Yousef Shweihat

Complete mediastinal and hilar lymph node staging of primary lung cancer by endobronchial ultrasound: Moderate sedation or general anesthesia?

We are responding to the concerns raised by Rice and colleagues regarding the Lung Cancer Guidelines1 related to the treatment for patients with potentially resectable stage IIIA lung cancer, in which N2 nodal metastases were histologically proven prior to surgery, our stage IIIA3. Our recommendations were based primarily on the randomized trials listed in Table 6.1 The two largest and most recent multicenter trials2,3 provided the most convincing data. In the European Organisation for Research and Treatment of Cancer (EORTC) 08941 trial,2 patients with histologically proven stage IIIA-N2 non-small cell lung cancer were administered induction chemotherapy. Only responders were randomized to either surgical resection with or without postoperative radiotherapy vs sequential radiotherapy without surgery. Rice et al note the fact that this trial accrued patients with “unresectable N2 disease” and question whether results would be applicable to patients with resectable stage IIIA. In the “Methods” section of their publication,2 the EORTC definition of “unresectable” was as follows: “(1) any N2 involvement by a nonsquamous carcinoma; (2) in the case of squamous cell carcinoma any N2 involvement exceeding level 4R in a right-sided tumor and level 5 and 6 for a left sidedtumor.” Essentially the EORTC considered unresectable all stage IIIA-N2 patients with single or multistation N2 metastases, which is exactly the focus of the stage IIIA chapter. The progression-free survival and the overall survival of the chemotherapy/surgery and chemoradiotherapy groups were not statistically different. The conclusion of the EORTC was “in view of its low morbidity and mortality, radiotherapy should be considered the preferred locoregional treatment for these [Stage IIIA-N2] patients.”2 The other large randomized, multicenter trial3 was Intergroup 0139, in which stage IIIA-N2 patients received induction chemoradiotherapy. Responders were randomized to surgical resection followed by chemotherapy vs completion of radiotherapy plus more chemotherapy. In this trial,3 the 30-day operative mortality was high overall at 7.9% and especially elevated in pneumonectomy patients (25.9%). Although the progression-free survival favored the surgical arm (median survival, 12.8 months in the surgical arm vs 10.5 months in the chemoradiotherapy arm, p 0.017), overall survival rates at 2 years and 5 years were not significantly different in the two treatment groups. Unfortunately, full data from this study have not been published, so we are unable comment on questions raised about any post hoc subgroup analysis. Of the earlier two small induction therapy studies in Table 6, the trial by Taylor et al4 was indeed retrospective and was included in error. The final study was the earlier, small Radiation Therapy Oncology Group 89-01, a randomized phase III trial5 of stage IIIA patients with histologically proven N2 disease. After induction chemotherapy, patients were randomized to surgery vs sequential radiotherapy followed by additional chemotherapy. There was no significant difference between the two treatment groups in progression-free survival or overall survival. Unfortunately, this study closed prematurely due to poor patient accrual, making the results inconclusive. Intuitively, surgical resection of the cancer seems ideal, particularly to thoracic surgeons (including one of the authors, L.A.R.). The occasional patient with complete N2 node clearing from induction chemotherapy (occurring in perhaps 20% of patients) may truly benefit from surgical resection, although it is likely concurrent radiotherapy in this subgroup would have an equally effective role. This may be the reason that the randomized trials show no superior survival benefit with surgery. After an exhaustive discussion of this controversial subset of stage IIIA reviewing primarily the two large randomized induction therapy trials,3,4 the Lung Cancer Guidelines Panel concluded that employing surgery for locoregional control did not provide a superior survival advantage. Therefore, the less morbid modality of radiotherapy added to chemotherapy delivered concurrently, when possible, is the preferred treatment regimen for stage IIIA.

Is chest tube insertion with ultrasound guidance safe in patients using clopidogrel

Background and objective:  Drainage of the pleural space is a common procedure. The safety of chest tube insertion in patients using clopidogrel has not been investigated.

Oesophageal applications of the convex curvilinear ultrasound bronchoscope; an illustrative case series

A series of cases is used to demonstrate use of convex curvilinear ultrasound bronchoscope via the oesophagus in the diagnosis of non‐nodal thoracic disease. This scope has a breadth of application that has not to date been fully explored. Criteria for preferential use of the oesophagus are delineated.

Isolated Candida infection of the lung

Candida pneumonia is a rare infection of the lungs, with the majority of cases occurring secondary to hematological dissemination of Candida organisms from a distant site, usually the gastrointestinal tract or skin. We report a case of a 77-year-old male who is life-long smoker with a history of rheumatoid arthritis and polymyalgia rheumatica, but did not take immunosuppressants for those conditions. Here, we present an extremely rare case of isolated pulmonary parenchymal Candida infection in the form pulmonary nodules without evidence of systemic disease which has only been described in a few previous reports.

Severe Pneumomediastinum Complicating EBUS-TBNA.

To the Editor: Pneumomediastinum infrequently complicates diagnostic bronchoscopy. Increased airway or alveolar pressure results in air leaks to the mediastinum through existing or induced defects. Excessive cough, recurrent episodes of increased abdominal pressure, vomiting, or sneezing can all induce spontaneous pneumomediastinum. Less commonly it has been documented with lung or neck infections, esophageal or tracheal tears, and rapid increases in altitude such as during plane flights or scuba diving, with mechanical ventilation, substance abuse, and after bronchoscopy. Pneumomediastinum may be, but is not always, associated with pneumothorax. We recently evaluated a 63-year-old male patient with a 2-day history of hemoptysis and a left upper-lobe lung mass with hilar adenopathy and a postobstructive process. Flexible white light bronchoscopy showed a normal airway except for an occluded left upper-lobe bronchus with sparing of the lingula. Multiple forceps biopsies were obtained from the apparent endobronchial lesion. Endobronchial ultrasound (EBUS)-guided lymph node biopsies were obtained from stations 4R, 4L, 7, and 11L. During the procedure there were no complications and no bleeding. The pathology report revealed moderately differentiated squamous cell cancer from only the left upper-lobe endobronchial biopsies. One day after discharge the patient returned to the emergency room with recurrent severe cough and chest and neck pain associated with increasing swelling of the neck. There was no hemodynamic or respiratory compromise. CT scan of the chest and neck (Fig. ​(Fig.1)1) to investigate the neck and chest “swelling” showed pneumomediastinum with extensive subcutaneous emphysema with no apparent pneumothorax. The patient was treated with cough suppressants, analgesics, and stool softeners, along with oxygen supplementation through a nasal cannula. The pneumomediastinum and subcutaneous emphysema resolved without any other intervention. The pneumomediastinum was felt to be iatrogenic and was most likely related to the bronchoscopic procedure. FIGURE 1 CT scan of the chest and neck showing pneumomediastinum and subcutaneous air (arrows). Lung mass in the left upper lobe (asterisk). Bronchoscopy with endobronchial ultrasound–guided transbronchial needle aspiration (EBUS-TBNA) is considered to be a very safe procedure and is certainly less invasive than mediastinoscopy or percutaneous needle biopsy. It has been increasingly utilized for the diagnosis of sarcoidosis, for unexplained mediastinal adenopathy, and for lung cancer staging. Complications from EBUS-TBNA are rare. Focal tracheal stenosis secondary to intramural hematoma following EBUS-TBNA has been reported.1 Barotrauma after ablation techniques has previously been seen.2 Pneumothorax was reported in 0.03% (2/7345) of procedures in a survey of 455 facilities in Japan.3 There was no pneumomediastinum reported. Hemorrhagic and infectious complications were the most common. A review of the AQuIRE registry for complications revealed no reported cases of pneumomediastinum, with a rate of pneumothorax of 0.2% reported among patients who did not undergo transbronchial biopsies.4 In a comprehensive review of all published articles on endosonography of the mediastinum (EBUS or EUS or their combination) from 1995 to 2012, von Bartheld et al5 did not report any case of pneumomediastinum. Most complications from this procedure were infectious. EUS was the main risk factor for complications, with 18 of 23 serious complications being observed in this group, compared with EBUS. To our knowledge, this is the first case of pneumomediastinum that is associated with EBUS-TBNA. It is unlikely that the positive pressure ventilation used during the procedure caused the pneumomediastinum. The procedure was performed through the LMA utilizing general anesthesia but with spontaneous ventilation and 5 cm water pressure support. In addition, the patient presented with pneumomediastinum >24 hours after the procedure, which makes it less likely to be related to the positive pressure and more likely related to a defect created by the procedure in the bronchial wall and exacerbated by cough. Although the direct cause of the pneumomediastinum cannot be certainly established, whether related to the TBNA or to the endobronchial biopsy, we would like to alert other bronchoscopists of the potential rare complication and stress upon the fact that conservative therapy should be the first line of treatment. Treatment should be aimed at decreasing intrathoracic pressure spikes by reducing coughing and straining. Oxygen therapy might hasten reabsorption of the subcutaneous nitrogen bubble as it does to a pneumothorax.

Pulmonary Varices in an Adult.

Received for publication April 2, 2015; accepted August 21, 2015. From the *Department of Internal Medicine, Division of Pulmonary and Critical Care, Marshall University; and wThe VA Medical Center, Huntington, WV. Disclosure: There is no conflict of interest or other disclosures. Reprints: Yousef R. Shweihat, MD, FCCP, DAABIP, Oma Byrd Center, 1249 15th Street, Suite #3, Huntington, WV 25701 (e-mail: shweihat@marshall.edu). Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved. IMAGES IN INTERVENTIONAL PULMONOLOGY

Dietary potassium and cardiovascular profile. Results from the modification of diet in renal disease dataset

Editor: We have recently reported that dietary potassium correlates negatively with body mass index (BMI) and proteinuria.1 Moreover, high potassium diets have a protective effect against the development of vascular damage induced by salt loading.2 In an effort to dissect the possible mechanisms of the benefits of dietary potassium, we studied the relationship between daily potassium intake and several markers of interest to cardiovascular disease and hypertension. We performed analysis on the baseline data of the National Institute of Healthfunded Modification of Diet in Renal Disease (MDRD) study. We performed bivariate correlation (Pearson) between dietary potassium (food only) intake and BUNtocreatinine ratio (BUN:Cr), serum calcium (mg/dL), hematocrit (%), hemoglobin A1C (%), serum uric acid (mg/dL), and stroke volume (SV) estimated according to a validated equation using noninvasive parameters.3 Our results revealed a significant positive correlation between daily potassium intake and BUN:Cr, hematocrit, and serum calcium and significant negative correlation with SV, serum uric acid, and hemoglobin A1C. The descriptive statistics of the variables studied, and bivariate correlations with dietary potassium are shown in Table. The statistical associations of dietary potassium intake with SV, BUN:Cr, serum calcium, and HCT are similar to those of thiazide diuretics. These similarities can be explained by the effect of orally ingested potassium on an illdefined gastrointestinal sensor that leads through a feedforward mechanism to dephosphorylation of the sodiumchloride cotransporter in the distal convoluted tubules. This effect is equivalent to the effect of thiazide diuretics and explains the antihypertensive property of dietary potassium.4 On the other hand, effects of dietary potassium on uric acid and hemoglobin A1C are opposite to what is expected from thiazide diuretics. Production of uric acid, the end product of xanthine metabolism in humans, yields an equimolar amount of superoxide. Experimentally, a highpotassium diet was shown to have a potent protective effect on left ventricular active relaxation independent of blood pressure, partly through the inhibition of cardiac NADPH oxidase activity.5 In another study, the antihypertensive effect of dietary potassium was accompanied by sympathetic nerve inhibition in saltsensitive hypertension, a marker of insulin resistance.6 Renalase, a monoamine oxidase in the blood that is primarily secreted by the kidneys can metabolize catecholamines and regulate sympathetic activity. Renalase mRNA and protein levels increased along with decreased catecholamine levels in plasma and led to a decrease in blood pressure in saltsensitive rats treated with high salt/potassium intake, compared with that of the high salt intake saltsensitive control rats.7 Moreover, reactive oxygen species are a critical mediator of the NaKATPase pump signaling, and their generation can be attenuated by potassium transit into the cells.8 Taking into consideration the type of the dataset analyzed and the crosssectional nature of the analysis, our results cannot be expanded beyond a correlation, but when taken together with other existing evidence from animal and human experiments, it is reasonable to conclude that the protective effects of a high potassium diet can be explained by its antihypertensive and antioxidant properties.

Pembrolizumab reactivates pulmonary granulomatosis

Sarcoid like reaction is a well-known entity that occurs as a consequence to several malignancies or their therapies. Immunotherapy has gained a lot of interest in the past few years and has recently gained approval as first line therapy in multiple advanced stage malignancies. Pneumonitis has been described as complication of such therapy. Granulomatous inflammation has been only rarely reported subsequent to immunotherapy. We describe a case of granulomatous inflammation reactivation affecting the lungs in a patient previously exposed to Pembrolizumab and have evidence of a distant granulomatous infection. We discuss potential mechanisms of the inflammation and assert the importance of immunosuppression in controlling the dis-inhibited immune system.

Congestive Adenopathy: A Mediastinal Sequela of Volume Overload.

Background:Endosonography has improved our ability to reach thoracic lymph nodes and to diagnose pathologic conditions with nodal involvement and has lowered the threshold for biopsy. The purpose of this study was to avoid unnecessary procedures, it is important to recognize benign adenopathy. Congestive heart failure (CHF) is both common and a common cause of adenopathy. The purpose of this study was to study the association between CHF and adenopathy and to describe the typical presentation of congestive adenopathy. Methods:We performed a retrospective correlation of computed tomographic (CT) and laboratory findings for patients admitted to hospital with a diagnosis of CHF. Results:Of 500 patients admitted with a diagnosis of CHF, 215 appeared to have CT scans of the chest, and not to have a potentially confounding etiology of adenopathy. The incidence of adenopathy in this study group was 68%. Pulmonary edema on CT and pleural effusion were both significantly associated with adenopathy (P<0.01 for both). The pattern of congestive adenopathy was one of enlargement of several mediastinal nodes and less likely to involve hilar nodes and single stations in isolation. Conclusion:Congestive adenopathy is common in patients with evidence for acute volume overload. The pattern of presentation should allow clinicians to recognize congestive adenopathy and to separate it from other adenopathy for which biopsy might be appropriate.

The role and safety of endobronchial ultrasound-guided transbronchial needle aspiration in the diagnosis and management of infected bronchogenic mediastinal cysts in adults

Bronchogenic and other duplication cysts are congenital abnormalities that can present at any age including adulthood years. They are usually asymptomatic and discovered incidentally on radiological imaging of the chest. They are commonly treated by surgical resection. Recently, endobronchial ultrasound has been used to assist in diagnosis when radiologic imaging is not definitive. Endobronchial ultrasound has been used rarely to drain infected cysts, a rare complication of the bronchogenic cyst. We present a unique case of an infected large bronchogenic cyst treated with endobronchial ultrasound drainage combined with conservative medical therapy. We also review the scarce available literature describing such an approach and its potential complications and add recommendations based on our experience in managing these anomalies.