.5% in controls, p = 0.082). FAS 670G/G genotype was more frequent in HRAG when compared to controls, 23.9% and 17.2% respectively, however it failed to reach significance level (p = 0.077). We did not find any significant associations for all polymorphisms in relation to GC or HRAG. NOD1 796G>A and TLR4 3725G>C gene polymorphisms were also not associated with Helicobacter pylori infection.ConclusionsACE, NOD1, TRL4 and FAS/FASL gene polymorphisms are not linked with gastric carcinogenesis in Caucasians, and therefore they should not be considered as potential biomarkers for identifying individuals with higher risk for GC.

Comparison of adjuvant and neoadjuvant chemotherapy in the management of advanced ovarian cancer: a retrospective study of 574 patients

BackgroundThere is a lack of clinical data on the validity of neoadjuvant chemotherapy in the treatment of ovarian cancer. The aim of this study was to compare the impact of the adjuvant and neoadjuvant chemotherapy regimens on the clinical outcomes in patients with advanced ovarian cancer.MethodsWe performed a retrospective analysis of 574 patients with advanced ovarian cancer admitted to four Lithuanian oncogynaecology departments during 1993–2000. The conventional combined treatment of cytoreductive surgery and platinum-based chemotherapy was applied to both the group that underwent neoadjuvant chemotherapy (n = 213) and to the control group (n = 361). The selection criterion for neoadjuvant chemotherapy was large extent of the disease. Overall and progression-free survival rates and survival medians were calculated using life tables and the Kaplan-Meier method.ResultsThere was no difference in median overall survival between stage III patients treated with adjuvant chemotherapy and neoadjuvant chemotherapy (25.9 months vs. 29.3 months, p = 0.2508) and stage IV patients (15.4 months vs. 14.9 months, p = 0.6108). Similarly, there was no difference in median progression-free survival between stage III patients treated with adjuvant chemotherapy and neoadjuvant chemotherapy (15.7 months vs. 17.5 months, p = 0.1299) and stage IV patients (8.7 months vs. 8.2 months, p = 0.1817). There was no difference in the rate of the optimal cytoreductive surgery between patients who underwent the neoadjuvant chemotherapy and patients primarily treated with surgery (n = 134, 63% vs. n = 242, 67%, respectively).ConclusionThere was no difference in progression-free or overall survival and in the rate of optimal cytoreductive surgery between the neoadjuvant and adjuvant chemotherapy groups despite the fact that patients receiving neoadjuvant chemotherapy had a more extensive disease. Multivariate analysis failed to prove that neoadjuvant chemotherapy could be considered as an independent prognostic factor for survival, and the findings need to be investigated in the future prospective randomised studies.

Retrospective analysis of the impact of platinum dose reduction and chemotherapy delays on the outcomes of stage III ovarian cancer patients

BackgroundOvarian cancer is a common gynaecological malignancy still remaining a challenge to treat. The objective of this study was to evaluate the impact of platinum dose reduction and chemotherapy delays on progression free survival and overall survival in patients with stage III ovarian cancer and to analyze reasons for such chemotherapy scheme modifications.MethodsMedical records of patients with FIGO stage III ovarian cancer were reviewed. Inclusion criteria involved FIGO stage III epithelial ovarian carcinoma; cytoreductive surgery performed and 6 courses of platinum-based chemotherapy completed; no neoadjuvant chemotherapy applied; and no history of previous malignancies. Progression free survival and overall survival were analyzed using Kaplan-Meier and Cox proportional hazards models.ResultsSignificant 3.3 times higher death risk in patients who experienced only chemotherapy delays compared with patients who did not experience any chemotherapy scheme modifications was established (HR = 3.3, 95% Cl: 1.2 – 8.5, p = 0.016). Increased death risk in patients who experienced only chemotherapy delays compared with patients who experienced both chemotherapy delays and platinum dose reduction was also established (HR = 2.3, 95% Cl: 1.1 – 4.8, p = 0.021). Main reasons for chemotherapy scheme modifications (in decreasing order) were the following: neutropenia, modifications with no objective medical reasons, renal disorders, anaemia, poor performance status, gastrointestinal symptoms and neuropathy. Overall survival in patients who experienced chemotherapy scheme modifications with no objective medical reasons was non-inferior than in patients who did not experience any chemotherapy scheme modifications.ConclusionsChemotherapy delays in patients with FIGO stage III ovarian cancer caused lower overall survival. The most common reason for chemotherapy scheme modifications was neutropenia.

A population‐based single nucleotide polymorphism array analysis of genomic aberrations in younger adult acute lymphoblastic leukemia patients

Adult acute lymphoblastic leukemia (ALL) is characterized by a high frequency of abnormal karyotypes some of which are related to outcome. Single nucleotide polymorphism (SNP) array analysis provides a highly sensitive platform to detect large and small genomic aberrations. SNP array profiling data in adult ALL are limited and further systematic studies of this patient group are needed. We performed a population‐based SNP array analysis of genomic aberrations and their influence on survival in 66 Lithuanian 18–65 year old ALL patients diagnosed between 2007 and 2013. Most aberrations were detected in chromosome arm 9p, chromosome arm 6q, chromosome arm 13q, and chromosome 17. The recurrently targeted copy number abnormalities involved several leukemia‐related genes—CDKN2A/B, MLL, IKZF1, PAX5, RB1, TP53, and ETV6. We identified several new recurrent aberrations with possible new target genes: SMARCA4 in 19p13.2, RNASEL in 1q25.3, ARHGEF12 in 11q23.3, and LYL1 in 19p13.2. Aberrations in chromosome 13 and the RB1 gene as well as CDKN2A/B gene status were related to the outcome.

Thrombotic risk assessment in 185 WHO-defined essential thrombocythemia patients: single center experience

Thrombosis risk in essential thrombocythemia (ET) patients can be assessed using different prognostic systems. Conventional risk factors include age more than 60 years and history of previous thrombosis. In addition, other factors such as JAK2 V617F mutations, cardiovascular risk factors, leukocytosis more than 11 × 109/l, thrombophilic factors and platelet count more than 1500 × 109/l are used in different hematology centers as high-risk features for thrombosis. Our study compared different risk model groups for thrombosis in 185 WHO-defined ET patients at the Hospital of Lithuanian University of Health Sciences Kaunas Klinikos. We found that patient distribution in low, intermediate- and high-risk groups varies using different risk stratification models. The biggest difference in risk assignment is evident in patients who are older than 60 years and have no other risk factors and in patients who are younger than 60 years but have other risk factors. This observation suggests that new prospective randomized clinical trials are needed to better stratify patients at risk for thrombosis.

Corticosteroid-Responsive Pulmonary Toxicity Associated with Fludarabine Monophosphate: A Case Report

Fludarabine monophosphate is an effective drug for the treatment of lymphoid malignancies. Myelosuppression, opportunistic infections, and autoimmune hemolytic anemia are the most common side effects of fludarabine. Herein we report a 55-year-old female that presented with fever and dyspnea after completing her third cycle of FMD (fludarabine, mitoxantrone, and dexamethasone) chemotherapy for stage IV non-Hodgkin follicular lymphoma. Chest X-ray revealed bilateral pneumofibrotic changes and chest CT showed bilateral diffuse interstitial changes with fibrotic alterations. No evidence of infectious agents was noted. The patient had a reduced carbon monoxide transfer factor (45%). Her symptoms and radiographic findings resolved following treatment with prednisolone. The literature contains several cases of fludarabine-associated interstitial pulmonary toxicity that responded to steroid therapy. Fludarabine-induced pulmonary toxicity is reversible with cessation of the drug and administration of glucocorticosteroids. Conflict of interest:None declared.

Duffy and Kidd Genotyping Facilitates Pretransfusion Testing in Patients Undergoing Long-Term Transfusion Therapy

Objective: Conventional serologic typing of red blood cell systems other than ABO and RhD can be inaccurate and difficult to interpret in patients who have recently undergone blood transfusion. While molecular-based assays are not used routinely, the usefulness of genotyping was investigated in order to determine patients who may benefit from this procedure. Materials and Methods: Blood samples were taken from 101 patients with haemato-oncological, chronic renal, or gastroenterological diseases and from 50 donor controls; the samples were tested for Fya and Fyb by applying serologic and genetic methods. All patients had received 3 or more units of RBCs during the last 3 months. An average of 6.1 RBC units were transfused per patient. The average length of time from transfusion until blood sampling was 24.4 days. The haemagglutination test was applied for serological analysis, and the restriction length polymorphism assay was used for genotyping. Results: In total, 33 (32.7%) patients showed positive reactions with anti-Fya or anti-Fyb while being negative genetically. False-positive Fya results were found in 23 samples, and false-positive Fyb in 10 specimens. During the last 3 months, significantly more RBC units were transfused to patients with discrepant results than to those with accurate phenotyping/genotyping results: median of 5 (mean ± SE: 6.85±0.69) versus median of 4 (mean: 5.71±0.51), respectively (p=0.025). The median length of time after the last transfusion was 25 days (mean: 28.72±2.23 days) in the group with accurate phenotyping/genotyping results versus a median of 14 days (mean: 15.52±1.95 days) in the group with discrepant results (p=0.001). Phenotypes and genotypes coincided in all donor samples. Conclusion: Genotyping assays for the Duffy system should be considered if the patient underwent blood transfusion less than 3 or 4 weeks before the sample collection. If the time frame from RBC transfusion exceeds 6 weeks, Duffy phenotyping can provide accurate results.

302PIMPACT OF ANTHRACYCLINE BASED CHEMOTHERAPY INTENSITY ON SURVIVAL OF EARLY BREAST CANCER PATIENTS

ABSTRACT Aim: The relation between chemotherapy dose intensity and patient outcome in the management of early stage breast cancer is still arguable. Randomised trials showed benefit of full standard doses of chemotherapy on schedule. The aim of this study is to assess the impact of chemotherapy dose and intensity related factors on 5-year overall survival in group of early breast cancer (EBC) patients, treated with anthracycline based chemotherapy. Methods: 1826 EBC cases diagnosed and treated in Affiliate of Lithuanian University of Health Sciences Kaunas Oncology Hospital from January 2004 to December 2007 were retrospectively analysed. Inclusion criteria were I – IIIA stage breast cancer and adjuvant anthracycline based chemotherapy. Only 294 patients were included in the analysis. Survival related endpoints were analysed with Kaplan-Meier estimates, long rank tests and Cox proportional hazards models. Results: Patients who have undergone either > 2 cycle-delay (delay at any cycle defined as >3 days vs. plan), or 7 day-delay across the whole chemotherapy systematic plan, or 85%. According to dose and intensity modifications 4 group were analysed: no reductions or delays, reductions only, delays only, both reductions and delays. Our results suggest that shorter survival is related with reductions only, delays only and both delays and reductions as compared to no reductions and delays (p 85%. RDI level HR (95 % CI) p 75% 4.05 (2.430-6.762) 50% 2.61 (1.406-4.837) 0.002 RDI 10.16 (4.872-21.169) Conclusions: Delayed chemotherapy cycles and treatment with insufficient dose of anthracyclines were associated with reduced overall survival in women with early stage breast cancer. Moreover, worse survival is associated with reduced RDI level. Disclosure: All authors have declared no conflicts of interest.