Disease Flare after Discontinuation of Crizotinib in Anaplastic Lymphoma Kinase-Positive Lung Cancer

We report the case of a 50-year-old male former smoker. He was diagnosed as having lung adenocarcinoma and treated with induction chemoradiation therapy followed by surgery and adjuvant chemotherapy. Molecular testing revealed that his tumor had an echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) rearrangement. Therefore, he was treated with crizotinib when his disease recurred. He achieved a partial response, which persisted for 10 months until progressive disease was confirmed. Crizotinib was continued for 1 month and the tumor size increased slightly. At that time, crizotinib was discontinued and he participated in a clinical trial of erlotinib ± Met inhibitor; however, his disease progressed rapidly after discontinuation of crizotinib, and the diagnosis of disease flare was made. Readministration of crizotinib was started immediately; however, his disease progressed rapidly, and he died 2 days after starting crizotinib retreatment. Currently, the incidence of disease flare is unknown and it is impossible to predict who will experience it. Therefore, continuing crizotinib after disease progression may be a reasonable option to avoid disease flare

Deep-Learning-Aided Detection of Mycobacteria in Pathology Specimens Increases the Sensitivity in Early Diagnosis of Pulmonary Tuberculosis Compared with Bacteriology Tests

The histopathological diagnosis of mycobacterial infection may be improved by a comprehensive analysis using artificial intelligence. Two autopsy cases of pulmonary tuberculosis, and forty biopsy cases of undetected acid-fast bacilli (AFB) were used to train AI (convolutional neural network), and construct an AI to support AFB detection. Forty-two patients underwent bronchoscopy, and were evaluated using AI-supported pathology to detect AFB. The AI-supported pathology diagnosis was compared with bacteriology diagnosis from bronchial lavage fluid and the final definitive diagnosis of mycobacteriosis. Among the 16 patients with mycobacteriosis, bacteriology was positive in 9 patients (56%). Two patients (13%) were positive for AFB without AI assistance, whereas AI-supported pathology identified eleven positive patients (69%). When limited to tuberculosis, AI-supported pathology had significantly higher sensitivity compared with bacteriology (86% vs. 29%, p = 0.046). Seven patients diagnosed with mycobacteriosis had no consolidation or cavitary shadows in computed tomography; the sensitivity of bacteriology and AI-supported pathology was 29% and 86%, respectively (p = 0.046). The specificity of AI-supported pathology was 100% in this study. AI-supported pathology may be more sensitive than bacteriological tests for detecting AFB in samples collected via bronchoscopy

Impaired endothelium-dependent vasodilator response in patients with pulmonary fibrosis.

[Background] Recent epidemiological evidence indicates an association between cardiovascular diseases and pulmonary fibrosis. The vascular endothelium acts to maintain vascular homeostasis through multiple mechanisms and impaired endothelial function can contribute to the development, progression and clinical expression of atherosclerosis. [Methods] We consecutively recruited 39 newly-diagnosed chronic interstitial pneumonitis/fibrosis patients without any specific etiology. We assessed endothelium-dependent vasodilator response of patients using digital pulse amplitude tonometry and compared the reactive hyperemia index (RHI) with age-, sex- and body mass index-matched control subjects (n = 30). We further investigated the relationships between RHI and clinical characteristics, laboratory cardiovascular risk factors, disease-related factors and circulating levels of inflammatory biomarkers. [Results] RHI was significantly lower in patients with chronic interstitial pneumonitis/fibrosis than in control subjects (p = 0.02). While circulating levels of total cholesterol, triglycerides, HbA1c and fasting glucose did not differ significantly between groups, patients with chronic interstitial pneumonitis/fibrosis had significantly lower high density lipoprotein levels and higher low density lipoprotein levels as compared with control subjects. Regarding disease-related factors, RHI was significantly associated with the diffusing capacity for carbon monoxide, alveolar-arterial oxygen pressure difference, 6-min walk distance and end-exercise oxygen saturation. Additionally, circulating levels of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 were inversely correlated with RHI. [Conclusions] We confirmed a possible link between pulmonary fibrosis and cardiovascular disease by demonstrating an impairment of endothelium-dependent vasodilator response, which was significantly associated with the severity of pulmonary fibrosis and circulating levels of adhesion molecules

Disseminated <i>Mycobacterium genavense</i> Infection Mimicking Sarcoidosis: A Case Report and Review of Literature on Japanese Patients

Sarcoidosis is a systemic inflammatory disease characterized by noncaseating epithelioid cell granulomas. However, certain infections can exhibit similar histological findings. We present a case of a 69-year-old man who was initially diagnosed with sarcoidosis and later was confirmed, through 16S rRNA sequencing, to have disseminated Mycobacterium genavense infection. Acid-fast bacteria were detected in the bone marrow biopsy using Ziehl–Neelsen staining, but routine clinical tests did not provide a definitive diagnosis. The patient tested negative for HIV, anti-interferon-gamma antibodies, and genetic immunodeficiency disorders. He was treated with multiple drugs, including aminoglycosides and macrolides, but showed no improvement in fever and pancytopenia. However, these clinical signs responded favorably to steroid therapy. We reviewed 17 Japanese cases of M. genavense infection. All cases were in males; 7/17 (41%) were HIV-negative; and 12/17 (71%) had a decreased CD4 count. Genetic analysis confirmed M. genavense isolation, and macrolides were used universally. Mycobacterium genavense infection is challenging to identify and mimics other systemic inflammatory diseases such as sarcoidosis. There are no standard treatment protocols. Our case report and Japanese case review contribute to understanding this rare disease

Standardized classification of lung adenocarcinoma subtypes and improvement of grading assessment through deep learning

The histopathological distinction of lung adenocarcinoma (LADC) subtypes is subject to high inter-observer variability, which can compromise the optimal assessment of the patient prognosis. Therefore, this study developed convolutional neural networks (CNNs) capable of distinguishing LADC subtypes and predicting disease-specific survival, according to the recently established LADC tumor grades. Consensus LADC histopathological images were obtained from seventeen expert pulmonary pathologists and one pathologist in training. Two deep learning models (AI-1 and AI-2) were trained to predict eight different LADC classes. Furthermore, the trained models were tested on an independent cohort of 133 patients. The models achieved high precision, recall, and F1-scores exceeding 0.90 for most of the LADC classes. Clear stratification of the three LADC grades was reached in predicting the disease-specific survival by the two models, with both Kaplan-Meier curves showing significance (P = 0.0017 and 0.0003). Moreover, both trained models showed high stability in the segmentation of each pair of predicted grades with low variation in the hazard ratio across 200 bootstrapped samples. These findings indicate that the trained CNNs improve the diagnostic accuracy of the pathologist and refine LADC grade assessment. Thus, the trained models are promising tools that may assist in the routine evaluation of LADC subtypes and grades in clinical practice