BackgroundGuidelines recommend endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) as an initial investigation technique for mediastinal nodal staging in lung cancer. However, EBUS-TBNA can be limited by the inadequacy of intact tissues, which might restrict its diagnostic yield in mediastinal lesions of certain etiologies. We have previously shown that EBUS-guided transbronchial mediastinal cryobiopsy can provide intact samples with greater volume.MethodsThis randomised study determined the diagnostic yield and safety of transbronchial mediastinal cryobiopsy monitored by endosonography for the diagnosis of mediastinal lesions. Patients with mediastinal lesion of 1 cm or more in the short axis were recruited. Following identification of the mediastinal lesion by linear EBUS, fine-needle aspiration and cryobiopsy were sequently performed in a randomised order. Primary endpoints were diagnostic yield defined as the percentage of patients for whom mediastinal biopsy provided a definite diagnosis, and procedure-related adverse events.ResultsOne hundred and ninety-seven patients were enrolled and randomly allocated. The overall diagnostic yield was 79.9% and 91.8% for TBNA and transbronchial mediastinal cryobiopsy, respectively (p=0.001). Diagnostic yields were similar for metastatic lymphadenopathy (94.1% versus 95.6%, p=0.58), while cryobiopsy was more sensitive than TBNA in uncommon tumors (91.7% versus 25.0%, p=0.001) and benign disorders (80.9% versus 53.2%, p=0.004). No significant differences in diagnostic yield were detected between TBNA first and cryobiopsy first groups. We observed 2 cases of pneumothorax and 1 case of pneumomediastinum.ConclusionsTransbronchial cryobiopsy performed under EBUS guidance is a safe and useful approach that offers diagnostic histological samples of mediastinal lesions.

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Long non-coding RNA plasmacytoma variant translocation 1 (PVT1) is up-regulated in various human cancers, and our results indicated that PVT1 was up-regulated in clear cell renal cell carcinoma tissues. The Cancer Genome Atlas cohort analysis revealed that in clear cell renal cell carcinoma, higher PVT1 expression correlated with advanced TNM stage, histological grade, and poor survival. PVT1 knockdown promoted apoptosis, inhibited renal cancer cell proliferation, decreased Mcl-1, and increased cleaved caspase-3 and cleaved PARP. PVT1 increased Mcl-1 mRNA levels in renal cancer cells by promoting mRNA stability without influencing its transcription. in vitro, the enhanced apoptosis arising from PVT1 suppression was attenuated by overexpressing Mcl-1. In addition, in vivo experiments showed that PVT1 knockdown repressed xenograft tumor growth, while Mcl-1 overexpression partially rescued xenograft tumor growth. These results indicate the PVT1/Mcl-1 pathway inhibits renal cancer cell apoptosis in vitro and in vivo. PVT1 may thus serve as a novel biomarker, and the PVT1/Mcl-1 pathway may be a useful therapeutic target for clear cell renal cell carcinoma.

Mediastinal biopsy is essential for the clinical diagnosis of mediastinal disease. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a well-established approach for obtaining diagnostic samples from mediastinal masses or enlarged lymph nodes which is proven to be minimally invasive and effective. However, the insufficiency of intact samples acquired might restrict the diagnostic efficacy of EBUS-TBNA for mediastinal lesions such as rare malignancy and granulomatous disorder. We here present an EBUS-guided approach for the cryobiopsy of mediastinal diseases that is capable of providing larger amounts of intact tissue with few observed complications.