Strong evidence indicates that tumor growth can be actively controlled by the immune system, and interleukins (ILs) are known to play an influential role in immune response regulation. Moreover, inflammatory cytokines are significantly involved in lymphoma pathogenesis. We aimed to investigate serum levels of IL-4 and IL-18 in aggressive non-Hodgkin's lymphoma (A-NHL) patients and their relationship with prognostic parameters and therapy outcome. These serum factors were measured by enzyme-linked immunosorbent assay in 46 patients with pathologically verified A-NHL before and after chemotherapy, and in 20 healthy controls. No significant difference in serum IL-4 (P = 0.11) and IL-18 (P = 0.261) levels was observed between the A-NHL and controls groups. None of the prognostic parameters analyzed significantly correlated with serum IL-4 concentration, while only lactate dehydrogenase (LDH) measurements were associated with IL-18 values. Serum IL-18 was elevated in the patients with high LDH levels compared to those exhibiting normal values (P = 0.045). In addition, no correlation was found between the concentrations of serum IL-4 and IL-18 in A-NHL patients (r = 0.188, P = 0.187). While IL-18 values did not change, serum IL-4 levels decreased following chemotherapy, independently from treatment response (P = 0.002). Our study is the first to report the response of serum IL-4 levels to chemotherapy. In conclusion, although IL-4 serum concentration has no diagnostic role, it is sensitivite to standard chemotherapy in A-NHL. However, serum IL-18 measurements have no diagnostic or prognostic role in this disease.

109 Background: Cbz + P demonstrated an overall survival benefit vs mitoxantrone + P in pts with mCRPC in the Phase III TROPIC trial. The CUP (CABAZ_C_05005) and EAP (NCT01254279) (both funded by Sanofi) were established to allow access to Cbz ahead of commercial availability. The programs are also evaluating Cbz safety in a real-world population. Data analyzed by age group (≤75 and >75 years) are presented here. Methods: Expected enrolment across both programs is 1,450 pts from 236 centres worldwide. Pts received Cbz 25 mg/m2 IV Q3W + P 10 mg QD until disease progression, death, unacceptable toxicity or physician/pt decision. G-CSF is administered as per ASCO guidelines. Results: As of May 30, 2012, 1,301 pts have enrolled (≤75 years: 1,061 pts [81.6%]; >75 years: 240 pts [18.4%]). Eastern Cooperative Oncology Group performance status and incidence of visceral metastases were generally balanced between treatment groups. The most frequent reasons for discontinuation were disease progression (46.8%) followed by adverse events (AEs; 24.4%) in pts ≤75 years, and AEs (36.4%) followed by disease progression (31.1%) in pts >75 years. Time from initial diagnosis to inclusion was greater in pts >75 years (median 79.66 months) than in pts ≤75 years (median 53.94 months), but time from mCRPC diagnosis to inclusion was approximately equivalent (>75 years: median 22.6 months; ≤75 years: median 20.94 months). G-CSF use was more frequent in pts >75 years (cycle 1: 62.9% of pts) compared with pts ≤75 years (cycle 1: 52.2% of pts). AEs of clinical concern were more frequent in the older age group (Grade ≥3 AEs: >75 years 64.2%; ≤75 years 54.8%). Grade ≥3 neutropenia was observed in 25.8% of pts >75 years and in 17.0% of pts ≤75 years. Conclusions: We observed several differences between age groups in baseline and on-treatment parameters, suggesting differences in the natural history of mCRPC (faster disease progression in pts ≤75 years than in pts >75 years) and secondary to treatment (AEs more frequent in pts >75 years compared with pts ≤75 years). Clinical trial information: NCT01254279.

ObjectiveWe investigated the prognostic clinicopathologic factors associated with overall survival (OS) and progression-free survival (PFS) in the once-daily continuous administration of first-line sunitinib in a consecutive cohort of Turkish patients with metastatic renal cell carcinoma (RCC).MethodsThe study enrolled 77 Turkish patients with metastatic RCC who received sunitinib in a continuous once-daily dosing regimen between April 2006 and April 2011. Univariate analyses were performed using the log-rank test.ResultsMedian follow-up was 18.5 months. In univariate analyses, poor PFS and OS were associated with 4 of the 5 factors in the Memorial Sloan-Kettering Cancer Center (MSKCC) score: Eastern Cooperative Oncology Group performance status of 2 or higher, low hemoglobin, high corrected serum calcium, and high lactate dehydrogenase. In addition to those factors, hypoalbuminemia, more than 2 metastatic sites, liver metastasis, non-clear cell histology, and the presence of sarcomatoid features on pathology were also associated with poor PFS; and male sex, hypoalbuminemia, prior radiotherapy, more than 2 metastatic sites, lung metastasis, nuclear grade of 3 or 4 for the primary tumour, and the presence of sarcomatoid features were also associated with poorer os. The application of the MSKCC model distinctly separated the PFS and OS curves (p < 0.001).ConclusionsOur study identified prognostic factors for PFS and OS with the use sunitinib as first-line metastatic RCC therapy and confirmed that the MSKCC model still appears to be valid for predicting survival in metastatic RCC in the era of molecular targeted therapy.

PURPOSE:Hypertension is one of the major side effects of sunitinib, an angiogenesis inhibitor used in the treatment of metastatic renal cell carcinomas (mRCC) and gastrointestinal stromal tumors (GIST). Endothelial dysfunction, an early and reversible event in the pathogenesis of atherosclerosis, is suggested to be one of the possible underlying mechanisms of hypertension caused by angiogenesis inhibitors. Coronary flow reserve (CFR) measurement by trans-thoracic Doppler echocardiography (TTDE) reflects coronary microvascular and endothelial functions, as a cheaper and an easy screening test. We have used TTDE to evaluate endothelial function and coronary microvascular function in mRCC and GIST patients under sunitinib treatment.METHODS:Eighteen metastatic cancer patients (16 mRCC and 2 GIST) on sunitinib treatment and 27 healthy subjects were enrolled in this cross-sectional study. Thyroid stimulating hormone (TSH), lipid profile, creatinine, hemoglobin, glucose, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), anthropometric and physical parameters of patients were recorded. CFR recordings were performed by the Vivid 7 echocardiography device.RESULTS:CFR was significantly lower in patients when compared with controls (1.82±0.4 vs 2.71±0.8, respectively; p < 0.001). Impaired CFR was found in 13 (72%) patients whereas all controls had normal CFR values. CFR was inversely correlated with the duration of sunitinib treatment (r=-0.36, p =0.01), high sensitivite (hs) CRP (r = -0.574, p =0.01) and ESR (r = - 0.5, p = 0.02).CONCLUSION:Our findings indicate that CFR is significantly impaired in cancer patients on sunitinib treatment. There is an inverse correlation between CFR and duration of sunitinib treatment and inflammation markers.

ABSTRACT Introduction The Phase III TROPIC study (NCT00417079) showed that CbzP provides a survival advantage vs mitoxantrone + P in pts with mCRPC previously treated with D (hazard ratio [HR] 0.70; P Methods Total enrolment is expected to be ∼1600 pts with mCRPC from 250 centres worldwide. Pts will receive CbzP (25 mg/m Q3W + 10 mg P oral QD) until progressive disease (PD), death, unacceptable toxicity, physician/pt decision or commercial availability of Cbz. Pts will be followed for 30 days after last administration for safety. Use of G-CSF is recommended as per ASCO guidance. Results Baseline and safety data from the first 919 pts enrolled in the 2 programmes in 30 countries are shown. Mean age was 68 yrs with 21.2% ≥ 75 yrs. All pts had ECOG ≤ 2; the most common sites of metastases were bone (91.7%), lymph nodes (regional 29.9% and distant 28.0%), lung (11.2%) and liver (9.9%). 16.8% had PD during their last D regimen. The median number of treatment cycles was 4 (range 1–16); median relative dose intensity (all cycles) was 99%. Among the 502 pts who stopped CbzP, the most common discontinuation reasons were PD (40.9%), adverse event (AE; 26.9%) and commercial availability of Cbz (15.8%). G-CSF was administered to 60.5% of pts (prophylactic and/or therapeutic use). Overall, 40.4% of pts had Grade 3–4 AEs possibly related to CbzP, the most common relevant being febrile neutropenia (FN; 6.1%), fatigue (3.6%), diarrhoea (3.0%) and nausea (1.0%). Of the 41 pts (4.5%) with AEs leading to death, 21 (2.3%) had at least 1 AE possibly related to CbzP. Conclusion These interim results provide additional safety data on CbzP use in the routine clinical practice setting across the globe. Treatment with CbzP was clinically manageable and FN rate was lower than in the TROPIC study, possibly due to the use of G-CSF as prophylaxis. Disclosure Z.I. Malik: Has participated in an advisory board for, and has received honoraria and funds to attend conferences from Sanofi, G. Di Lorenzo: Has acted as a compensated consultant for Sotio and TEVA, P. Parente: Has participated in an advisory board for, and has received research funding from, Sanofi, W.R. Gerritsen: Has acted as a compensated consultant for Algaia Biomedical Ventures, S. Hitier: Is a Sanofi employee (biostatistician) and owns shares in Sanofi, A. Heidenreich: Has participated in advisory boards for Sanofi, Janssen Cilag and Astellas. Has received honoraria from, Sanofi, Astellas, Amgen and Janssen Cilag, A. Bahl: Has participated in an advisory board for, and received research funding from Sanofi. All other authors have declared no conflicts of interest.

e15112 Background: Recent data have shown that cardiotoxicity represents a potentially important side-effect in patients treated with sunitinib. We reviewed cardiac adverse events in patients with metastatic renal cell carcinoma (RCC) who underwent treatment with this agent. Methods: The medical records of 74 patients with metastatic RCC, treated with sunitinib at Institute of Oncology, Istanbul University, were retrospectively reviewed. Sunitnib was administered continuosly at a dose of 37, 5 mg (92% of patients) or 25 mg (8% of patients) daily without interruption as second-line treatment after interferone or as first-line treatment. Baseline echocardiography and ECG were performed. All patients had their blood pressure measured at baseline and mountly at the time of clinic visits. For patients experiencing symptomatic cardiotoxicity, clinical evaluations and laboratory, radiographic and cardiac tests carried out at the time of diagnosis of cardiotoxicity were reviewed in detail. Median follow-up was 12 months. Results: Median age of patients was 58 (26-80) years. Thirty seven (56%) patients have been using at least one type of antihypertensive drugs. Before initiation of sunitinib, history of smoking, hypertension, diabetes mellitus, coronary artery diesase and chronic renal failure, were present in 26 (38%), 27 (37%), 12 (16%), 8 (11%) and 4 (6%) patients respectively. Two patients had myocardial infarction, one patient had long QT syndrome, 2 patients had grade 3 systolic cardiac dysfunction under suntinib treatment. In patients with history of hypertension, hypertensive pulmonary edema (1 patient) and grade 3-4 hypertension (4 patients) occurred. Cardiac tamponade developed in a patient without hypothyroidism and with cytologically confirmed uninvolvement of pericardial effusion. Conclusions: Patients undergoing sunitinib, especially those with a previous history of hypertension and coronary heart disease, are at increased risk for cardiovascular events and should be monitored for exacerbations of their hypertension and for evidence of LVEF dysfunction and myocardial ischemia during treatment.

e15135 Background: The optimal management of stage I nonseminomatous testis cancer varies according to the centers' expertise. Available treatment strategies include close surveillance, retroperito...

Objective: To study the incidence of vascular disorders and to estimate their contribution to the severity and prognosis of Behcet's disease (BD). Subjects and methods. Ninety-five patients with evident BD, followed up at Research Institute of Rheumatology, Russian Academy of Medical Sciences, in the January 2006 to October 2009, were examined. Their mean age was 29,7 years; malefemale ratio was 3,7. The onset of the disease was chiefly at the age of 21-30 years in 36,8% of the patients. Vascular pathology was evaluated by the following techniques: vascular duplex scanning; brain magnetic resonance imaging in the mode of venosinusography, contrast-enhancement chest computed tomography, chest and abdominal angiography. The data were statistically processed by the programs Statistica 6.0 (Statsoft, USA) and EpiInfo 5.0 recommended by the WHO. Parametric and non-parametric statistical methods were used. Results. Vascular diseases were diagnosed in 26,3% of the patients. The venous bed was mainly involved (88%), the proportion of patients with arterial pathology was 12%. Vascular death occurred in 2 men aged 20 and 18 years due to pulmonary artery rupture aneurysm and brain sagittal sinus thrombosis. Assessment of an association of vascular disorders with other clinical manifestations of BD revealed their correlation with erythema nodosum and epididymitis. The risk for vascular events in erythema nodosum was 5 times greater (OR=5,03; 95% CI 1,54-17,41), the risk was higher in men than that in women (OR=7,11; 95% CI 1,83-30,02 versus OR=2,15; 95% CI 0,16-61,38). The male vascular risk is associated with epididymitis (OR=6,71; 95% CI 1,25-39,89). In erythema nodosum concurrent with epididymitis, the relative vascular risk was increased up to 21; 95% CI 2,15-503,94. Conclusion. Vascular disorders in BD were diagnosed in one fourth of the patients, mainly in young male patients. Severe thromboses with the development of chronic venous insignificance, Budd-Chiari syndrome, pulmonary and iliac artery aneurysms, and arterial thromboses were observed in male patients only. Vascular events were associated with erythema nodosum and epididymitis; in these concomitances, the vascular risk was substantially increased. Vascular death rates were 2,2%.

Cardiac re-operations are associated with increased morbidity and mortality rates due to adhesion of tissues in the anterior mediastinum. Especially, previous usage of left internal thoracic artery constitutes a major challenge for cardiovascular surgeons. In such cases, the left lung frequently adheres to the thoracic wall and may be injured during dissection. This leads to air leak and the complication may in turn increase the risk of mediastinal infections and the hospital stay. A bronchopleural fistula case treated by a novel technique is reported. In patient iatrogenic bronchopleural fistula occured during dissection of the adhesions which resulted due to the first coronary artery bypass grafting and left internal thoracic artery usage. The air leakage was successfully controlled and treated by a novel method: self adhesive BioGlue immersed and coated Surgicel patch. Although it is a single case experience it may be a promising method as it is less traumatic when compared to the classical treatment methods of bronchopleural fistula.

Whilst the etiology of the MALT (Mucosa Associate Lymphoid Tissue) lymphoma is not perfectly clarified, the blamed mechanism is a mature B-cell lymphoproliferative processes. This process is considered to have developed in connection with chronic antigenic stimulation which belongs to the extranodal marginal zone B-cell non-hodgkin indolent lymphoma class. A majority of the MALT lymphoma appear in the gastrointestinal system yet they may appear in tissue and organs like orbita, conjunctiva, lacrimal gland, bladder, lung, dura, thyroid, breast, and skin. Generally they have slow course and favorable prognoses. Chemotherapy and radiotherapy treatment options might be used. In this article, we are reporting 43 year old, female conjunctival MALT lymphoma demonstrative case with clinic and pathological specifications.

Background : The transperitoneal approach (TP) to the aorta is the most widely accepted surgical approach in aortic surgery as it is simple, fast and provides excellent exposure of the intra-abdominal cavity and vascular structures. In recent years, there has been an increasing interest in the retroperitoneal (RP) approach to the aorta since it has been described as having a better outcome, i.e., preserving pulmonary function and gastro-intestinal physiology, reducing the intra-operative blood loss, minimising patient discomfort or pain, decreasing the incidence of wound complications and shortening ICU and hospital stay. The aim of this study is to compare the transperitoneal and retroperitoneal approaches in aortic surgery for aorto-iliac occlusive disease (AIOD).Methods : From December 2003 to June 2006, a total of 153 consecutive patients who had undergone aortic surgery for AIOD, were studied retrospectively. The TP approach was used in 85 patients and the RP approach in 68 patients. Demographic features, intra-operative and postoperative data were analysed and compared according to the approach used.Results : The mean operating time (83.6 +/- 23 vs. 104.4 +/- 30 min, p < 0.001) and mean aortic cross-clamp time (18.4 +/- 3 vs. 15.2 +/- 3 min, p < 0.0412) were significantly longer in the RP group. Peri-operative blood loss (700 +/- 350 vs. 650 +/- 330 ml, p < 0.683) and mortality rate <= 30 day (1 / 1.2% vs. 0/0.0%, p < 0.896) were similar between the groups. The operative 30 day mortality rate was 0.7% (1 of 153) overall. The RP group had an earlier return of bowel functions (17.1 +/- 3 vs. 24.2 +/- 5 hrs, p < 0.001), earlier resumption of diet (26.4 +/- 4 vs. 31.4 +/- 5 hrs, p < 0.001), shorter period of intubation (3.5 +/- 2 vs. 6.5 +/- 3 hrs, p < 0.001), ICU stay (1.5 +/- 1 vs. 4.2 +/- 1 hrs, p < 0.001) and hospital stay (4.0 +/- 1 vs. 5.9 +/- 1 days, p < 0.001). Mean effort-pain scores were significantly lower in the RP group (3.8 +/- 1 vs. 5.3 +/- 1, p < 0.001). Incidence of pulmonary complications (4.4%, 3 of 68 vs. 7.3%, 8 of 85, p < 0.001), paralytic ileus (1.5%, 1 of 68 vs. 3.5%. 3 of 85, p < 0.001) were also lower in the RP group. Wound complications were more common in the TP group (4.7%, 4 of 85 vs. 10.3%, 7 of 86, p < 0.001). Most cases in both groups were related to incisional hernia or evisceration.Conclusion : This report presents our experience with the use of TP and RP approaches in a patient population merely consisting of AIOD. The RP approach was associated with a significantly lower incidence of postoperative pulmonary complications, rapid recovery of gastro-intestinal functions, shorter ICU and hospital stay, less peri-operative blood loss and lower mean effort-pain scores. We conclude that the RP approach is a safe and feasible technique that exposes patients to less postoperative complications.