Background Endobronchial ultrasound (EBUS) elastography assists in the differentiation of benign and malignant lymph nodes (LNs) during transbronchial needle aspiration (TBNA). However, previous studies have not compared B‐mode sonographic images (BSIs) and EBUS elastography images (EEIs) with final pathological diagnoses in radiologically normal‐sized (computed tomography [CT]‐negative) LNs. Methods Consecutive patients with CT‐negative LNs, who received EBUS‐TBNA, were retrospectively reviewed. Images of BSIs and EEIs of each LN were stored and independently evaluated. EEIs were assessed by calculating the stiffness area ratio (SAR, blue/overall areas). The receiver operating characteristic curve was used to calculate the cutoff value for the SAR. Diagnostic test parameters were evaluated for each EBUS finding. Results A total of 132 patients (149 LNs) were enrolled, and the median SAR of malignant LNs was significantly higher than that of benign LNs (0.58 vs. 0.32, P < 0.001). At the SAR cutoff of 0.41, the sensitivity, specificity, positive predictive value, negative predictive value (NPV), and diagnostic accuracy rate (DAR) of elastography were 88.2%, 80.2%, 78.9%, 89.0%, and 83.9%, respectively. The logistic regression analysis showed that elastography was the strongest predictor of malignancy (odds ratio, 18.5; 95% confidence interval [CI]: 6.48–52.6; P < 0.001). The highest NPV (96.6%) was achieved with a combination of BSIs and EEIs. Conclusions EBUS elastography predicted malignant LNs with a high DAR and NPV in CT‐negative LNs. The NPV was highest when EEIs were combined with BSIs. Therefore, the combined evaluation of CT‐negative LNs using EEIs and BSIs may help bronchoscopists perform EBUS‐TBNA more efficiently. Key points Significant findings of the study Endobronchial ultrasound elastography accurately predicted malignancy with a high diagnostic accuracy rate and negative predictive value in radiologically normal‐sized lymph nodes. The additional use of B‐mode sonographic features resulted in a higher negative predictive value. What this study adds Endobronchial ultrasound elastography can guide the accurate collection of specimens with transbronchial needle aspiration, even in radiologically normal‐sized lymph nodes. It can also readily distinguish benign and malignant lymph nodes, thus avoiding unnecessary punctures.

A previously healthy 29-year-old Japanese complaining of dry cough and dyspnea was admitted with tachycardia and low blood pressure. A physical examination revealed a 45mm round abdominal subcutaneous mass (Picture 1). Chest

SMARCA4 (switch/sucrose non-fermentable-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4)-deficient thoracic tumours have shown poor prognosis in clinical settings. Although the optimal treatment for SMARCA4-deficient thoracic tumours remains unclear, existing studies indicate a favourable response of these tumours to immune checkpoint inhibitors (ICIs). However, there are no reports of fatality in SMARCA4-deficient small-cell lung carcinoma (SCLC) with hyperprogressive disease (HPD) upon treatment with ICIs. Herein, we report a patient with SMARCA4-deficient SCLC who had HPD after the first ICI treatment. A 35-year-old man was treated with nivolumab, subsequent to cytotoxic chemotherapy. A week after nivolumab initiation, chest computed tomography revealed marked increase in pleural effusion in the right lung and chest wall dissemination of the tumour, which concur with the definition of HPD. This is the first study to report the occurrence of HPD after treatment with ICIs in a patient with SMARCA4-deficient SCLC. Analysis of additional data is necessary to determine the optimal treatment for these patients.

Granulocyte colony stimulating factor (G-CSF) has been reported to ameliorate impaired liver function in patients with advanced liver diseases through mobilization and proliferation of hepatic progenitor cells (HPCs). However, the underlying mechanisms remain unknown. We previously showed that G-CSF treatment increased the number of bone marrow (BM)-derived cells migrating to the fibrotic liver following repeated carbon tetrachloride (CCl 4 ) injections into mice. In this study, we identified opioid growth factor receptor-like 1 (OGFRL1) as a novel BM cellderived accelerator of fibrotic liver regeneration in response to G-CSF treatment. Endogenous Ogfrl1 was highly expressed in the hematopoietic organs such as the BM and spleen, whereas the liver contained a relatively small amount of Ogfrl1 mRNA. Among the peripheral blood cells, monocytes were the major sources of OGFRL1. Endogenous Ogfrl1 expression in both the peripheral blood monocytes and the liver was decreased following repeated CCl 4 injections. An intrasplenic injection of cells overexpressing OGFRL1 into CCl 4 -treated fibrotic mice increased the number of HPC and stimulated proliferation of hepatic parenchymal cells after partial resection of the fibrotic liver. Furthermore, overexpression of OGFRL1 in cultured HPC accelerated their differentiation as estimated by increased expression of liver-specific genes such as hepatocyte nuclear factor 4α, cytochrome P450, and fatty acid binding protein 1, although it did not affect the colony forming ability of HPC. These results indicate a critical role of OGFRL1 in the mobilization and differentiation of HPC in the fibrotic liver, and administration of OGFRL1-expressing cells may serve as a potential regenerative therapy for advanced liver fibrosis. STEM CELLS 2019; 37:89-101 SIGNIFICANT STATEMENTThe liver is well-known to possess high regenerative capacity in response to injury. However, its regeneration is impaired in the case of advanced liver fibrosis when mature hepatocytes can hardly self-proliferate. Hepatic progenitor cells (HPCs) have been implicated as a source of hepatocytes in regeneration of the fibrotic liver, and efficient mobilization of HPC represents an important strategy to treat liver fibrosis. This study identified a novel blood cell-derived factor that accelerates regeneration of the fibrotic liver through mobilization of HPC. Administration of cells overexpressing this factor may serve as a potential regenerative therapy for advanced liver fibrosis.

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