J. Terrill Huggins

Using Endobronchial Ultrasound Features to Predict Lymph Node Metastasis in Patients With Lung Cancer

PURPOSES Reliable staging of the mediastinum determines TNM classification and directs therapy for non-small cell lung cancer (NSCLC). Our aim was to evaluate predictors of mediastinal lymph node metastasis in patients undergoing endobronchial ultrasound (EBUS). METHODS Patients with known or suspected lung cancer undergoing EBUS for staging were included. Lymph node radiographic characteristics on chest CT/PET scan and ultrasound characteristics of size, shape, border, echogenicity, and number were correlated with rapid on-site evaluation (ROSE) and final pathology. Logistic regression (estimated with generalized estimating equations to account for correlation across nodes within patients) was used with cancer (vs normal pathology) as the outcome. ORs compare risks across groups, and testing was performed with two-sided α of 0.05. RESULTS Two hundred twenty-seven distinct lymph nodes (22.5% positive for malignancy) were evaluated in 100 patients. Lymph node size, by CT scan and EBUS measurements, and round and oval shape were predictive of mediastinal metastasis. Increasing size of lymph nodes on EBUS was associated with increasing malignancy risk (P = .0002). When adjusted for CT scan size, hypermetabolic lymph nodes on PET scan did not predict malignancy. Echogenicity and border contour on EBUS and site of biopsy were not significantly associated with cancer. In 94.8% of lymph nodes with a clear diagnosis, the ROSE of the first pass correlated with subsequent passes. CONCLUSIONS Lymph node size on CT scan and EBUS and round or oval shape by EBUS are predictors of malignancy, but no single characteristic can exclude a visualized lymph node from biopsy. Further, increasing the number of samples taken is unlikely to significantly improve sensitivity.

Successful Real-Time Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration of a Hilar Lung Mass Obtained by Traversing the Pulmonary Artery

The utility and safety of transbronchial needle aspiration is well described. Serious complications from transbronchial needle aspiration are exceedingly rare. The addition of endoscopic ultrasonographic techniques in the form of endoscopic ultrasonography and, more recently, endobronchial ultrasonography has added valuable information regarding lymphatic anatomy of the hilum and mediastinum. In addition, the use of real-time ultrasound gives the operator visual feedback of needle placement and proximity to major surrounding structures such as the heart and great vessels. Here, the authors present the case of a 74-year-old man with a left hilar mass who underwent biopsy by means of intentional traverse of the pulmonary artery.

Dasatinib-induced pleural effusions: a lymphatic network disorder?

Dasatanib, which has been approved for rescue therapy for patients with imatinib-resistant chronic myelogenous leukemia and Philadelphia chromosome positive acute lymphoblastic leukemia, is a novel, orally available multitargeted kinase inhibitor of BCR-ABL and SRC family kinases (Quintas-Cardama et al, J Clin Oncol 2007;25:3908-14). It binds to both active and inactive conformations of the ABL gene and is 325 times more potent than imatinib in inhibiting the growth of BCR/ABL cells in vitro (Morelock and Sahn, Chest 1999;116:212-21; Huggins and Sahn, Clin Chest Med 2004;25:141-53). Although dasatinib is a generally well-tolerated drug in the treatment of Philadelphia chromosome positive hematopoetic malignancies, pleural effusions have been frequently noted and have been reported in up to 35% of patients (Sahn SA. Drug-induced pleural disease. In: Camus P, Rosenow E, editors. Drug-induced iatrogenic lung disease. London: Hodder Arnold; 2009). Although there have been numerous reports of effusions, none have provided complete pleural fluid analysis; therefore, we report 2 patients with dasatinib-induced pleural effusion with complete pleural fluid analysis.

Intrapleural therapy: Intrapleural therapy

Numerous intrapleural therapies have been adopted to treat a vast array of pleural diseases. The first intrapleural therapies proposed focused on the use of fibrinolytics and DNase to promote fluid drainage in empyema. Numerous case series and five randomized controlled trials have been published to determine the outcomes of fibrinolytics in empyema treatment. In the largest randomized trial, the use of streptokinase had no reduction in mortality, decortication rates or hospital days compared with placebo in the treatment of empyema. Criticism over study design and patient selection may have potentially affected the outcomes in this study. The development of dyspnoea is common in the setting of malignant pleural effusions. Pleural fluid evacuation followed by pleurodesis is often attempted. Numerous sclerosing agents have been studied, with talc emerging as the most effective agent. Small particle size of talc should be avoided because of increased systemic absorption potentiating toxicity, such as acute lung injury. Over the past several years, the use of chronic indwelling pleural catheters have emerged as the preferred modality in the treating a symptomatic malignant pleural effusion. For patients with malignant‐related lung entrapment, pleurodesis often fails due to the presence of visceral pleural restriction; however, chronic indwelling pleural catheters are effective in palliation of dyspnoea. Finally, the use of staphylococcal superantigens has been proposed as a therapeutic model for the treatment of non‐small lung cancer. Intrapleural instillation of staphylococcal superantigens increased median survival by 5 months in patients with non‐small cell lung cancer with a malignant pleural effusion.

Safety of Nintedanib Added to Pirfenidone Treatment for Idiopathic Pulmonary Fibrosis

We assessed safety and tolerability of treatment with pirfenidone (1602–2403 mg·day−1) and nintedanib (200–300 mg·day−1) in patients with idiopathic pulmonary fibrosis (IPF). This 24-week, single-arm, open-label, phase IV study (ClinicalTrials.gov identifier NCT02598193) enrolled patients with IPF with forced vital capacity % pred ≥50% and diffusing capacity of the lung for carbon monoxide % pred ≥30%. Before initiating nintedanib, patients had received pirfenidone for ≥16 weeks and tolerated a stable dose of ≥1602 mg·day−1 for ≥28 days. The primary end-point was the proportion of patients who completed 24 weeks of combination treatment on pirfenidone (1602–2403 mg·day−1) and nintedanib (200–300 mg·day−1). Investigators recorded treatment-emergent adverse events (TEAEs), attributing them to pirfenidone, nintedanib, both or neither. 89 patients were enrolled; 73 completed 24 weeks of treatment (69 meeting the primary end-point) and 16 discontinued treatment prematurely (13 due to TEAEs). 74 patients had 418 treatment-related TEAEs, of which diarrhoea, nausea and vomiting were the most common. Two patients had serious treatment-related TEAEs. Combined pirfenidone and nintedanib use for 24 weeks was tolerated by the majority of patients with IPF and associated with a similar pattern of TEAEs expected for either treatment alone. These results encourage further study of combination treatment with pirfenidone and nintedanib in patients with IPF. Combined pirfenidone and nintedanib was tolerated by the majority of patients with IPF, encouraging further study http://ow.ly/1Iq030kaZuD

A 37-Year-Old Woman With Diabetes Mellitus, Systemic Hypertension, and Chronic Kidney Disease Admitted With Multifocal Pneumonia and Empyema

Manuscript received November 15 , 2013 ; revision accepted February 28 , 2014 . AFFILIATIONS: From the Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine (Drs Huggins, Kummerfeldt, Nestor, and Pastis) and the Division of Nephrology (Drs Karakala and Campbell), Medical University of South Carolina, Charleston, SC; and the Division of Pulmonary and Critical Care (Dr Doelken), Albany Medical Center, Albany, NY. CORRESPONDENCE TO: J. Terrill Huggins, MD, Medical University of South Carolina, Pulmonary, Critical Care, Allergy and Sleep Medicine, 96 Jonthan Lucas St, Charleston, SC; e-mail: hugginjt@musc.edu