ABSTRACT
Metastatic extramammary Paget's disease is a rare adenocarcinoma with poor prognosis. Several reports of human epidermal growth factor receptor 2 alterations point to its pathogenic role in the disease. However, the occurrence of treatment resistance to anti-HER2 therapy demand the need for further knowledge. We report of a patient with metastatic penoscrotal extramammary Paget's disease, with an ERBB2S310F mutation, in which near complete response was achieved upon treatment with trastuzumab and carboplatin. However, after 10 cycles of trastuzumab and carboplatin, widespread metastasis re-occurred. Analysis of a newly developing metastasis revealed additional genomic alterations including ERBB3A232V and PIK3CAG106V point mutations as well as MET and CDK6 amplification, providing a potential mechanism of acquired treatment resistance. Therefore, ERBB family inhibitor afatinib was initiated. Unfortunately, the patient succumbed to disease-related complications shortly after treatment initiation. This is the first report of ERBB2S310F mutated, metastatic extramammary Paget's disease with secondary resistance to trastuzumab / carboplatin, potentially due to additional acquired genomic alterations. This case contributes to the growing evidence of HER2 in the pathogenesis of metastatic extramammary Paget's disease and emphasizes the importance of repetitive, genomic analysis in rare diseases.
ABSTRACT
Background Smartphone manufacturers offer mobile health monitoring technology to their customers, including apps using the built-in camera for heart rate assessment. This study aimed to test the diagnostic accuracy of such heart rate measuring apps in clinical practice. Methods The feasibility and accuracy of measuring heart rate was tested on four commercially available apps using both iPhone 4 and iPhone 5. 'Instant Heart Rate' (IHR) and 'Heart Fitness' (HF) work with contact photoplethysmography (contact of fingertip to built-in camera), while 'Whats My Heart Rate' (WMH) and 'Cardiio Version' (CAR) work with non-contact photoplethysmography. The measurements were compared to electrocardiogram and pulse oximetry-derived heart rate. Results Heart rate measurement using app-based photoplethysmography was performed on 108 randomly selected patients. The electrocardiogram-derived heart rate correlated well with pulse oximetry ( r = 0.92), IHR ( r = 0.83) and HF ( r = 0.96), but somewhat less with WMH ( r = 0.62) and CAR ( r = 0.60). The accuracy of app-measured heart rate as compared to electrocardiogram, reported as mean absolute error (in bpm ± standard error) was 2 ± 0.35 (pulse oximetry), 4.5 ± 1.1 (IHR), 2 ± 0.5 (HF), 7.1 ± 1.4 (WMH) and 8.1 ± 1.4 (CAR). Conclusions We found substantial performance differences between the four studied heart rate measuring apps. The two contact photoplethysmography-based apps had higher feasibility and better accuracy for heart rate measurement than the two non-contact photoplethysmography-based apps.
