losartan-potassium and Paraneoplastic-Syndromes

The modern views on the coexistence of secondary polycythaemia with benign and malignant tumours of varying origin are reviewed describing certain mechanisms determining this association. The diagnostic management of secondary polycythaemia is outlined calling attention to the necessity of ruling out coexistence of a neoplasm.

Topics: Adenocarcinoma; Cerebellar Neoplasms; Erythrocyte Count; Erythropoietin; Hemangiosarcoma; Humans; Kidney Neoplasms; Liver Neoplasms; Paraneoplastic Syndromes; Polycythemia

Topics: Anemia; Bone Marrow Transplantation; Clinical Trials as Topic; Double-Blind Method; Erythropoietin; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoietic Cell Growth Factors; Humans; Immunologic Factors; Interleukin-3; Macrophage Colony-Stimulating Factor; Myelodysplastic Syndromes; Neoplasms; Paraneoplastic Syndromes; Randomized Controlled Trials as Topic; Recombinant Proteins

Topics: Anemia; Animals; Biological Assay; Diagnosis, Differential; Enzyme-Linked Immunosorbent Assay; Erythropoietin; Humans; Paraneoplastic Syndromes; Polycythemia; Predictive Value of Tests; Radioimmunoassay; Reference Values

It is noted that while a wide variety of syndromes have been associated with hypernephroma in the clinical literature, there is clear understanding of the pathophysiology of these effects only in the cases of the endocrine disorders where direct tumor production of hormone can be demonstrated in vitro. Furthermore, this knowledge has done little to alter the care of patients with the disease, except for indications that indomethacin might be of benefit in some patients with hypercalcemia and that one might consider the use of converting enzyme inhibitors in patients with hypernephroma and hypertension. The overall approach to the disease is still surgical. Resection of the tumor also removes the paraneoplastic syndrome. Persistence or recurrence of a syndrome suggests the continued presence of the neoplasm, with the considerations for prognosis which that fact entails. To that degree, at least, these conditions are useful as tumor markers, but such use is limited because they are inconsistent. Further studies of pathophysiology of paraneoplastic syndromes will lead to better understanding of processes of cell differentiation and regulation, and possibly better ways to manage the patients in which they occur.

Topics: Carcinoma, Renal Cell; Chorionic Gonadotropin; Erythropoietin; Glucagon-Like Peptides; Humans; Hypercalcemia; Kidney Neoplasms; Paraneoplastic Endocrine Syndromes; Paraneoplastic Syndromes; Parathyroid Hormone; Prolactin; Prostaglandins; Renin

Paraneoplastic erythrocytosis can be brought on by ectopic erythropoietin production usually in kidney, brain, and liver tumor with increase of serum erythropoietin level. We report here a paraneoplastic erythrocytosis of colon cancer with serum erythropoietin within the normal reference, which required an immunohistologic test for erythropoietin-antibody to be diagnosed.. Our case report was of a 75-year-old woman with erythrocytosis. Her hemoglobin and serum erythropoietin levels were 191 g/dL and 12.6 IU/L (reference range, 9.1-32.8), respectively. Colonoscopy revealed an advanced sigmoid colon tumor 20 mm in diameter. She underwent colectomy, and immunohistochemical examination showed the colon adenocarcinoma was focally positive for erythropoietin-antibody. One month after the surgery, her hemoglobin level decreased to 117 g/L.. Colon cancer can cause paraneoplastic erythrocytosis, and it is important to consider not simply the absolute serum erythropoietin level but also the serum erythropoietin level relative to simultaneously measured hemoglobin level. We should include paraneoplastic erythrocytosis as a differential diagnosis in cases of high hemoglobin level unexplained by other diseases.

Topics: Adenocarcinoma; Aged; Colonic Neoplasms; Erythropoietin; Female; Humans; Paraneoplastic Syndromes; Polycythemia; Reference Values

We describe the first reported case, in an 82-year-old man, of erythrocytosis caused by an erythropoietin (EPO)-producing thymic carcinoma. The patient underwent computed tomography-guided fine-needle aspiration of a 6-cm anterior mediastinal mass, and histological findings revealed thymic squamous cell carcinoma. The existence of EPO was confirmed immunohistochemically using the tumor tissue. Postoperative clinical improvement of erythrocytosis and the decline of EPO suggest a paraneoplastic nature of erythrocytosis as seen in this patient.

Topics: Aged, 80 and over; Biopsy, Fine-Needle; Carcinoma, Squamous Cell; Erythropoietin; Humans; Immunohistochemistry; Male; Paraneoplastic Syndromes; Phlebotomy; Polycythemia; Thymectomy; Thymoma; Thymus Neoplasms; Time Factors; Tomography, X-Ray Computed; Treatment Outcome

Signalling by erythropoietin (EPO) is increasingly recognised as a relevant mechanism in tumour biology, potentially leading to enhanced proliferation, angiogenesis and therapy resistance. Paraneoplastic polycythemia by cancerous overproduction of EPO is a rare event, but most frequently seen in patients with renal cell carcinoma (RCC). The majority of clear cell RCC displays a strong activation of the transcription factor regulating EPO, the Hypoxia-inducible Factor (HIF). Therefore, it is unclear why only a small minority of patients develop polycythemia. We studied 70 RCC for EPO gene and HIFalpha isoform expression. 34% of all RCC showed expression of EPO mRNA in RNase protection assays, which were almost exclusively of the clear cell type. Only 1 patient presented with polycythemia. In situ hybridisation revealed that expression of EPO was in the tumour cells. Expression of EPO mRNA was always associated with activation of HIF, which could involve HIF-1alpha and/or HIF-2alpha. The frequency of EPO gene expression in RCC is therefore much higher than the prevalence of polycythemia. Furthermore, activation of HIF appears necessary for EPO gene expression in RCC, but is clearly not the only determinant. Further to the reported expression of EPO receptors in tumour tissues, the finding of widespread expression of EPO in RCC supports the recent notion of an involvement of this system in paracrine or autocrine effects of tumour cells.

Topics: Adenocarcinoma, Clear Cell; Basic Helix-Loop-Helix Transcription Factors; Carcinoma, Renal Cell; Cell Line, Tumor; Erythropoietin; Gene Expression Regulation, Neoplastic; Germany; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Immunoblotting; In Situ Hybridization; Kidney Neoplasms; Paraneoplastic Syndromes; Polycythemia; Prevalence; Ribonucleases; RNA, Messenger; Signal Transduction; Tumor Cells, Cultured; Up-Regulation

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Erythropoietin; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Middle Aged; Paraneoplastic Syndromes; Phlebotomy; Polycythemia; Prednisone; Rituximab; Vincristine

Topics: Anemia; Diphosphonates; Erythropoietin; Hematopoietic Stem Cell Transplantation; Humans; Multiple Myeloma; Osteolysis; Pain; Paraneoplastic Syndromes; Recombinant Proteins

In rats with Mat Lylu prostatic carcinoma, significant changes in blood composition and red blood cell (RBC) characteristics were observed. Anaemia, characterised by a decrease in the number of RBC and the reduction of haemoglobin and the iron content in plasma, was correlated with tumour size and the accumulation of spermidine and spermine in the RBC. In large tumours, spermidine levels were increased by 8-fold over normal value. Spleen weight and splenic spermidine concentrations were enhanced in animals with tumours. After splenectomy, the rate of tumour growth decreased by 30%. It is proposed that anaemia in tumour-bearing animals is caused by enhanced RBC lysis, owing to the alteration of the rheological properties of RBC. These may be caused by the alterated surface characteristics due to polyamine accumulation. RBC lysis and high concentrations of polyamines in RBC and spleen appear, not only to favour tumour growth, but also to compromise the immunological defence mechanisms against neoplastic invasion.

Topics: Anemia; Animals; Erythrocyte Count; Erythrocytes; Erythropoietin; Iron; Male; Neoplasm Transplantation; Paraneoplastic Syndromes; Polyamines; Prostatic Neoplasms; Rats; Rats, Inbred Strains; Spleen; Urea

Hepatocellular carcinoma (HCC) is a common malignancy in southeast Asia and sub-Saharan Africa. During its clinical course, patients may manifest a variety of paraneoplastic syndromes, including erythrocytosis. However, there are few reports on the clinical and biochemical characteristics of HCC patients who manifest erythrocytosis. The purpose of this study is to evaluate the incidence of erythrocytosis in a large series of the Chinese patients with HCC, and to investigate the association of erythrocytosis with tumor volume and with serum levels of alpha-fetoprotein (AFP) and erythropoietin.. Among 792 Chinese HCC patients who were seen during a 3-year period, we identified HCC patients with erythrocytosis as those with hemoglobin levels greater than 16.7 gm/dL (two standard deviations above the mean hemoglobin level of matched normal controls). The tumor size and serum levels of AFP and erythropoietin were evaluated in HCC patients with erythrocytosis to compare with HCC patients without erythrocytosis.. 20 (2.5%) of 792 Chinese HCC patients presented with erythrocytosis. Nineteen of these 20 HCC patients were found to have either bi-lobar tumor involvement or a large tumor mass confined to one lobe of the liver. The estimated mean tumor volume of HCC patients with erythrocytosis was 50% of whole liver. When compared with HCC patients without erythrocytosis, the 20 HCC patients with high hemoglobin levels had significantly higher serum levels of AFP and erythropoietin (356,343 +/- 145,807 vs. 16,881 +/- 10,425 ng/mL, 135 +/- 45 vs. 25 +/- 4 mU/mL, respectively, p < 0.01).. Base on our findings, detection of erythrocytosis in a patient with HCC would indicate the presence of a large tumor burden, and high serum levels of both AFP and erythropoietin should be associated with this paraneoplastic syndrome.

Topics: alpha-Fetoproteins; Carcinoma, Hepatocellular; Erythropoietin; Female; Humans; Liver Neoplasms; Male; Middle Aged; Paraneoplastic Syndromes; Polycythemia

Topics: Aged; Carcinoma, Hepatocellular; Erythrocyte Count; Erythropoietin; Hepatorenal Syndrome; Humans; Liver Cirrhosis, Alcoholic; Liver Neoplasms; Male; Paraneoplastic Syndromes; Polycythemia

The paraneoplastic syndrome of erythrocytosis is associated with a variety of neoplasms including renal adenocarcinoma, cerebellar hemangioma, and hepatoma. We now report the characterization of the biological and molecular features of an erythropoietin-secreting human renal adenocarcinoma, designated RCCEp+. Serial transplantation of the tumor in athymic mice resulted in a dramatic increase in hematocrit and serum erythropoietin concentration. Growth in vitro was accompanied by a constant rate of erythropoietin secretion. Karyotype analysis demonstrated several unusual features, including the absence of 3p deletions and near tetraploidy. Erythropoietin mRNA was demonstrated by Northern blot both in freshly excised tumor and in tumor cells growing in vitro. Erythropoietin secretion was constitutive and was not induced either by cobalt or hypoxia. Southern blot analysis revealed no rearrangement of the erythropoietin gene in the tumor. Interestingly, in situ hybridization demonstrated erythropoietin mRNA in only a small population of the tumor cells. Further studies of RCCEp+ should prove useful in elucidating the molecular basis for this paraneoplastic syndrome.

Topics: Animals; Carcinoma, Renal Cell; Erythropoietin; Female; Gene Expression; Humans; In Situ Hybridization; In Vitro Techniques; Kidney Neoplasms; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Paraneoplastic Syndromes; Polycythemia; RNA, Messenger; Transplantation, Heterologous; Tumor Cells, Cultured

The prevalence of increased serum immunoreactive erythropoietin (Epo) was determined in a prospective study of 49 patients with renal cell carcinoma. Measured by a monoclonal antibody based commercial enzyme-linked immunoassay, the Epo concentration was above the normal range, determined in nonanemic humans, in four of the renal carcinoma patients. Since three of these were anemic, their increased Epo level was considered to be appropriate. The high estimate of serum Epo (218 U/l) in the fourth patient, who was not anemic, was not confirmed when tested by radioimmunoassay. Thus, in contrast with earlier studies, our results indicate that increased Epo is not a clear serological renal cell carcinoma marker. In addition, when monolayer cell cultures of 14 different established human renal carcinoma lines were screened, none of these released immunoreactive Epo in measurable amounts.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Renal Cell; Cell Hypoxia; Enzyme-Linked Immunosorbent Assay; Erythropoietin; Female; Humans; Kidney Neoplasms; Male; Middle Aged; Paraneoplastic Syndromes; Prevalence; Prospective Studies; Tumor Cells, Cultured

Paraneoplastic erythrocytosis in patients with Wilms' tumors is exceedingly rare, with only three reported cases in the literature. We report a case of a young man with Wilms' tumor with a significant erythrocytosis but a normal serum erythropoietin level and a tumor that elaborated erythropoietin.

Topics: Adult; Erythropoietin; Humans; Kidney Neoplasms; Male; Paraneoplastic Syndromes; Polycythemia; Wilms Tumor

Topics: Adrenocorticotropic Hormone; Bartter Syndrome; Calcitonin; Choriocarcinoma; Corticotropin-Releasing Hormone; Erythropoietin; Female; Gonadotropins; Humans; Hypercalcemia; Hypoglycemia; Male; Paraneoplastic Endocrine Syndromes; Paraneoplastic Syndromes; Pregnancy; Prolactin; Renin; Repressor Proteins; Teratoma; Testicular Neoplasms; Thyrotropin