ABSTRACT
Bevacizumab is a monoclonal antibody against vascular endothelial growth factor (VEGF) that is used to treat patients with various cancers. However, it is known to be associated with adverse events, such as hypertension and proteinuria. The histology of bevacizumab-induced nephropathy is known as thrombotic microangiopathy or minimal change nephrotic syndrome. Recently, however, the terms "bevacizumab-associated glomerular microangiopathy" and "anti-VEGF therapy-induced glomerular microangiopathy" have been proposed. We present a case of a 68-year-old woman who was administered postoperative chemotherapy (carboplatin, paclitaxel, and bevacizumab) for stage IV ovarian cancer. Proteinuria and hypertension appeared after three courses; however, six courses were completed. Then, gemcitabine and carboplatin were administered for recurrence of her cancer. She was diagnosed with nephrotic syndrome after eight courses. Renal biopsy showed accumulation of periodic acid-Schiff (PAS)-positive substances in the capillary walls and para-mesangial areas. Double contouring of basement membranes was also observed. Immunofluorescence microscopy revealed positive staining for IgG, IgA, IgM, C3, C4, and C1q. Immunosuppressive therapy was administered, but was ineffective. Further examination by electron microscopy and immunostaining led to a diagnosis of bevacizumab-associated glomerular microangiopathy.
Subject(s)
Antineoplastic Agents, Immunological/adverse effects , Bevacizumab/adverse effects , Kidney Glomerulus/blood supply , Ovarian Neoplasms/drug therapy , Thrombotic Microangiopathies/chemically induced , Aged , Antineoplastic Agents, Immunological/therapeutic use , Bevacizumab/therapeutic use , Biopsy , Drug Therapy/methods , Drug-Related Side Effects and Adverse Reactions , Female , Fluorescent Antibody Technique/methods , Glomerular Mesangium/pathology , Glomerular Mesangium/ultrastructure , Humans , Kidney Glomerulus/pathology , Microscopy, Electron/methods , Neoplasm Regression, Spontaneous , Neoplasm Staging , Nephrotic Syndrome/diagnosis , Nephrotic Syndrome/urine , Ovarian Neoplasms/complications , Ovarian Neoplasms/surgery , Postoperative Care/methods , Proteinuria/diagnosis , Thrombotic Microangiopathies/diagnosisABSTRACT
Transfusion is believed to be the main cause of iron overload in Japan. A nationwide survey on post-transfusional iron overload subsequently led to the establishment of guidelines for iron chelation therapy in this country. To date, however, detailed clinical information on the entire iron overload population in Japan has not been fully investigated. In the present study, we obtained and studied detailed clinical information on the iron overload patient population in Japan. Of 1109 iron overload cases, 93.1% were considered to have occurred post-transfusion. There were, however, 76 cases of iron overload of unknown origin, which suggest that many clinicians in Japan may encounter some difficulty in correctly diagnosing and treating iron overload. Further clinical data were obtained for 32 cases of iron overload of unknown origin; median of serum ferritin was 1860.5 ng/mL. As occurs in post-transfusional iron overload, liver dysfunction was found to be as high as 95.7% when serum ferritin levels exceeded 1000 ng/mL in these patients. Gene mutation analysis of the iron metabolism-related genes in 27 cases of iron overload with unknown etiology revealed mutations in the gene coding hemojuvelin, transferrin receptor 2, and ferroportin; this indicates that although rare, hereditary hemochromatosis does occur in Japan.
Subject(s)
Iron Overload/epidemiology , Iron Overload/etiology , Adolescent , Adult , Aged , Aged, 80 and over , Female , Ferritins/blood , Hemochromatosis/diagnosis , Hemochromatosis/epidemiology , Humans , Iron/metabolism , Iron Overload/genetics , Japan/epidemiology , Liver Diseases/etiology , Male , Metabolic Networks and Pathways/genetics , Middle Aged , Mutation , Surveys and Questionnaires , Transfusion Reaction , Young AdultABSTRACT
Few studies have described the etiologic factors associated with rapid AIDS onset during primary HIV-1 infection. Our molecular epidemiological study identified a cluster of individuals infected with HIV-1 variants characterized by novel mutations in the p6 and pol/vif genes during 2011 and 2013 in Osaka, Japan. Individuals positive for the novel HIV-1 variant showed rapid disease progression, suggesting a role of viral mutations in the fostering of the clinical course of HIV-1 infection.
Subject(s)
HIV Infections/pathology , HIV Infections/virology , HIV-1/genetics , Mutation, Missense , gag Gene Products, Human Immunodeficiency Virus/genetics , pol Gene Products, Human Immunodeficiency Virus/genetics , vif Gene Products, Human Immunodeficiency Virus/genetics , Amino Acid Sequence , Cluster Analysis , HIV Infections/epidemiology , HIV-1/classification , HIV-1/isolation & purification , Humans , Japan/epidemiology , Molecular Epidemiology , Molecular Sequence DataABSTRACT
A 49-year-old pre-menopausal woman was diagnosed with left breast cancer(T2N0M0, stage II A). She was also diagnosed with chronic renal failure for the first time. We performed left breast conserving surgery and sentinel lymph node biopsy. Afterwards, we administered TC therapy(docetaxel 75mg/m / 2, cyclophosphamide 250 mg/m2)as adjuvant therapy every four weeks. No serious side effects occurred during therapy. TC therapy was a safe regimen for a patient with chronic renal failure in our case.
