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ABSTRACT: The conflicting data are reported on the clinical significance of VEGF deregulation and intensity of angiogenesis in multiple
myeloma. The aim of this study was to evaluate the incidence and prognostic significance of VEGF expression and microvessel
density (MVD) in multiple myeloma, as well as the relationship of their expression with selected clinical data, histological
features, and proliferative activity of myeloma cells. We analyzed bone marrow biopsy specimens obtained from 59 patients
with newly diagnosed multiple myeloma. Expression of VEGF and MVD was analyzed using standard immunohistochemical method (antibodies
against VEGF and CD34, respectively) on B5-fixed and routinely processed paraffin-embedded bone marrow specimens. MVD was
estimated by counting the number of microvessels in three “hot spots” at 400× magnification. VEGF immunoreactivity was estimated
on the basis of intensity and percentage of positive plasma cells. VEGF was expressed in 47/59 (79.7%) specimens. There was
no significant correlation between VEGF overexpression and age, clinical stage, the extent of osteolytic lesions, type of
monoclonal protein, hemoglobin concentration, platelet count, serum concentration of creatinine, calcium, and albumins, the
extent of bone marrow infiltration, histological grade, and proliferative activity index (measured with Ki-67 immunoreactivity).
No significant difference was observed regarding the overall survival between VEGF-positive and VEGF-negative patients (29
vs. 34 months, P=0.8). Median MVD was 15, ranging from 1 to 89 microvessels per three “hot spots”. There was significant correlation between
MVD and histological grade, the extent of bone marrow infiltration, and proliferative activity. Significant difference was
observed regarding the overall survival between patients with low MVD (<15) and patients with high MVD (≥15) (46 vs. 22 months,
P=0.009; univariate analysis). The results of this study did not reveal clinical significance of VEGF overexpression in multiple
myeloma. On the contrary, the extent of bone marrow angiogenesis is an indicator of biological potency of malignant clone
and a predictor of poor survival in newly diagnosed myeloma.
Medical Oncology 04/2012; 25(4):451-457. · 2.14 Impact Factor
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ABSTRACT: The conflicting data are reported on the clinical significance of VEGF deregulation and intensity of angiogenesis in multiple myeloma. The aim of this study was to evaluate the incidence and prognostic significance of VEGF expression and microvessel density (MVD) in multiple myeloma, as well as the relationship of their expression with selected clinical data, histological features, and proliferative activity of myeloma cells. We analyzed bone marrow biopsy specimens obtained from 59 patients with newly diagnosed multiple myeloma. Expression of VEGF and MVD was analyzed using standard immunohistochemical method (antibodies against VEGF and CD34, respectively) on B5-fixed and routinely processed paraffin-embedded bone marrow specimens. MVD was estimated by counting the number of microvessels in three "hot spots" at 400x magnification. VEGF immunoreactivity was estimated on the basis of intensity and percentage of positive plasma cells. VEGF was expressed in 47/59 (79.7%) specimens. There was no significant correlation between VEGF overexpression and age, clinical stage, the extent of osteolytic lesions, type of monoclonal protein, hemoglobin concentration, platelet count, serum concentration of creatinine, calcium, and albumins, the extent of bone marrow infiltration, histological grade, and proliferative activity index (measured with Ki-67 immunoreactivity). No significant difference was observed regarding the overall survival between VEGF-positive and VEGF-negative patients (29 vs. 34 months, P = 0.8). Median MVD was 15, ranging from 1 to 89 microvessels per three "hot spots". There was significant correlation between MVD and histological grade, the extent of bone marrow infiltration, and proliferative activity. Significant difference was observed regarding the overall survival between patients with low MVD (<15) and patients with high MVD (> or = 15) (46 vs. 22 months, P = 0.009; univariate analysis). The results of this study did not reveal clinical significance of VEGF overexpression in multiple myeloma. On the contrary, the extent of bone marrow angiogenesis is an indicator of biological potency of malignant clone and a predictor of poor survival in newly diagnosed myeloma.
Medical Oncology 05/2008; 25(4):451-7. · 2.14 Impact Factor
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ABSTRACT: We report the case of a littoral-cell angioma of the spleen, a recently described benign vascular tumour, whose imaging and pathological characteristics have been discussed only by a few authors. The diagnosis was made after elective splenectomy. The CT images, scintigraphy and histological specimens are presented, and differential diagnoses discussed.
Clinical & Laboratory Haematology 11/2006; 28(5):317-20. · 1.11 Impact Factor
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ABSTRACT: We report the case of a littoral-cell angioma of the spleen, a recently described benign vascular tumour, whose imaging and pathological characteristics have been discussed only by a few authors. The diagnosis was made after elective splenectomy. The CT images, scintigraphy and histological specimens are presented, and differential diagnoses discussed.
Clinical & Laboratory Haematology 09/2006; 28(5):317 - 320. · 1.11 Impact Factor
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ABSTRACT: The aim of this investigation was to estimate the possibility of predicting the splenectomy response in patients with chronic immune thrombocytopenic purpura (ITP). The patients' age, sex, megakaryocytes abundance, platelet blood count, production, life span, sequestration/destruction site were considered as possible predictive factors. Thirty-four ITP patients (23 female and 11 male) aged from five to 83 years were investigated. Platelet blood count ranged from 4 to 106 x 10(9)l (mean value was 43 x 10(9)/l). Megakaryocyte abundance was determined in 19/34 ITP patients. Megakaryocytes were numerous in 11/19, present in 7/19 ITP patients and in one patient low megakaryocyte number was registered. In all 34 ITP patients autologous platelet labelling with 111In-oxinate was performed and labelled platelets were reinjected to the ITP patients. This enabled platelet life span, production, sequestration index and sequestration/destruction site determination. Platelet life span ranged from 0,4-5 days (mean value was 1 day). Mean value for platelet production index was 1,1. Platelet sequestration/destruction site in 16 ITP patients was the spleen, and in two it was the liver. Mixed platelet sequestration/destruction site (the liver and the spleen) was registered in 7 ITP patients, while predominantly splenic sequestration/destruction was present in 9 ITP patients. All 34 ITP patients were later submitted to splenectomy, which is a therapeutic option in ITP. Splenectomy result was favorable in 28/34 ITP patients while it was unfavorable in 6/34 (17,6%). Highly significant correlation was noticed between the splenectomy result and platelet sequestration site (p < 0.01). On the other hand, there was no correlation between the splenectomy result on one side, and patient's age, sex, megakaryocyte abundance, platelet production, life span and blood count on the other. Splenectomy result was favorable in all ITP patients with splenic sequestration/detruction of labelled platelets. It was unfavorable in ITP patients with hepatic sequestration of labelled platelets. In ITP patients with mixed platelet sequestration (hepatic and splenic) there were more unfavorable than favorable splenectomy results. Non-invasive method of platelet labelling and platelet sequestration/ /destruction site determination makes easier the clinicians' and ITP patients' decision for the splenectomy in the case when the spleen is the only sequestration site of the labelled platelets, and against the splenectomy, when exclusively hepatic platelet sequestration/destruction is registered.
Glas. Srpska akademija nauka i umetnosti. Odeljenje medicinskih nauka. 01/2005;
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ABSTRACT: Taking into consideration the existing disagreement in the literature, the aim of this paper was to estimate the value of the initial kinetics of autologous platelets labelled with 111In-oxinate, performed during the first 20 minutes after their intravenous injection. Two hypothesis were tested: 1. Initial 111In-platelet kinetics indicates the platelet sequestration site (in patients with normal mean platelet life span)/destruction site (in patients with shortened mean platelet life span), 2. Initial 111In-platelet kinetics indicates the quality of platelet separation and labelling procedure. We performed initial labelled platelet kinetics in thrombocytopenic patients (in order to test the first hypothesis) as well as in control (healthy) subjects (in order to test the second hypothesis). Thirty-nine persons were investigated: 33 with thrombocytopenia: 25 with shortened mean platelet life span, caused by chronic im mune thrombocytopenic purpura (ITP), eight with normal platelet life span and thrombocytopenia caused by myelodysplastic syndrome (MDS), six healthy, control subjects (C). In all 39 persons platelet blood count on the day of platelet labelling was determined, autologous platelet labelling with 111In-oxinate was performed, general and differential yields of platelet labelling (GYL and DYL), as well as mean labelled platelets life span were determined. Besides that, initial labelled platelets kinetics was performed with initial 111In-platelets accumulation in the liver (IPAL) calculation, as well as the late platelet kinetics for platelet sequestration index and platelet sequestration/destruction site determination. We obtained two types of initial labelled platelets kinetics (not only in the patients with shortened platelet life span, but also in the subjects with normal labelled platelets life span), which differed in the IPAL value and in the ratio of the liver and the heart radioactivity: IPAL < 20% and IPAL>20%. We found statistically significant difference in GYL and DYL between the two groups: IPAL<20% and IPAL > 20%. Both yields were higher in IPAL<20% group. There was no significant difference between the two IPAL groups in the platelet blood count, labelled platelet life span, sequestration index and sequestration site. No correlation could be found between IPAL on one side and platelet blood count, sequestration index, and sequestration site on another. We concluded that initial labelled platelet kinetics could not indicate the platelet sequestration/destructon site (which is accomplished by the late labelled platelets kinetics), but nevertheless, it is very sensitive and useful method of platelet separation and labelling quality control. While in vitro quality control parameters (GYL and DYL) indicate the quality of only one part of this procedure, initial labelled platelet kinetics reflects discrete platelet function disturbance that might happen from the moment of blood sample collection till the labelled platelets intravenous injection.
Glas. Srpska akademija nauka i umetnosti. Odeljenje medicinskih nauka. 01/2005;
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ABSTRACT: Immune thrombocytopenic purpura (ITP) associated with pregnancy often involves considerable risk both for mother and child, and usually worsens in the third trimester of gestation. Pregnancy and delivery are especially difficult in patients with severe ITP (platelet count below 20 x 10(9)/L), who are resistant to prednisone and high dose intravenous immunoglobulin (IVIgG). In those cases we applied cesarean section (CS), to prevent intracranial haemorrhage due to fetal/neonatal ITP, and splenectomy at the same time as an effective therapeutic strategy for ITP. We present 5 patients (4 with chronic ITP and 1 with ITP associated with HIV infection), aged 21-35 years, with severe ITP (platelet count 2-10 x 109/L), resistant to prednisone (1-2 mg/kg), and 2/3 were resistant to IVIgG (0.4 g/kg x 5 d). Four patients with severe resistant ITP were supported with 1-2 doses of platelets from cell separator before CS and 1-3 dose during splenectomy. One patient increased platelet count to 55 x 109/L after treatment with IVIgG and splenectomy following CS were done without platelet transfusion. Splenectomy was performed immediately after CS in all patients, and two of them were hysterectomised (one with HIV infection). After splenectomy, platelet count was normalised in all patients, and they had no haemorrhage, wound haematoma formation or any adverse events. But ITP relapsed in 2/5 patients after 1-2 months. Two newborns had severe thrombocytopenia, which solved spontaneously after 3 days in one or after treatment with IVIgG in other. We propose that splenectomy following cesarean section should be considered as approach for delivery and treatment option for mothers with severe resistant ITP.
Acta chirurgica iugoslavica 02/2002; 49(3):51-4.
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A Milovanović,
M Popović,
M Petrović,
R Colović,
D Bosković,
M Colović, I Elezović,
S Matić,
M Zuvela,
S Knezević,
V Dugalić,
A Antic
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ABSTRACT: Splenectomy--the surgical removal of spleen is being performed in cases of: traumatic spleen rupture, as part of other surgical procedures, number of hematological, infectious and metabolic disorders. During the years 1988.-2001., there were 396 splenectomies performed at the First surgical clinic, for the cause of: autoimmune disorders 187 (47.34%), lymphoproliferative diseases 89 (22.59%). Hodgkin disease 35(8.94%), myeloproliferative disease 39 (9.95%), as part a of "staging" laparotomy 37(9.34%), other hematological disorders 7(2.20%). The spleen of [table: see text] 244 patients weighted 500-1500 g(61.62%), in 56 patients (14.14%) weighted less than 500 g, and in 96 patients (24.24%) spleen weighted more than 1500 g. Patients with thrombocytes less than 40,000/l 16 (4.04%) were perioperativly treated with fresh thrombocytes. Postoperative morbidity and mortality were registered in 54 (13.64%), i.e. 8 (2.02%) patients. Delayed results depended on primary disorder, comorbidities and supportive therapy. In this article, the particularities of the operative procedure were discussed, as well as importance of cooperation of surgeon and hematologist in perioperative treatment.
Acta chirurgica iugoslavica 02/2002; 49(3):73-9.
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Acta chirurgica iugoslavica 02/2002; 49(3):35-9.
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ABSTRACT: Splenectomy is definitive treatment for idiopathic thrombocytopenic purpura (ITP) because it removes both the sites of autoantibody producing cells and also the major site of platelet destruction. The purpose of this study was to evaluate long term results of splenectomised patients with ITP and to determine predictor factors for good response. A 167 patients with chronic ITP (136 females, 31 males), median aged 35 years (17-74) was splenectomised after 2 to 160 months (Median 12) from diagnosis of ITP. Indications for splenectomy were: 6 weeks of steroid therapy with platelet count below 10 x 10(9)/l or 3 months with platelet count under 30 x 10(9)/l, or treatment with prednisone above 30 mg more of 6 months to increase platelet count over 30 x 10(9)/l, or repeated relapses. Postoperative complications developed in 16 patients (9.5%), 3 of them died (1.8%) due to thromboembolism and 17 patients discontinued later controls. During follow up to 172 months (Median 62) 111/147 splenectomised patients were in remission (75.5%), 99 in complete (above 100 x 10(9)/l), 12 in partial (50-100 x 10(9)/l) and 36 patients (24.5%) were relapsed (below 50 x 10(9)/l). Remission was achieved in 79/88 patients (89.8%) with good response to prednisone before splenectomy toward 32/62 patients (51.6%) with poor response to prednisone (p < 0.01). Remission was obtained in 9/11 patients (81.8%) who responded well to intravenous immune globulin (0.4 g/kg x 5 d) and only in 1/8 who did not (p < 0.05). Higher response rate was achieved in patients under 40 years of age (81.6%) than in older ones (63.4%) (p < 0.05). No difference was shown between sex and time intervals (3, 6, 12, 24, 36 or over 36 months) from diagnosis to splenectomy. Splenectomy is an effective treatment of refractory ITP with response rate of 75.5% after median follow up of 62 months. In our patients better results on splenectomy were associated with age less than 40 years, good responses to steroid, and intravenous immune globulin.
Acta chirurgica iugoslavica 01/2002; 49(3):29-34.
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ABSTRACT: The authors report a case of therapy-related acute promyelocytic leukemia (t-APL), with typical cytogenetic translocation t(15;17), which appeared following chemotherapy (ABVD), and radiotherapy for Hodgkin's disease (IIB). After treatment with all-trans retinoic acid (Vesanoid(R) 45 mg/m2 daily) complete remission of t-APL was achieved. Then only one course of chemotherapy '3+7' (doxorubicin 45 mg/m2 1-3 d, cytosar 200 mg/m2 1-7d) was applied and the patient interrupted further treatment in July 1994. Four years later she had a normal pregnancy and delivered a healthy female infant in December 1998.
Medical Oncology 09/2000; 17(3):222-4. · 2.14 Impact Factor
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ABSTRACT: We report a 34-year-old woman with sequentially occurring autoimmune diseases that are possibly triggered by numerous ovulation inductions. At the ages of 26-32 years, she experienced 27 uncontrolled ovulation induction cycles using clomiphene citrate (CC) or CC plus human menopausal gonadotropin plus human chorionic gonadotropin. She became pregnant at the ages of 27, 30 and 31 with subsequent pregnancy loss in the 28th, 8th and 10th week of gestation, respectively. Insulin-dependent diabetes mellitus (IDDM) developed at the age of 28. During the second year of ovulation induction, at the age of 27, she developed arthralgia that worsened and became migratory from the age of 31. Thrombocytopenia appeared at the age of 33. The diagnosis of systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) was established at the age of 34. To the best of our knowledge, this is the first case of concurrent IDDM, SLE and APS in a patient associated with ovulation inductions. Excessive levels of estradiol achieved during the ovulation inductions could play a role in the expression of multiple autoimmune diseases in the susceptible woman.
Gynecological Endocrinology 07/2000; 14(3):153-7. · 1.58 Impact Factor
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ABSTRACT: The extent of megakaryocytopoiesis (Mk-poiesis) and clinical outcome are evaluated in 14 patients with severe refractory chronic immune thrombocytopenia (rchr ITP). Three out of 14 patients died due to hemorrhage. The number of bleeding episodes and the number of treatment modalities proved to be both sensitive prognostic survival parameters (p < 0.05). Thirty two corticosteroid responsive chr ITP patients (chr ITPPR), 15 not treated patients (chr ITP(NT)) and 14 healthy volunteers (C) served as a control. There was a significant difference in the platelet count between the study groups (p < 0.05). The number of megakaryocytes and promegakaryoblasts per mm3 of bone marrow were significantly lower in rchr ITP patients (p < 0.05) than in chr ITP(PR) and in chr ITP(NT) group, thus implying an inadequate Mk-poiesis in rITP chr patients. From the data presented here it may be suggested that the inadequate Mk-poiesis is operating in rchr ITP.
Hematology and Cell Therapy 08/1999; 41(4):163-8.
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ABSTRACT: Between February 1992 and November 1996 we treated 30 newly diagnosed acute promyelocytic leukaemia (APL) patients either with oral all-trans-retinoic acid (ATRA) alone (45 mg m-2) or with a simultaneous combination of ATRA (45 mg m-2), daunorubicin (DNR, 50 mg/m-2 for 3 days) and cytosine arabinoside (ARA-C, 200 mg m-2 for 7 days). There were 15 patients in each group. Patients with a white blood cell count < 5 x 10(9)/l at diagnosis received only ATRA as an induction therapy. Patients with initial white blood cell count > 5 x 10(9)/l received a combination of ATRA, DNR and ARA-C as an induction therapy. Within the first 20 days of induction, there were two early deaths in the group of patients receiving only ATRA, and six early deaths in the group of patients treated with a combination of ATRA and chemotherapy. Ten out of 13 patients (76.9%) receiving ATRA only achieved complete remission (CR) whereas seven out of nine patients (77.8%) receiving ATRA with chemotherapy achieved CR. Initial median peripheral white blood cell counts were significantly lower in the group of patients treated with ATRA alone (2.3 x 10(9)/l) than in the group of patients receiving ATRA and chemotherapy (14.0 x 10(9)/l). Morphological evidence of differentiation was noted in all patients entering CR. Patients in both groups who achieved CR received one course of standard '3 + 7' chemotherapy (DNR 45 mg m-2, 1-3 days, ARA-C 200 mg m-2, 1-7 days) followed by two courses of standard '2 + 5' chemotherapy (DNR 50 mg m-2 1-2 days, ARA-C 200 mg m-2 1-5 days) as a consolidation therapy. Patients not achieving remission (three out of 13 in the ATRA group and two out of nine in ATRA+chemotherapy group) did not respond to salvage chemotherapy and all died within 3 months of diagnosis. Only one out of 10 patients (10%) in CR, treated with ATRA is in relapse after 18 months. In patients treated with ATRA alone two out of 10 (20%) survived 58 months following diagnosis whereas in the ATRA+chemotherapy group one out of seven has already survived their 58th month since diagnosis. Four out of eight patients with an early death died of retinoic acid syndrome. Other toxicities due to ATRA were minimal (cheilitis, xerosis, dermatitis, diarrhoea, liver damage or pseudotumor cerebri).
Medical Oncology 06/1997; 14(2):65-72. · 2.14 Impact Factor
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ABSTRACT: Comparison of long term follow-up studies showed that irrespectively of the route of acquisition of HIV infection, the time of progression to AIDS was similar and after 10 years, about 50 per cent of HIV infected individuals had developed AIDS. On the other side, it has been shown that zidovudine improves survival in advanced HIV disease, and that successful results initiated clinical studies with early intervention to determine whether zidovudine could delay the onset of AIDS and prolong the symptom-free clinical stage. The paper reviews results from two main studies, ACTG 019 and ACTG 016, showing that zidovudine treatment reduced disease progression when started in early stages of HIV infection, before development of AIDS. These results influenced the FDA to approve zidovudine for use in HIV infected individuals, both symptomatic and asymptomatic, whose CD4 cell counts are below 500/mm3.
Srpski arhiv za celokupno lekarstvo 12/1992; 120 Suppl 5:30-2. · 0.19 Impact Factor
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ABSTRACT: A rare form of plasma cell dyscrasia characterized by associated polyneuropathy, organomegaly, endocrinopathy, M protein and skin changes has been termed the POEMS syndrome. The pathophysiology is unknown; plasma cell dyscrasia is essential; secondary manifestations are unexplained. We report a 67-year-old man with a 7-month history of progressive weakness and numbness of the legs. Clinical examination revealed sensorimotor polyneuropathy, predominantly affecting the lower extremities, hepatomegaly, and skin haemangiomas. Additional investigations disclosed IgG-lambda monoclonal serum protein, endocrine abnormalities, elevated cerebrospinal fluid protein level and an osteoblastic lesion of the lumbar vertebra. Biopsy of the osteosclerotic vertebra showed a marked lymphoplasmocytic infiltrate. MRI of the liver disclosed two haemangiomas; this association has not been reported previously.
Journal of Neurology 02/1992; 239(1):49-52. · 3.47 Impact Factor
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Bone Marrow Transplantation 01/1990; 4 Suppl 3:61. · 3.75 Impact Factor
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ABSTRACT: 215 teeth were extracted in 62 haemophiliacs following a single infusion of factor VIII supplemented with antifibrinolytics. Tooth sockets were packed with Sorbacel gauze soaked with an antifibrinolytic. 1 group was sutured and the other left open. Primary closure of the extraction wound did not show direct effect on haemostasis. However, the size of the clot showed a statistically significant difference between the primary closure and open wound groups. The authors conclude that primary closure of the extraction wound protects the blood clot, makes the postoperative period more comfortable for patients and may subsequently decrease the risk of postoperative bleeding.
International Journal of Oral and Maxillofacial Surgery 03/1989; 18(1):14-6. · 1.51 Impact Factor
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European Journal Of Haematology 02/1989; 42(1):105-6. · 2.61 Impact Factor
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Acta chirurgica iugoslavica 02/1989; 36 Suppl 2:468-71.
