A comprehensive diagnostic approach to cardiac events in cancer patients receiving antineoplastic therapy: A systematic review.

Oncologic patients are vulnerable to a broad spectrum of cancer related cardiovascular complications during and/or after antineoplastic treatment. This article is dealing with the main drugs used in real world clinical practice, including conventional chemotherapy, targeted therapy, immunotherapy, radiotherapy and their potential cardiovascular toxicity. Diagnosis of cancer- related cardiovascular events requires thorough clinical evaluation, multimodality imaging techniques and cardiac biomarkers according to established guidelines of cardio-oncology. Multidisciplinary approach and individualized strategies are essential and crucial in confronting oncologic patients.

Thromboembolic events in patients with paroxysmal nocturnal hemoglobinuria (PNH): Real world data of a Greek nationwide multicenter retrospective study.

Thrombosis is the most common and a life-threatening complication in patients with Paroxysmal Nocturnal Hemoglobinuria. One-third of patients with PNH experience at least one thromboembolic event during the course of the disease, with thrombosis being the most common cause of death in these patients. The mechanism of thrombosis in PNH is complex and continues to be of great research interest. Since the introduction of C5 complement inhibitors in the treatment of PNH, the incidence of thromboembolic events has decreased substantially. We retrospectively analyzed data concerning the thrombotic episodes of 41 patients with PNH from 14 different national hematology centers in Greece. Sixteen patients (39%) experienced at least one episode of thrombosis, including, seven (43.8%) at diagnosis, seven (43.8%) during the course of the disease and two (12.5%) patients prior to PNH diagnosis. Nearly half of these individuals (n=7, 43.8%) had multiple episodes of thrombosis during the course of their disease. The most common sites of thrombosis were intra-abdominal veins. Three out of 26 patients developed thrombosis while on eculizumab. In none of the 16 patients, the thrombotic event was fatal. Our findings, despite the small number of patients, confirmed that thrombosis continues to be a significant complication of PNH affecting more than one third of the patients.

Association of GPIa C807T polymorphism with unexplained female infertility and IVF implantation failure.

Glycoprotein Ia (GPIa), also known as integrin alpha 2 (ITGA2), together with GPIIa (ITGB1), form the heterodimer integrin α2ß1. This complex is a major collagen receptor on the membrane of platelets, which is involved in thrombus formation through platelet adhesion and activation.

Association of plasminogen activator inhibitor-type 1 (PAI-1) -675 4G/5G polymorphism with unexplained female infertility.

BACKGROUND: Infertility is a major issue of concern for couples at reproductive age.  The underlying causes of infertility remain unknown in 15-30 % of the cases. Plasminogen activator inhibitor type 1 (PAI-1), which is a major fibrinolytic factor, has been associated with increased infertility risk.  DNA variants at PAI-1, such as -675 4G/5G promoter polymorphism, have been implicated in infertility-related reproductive disorders, possibly due to a molecular mechanism involving implantation failure. This study aims to investigate the association of PAI-1 4G/5G polymorphism to otherwise unexplained female infertility in a sample of women of Greek ethnic origins. METHODS: We enrolled in this study 222 women from the population of Northern Greece; 115 women with unexplained infertility (group 1) and 107 normal fertile women (group 2). All participants were genotyped for PAI-1 -675 by real-time polymerase chain reaction. RESULTS: Our results indicate an association with the PAI-1 4G allele in our sample of women with unexplained infertility. The dominant genetic model supports the association, in contrast to the recessive genetic model. CONCLUSIONS: Our results indicate that PAI-1 4G/5G polymorphism is a promising screening factor which could potentially be a target for certain cases of unexplained female infertility. However, they should be interpreted with caution and should be validated in larger studies and diverse populations. In addition, other variants in genes involved in thrombophilia might need to be considered. HIPPOKRATIA 2017, 21(4): 180-185.

Fulminant Epstein-Barr virus-associated hemophagocytic syndrome in a renal transplant patient and review of the literature.

We describe a rare fulminant case of Epstein-Barr virus-associated hemophagocytic syndrome (HPS) in a 37-year-old female renal transplant patient, indistinguishable from severe sepsis clinically and in the laboratory. HPS involves rapidly escalating immune system activation, resulting in a cytokine cascade, which can, especially in immunocompromised patients, lead to multi-organ failure, and even death. Thirty-two Herpesviridae-associated HPS cases in renal transplant patients have been reported and are reviewed. Overall mortality is 47% (15/32 cases).

Treatment of a patient with classical paroxysmal nocturnal hemoglobinuria and Budd-Chiari syndrome, with complement inhibitor eculizumab: Case Report.

Background. Paroxysmal nocturnal haemoglobinuria (PNH) is a rare acquired clonal disorder of hematopoietic stem cells involving all blood cells. Erythrocytes have increased susceptibility to complement-mediated haemolysis. Thrombosis is the leading cause of mortality and follows episodes of acute hemolysis. Eculizumab, a monoclonal antibody blocking activation of complement C5 is currently used in the treatment of PNH. Recent results demonstrated that eculizumab effectively reduces thrombosis. Description of case. We present a 30-year-old male patient admitted with abdominal and lumbar pain. Thorough investigation revealed severe hemolytic anemia requiring transfusions and hepatosplenomegaly. Imaging findings were compatible with a Budd-Chiari syndrome. Flow cytometry confirmed the PNH diagnosis. Due to refractory ascites he underwent a transjugular intrahepatic portal-systemic shunt (TIPS) and eculizumab administration was started. Results. He has already completed three years of eculizumab treatment and he is transfusion independent. There is also a significant reduction in fatigue with improvement in his quality of life. Doppler scans of his TIPS persistently show it to be patent. Conclusions. Classical PNH patients with thrombosis and severe intravascular hemolysis are particularly challenging to manage. For these patients, eculizumab is a reasonable therapeutic option, expecting that by decreasing the risk for thrombosis, life expectancy may be increased.

Prevalence of thrombophilic mutations in patients with unprovoked thromboembolic disease. A comparative analysis regarding arterial and venous disease.

BACKGROUND: Thromboembolic disease (TED) represents one of the main reasons of morbitity and mortality in Western World. Venous and arterial thrombotic disorders have long been viewed as separate pathophysiological entities. However, in recent times the separate nature of arterial and venous thrombotic events has been challenged. Although inherited thrombophilia's predominant clinical manifestation is venous thrombosis, its contribution to arterial thrombosis remains controversial. Purpose  of  the  study  was  to  evaluate  the  prevalence  of  the  most common  thrombophilic  mutations, FV Leiden G1691A-FVL and FII G20210A-PTM and to assess  the  differences between venous, arterial and mixed thrombotic events. Testing  for polymorphism MTHFR C677T and  antithrombin,  protein  C  and  protein  S was also performed. Correlations with  dyslipidemia, smoking, obesity, homocysteine and antiphospholipid antibodies were made. METHODS: 515 patients with unprovoked TED, 263 males, median age 44 years, were studied. Patients were divided into three groups: 258 with venous thrombosis (group A), 239 with arterial (group B) and 18 with mixed episodes (group C). All patients were interviewed regarding family history of TED, origin, smoking and dyslipidemia. Body mass index (BMI) had been calculated. Molecular assessment of the FVL, PTM and MTHFR C677T was performed. Antithrombin, protein C, protein S, APCR, homocysteine, antiphospholipid antibodies and lipid profile were also measured. RESULTS: The population studied was homogenous among three groups as regards age (p=0.943), lipid profile (p=0.271), BMI (p=0.506), homocysteine (p=0.177), antiphospholipid antibodies (p=0.576), and positive family history (p=0.099). There was no difference in the prevalence of FVL between venous and arterial disease (p=0.440). Significant correlation of PTM with venous TED was found (p=0.001). The number of positive and negative for MTHFR presented statistically significant difference with a support in arterial disease (p=0.05). Moreover, a 2-fold increase in the risk of venous thrombosis in FVL positive patients (odds ratio: 2.153) and a positive correlation of homocysteine levels with MTHFR C677T (p<0.001) was found. CONCLUSIONS: Correlation of PTM with venous thrombosis was established. Analysis showed no difference in prevalence of FVL between venous and arterial thrombosis, indicating that FVL might be a predisposing factor for arterial disease. A significant increase in MTHFR C677T prevalence in arterial disease was found. In conclusion, young patients with unprovoked arterial disease should undergo evaluation for thrombophilic genes. Identification of these mutations is important in the overall assessment and management of patients at high risk. Findings will influence the decisions of stratified approaches for antithrombotic therapy either primary or secondary thromboprophylaxis, the duration of therapy, the potential for avoiding clinical thrombosis by risk factor modification and the genetic counselling of family members. However, further studies are needed to clarify the nature of the association regarding venous and arterial thrombotic events.

A breast fibroadenoma mimicking an extranodal deposit of Hodgkin's lymphoma in 67Ga imaging.

We present the case of a young woman with classical nodular sclerosing Hodgkin's lymphoma (clinical stage IIB). During staging work-up, intense gallium-67 ((67)Ga) accumulation in a left breast lump raised the suspicion of an extranodal deposit, but biopsy favoured a benign histology. A post-treatment (67)Ga scan showed complete remission of the disease with normal tracer uptake in the left breast. However, a few months after treatment, a faint left mammary concentration of (67)Ga was observed. The breast mass was excised and histopathology was consistent with fibroadenoma. This unusual presentation is a new addition to the literature on false-positive (67)Ga findings and chemotherapy-associated tracer changes.

Primary cutaneous T-cell-rich B-cell lymphoma: a case report and literature review.

T-cell-rich B-cell lymphoma (TCRBCL) is a recently recognized B-cell lymphoma variant, characterized by a minor population of neoplastic B-cells existing in a background of predominant reactive T-lymphocytes. It is a rare entity, accounting for approximately 1 to 2% of all non-Hodgkin's lymphomas. It has both nodal and extranodal presentation. Primary cutaneous TCRBCL is an extremely rare lymphoma and only 16 cases have been documented thus far in the medical literature. We report the case of a 46- year-old man that presented with a slowly-growing, painless skin nodule on the left temporofrontal region of the scalp. A complete surgical excision was performed and histological examination revealed diffuse infiltration of the dermis by TCRBCL. A complete surgical excision of the skin lesion and systemic chemotherapy seems to have been effective because the patient is disease-free 2 years after the initial diagnosis was made. This study reports a very rare case of TCRBCL presented primarily in the skin. Because of its rarity, it is especially important to make the correct diagnosis using the appropriate immunohistochemical stains and apply the proper therapy.

Primary adrenal lymphoma presenting as Addison's disease. Case report and review of the literature.

Primary Adrenal Lymphoma (PAL) is a very rare clinical entity. Adrenal insufficiency is a common complication of this pathology. Most patients present with clinical and laboratory findings of adrenal insufficiency and bilateral enlargement of the adrenal glands. We present a 78-year-old woman admitted to our institution with typical clinical and laboratory findings of adrenal insufficiency. Computerized tomography (CT) of the abdomen revealed bilateral enlargement of the adrenal glands. The patient was eventually diagnosed with a diffuse large B-cell lymphoma after a CT-guided needle adrenal biopsy and treated with combined immuno-chemotherapy (R-LPD-COP). Twenty months after the initial evaluation, she is in good condition, with no signs of adrenal insufficiency.

Non-thromboembolic pulmonary hypertension in multiple myeloma, after thalidomide treatment: a pilot study.

BACKGROUND: Multiple myeloma (MM) is thrombogenic as a consequence of multiple hemostatic effects and endothelial damage. Thalidomide has been associated with an increased risk of thromboembolic pulmonary hypertension (PH). PH in the absence of venous thromboembolism has also been described in MM patients during thalidomide treatment. AIM: Detection of clinical and subclinical nonthromboembolic PH in MM patients after thalidomide treatment. PATIENTS AND METHODS: Eighty-two patients, 46-82 years (median age 61 years), 42 males, were studied. They underwent echocardiographic study at baseline, 1 month thereafter, 6 months later and whenever symptoms indicating deterioration of cardiac function appeared. Echocardiographic signs of PH were especially identified. RESULTS: Clinical and echocardiographic evaluation revealed four patients (out of 82 patients, 4.87%) with PH. Nonimaging and imaging diagnostic methods excluded thromboembolic PH. Statistical analysis demonstrated significant correlation between structural heart disease and PH (r = 14.078; P = 0.008). No significant correlation between age (r = 0.770; P = 0.724), gender (r = 1.157; P = 0.285), International Staging System (ISS) (r = 0.316; P = 0.716) and PH was found. CONCLUSIONS: Preexisted endothelial dysfunction due to structural cardiac disease enhances the vasoactive substances release causing increased pulmonary vascular resistance. Thalidomide possibly causes a vasodilator and vasoconstriction imbalance, which may cause abnormal pulmonary vascular response interfering to a vicious circle perpetuating PH.

Non-Hodgkin's lymphoma involving the uterine cervix after treatment for Hodgkin disease.

The occurrence of second malignancies is an important late event following the treatment of Hodgkin's disease (HD). Occurrence of a non-Hodgkin's lymphoma (NHL) involving the uterine cervix after treatment for HD has not been previously reported. We describe a rare case of a 34-year old woman, with NHL involving the uterine cervix 7.5 years after treatment for HD. The follow-up of patients treated for HD should also include regular gynecological evaluation. In cases of abnormal findings, accurate diagnosis can only be made histologically.

Cyclin D1 by flow cytometry as a useful tool in the diagnosis of B-cell malignancies.

The translocation (11;14)(q13;q32) and its molecular counterpart the BCL-1 rearrangement are features observed in mantle cell lymphoma (MCL) and less commonly in other B-cell disorders. This rearrangement leads to cyclin D1 overexpression, which may be the main pathogenic event in these tumours and is therefore recognised as a diagnostic marker. We developed a flow cytometry method to detect cyclin D1 overexpression using the monoclonal antibody (MoAb) 5D4, and characterised its frequency in 93 B-cell malignancies. The competitive reverse transcriptase polymerase chain reaction (RT-PCR) for cyclin D1, D2 and D3 was then performed on 40 of these cases to assess the validity of the flow cytometry method. Fluorescence in situ hybridisation (FISH) to detect t(11;14)(q13;q32) was carried out on 31 cases and results were compared with cyclin D1 expression by flow cytometry. Twenty five cases showed cyclin D1 expression using 5D4, including MCL (12/13, 92%), chronic lymphocytic leukaemia (CLL) (4/30), B-prolymphocytic leukaemia (B-PLL) (1/4), splenic lymphoma with villous lymphocytes (SLVL) (4/13), hairy cell leukaemia (HCL) (1/7) and other B-non Hodgkins Lymphoma (B-NHL) (3/15). There was a good correlation between flow cytometry results and RT-PCR in 36/40 cases (90%), and with FISH for t(11;14) in 25/31 cases (80%). We concluded that the detection of cyclin D1 expression by flow cytometry in cell suspensions could be applied routinely to the study of B-lymphoproliferative disorders and may be of value for their diagnosis and management.

Pituitary-testicular axis in men with beta-thalassaemia major.

Delayed puberty and hypogonadism are frequently observed in patients with homozygous beta-thalassaemia. We evaluated the pituitary-testicular axis in 30 thalassaemic men, aged from 17 to 35 years who were regularly transfused and underwent chelation therapy, while emphasis was given to pituitary reserves of gonadotrophins and the correlation of hormones with serum ferritin (SF). The investigation included endocrinological examination, evaluation of serum basal levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), free testosterone and gonadotrophin-releasing hormone (GnRH) test and also spermiograms. According to the results, patients were divided into three groups: group A, which included 18 eugonadal patients with moderately elevated SF, group B which included six patients who had hypogonadotrophic hypogonadism and excessive elevation of SF, and group C, which included six patients characterized as intermediate, with regard to sexual maturation and SF levels. In conclusion, beta-thalassaemia major leads to variable pituitary iron overload and thus hypophyseal damage. This endocrine disturbance is becoming less frequent nowadays with early and intensive chelation therapy.