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Background: In recent years, osimertinib has been increasingly used as a therapeutic drug for epidermal growth factor receptor(EGFR)mutation-positive lung cancer, with heart failure rarely reported as an adverse event. We report here a case of a significantly decreased ejection fraction and heart failure that were induced by osimertinib. We consider the case important and include a discussion of relevant previous reports., Case: The patient was a 73-year-old woman who had been on oral gefitinib as first-line treatment for EGFR mutation-positive(exon19 deletion)non-small cell lung cancer for approximately 1 year and 2 months. Thereafter, she tested positive for an EGFR resistance mutation(T790M); and accordingly, oral osimerti- nib was started at 80mg/day as second-line treatment. After continuing this treatment for 6 months with no particular adverse events, she visited our hospital and was found to have dyspnea on exertion and increased pleural effusion. Based on these findings, cancer relapse was suspected, and the patient was hospitalized for detailed examinations. She was diagnosed with heart failure based on the elevated BNP level that was found in a blood test and CT and echocardiography findings, and her ejection fraction deteriorated to 19% from a pretreatment level of 59%. The conditions improved after diuretic and b- blocker treatment. Given the absence of any possible cause of heart failure or reduced ejection fraction in her past history of illness and medication, we concluded that these conditions were induced by osimertinib., Conclusion: While heart failure induced by EGFR-TKIs has been rarely reported, osimertinib may cause cardiomyopathy due to human epidermal growth factor receptor type 2(HER2)inhibitory activity.

A 76-year-old man, diagnosed with chronic myeloid leukemia in 2010, had been on nilotinib for 7 years. He presented with right hemiparesis in September 2017. He had no history of hypertension, diabetes, hyperlipidemia, heart disease, or smoking. Brain MRI revealed a border-zone infarction of the left cerebral hemisphere and a rapidly progressing severe left internal carotid artery (ICA) stenosis. He was initiated on clopidogrel and bosutinib instead of nilotinib. He presented with right hemiparesis once again in December 2017. Brain MRI revealed the border-zone infarction of the left cerebral hemisphere and a more progressed, severe bilateral ICA stenosis. A carotid ultrasound demonstrated iso-intense and concentrically narrowed ICA on both sides. Carotid artery stenting of the left ICA was performed in February 2018, and clopidogrel was replaced by cilostazol to provide a drug-induced rush. Carotid artery stenting of the right ICA was performed in June 2018 and cervical angiogram demonstrated that there were no residual artery stenoses in the bilateral stent. In recent years, several case reports suggest that tyrosine kinase inhibitors (TKIs) are associated with progressive artery stenosis and cause cerebral infarction. Brain imaging tests should be conducted to evaluate arterial stenosis progression for patients with a history of taking TKI when an arterial vascular event occurs.

We encountered 2 cases of T790M-positive non-small cell lung cancer in patients who developed toxic erythema within a week after initiation of osimertinib(80mg/day)therapy. Since osimertinib was regarded as the suspected drug, we adminis- tered desensitization therapy for osimertinib at an initial dose of 10mg/day. During the process of dose escalation, slight eruption and flare were observed, but we were able to provide appropriate treatment. Osimertinib therapy was continued and conferred tumor reduction in both cases. We report the clinical course and suggest that desensitization therapy is an alternative therapy for patients who present with drug-induced allergic reaction.

Objective: Obtaining the information on safety and effectiveness of radiopharmaceutical synthesizer NEPTIS plug - 01 and florbetapir ( 18 F) injection solution synthesized by NEPTIS plug - 01 from the post marketing surveillance study., Methods: Regarding the safety evaluation, failure of device and adverse events were recorded. Regarding the effectiveness evaluation, we assessed the quality of PET images and the impact on the clinical diagnosis., Result: During the study period, 12 patients were enrolled. No adverse event was reported from those 12 patients. Two events in 2 patients were reported as a failure of device (In a subsequent investigation, those failures were thought to be caused by inadequacy of procedure manual, which has been revised now). For the quality of PET images, all 12 cases were "good" or "excellent", regardless of the positive or negative of amyloid plaque. The attending physician's diagnosis was changed in 9 patients following the PET imaging., Conclusion: NEPTIS plug-01 and florbetapir ( 18 F) were safe and has a favorable effectiveness profile in 12 patients under daily clinical setting.

Two cases of occupational dye users were found to have bladder tumors. Case 1 was a 32-year-old male, who had worked at the Yuzen process for the last 7 years. Multiple papillary tumors were seen on the whole wall of the bladder endoscopically and total cysto-urethrectomy and ileal conduit were performed. The pathological examination of the bladder tumors revealed non-invasive transitional cell carcinoma grade I--II. His post-operative course has been uneventful without any signs of tumor recurrence for 31 months. Case 2 was a 46-year-old male, who had worked at the throwing stained silk for the last 28 years. He suffered from severe hematuria for six months. A big egg-sized nonpapillary tumor on the posterior wall of the bladder was found and bilateral cutaneous-ureterostomy was performed but severe gross hematuria remained. Total cysto-urethrectomy was performed but the patient died of progressive disease 5 months later. The bladder tumor was a grade III invasive transitional cell carcinoma. The fact that process workers in the dye manufacturing industry have a high risk of bladder cancer has been well known and mass screening examination on them has been systematically performed. Though there is a higher relative risk of bladder cancer in occupational dye users, systematic screening examination has not been done. We emphasize the necessity for establishing systematic mass screening examination of occupational dye users for the early diagnosis of bladder cancer.