SummaryDefence against the reactive oxidants produced during aerobic metabolism is a complex process and is provided by a system of enzymes and antioxidant compounds capable of preventing excess radical production, neutralising free radicals and repairing the damage caused by them. Regulation of the antioxidant system must provide suYcient, properly located, antioxidant compounds and enzymes. Damage to this system has been proved to play a role in various disorders. Long-term complications of diabetes mellitus are supposed to be partially mediated by oxidative stress. The authors summarise experimental and clinical investigations in this field and analyse the possible importance of the changes in the antioxidant system in the development of diabetic vascular complications.

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In the absence of intestinal metaplasia H. pylori infection increases both apoptotic activity and expression of p53 oncoprotein in the gastric mucosa. The lack of increased apoptosis with a higher p53 expression in the presence of intestinal metaplasia suggests an increased genetic instability and also may suggest that mutation of the p53 gene is an early step in the multistep process of gastric carcinogenesis.

Endogenously formed nitrogen and oxygen free radicals are believed to be involved in human cancer etiology. Plasma nitrate/nitrite originates from endogenous nitric oxide production in fasting humans, decrease in superoxide scavenger activity (SSA), and free sulfhydryl groups (SH) reflects the amount of superoxide anion generated, and nitrotyrosine is believed to be formed by the interaction of tyrosine and peroxynitrite in vivo. The aim of the current study was to measure plasma nitrate/ nitrite, SSA, and SH in 69 patients (mean age +/- standard deviation, 66 +/- 11 years) with colorectal carcinoma. Nitrotyrosine was measured from both the plasma and tumor tissues in 32 patients. All patients had adenocarcinoma of the colon or rectum. Twenty-five patients were classified as stage B according to Dukes classification as modified by Astler-Coller, 13 were classified as stage C, and 31 patients were classified as stage D. To determine whether the changes are specific for colorectal cancer, 20 patients with active inflammatory bowel disease (IBD; mean age, 52 +/- 18 years) and 30 healthy volunteers, who served as control subjects (mean age, 48 +/- 11 years), were studied. Plasma nitrate/nitrite was measured by the modified Griess method, SSA was measured by an electron/spin resonance spin trapping method, free SH was measured by Ellman's method, and the presence of nitrotyrosine in the plasma and tumor tissue was detected by high performance liquid chromatography (HPLC) using C- 18-derivatized silica (5 microm) column (C18S, Crestpaque, New York, NY, USA) and at a wavelength of 274 nm. Patients with colorectal carcinoma and with active IBD had a significantly higher plasma nitrate/ nitrite level (51.2 +/- 26.2 microm and 56.0 +/- 14.6 microm versus. 29.6 +/- 6.3 microm; p < 0.01), and a lower SSA level (39 +/- 11.5 U/g protein and 52.0 +/- 18.9 U/g protein versus. 88 +/- 25.1 U/g protein; p < 0.05) and SH level (7.7 +/- 3.89 microm protein and 6.4

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Backgound: Epithelial cell proliferation activity has been reported both to be unaltered and increased in Helicobacter pylori (H. pylori) associated chronic gastritis. The proliferation rate decreased following H. pylori eradication, but results are controversial whether this change is dependent on the success of eradication. We compared the cell proliferation activity of H. pylori positive and negative gastric epithelial biopsies in chronic gastritis with and without intestinal metaplasia (IM) and gastric cancer by the expression of proliferation cell nuclear antigen (PCNA) and Tv image cytometry, and assessed the effect of H. pylori eradication on the cell proliferation rate in the gastric epithelium. Methods: Brush smears and antral biopsies were taken from 70 patients (42 men, 28 women, mean age 58 ± 15 y.o.) on routine endoscopy. Patients were divided into four groups according to the histology; normal epithelia (n=10), chronic gastritis without IM (n=24), chronic gastritis with IM (n=20), and gastric carcinoma (n=16). Thirty‐three patients were H. pylori positive, and success of eradication was controlled in 24 cases. Cell proliferation was measured by immunohistochemistry using PCNA labeling index (LI) and by Tv image cytometry evaluating 12 morpho‐ and densitometric parameters of each nuclei and 6 additional parameters of each smear. Results: PCNA LI, DNA index and S + G2 ratio were all higher in chronic gastritis than in the normal epithelium, and were further increased in carcinoma. The lower PCNA LI observed in chronic gastritis with IM corresponds to the lower S phase ratio determined by Tv image analysis. In H. pylori positive cases, the proliferation activity was 69.3 ± 13.05% prior to the eradication and it decreased to 55.8 ± 23.31% after the successful eradication therapy. When immunohistochemistry was compared with Tv image cytometry, PCNA LI significantly correlated with the percentage of cells in G1 phase (r=−0.415) and S phase (r=0.385), Integrated Optical Density mean (r=0.598), density maximum (r=0.608), surface (r=0.670), layers (r=0.638), diameter minimum (r=0.619), diameter maximum (r=0.730) and perimeter (r=0.501), respectively (p < 0.05). Conclusions: Epithelial cell turnover is increased in chronic gastritis with or without IM, and in gastric carcinoma. The lower PCNA LI observed in chronic gastritis with IM corresponds to the lower S phase ratio determined by Tv image analysis. Cell proliferation decreases after successful H. pylori eradication. Both methods proved to be reliable for the determination of epithelial cell proliferation.

4915 Primary mediastinal large B-cell lymphoma (PMBCL) is a subtype of diffuse large B-cell lymphoma (DLBCL) with unique clinical and radiological appearance and distinct histopathologic and genetic features. PMBCL accounts for approximately 3% of primary lymphoid tumors. Because of the relative rarity of this disease there are not enough prospective randomised trials with sufficient number of patients and therefore there is not a standard treatment either. Before the rituximab era contradictory results were published with standard cyclophosphamide, doxorubicin, oncovine, prednisone (CHOP) treatment and radiotherapy. The most favourable results were obtained with the combination of third-generation regimens (methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin/MACOP-B/, etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin/VACOP-B/) and radiotherapy. Immuno-chemotherapy has been an important step forward in the efficiency of the treatment of PMBCL patients. The addition of rituximab (R) to the standard CHOP-21 regimen has significantly improved the remission rate, the overall survival (OS), the event-free survival (EFS) and the disease-free survival rate. An American working group has obtained more than 90% OS and EFS rates with using dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab (DA-EPOCH-R) alone without radiotherapy (Dunleavy et al, Blood 2005). A German working group published excellent results with CHOP-14 treatment of DLBCL patients younger than 60 years and with R-CHOP-14 treatment of elderly patients (Pfreundschuh et al, Blood 2004 and Pfreundschuh et al, Blood 2005). We have treated 23 newly diagnosed PMBCL patients with R-CHOP-14 regimen between July 2005 and July 2009. The median age of the 17 women and 6 men was 32 years (range 21–53). 11 patients had stage I and another 11 patients had stage II disease. Among these patients 4 and 3 cases had extranodal manifestations (5 pleural, 3 pericardial and 2 lung infiltrations). Only 1 patient had stage IV disease (with lung involvement). Elevated lactate dehydrogenase (LDH) levels were found in 22 cases. Bulky mediastinal tumor (>10 cm) was observed in 18 patients but all 23 patients had a mass larger than 7 cm. All 23 patients were considered to have good prognosis (revised International Prognostic Index/R-IPI/: 1–2). The mean number of chemotherapy regimens was 7,1 (range 4–8). In 20 cases radiotherapy (average dose 36 Gy) was used post chemotherapy as consolidative treatment. As a result, 21 patients obtained complete remission confirmed with a PET/CT scan. In 1 case even the repeated PET/CT scan could not clear the effect of the therapy but she is supposedly in complete remission because of the relatively long event-free survival and the morphologic improvement of the CT image. One patient who only obtained partial remission after chemotherapy and stayed PET/CT scan positive, underwent autologous stem cell transplantation and then achieved complete remission confirmed with PET/CT scan. During the median 32 months follow-up (range 12–61) no relapse has occurred. One patient died of acute arterial haemorrhage due to an acute tuberculosis infection after 13 months follow-up time. The 3 years overall survival rate was 95,6% and the event-free survival rate was 91,3% respectively. The authors have found the well tolerable R-CHOP-14 regimen combined with radiotherapy very effective in PMBCL patients and recommend this treatment. This combination was found more effective than the third-generation or R-CHOP-21 regimens and similar to DA-EPOCH-R treatment. Decreasing or completely withholding the radiotherapy may be considered in cases of negative interim PET/CT scans. Disclosures: No relevant conflicts of interest to declare.

In Hungary, the cost of lenalidomide-based therapy is covered only for relapsed multiple myeloma (MM) patients, therefore lenalidomide is typically used in the second-line either as part of a triplet with proteasome inhibitors or as a doublet. Lenalidomide-dexamethasone is a standard treatment approach for relapsed/refractory MM, and according to recent large randomized clinical trials (RCT, the standard arm of POLLUX, ASPIRE, TOURMALINE), the progression-free survival (PFS) is expected to be approximately 18 months. We surveyed ten Hungarian centers treating MM and collected data of 278 patients treated predominantly after 2016. The median age was 65 years, and patients were distributed roughly equally over the 3 international staging system groups, but patients with high risk cytogenetics were underrepresented. 15.8% of the patients reached complete response, 21.6% very good partial response, 40.6% partial response, 10.8% stable disease, and 2.5% progressed on treatment. The median PFS was unexpectedly long, 24 months, however only 9 months in those with high risk cytogenetics. We found interesting differences between centers regarding corticosteroid type (prednisolone, methylprednisolone or dexamethasone) and dosing, and also regarding the choice of anticoagulation, but the outcome of the various centers were not different. Although the higher equivalent steroid dose resulted in more complete responses, the median PFS of those having lower corticosteroid dose and methylprednisolone were not inferior compared to the ones with higher dose dexamethasone. On multivariate analysis high risk cytogenetics and the number of prior lines remained significant independent prognostic factors regarding PFS (p &lt; 0.001 and p = 0.005). Our results show that in well-selected patients Lenalidomide-dexamethasone can be a very effective treatment with real-world results that may even outperform those reported in the recent RCTs. This real world information may be more valuable than outdated RCT data when treatment options are discussed with patients.