Sinan Yavuz

Pronostic significance of angiogenic/lymphangiogenic, anti-apoptotic, inflammatory and viral factors in 88 cases with diffuse large B cell lymphoma and review of the literature

BACKGROUND Diffuse large B cell lymphoma (DLBCL) is the most common subtype of Non-Hodgkins lymphomas (NHL). The outcome of these patients shows a wide variation. We evaluated the effect of six biologic parameters including Cyclooxygenase-2 (Cox-2), Survivin, Epstein Barr Virus (EBV), Vascular Endothelial Growth Factor-A (VEGF-A), Vascular Endothelial Growth Factor-C (VEGF-C), Thrombospondin-1 (TSP-1) and clinical parameters. PATIENTS AND METHODS A follow up study was conducted and 88 cases with DLBCL were included in the study. The data of 72 patients were eligible for the survival analyses. Immunohistochemistry was used to detect these parameters. RESULTS The ratio of positive cases for Cox-2, VEGF-A, Survivin, VEGF-C, EBV, TSP-1 were 71.6%, 64.8%, 60.2%, 36.4%, 21.6%, 14.8%, respectively. Survivin (+) cases showed higher LDH levels and VEGF-A (+) cases showed higher beta 2 microglobulin (B2M) levels compared with (-) cases. Mean survival rates were found to be significantly shorter in cases expressing VEGF-A, VEGF-C, EBV and Survivin than cases not expressing these. EBV expression (HR: 3.78; 95%CI: 1.47-9.74; p=0.006), VEGF-C expression (HR: 3.22; 95%CI: 1.07-9.68; p=0.037) and extranodal involvement (HR: 3.02; 95%CI: 1.01-8.97; p=0.047) were found to be independent risk factors for prognosis according to the Cox regression analysis. COMMENT Lymphangiogenesis (VEGF-C) and EBV related viral lymphomagenesis have been found to be related with prognosis in DLBCL patients.

IDA-FLAG regimen for the therapy of primary refractory and relapse acute leukemia: a single-center experience.

We evaluated efficacy and toxicity profiles of fludarabine, Ara-C, idarubicin, and G-CSF (Ida-FLAG) combination chemotherapy in 56 refractory and/or relapsed acute leukemia patients. Patients were treated with fludarabine phosphate 25 mg/m2/d (d1-5), Ara-C 2 g/m2/d (d1-5), idarubicin 12 mg/m2/d (d1-3), G-CSF was given subcutaneously from sixth day until absolute neutrophil count (ANC) >500/μL. One third of the acute myeloblastic leukemia (AML) and 45% of acute lymphoblastic leukemia (ALL) cases were primary refractory disease. In AML patients, complete remission (CR) was achieved in 15 cases (53.6%). One case showed partial remission (PR) (3.6%) and 12 cases (42.8%) had resistant to this regimen (RD). Grade IV hematologic toxicity occurred in all AML cases. Leukocyte recovery time was 16 days. Nonhematologic complications were mild to moderate nausea, vomiting, and mucositis and could be controlled by routine measures. Stem cell transplantation was performed in 5 patients and all achieved CR, 2 autologous and 3 allogeneic. In ALL patients, CR and PR were obtained in 8 (42.2%) and 2 (10.5%) of 22 cases; disease was resistant to Ida-FLAG in 9 (47.3%) cases. Grade IV hematologic toxicity occurred in all ALL cases. Leukocyte recovery time was 17 days. Nonhematologic toxicity consisted of nausea, vomiting, and mucositis and could be controlled by supportive therapy. Autologous transplantation was performed in 1 patient, but relapse disease occurred after 5 weeks. There was no correlation between response rate and leukemia subtype (AML versus ALL), leukocyte count, age, sex, disease status (de novo versus secondary), and RFS (early versus late relapse) (P > 0.05). Median survival was 16 weeks in all cases (22 weeks in AML versus 13 weeks). At present, only 3 patients are alive and 2 of these are in continuous remission. The rest of the patients died. In conclusion, Ida-FLAG is a good choice in cases with refractory/relapsing acute leukemia for salvage chemotherapy. High efficacy and a low-toxicity profile are preferable properties of this regimen, and this regimen has been found to be useful for cytoreduction, especially in candidates for allo-SCT.

The prognostic significance of VEGF-C and VEGF-A in non-Hodgkin lymphomas.

Angiogenesis and lymphangiogensis are important in the proliferation and survival of the malignant hemeopoietic neoplasms. The aim of this study is to determine the prognostic role of angiogenesis and lymphangiogenesis in the development of lymphoma. For this aim, VEGF-A and VEGF-C were explored by immunohistochemistry in 177 cases. VEGF-C and VEGF-A were found to be positive in 34 and 61% of the samples. There was a good correlation between VEGF-C and VEGF-A expression (p = 0.0001). The clinical prognostic indicators were not significantly different between VEGF-C (+) and (−) and/or VEGF-A (+) and (−) cases. Overall survival (OS) rate was shorter in cases with VEGF-A (+) and VEGF-C (+) cases than with negative cases (p = 0.03 and p = 0.0005, respectively). The OS was significantly shorter in aggressive lymphomas expressing VEGF-A and VEGF-C but not in indolent lymphomas. The results of Cox regression analyses showed that VEGF-A and VEGF-C expressions are independent prognostic parameters (OR: 2.6, 95% CI: 1.3–5.0 for both (+) cases). In conclusion, VEGF-C and VEGF-A were positive in 34 and 61%, respectively, of the cases with NHL. The significant correlation between VEGF-C and VEGF-A suggests that lymphangiogenesis is important in the pathogenesis of lymphomas as shown in angiogenesis. The significantly shorter survival rates of VEGF-C and/or VEGF-A expressions indicate that angiogenesis and lymphangiogenesis are important in clinical outcome. Autocrine VEGF-A and VEGF-C crostalks in lymphoma cells are important in lymphoma biology and inhibition of these signals with anti-angiogenic/anti-lymphangiogenic drugs and combination with chemo-immunotherapy regimens will be more useful in these cases.

Vasculitis Associated with All Trans Retinoic Acid (ATRA) in a Case with Acute Promyelocytic Leukemia

All trans retinoic acid is the drug of choice in the treatment of acute promyelocytic leukemia. But this drug has some side effects, some of which may be life-threatening. Retinoic acid syndrome is the most frequent and dangerous side effect of this differentiation inducing agent. Other side effects include Sweets syndrome, vasculitis, hypercalcemia, bone marrow necrosis and fibrosis, thromboembolic events, erythema nodosum, granulomatous proliferation and some pulmonary complications. Here, we report vasculitis in a case with APL treated with ATRA and review the literature.

Extramedullary relapse in the pleura in acute promyelocytic leukemia

Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloblastic leukemia with specific clinical, morphologic and genetic features and a good response to all trans retinoic acid (ATRA). However, extramedullary (EM) relapse is an interesting feature of these cases, especially those treated with ATRA. Recently, we have encountered an EM relapse in the pleura in a case with APL receiving an ATRA containing regimen. This case is reported and the relevant literature is reviewed.

VEGF-C expression in breast cancer: clinical importance.

It is well known that angiogenesis and lymphangiogenesis play important roles in tumor occurrence and progression. The vascular endothelial growth factor (VEGF) family is the most important family of proteins involved in angiogenesis, and VEGF-C is the most important molecule in lymphangiogenesis. Lymphangiogenesis plays an important role in lymphovascular invasion, metastasis to regional lymph nodes, and distant organ metastasis. In this study, the rate of VEGF-C was investigated in 217 patients with breast cancer. VEGF-C was evaluated by immunohistochemistry and its expression was compared with that of well-known prognostic indicators, such as tumor stage and grade, axillary lymph node involvement, estrogen and progesterone receptor status, c-erb-B2 expression, and extent of lymphovascular invasion. The patient population included 8 men, in addition to women before (n=108), during (n=9), and after (n=92) menopause. Patients had been diagnosed with invasive ductal (n=181) or invasive lobular (n=22) carcinoma, mixed (n=8) or medullary (n=1) carcinoma, or ductal carcinoma in situ (n=5). Tumors ranged from stage 0 to IV and grade I to III and the distribution of estrogen-positive (n=100) and estrogen-negative (n=110) receptor tumors was almost equal. The number of patients with c-erbB2 tumors ranged from 21 to 49 for each tumor stage, and the number of patients with VEGF-C-negative tumors ranged from 28 to 59 for each tumor stage. No important association between VEGF-C expression and other prognostic indicators was found. However, this may be a result of the lack of standardization among the methods used to determine VEGF-C expression. Also, the lymphangiogenic effect may not be overt because of the variety of VEGFR-3 variants, which included nonfunctional variants. To determine the relationship among angiogenesis, lymphangiogenesis, and prognosis, more standardized methods to demonstrate the angiogenesis, and prospective studies to cover a larger, more homogenous patient population are needed.

Granulomatous reaction after chemotherapy for Hodgkin's disease

There are some reports that relate the coexistence of sar-coidosis and lymphoma. This coexistence has been calledthe sarcoidosis–lymphoma syndrome. Generally, sarcoido-sis precedes the lymphoma in these cases. On the other handthere are some other reports about sarcoidosis or sarcoid likereaction following the therapy of lymphoma. We report herea case with sarcoid like reaction developing after systemicchemotherapy for Hodgkin’s disease (HD) and discuss thepossible definitions.1. Case reportA 55-year-old man was admitted to our hospital withrelapsed HD. He had a history of lymphocyte rich-HD dia-gnosed in November 1999. He had cervical and abdomi-nal lymph nodes, right pleural effusion, splenomegaly andconstitutional symptoms. He had the history of six coursesof ABVD chemotherapy at another hospital. Cervical, tho-racic and abdominal CT scans were found to be normaland 2-microglobulin ( 2M) was within normal limits(2772ng/ml) after chemotherapy. Two months later he com-plained of constitutional symptoms and at that time, CTscans showed cervical, intraabdominal and retroperitoneallymph nodes, splenomegaly and mediastinal lymph nodes.Physical examination disclosed cervical and inguinallymph nodes. Laboratory results: Hb was 11.7g/dl, Hctwas 35.4%, WBC was 10 × 10

Staging with PET-CT in Patients with Locally Advanced Non Small Cell Lung Cancer is Superior to Conventional Staging Methods in Terms of Survival

BACKGROUND Of patients with non small cell lung cancer (NSCLC), around one third are locally advanced at the time of diagnosis. Because only a proprotion of stage III patients can be cured by surgery, in order to improve the outcomes, sequential or concurrent chemoradiation, or concurrent chemoradiation with induction or consolidation is offered to the patients with locally advanced NSCLC. Today, PET combined with computerized tomography (PET-CT) is accepted as the most sensitive technique for detecting mediastinal lymph node and extracranial metastases from NSCLC. We aimed to compare PET-CT and conventional staging procedures for decisions regarding curative treatment of locally advanced NSCLC. MATERIALS AND METHODS A total of 168 consecutive patients were included from Acibadem Kayseri Hospital, Acibadem Adana Hospital and Kayseri Research and Training Hospital in this study. RESULTS While the median PFS was 13.0 ± 1.9 months in the PET-CT group, it was only 6.0 ± 0.9 in the others (p<0.001). The median OS values were 20.5 ± 15.6 and 11.5 ± 1.5 months, respectively (p<0.001). DISCUSSION As a result, we found that staging with PET CT has better results in terms of survival staging. This superiority leads to survival advantage in patients with locally advanced NSCLC.

Dramatic response with capecitabine after cranial radiation to the brain parenchymal and leptomeningeal metastases from lung cancer.

It is known that the prognosis of Non Small Cell Lung Cancer with brain metastasis are very poor with a median survival of only a few months. Although some chemotherapeutic agents penetrate the blood brain barrier generally chemotherapy results are bad but efficiency may be better after radiotherapy. For this reason brain metastatic disease requires some efforts to improve the response rate. Here we reported a case with lung cancer metastatic to the brain and we discussed the good response to capecitabine after cranial radiotherapy (C).

Gravin gene expression in acute leukaemias: clinical importance and review of the literature.

The aim of this study was to determine the expression of Gravin (a tumor suppressor gene belonging to the A kinase anchoring protein family) in samples of acute leukaemia and to explore its association with the prognosis. The study group consisted of 162 people (137 patients with acute leukaemia and 25 volunteers as control). Real-time quantitative PCR was used to determine the gene expression and β Actin used as a control gene. The results were evaluated with Comparative Ct method. Gravin β-Actin ΔCt was statistically different between patients and controls (p value < 0.001). The Gravin expression was found to be decreased 11-fold when compared with controls and was found to be decreased in 106 cases (77.5%). There was an inverse correlation between gravin expression and overall survival. The Gravin expression was found to be decreased in samples of acute leukaemia and was associated with an inferior overall survival. Because of paradoxical results, there is a need for more studies exploring gravin isoforms and other related gene expressions.