Venizelion General Hospital of Heraklion

Irákleion, Greece

Venizelion General Hospital of Heraklion

Irákleion, Greece

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Chatzipantelis P.,Athens General Hospital | Mastorakis E.,Venizelion General Hospital of Heraklion | Tzortzakakis D.,Venizelion General Hospital of Heraklion | Salla C.,Athens General Hospital
Acta Cytologica | Year: 2010

Background: Primay renal lymphoma is a rare disease (<1% of kidney lesions). We present a case of renal large B-cell type non-Hodgkin's lymphoma (NHL) with right sided pleural involvemest. Case: A 70-year-old man was admitted with persistent, painless, macroscopic hematuria for 1 month. Ultrasound examination, abdominal computed tomography and magnetic resonance imaging techniques revealed a large tumor in the right kidney extending in the perirenal area. The patient underwent a radical nephrectomy for suggested renal cell carcinoma. He developed thoracic pain and pleural effusion in the 10 days after surgery. The pleural fluid was cytologically processed using conventional and ThinPrep (Cytyc Corporation, Boxborough, Massachusetts. U.S.A.) cytopreparatory techniques, slides were Papanicolaou and Giemsa stained, and immunocytochemistry was performed on the ThinPrep slides. The cytologic examination of the fluid specimes revealed a highly cellular smear composed of dispersed neoplastic cells of intermediate and large size. Immunocytochemically, the neoplastic cell were: CD45 (LCA) (+), CD20 (+), CK7 (-), CK20 (-), NSE (-), CD45 RO (UCHL-1) (-) and CD30 (-). On cytomorphologic and immunocytologic Histologic evaluation of the nephrectomy specimen revealed infiltrating, diffuse large cell renal NHL, B-cell type, of immunoblastic and centroblastic morphology. This NHL was considered a renal primary because no peripheral lymphadenopathy or hepatosplenomegaly was revealed by the imaging techniques. Conclusion: Cytomorphologic and immunocytologic examination revealed the typical features of a renal large B-cell type NHL in a case with pleural involvement © The International Academy of Cytology.


Lydakis C.,Venizelion General Hospital of Heraklion | Ioannidou D.,Venizelion General Hospital of Heraklion | Koumpa I.,Venizelion General Hospital of Heraklion | Giannikaki E.,Venizelion General Hospital of Heraklion | And 3 more authors.
Clinical Rheumatology | Year: 2012

We present a case of a patient treated with etanercept (TNF-a antagonist) for psoriatic arthritis, who then developed clinical symptoms of lepromatous leprosy. She presented with multiple erythematous plaques on trunk, face and extremities, saddle nose deformity, alopecia, articular deformities of the feet and peroneal neuropathy. The clinical suspicion of Hansen's Disase was confirmed by the biopsy findings (lepromatous leprosy). On further questioning, the patient stated that her father was diagnosed with leprosy 70 years ago and had spent some years in a leper colony in Spinalonga island in Southern Greece in the 1940s. This first report of Hansen's disease after administration of etanercept highlights the need of careful risk assessment of patients for whom antiTNF treatment is planned. © 2011 Clinical Rheumatology.


Sfiridaki K.,Venizelion General Hospital of Heraklion | Pappa C.A.,Venizelion General Hospital of Heraklion | Tsirakis G.,University of Crete | Kanellou P.,University of Crete | And 5 more authors.
Mediators of Inflammation | Year: 2011

An essential cytokine system for the osteoclast biology in multiple myeloma (MM) consists of the receptor of activator of NF-κB ligand (RANKL), its receptor (RANK), and the soluble decoy receptor, osteoprotegerin (OPG). Myeloma cells cause imbalance in OPG/RANKL interactions. We measured serum levels of OPG, soluble (s) RANKL, sRANKL/OPG ratio, markers of disease activity [LDH, CRP, interleukin-6 (IL-6), β2-microglobulin (B2M)], and angiogenic factors [hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF)], in 54 newly diagnosed MM patients and in 25 of them in plateau phase. All the above values were higher in MM patients compared to controls and decreased in plateau phase. sRANKL and RANKL/OPG were higher with advancing disease stage and skeletal grade. Significant correlations were found among RANKL and RANKL/OPG with HGF, LDH, VEGF, IL-6, and B2M. In conclusion, RANKL and OPG play significant roles in MM pathophysiology, as regulators of bone turnover and mediators of angiogenesis. Copyright © 2011 K. Sfiridaki et al.


Pappa C.A.,Venizelion General Hospital of Heraklion | Tsirakis G.,University of Crete | Devetzoglou M.,University of Crete | Zafeiri M.,University of Crete | And 6 more authors.
Tumor Biology | Year: 2014

Angiogenesis is a crucial process in growth and progression of multiple myeloma (MM). Mast cells (MCs) play an important role in MM angiogenesis. Various angiogenic mediators secreted by MCs regulate endothelial cell proliferation and function. Among them, ELR+ CXC chemokines, such as growth-related oncogen-alpha (GRO-α) and epithelial neutrophil activating protein-78 (ENA-78), have been described as potential mediators in regulation of angiogenesis. The purpose of the study was to quantify MCs in bone marrow (BM) biopsies of MM patients, expressed as MC density (MCD), and correlate it with serum concentrations of vascular endothelial factor (VEGF), GRO-α, ENA-78. Fifty-four newly diagnosed MM patients and 22 healthy controls were studied. Tryptase was used for the immunohistochemical stain of MCs. VEGF, GRO-α, and ENA-78 were measured in sera by ELISA. MCD and serum levels of GRO-α, ENA-78, and VEGF were significantly higher in MM patients compared to controls (p<0.001 in all cases). MCD was significantly increasing with increased stage of the disease (p<0.001). Furthermore, significant correlations were found between MCD with VEGF, GRO-α, and ENA-78. These findings support that MCs participate in the pathophysiology of MM and is implicated in the angiogenic process and disease progression. © 2014 International Society of Oncology and BioMarkers (ISOBM).


Tsirakis G.,University Hospital of Heraklion | Pappa C.A.,Venizelion General Hospital of Heraklion | Kolovou A.,General Hospital of Chania | Kokonozaki M.,University Hospital of Heraklion | And 2 more authors.
Hematology | Year: 2015

Objective: Interleukin-22 (IL-22) is a cytokine participating in many aspects of inflammation. Multiple myeloma (MM) is a malignant disease of plasma cells with characteristic immune deregulation. We estimated serum levels of IL-22 in MM patients, both in activity and remission, in order to apprehend its possible participation in MM biology. Methods: We measured serum levels of IL-22 along with beta-2 microglobulin (B2M), paraprotein, and interleukin-1beta (IL-1beta), as well as degree of bone marrow infiltration, in 51 patients with active MM and in 22 of them in remission. Results: We found that IL-22 was higher in active MM patients, compared to both controls and patients in remission, and also in patients in remission compared to controls. Moreover, IL-22 was increasing in parallel with the disease stage and also correlated with B2M, IL1-beta, and degree of infiltration. Discussion:We suggest that the elevated levels of IL-22 in active MMpatients, in parallel with disease activity, and in positive correlation with IL-1beta, may represent the inflammatory element of the disease. This increased occurrence of IL-22 may enhance myeloma proliferation and growth, and moreover, may participate in the mechanisms of immune deregulation. © W. S. Maney & Son Ltd 2015.


Tsirakis G.,University Hospital of Heraklion | Pappa C.A.,Venizelion General Hospital of Heraklion | Kaparou M.,University Hospital of Heraklion | Boula A.,Venizelion General Hospital of Heraklion | And 4 more authors.
Tumor Biology | Year: 2013

Soluble interleukin-6 receptor (sIL-6R) is part of IL-6 receptor that may stimulate cells that do not express the whole molecule. It may enhance myeloma cell proliferation and furthermore angiogenesis. The aim of the study was to evaluate the clinical significance and the relationship between serum levels of sIL-6R, with various stimulators of angiogenesis, such as hepatocyte growth factor (HGF) and interleukin-18 (IL-18) and with markers of proliferation, such as beta-2 microglobulin (B2M) levels and plasma cell Ki-67 proliferation index in the bone marrow, in patients with multiple myeloma (MM). We studied 45 newly diagnosed MM patients. Serum levels of sIL-6R, HGF, IL-18, and B2M and Ki-67 proliferation index (Ki-67 PI) in bone marrow's plasma cells were determined. The mean concentrations of sIL-6R, HGF, IL-18, and B2M and the value of Ki-67 were significantly higher in the patients compared to controls and with increasing disease stage. sIL-6R was strongly positively correlated with HGF, IL-18, B2M, and Ki-67 PI. There is a positive correlation between plasma cell growth, as determined by Ki-67 PI, and different angiogenic cytokines, such as HGF and IL-18, with sIL-6R. This relationship suggests the significant role of these cytokines in the proliferation and disease activity in MM patients. © 2012 International Society of Oncology and BioMarkers (ISOBM).


Pappa C.A.,Venizelion General Hospital of Heraklion
Journal of cancer research and clinical oncology | Year: 2014

Angiogenesis is an essential process for the expansion of multiple myeloma (MM). Angiopoietin-2 (Ang-2), Ang-1 and their receptor possess important roles in this procedure. The aim of the study was to measure serum levels of Ang-2 along with known markers of angiogenesis and to estimate their prognostic impact on the survival. Bone marrow microvascular density (MVD), estimated by CD31, and circulating levels of known angiogenic factors Ang-2, interleukin-6, soluble CD105 and platelet-derived growth factor-AB, measured by ELISA, were measured in 77 newly diagnosed patients with active MM and in 57 of them who responded to chemotherapy. All measured parameters were increased in MM patients, were also increasing in advanced disease and decreased after effective treatment. Ang-2 correlated positively with the other angiogenic factors and MVD. Moreover, Ang-2 values above the median were accompanied by worse survival. Ang-2 correlates strongly with the angiogenic process and its serum levels are importantly prognostic for survival, highlighting the role of angiopoietins pathway in the biology of MM.


Tsirakis G.,University of Crete | Pappa C.A.,Venizelion General Hospital of Heraklion | Psarakis F.E.,Venizelion General Hospital of Heraklion | Fragioudaki M.,University of Crete | And 4 more authors.
Medical Oncology | Year: 2012

Multiple myeloma (MM) is a disease of plasma cells that express the CD40 receptor. Binding of the CD40 by its natural ligand, CD40 ligand (CD40L), produces growth arrest and/or apoptosis in MM. To evaluate serum levels of soluble CD40L (sCD40L) in MM patients and to correlate them with markers of disease activity and angiogenesis, such as vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), interleukin-6 (IL-6), proliferation marker Ki-67 proliferation index (Ki-67 PI) and bone marrow plasma cell infiltration, fifty-eight MM patients were studied in diagnosis and 43 of them after completion of treatment. Serum levels of sCD40L, VEGF, HGF and IL-6 were measured by ELISA, whereas Ki-67 PI and bone marrow plasma cell infiltration were measured by immunohistochemistry. Pre-treatment levels of sCD40L in MM patients were higher compared to controls and to their levels after effective treatment. Treatment regimen did not affect the degree of reduction of sCD40L levels, whereas patient in partial remission had increased levels compared to those with better response. Significant differences were found among disease stages. There were also positive correlations between CD40L with HGF, VEGF, IL-6 and Ki-67 PI. Elevated serum sCD40L is found in patients with advanced MM stage and can be reduced after effective treatment. Increased levels of this mediator are correlated with angiogenic cytokines, providing evidences that CD40L/CD40 interactions play a significant role in the mechanisms of angiogenesis in MM patients. © 2012 Springer Science+Business Media, LLC.


Fragioudaki M.,University of Crete | Boula A.,Venizelion General Hospital of Heraklion | Tsirakis G.,University of Crete | Psarakis F.,University Hospital of Heraklion | And 5 more authors.
Annals of Hematology | Year: 2012

B cell-activating factor (BAFF) is a cytokine that plays a major role in the maintenance of normal B-cell development and homeostasis. It has been suggested that in multiple myeloma (MM) it might have regulatory effects on the proliferation and viability of malignant plasma cells. The aim of this study was to evaluate serum levels of BAFF in 52 newly diagnosed MM patients, with varying disease severity, in order to see the correlations between BAFF and indices of MM activity, such as interleukin-6, C-reactive protein, lactate dehydrogenase, and beta-2 microglobulin, and to explore the clinical significance of BAFF in predicting the disease activity of MM. We found increased BAFF serum levels in MM patients, increased in advanced stages, and decreased in plateau phase. We also found significant correlations between BAFF serum levels with the above parameters of disease activity. We conclude that BAFF may play an important role in pathogenesis of MM, could be used as a marker of disease activity, and a possible therapeutic target. © 2012 Springer-Verlag.


PubMed | Venizelion General Hospital of Heraklion
Type: Journal Article | Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine | Year: 2014

Angiogenesis is a crucial process in growth and progression of multiple myeloma (MM). Mast cells (MCs) play an important role in MM angiogenesis. Various angiogenic mediators secreted by MCs regulate endothelial cell proliferation and function. Among them, ELR(+) CXC chemokines, such as growth-related oncogen-alpha (GRO-) and epithelial neutrophil activating protein-78 (ENA-78), have been described as potential mediators in regulation of angiogenesis. The purpose of the study was to quantify MCs in bone marrow (BM) biopsies of MM patients, expressed as MC density (MCD), and correlate it with serum concentrations of vascular endothelial factor (VEGF), GRO-, ENA-78. Fifty-four newly diagnosed MM patients and 22 healthy controls were studied. Tryptase was used for the immunohistochemical stain of MCs. VEGF, GRO-, and ENA-78 were measured in sera by ELISA. MCD and serum levels of GRO-, ENA-78, and VEGF were significantly higher in MM patients compared to controls (p<0.001 in all cases). MCD was significantly increasing with increased stage of the disease (p<0.001). Furthermore, significant correlations were found between MCD with VEGF, GRO-, and ENA-78. These findings support that MCs participate in the pathophysiology of MM and is implicated in the angiogenic process and disease progression.

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