A Case Report of Graves' Disease Induced by the Anti-Human Programmed Cell Death-1 Monoclonal Antibody Pembrolizumab in a Bladder Cancer Patient.

Immune checkpoint inhibitors, such as anti-programmed cell death-1 (anti-PD-1), have been widely used in the treatment of malignancies. However, these drugs can cause immune-related adverse events resembling autoimmune diseases. There are some reports of Graves' disease (GD) induced by anti-cytotoxic T-lymphocyte-associated antigen 4 antibodies, but reports which discussed GD induced by anti-PD-1 antibodies are very rare. We report the case of a 61-year-old man with bladder cancer who presented with severe diarrhea, fatigue, palpitation, body weight loss, and hyperthyroidism after the fifth treatment with the anti-PD-1 monoclonal antibody pembrolizumab. His thyroid function prior to pembrolizumab administration had been subclinical hyperthyroidism, despite a negative thyroid-stimulating hormone receptor antibody (TRAb) level. On admission, pembrolizumab administration was discontinued. Graves' disease was diagnosed based on a positive TRAb test result and the ultrasonographic finding of increased blood flow in the superior thyroid artery. Based on colonoscopy findings, the cause of diarrhea was diagnosed as active colitis. His diarrhea was improved with prednisolone, and thyroid function was treated with potassium iodide and thiamazole. This case report of GD with positive TRAb induced by the anti-PD-1 antibody pembrolizumab may contribute to the understanding of the mechanism underlying the association between GD and autoimmune activation via PD-1.

Cancer therapeutics-related cardiac dysfunction in a patient treated with abiraterone for castration-resistant prostate cancer.

Abiraterone is an agent effective for castration-resistant prostate cancer, but there have been no reports of cardiotoxic effects inducing cardiomyopathy, to our knowledge. We present a case of an 86-year-old man with castration-resistant prostate cancer treated with abiraterone. He had received an androgen receptor antagonist (bicalutamide) and a gonadotropin-releasing hormone antagonist (degarelix) for 3 years. These agents were changed to enzalutamide due to elevation of plasma prostate-specific antigen level of 129 ng/mL. One year later, the oral androgen receptor inhibitor (enzalutamide) caused drug-induced lung injury and was changed to abiraterone. Transthoracic echocardiography (TTE) revealed normal left ventricular systolic function, and left ventricular ejection fraction (LVEF) was 67%. Four weeks after administration of abiraterone, he complained of dyspnea on effort and bilateral leg edema, and he was diagnosed with heart failure. TTE showed hypokinesis of the diffuse LV, and LVEF decreased to 45%. The various causes of heart failure were excluded. Since a cardiotoxic effect of abiraterone was suspected, administration of abiraterone was discontinued. Two weeks after cessation of abiraterone, LVEF ameliorated to 57%, and then 5 months after cessation of abiraterone, LVEF further improved to 65%. To our knowledge, this is the first report of definite cancer therapeutics-related cardiac dysfunction due to a hormonal agent such as abiraterone diagnosed according to the American Society of Echocardiography and European Association of Cardiovascular Imaging criteria.

A Case of Severe Rectal Hemorrhage Possibly Caused by Radiation Recall after Administration of Gemcitabine.

Radiation recall is an acute inflammatory reaction that can be triggered when systemic agents are administered long time after radiotherapy. Because radiotherapy is now indicated for many types of cancer, care should be taken regarding possible toxic events relating to radiotherapy in combination with radio-sensitizing agents. Gemcitabine, one such anti-cancer agent, is widely used, especially for urologic cancers. We report an intriguing case of possible radiation recall in the rectum caused by gemcitabine administration 37 years after radiation therapy. From a review of the literature, it appears that there have been no reported cases of radiation recall in the rectum with such a long interval between radiation therapy and chemotherapy. Here, we describe the case and provide a literature review.