Emerging Perspectives on mTOR Inhibitor-Associated Pneumonitis in Breast Cancer.

Substantial improvements in the early detection and treatment of breast cancer have led to improvements in survival, but breast cancer remains a significant cause of morbidity and mortality in women. In 2012, the mammalian target of rapamycin (mTOR) inhibitor everolimus was approved by the U.S. Food and Drug Administration for the treatment of advanced breast cancer in patients resistant to endocrine therapy. Although everolimus is generally well tolerated, mTOR inhibitor-associated pneumonitis is one of the most common adverse drug events leading to treatment discontinuation. To date, the underlying pathophysiology of this toxicity is unclear, and this uncertainty may hinder the optimization of management strategies. However, experiences from breast cancer and renal cell carcinoma clinical trials indicate that mTOR inhibitor-associated pneumonitis can be effectively managed by early detection, accurate diagnosis, and prompt intervention that generally involves everolimus dose reductions, interruptions, or discontinuation. Management can be achieved by a multidisciplinary approach that involves the collaborative efforts of nurses, oncologists, radiologists, infectious disease specialists, pulmonologists, clinical pharmacists, and pathologists. Comprehensive education must be provided to all health care professionals involved in managing patients receiving everolimus therapy. Although general recommendations on the management of mTOR inhibitor-associated pneumonitis have been published, there is a lack of consensus on the optimal management of this potentially serious complication. This article provides an overview of mTOR inhibitor-associated pneumonitis, with a focus on the detection, accurate diagnosis, and optimal management of this class-related complication of mTOR inhibitor therapy. IMPLICATIONS FOR PRACTICE: This article summarizes the pathogenesis, clinical presentation, incidence, detection, and optimal management of everolimus-related noninfectious pneumonitis in breast cancer. In particular, this article provides a detailed overview of the important aspects of the detection, accurate diagnosis, and appropriate management of mammalian target of rapamycin inhibitor-associated pneumonitis. In addition, this article emphasizes that effective management of this adverse drug event in patients with breast cancer will require a multidisciplinary approach and collaboration among various health care professionals.

Randomized Trial of Pleural Fluid Drainage Frequency in Patients with Malignant Pleural Effusions. The ASAP Trial.

RATIONALE: Patients with malignant pleural effusions have significant dyspnea and shortened life expectancy. Indwelling pleural catheters allow patients to drain pleural fluid at home and can lead to autopleurodesis. The optimal drainage frequency to achieve autopleurodesis and freedom from catheter has not been determined. OBJECTIVES: To determine whether an aggressive daily drainage strategy is superior to the current standard every other day drainage of pleural fluid in achieving autopleurodesis. METHODS: Patients were randomized to either an aggressive drainage (daily drainage; n = 73) or standard drainage (every other day drainage; n = 76) of pleural fluid via a tunneled pleural catheter. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the incidence of autopleurodesis following the placement of the indwelling pleural catheters. The rate of autopleurodesis, defined as complete or partial response based on symptomatic and radiographic changes, was greater in the aggressive drainage arm than the standard drainage arm (47% vs. 24%, respectively; P = 0.003). Median time to autopleurodesis was shorter in the aggressive arm (54 d; 95% confidence interval, 34-83) as compared with the standard arm (90 d; 95% confidence interval, 70 to nonestimable). Rate of adverse events, quality of life, and patient satisfaction were not significantly different between the two arms. CONCLUSIONS: Among patients with malignant pleural effusion, daily drainage of pleural fluid via an indwelling pleural catheter led to a higher rate of autopleurodesis and faster time to liberty from catheter. Clinical trial registered with www.clinicaltrials.gov (NCT 00978939).

Patient-derived xenografts faithfully replicated clinical outcome in a phase II co-clinical trial of arsenic trioxide in relapsed small cell lung cancer.

BACKGROUND: SCLC has limited treatment options and inadequate preclinical models. Promising activity of arsenic trioxide (ASO) recorded in conventional preclinical models of SCLC supported the clinical evaluation of ASO in patients. We assessed the efficacy of ASO in relapsed SCLC patients and in corresponding patient-derived xenografts (PDX). METHODS: Single arm, Simon 2-stage, phase II trial to enroll patients with relapsed SCLC who have failed at least one line of therapy. ASO was administered as an intravenous infusion over 1-2 h daily for 4 days in week 1 and for 2 days in weeks 2-6 of an 8-week cycle. Treatment continued until disease progression. Pretreatment tumor biopsy was employed for PDX generation through direct implantation into subcutaneous pockets of SCID mice without in vitro manipulation and serially propagated for five generations. Ex vivo efficacy of cisplatin (3 mg/kg i.p. weekly) and ASO (3.75 mg/kg i.p. every other day) was tested in PDX representative of platinum sensitive and platinum refractory SCLC. RESULTS: The best response in 17 evaluable patients was stable disease in 2 (12 %), progressive disease in 15 (88 %) patients and median time-to-progression of seven (range 1-7) weeks. PDX was successfully grown in 5 of 9 (56 %) transplanted biopsy samples. Serially-propagated PDXs preserved characteristic small cell histology and genomic stability confirmed by immunohistochemistry, short tandem repeat (STR) profiling and targeted sequencing. ASO showed in vitro cytotoxicity but lacked in vivo efficacy against SCLC PDX tumor growth. CONCLUSIONS: Cisplatin inhibited growth of PDX derived from platinum-sensitive SCLC but was ineffective against PDX from platinum-refractory SCLC. Strong concordance between clinical and ex vivo effects of ASO and cisplatin in SCLC supports the use of PDX models to prescreen promising anticancer agents prior to clinical testing in SCLC patients. Trial Registration The study was registered at http://www.clinicaltrials.gov (NCT01470248).

Lung abscess: the non-conservative management: a narrative review.

Background and Objective: Systemic antibiotics are the best treatment options for lung abscesses. However, up to 37% of lung abscesses do not respond to antibiotics and may require additional interventions. Percutaneous transthoracic tube drainage (PTTD), endoscopic catheter drainage (ECD) and surgical resection are additional options available when first line therapy with systemic antibiotics are unsuccessful. In this narrative review, we summarize all available interventional procedures, techniques, complications, safety, and contraindications. Methods: A literature search was performed using Medline/PubMed from January 1980 to October 2023. Key words: "lung abscess", "pulmonary abscess", "endoscopic drainage", "percutaneous drainage", "tube drainage". Pediatric patients were excluded from this study. Key Content and Findings: PTTD and ECD are fairly safe procedures. Performing PTTD or ECD without delay may shorten the duration of hospital stay. This may lower the burden on health care. Moreover, draining abscesses may relieve discomfort in the clinical symptoms associated with abscesses. The primary factor in choosing ECD over PTTD is the location of the abscess, and the presence of a bronchial airway leading to the abscess for successful ECD. ECD has lower rate of complications and mortality; and similar success rate compared to PTTD. While mortality has been reported with PTTD, ECD appears to be safer according to present data. Conclusions: PTTD and ECD are safe procedures, with low complication rates. ECD has a lower complication rate than PTTD does.

Interventional Pulmonology Productivity, Compensation, and Practice Benchmarks: The AABIP 2022 Report.

BACKGROUND: Interventional pulmonology (IP) is a growing field that has not yet been recognized by the American Board of Medical Specialties or incorporated into national benchmark organizations. As a result, there is a lack of data on IP practice patterns, physicians' compensation and productivity targets. METHODS: We sent an anonymous survey to 647 current or past physician members of the AABIP. Domains included demographics, training background, academic rank, practice settings, work relative value unit (wRVU) targets, salary, and career satisfaction. RESULTS: The response rate to the survey was 28.3%; 17.8% were female. The median salary for IP faculty in academic institutions was $320,000 for assistant professors, $338,000 for associate professors, and $350,000 for full professors. Salaries were lower for women than for men in academic practice, even after adjusting for the number of years in practice (mean salary difference after adjustment $57,175, 95% CI: $19,585-$94,764, P =0.003). The median salary for private practice was higher at $428,000. Among respondents that used wRVU targets, the median targets for academic and private practice were 5500 and 6300, respectively. The majority of IP physicians are satisfied with their career choice. CONCLUSIONS: Productivity targets in IP are used less than half the time, and when they are used, they are set in line with the lower wRVU of IP procedures. IP compensation is higher than that of general pulmonary medicine, as reported by national benchmark associations. In academic practices, gender differences in salaries were found.

Safety and Feasibility of Photodynamic Therapy for Ablation of Peripheral Lung Tumors.

BACKGROUND: Newer navigational bronchoscopy technologies render peripheral lung lesions accessible for biopsy and potential treatment. We investigated whether photodynamic therapy (PDT) delivered via navigational bronchoscopy is feasible and safe for ablation of peripheral lung tumors. METHODS: Two studies evaluated PDT in patients with solid peripheral lung tumors followed by clinical follow-up (nonresection study, N=5) or lobectomy (resection study, N=10). Porfimer sodium injection was administered 40 to 50 hours before navigational bronchoscopy. Lesion location was confirmed by radial probe endobronchial ultrasonography. An optical fiber diffuser was placed within or adjacent to the tumor under fluoroscopic guidance; laser light (630 nm wavelength) was applied at 200 J/cm of diffuser length for 500 seconds. Tumor response was assessed by modified Response Evaluation Criteria in Solid Tumors at 3 and 6 months postprocedure (nonresection study) and pathologically (resection study). RESULTS: There were no deaths, discontinuations for adverse events, or serious or grade ≥3 adverse events related to study treatments. Photosensitivity reactions occurred in 8 of 15 patients: 6 mild, 1 moderate, 1 severe (elevated porphyrins noted in blood after treatment). Among 5 patients with clinical follow-up, 1 had complete response, 3 had stable disease, and 1 had progressive disease at 6 months follow-up. Among 10 patients who underwent lobectomy, 1 had no evidence of tumor at resection (complete response), 3 had 40% to 50% tumor cell necrosis, 2 had 20% to 35%, and 4 had 5% to 10%. CONCLUSION: PDT for nonthermal ablation of peripheral lung tumors was feasible and safe in this small study. Further study is warranted to evaluate efficacy and corroborate the safety profile.

Endobronchial lipoma.

Endobronchial lipomas are rare benign lung tumors that can cause bronchial obstruction and parenchymal damage. While an uncommon etiology, they are often misdiagnosed due to a clinical presentation similar to obstructive pulmonary pathologies such as COPD and asthma. Upon review of English-language literature, under 50 cases of endobronchial lipomas were documented in the prior 10 years (2011-2021). There are no clear guidelines regarding the management of this particular entity, but typically interventional debulking is the treatment of choice. Here we present another unique case of endobronchial lipoma along with our diagnostic and therapeutic methodology. The patient underwent bronchoscopic debulking via a cryotherapy probe. Based on the histopathologic analysis, a diagnosis of endobronchial lipoma was made. Endobronchial lipomas must remain in any clinician's differential when a patient presents with dyspnea. We report the unique location of this lipoma based on our literature review and the importance of investigating endobronchial lesions due to a possible diagnosis of endobronchial lipoma.

Electromagnetic navigation bronchoscopy.

In 2009, lung cancer was estimated to be the second most common form of cancer diagnosed in men, after prostate, and the second, after breast cancer, in women. It is estimated that it caused 159,390 deaths more than breast, colon and prostate cancers combined. While age-adjusted death rates for this cancer have been declining since 2000, they remain high.

Low utilisation of bronchoscopy to assess COVID-19 respiratory infection: a multicenter experience.

OBJECTIVE: For the diagnosis of COVID-19, the yield of nasopharyngeal (NP) swabs is unclear, and bronchoalveolar lavage (BAL) is obtained to confirm the diagnosis. We assessed the utilisation of bronchoscopy for COVID-19 diagnosis in a multicenter study and compared the diagnostic yield of BAL versus NP swabs. METHODS: This retrospective study included all patients who were admitted with clinical presentation concerning for COVID-19 and underwent BAL from 1 March to 31 July 2020 at four tertiary care centres in North America. We also compared concordance of BAL with NP swabs for diagnosis of COVID-19 infection. RESULTS: Fifty-three patients, with clinical suspicion for COVID-19 and admitted for respiratory failure, underwent bronchoscopy to collect BAL for SARS-CoV-2 testing. During the same period, 2039 bronchoscopies were performed on patients not infected with COVID-19. Of 42 patients with NP swabs and BAL collected within ≤7 days, 1 was NP swab negative but positive by BAL for SARS-CoV-2 (n=1/42 (2.4%)). Across a wide array of testing platforms, the overall agreement between NP swabs and BAL results was 97.6% (95% CI: 93.0% to 100%) with Cohen's k of 0.90 (95% CI: 0.69 to 1.00). The sensitivity, specificity, positive and negative predictive values of NP swabs compared with BAL were 83.3% (95% CI: 53.5% to 100%), 100%, 100% and 97.3% (95% CI: 92.1% to 100%), respectively. CONCLUSIONS: BAL was used infrequently to assess COVID-19 in busy institutions. NP swabs have a high concordance with BAL for COVID-19 testing, but negative NP swabs should be confirmed with BAL when clinical suspicion is high.

A rare nonmalignant mass of the pancreas: case report and review of pancreatic sarcoidosis.

Sarcoidosis is a systemic granulomatous disease of unknown etiology affecting patients from all genetic backgrounds. Pancreatic involvement is rare; the first case was described on autopsy in 1937. We present a case of pancreatic sarcoidosis without a history of the disease presenting as biliary obstruction mimicking pancreatic malignancy. We also review the literature with respect to management and outcomes of similar cases. The patient described here presented with all the signs and symptoms of a pancreatic malignancy, which was confirmed on a CT scan; the positron emission tomography scan and the CA 19-9 level were also confirmatory of the suspected diagnosis. In this setting, if the mass looks resectable, a Whipple procedure would be the next logical step. However, such strategy would be aggressive management for a benign condition that could be palliated with diverting rather than resective procedures without changing the outlook of the disease. We suggest keeping a high index of suspicion in patients with a history of the disease if demographic concordance exists.

Anesthetic Considerations for Automated High-Frequency Jet Ventilation During Electromagnetic Navigation Bronchoscopy.

Newly advanced diagnostic bronchoscopic procedures, such as electromagnetic navigation bronchoscopy using navigation system technology (superDimension, Medtronic), provides computed tomography referenced and computerized 3-dimensional imaging. To increase accuracy and higher diagnostic biopsy yield, electromagnetic navigation bronchoscopy necessitates special anesthetic and ventilation techniques providing the interventional pulmonologist minimal respiratory lung motion. This anesthetic meets 2 important goals by limiting almost all interference from diaphragmatic and lung movement while allowing the anesthesia provider to achieve hands-free management. Proposed here is an anesthetic ventilation technique by automated high-frequency jet ventilation (HFJV) via double-lumen micro jet endotracheal tubes. This ventilation technique delivers consistent very low tidal volumes. Automated HFJV provides the pulmonologist the advantage of more accurate navigation and target alignment in this Global Positioning System-guided biopsy procedure. The technique offers essentially no chest motion, without interrupting ventilation. Additionally, HFJV allows the anesthetist better availability to attend to total intravenous anesthesia, adjustments, and interventions. The intention of this article is to detail an anesthetic method that provides a hands-free technique that requires only one anesthesia provider.

Jet Ventilation Decreases Target Motion and Increases Yield of ENB Especially in Lesions With Negative Bronchus Sign.

BACKGROUND: Electromagnetic navigational bronchoscopy (ENB) is used to obtain peripheral lung tissue samples for evaluation and staging of central and peripheral lung lesions. Jet ventilation delivers and maintains a sustained airway pressure at high frequency, chest wall and diaphragmatic movement is drastically reduced compared with traditional ventilation. The current study looks to examine the effectiveness of tissue sampling (diagnostic yield) while using jet ventilation on target-lesion movement when compared with traditional ventilation. METHODS: A total of 36 patients received total intravenous anesthesia with both jet and traditional ventilation during ENB procedure where sensor to lesion displacement was recorded. When planning the ENB procedure, the presence or absence of a viable airway to the lesion was recorded. Sensor to lesion movement was recorded and compared for significance using χ and t tests, utilizing stringent P-values. RESULTS: Overall patients with an airway to the lesion (n=23) had a higher proportion of successful diagnostic biopsies, 83% compared with those patients that lacked an airway to the lesion (n=13) 70% proportion of successful diagnostic biopsies. When using jet ventilation, the chance of nonzero displacement was 8.3% (0.14 mm), regardless of the presence of an airway. Compared with traditional ventilation, the chance of a nonzero displacement between the sensor and target-lesion was 83% (6.4 mm), independent of airway presence to the lesions. CONCLUSION: In patients without an airway, jet ventilation significantly decreased target displacement when compared with traditional ventilation (2 vs. 17 mm). In patients with direct airway to the lesion, jet ventilation did not significantly decrease target displacement when compared with the traditional approach.

Effect of Routine Clopidogrel Use on Bleeding Complications After Endobronchial Ultrasound-guided Fine Needle Aspiration.

BACKGROUND: Endobronchial ultrasonography has proven to be highly sensitive and specific in the diagnoses of patients with mediastinal and hilar adenopathy. Many of these patients are on a combination of clopidogrel (a compound that inhibits adenosine diphosphate-induced platelet aggregation) and aspirin due to neurological and/or cardiac-related comorbidities, and stopping anticoagulation may place these patients at high risk for potential complications. Our group has previously showed that thoracentesis with an 8-french catheter is safe in patients receiving clopidogrel and aspirin with low risk of complications. In this manuscript, we report the outcomes of the largest prospective multicenter series of patients undergoing endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) while receiving clopidogrel. METHODS: Patients presenting to our institutions with mediastinal/hilar adenopathy, requiring EBUS-TBNA, and actively taking clopidogrel and aspirin were included in the study. If the medication could be held for 5 to 7 days before the procedure, the patient was excluded. EBUS-TBNA was performed by an interventional pulmonology faculty on a total of 42 patients. All patients received total intravenous anesthesia, and a total of 92 nodes were sampled. First, 3 passes were performed with a 22-G needle. If no complications were encountered, we followed with additional 3 passes with a 21 G. Rapid onsite evaluation was performed in all patients. Bleeding at the puncture site was considered significant if it required cold saline, topical sympathomimetic, or balloon tamponade for hemostasis. Bleeding was considered nonsignificant if no interventions were required to achieve hemostasis. RESULTS: We were able to perform all procedures successfully using both the 21 and 22-G needles. One patient required 30 mL cold saline installation to accomplish hemostasis with the 21 and 22-G needles. Our yield was comparable with the current literature. No statistically significant complications occurred during the procedure. All patients were contacted within 24 hours, and none reported bloody sputum. CONCLUSION: We suggest that EBUS-TBNA, using 22 and 21-G needles, is safe with high yields in patients with mediastinal/hilar adenopathy, actively taking clopidogrel and aspirin, and are at high risk for thrombotic complications if the medication is discontinued.

Electromagnetic Navigation Bronchoscopy for Peripheral Pulmonary Lesions: One-Year Results of the Prospective, Multicenter NAVIGATE Study.

INTRODUCTION: Electromagnetic navigation bronchoscopy (ENB) is a minimally invasive technology that guides endoscopic tools to pulmonary lesions. ENB has been evaluated primarily in small, single-center studies; thus, the diagnostic yield in a generalizable setting is unknown. METHODS: NAVIGATE is a prospective, multicenter, cohort study that evaluated ENB using the superDimension navigation system (Medtronic, Minneapolis, Minnesota). In this United States cohort analysis, 1215 consecutive subjects were enrolled at 29 academic and community sites from April 2015 to August 2016. RESULTS: The median lesion size was 20.0 mm. Fluoroscopy was used in 91% of cases (lesions visible in 60%) and radial endobronchial ultrasound in 57%. The median ENB planning time was 5 minutes; the ENB-specific procedure time was 25 minutes. Among 1157 subjects undergoing ENB-guided biopsy, 94% (1092 of 1157) had navigation completed and tissue obtained. Follow-up was completed in 99% of subjects at 1 month and 80% at 12 months. The 12-month diagnostic yield was 73%. Pathology results of the ENB-aided tissue samples showed malignancy in 44% (484 of 1092). Sensitivity, specificity, positive predictive value, and negative predictive value for malignancy were 69%, 100%, 100%, and 56%, respectively. ENB-related Common Terminology Criteria for Adverse Events grade 2 or higher pneumothoraces (requiring admission or chest tube placement) occurred in 2.9%. The ENB-related Common Terminology Criteria for Adverse Events grade 2 or higher bronchopulmonary hemorrhage and grade 4 or higher respiratory failure rates were 1.5% and 0.7%, respectively. CONCLUSIONS: NAVIGATE shows that an ENB-aided diagnosis can be obtained in approximately three-quarters of evaluable patients across a generalizable cohort based on prospective 12-month follow-up in a pragmatic setting with a low procedural complication rate.

Point-of-Care Ultrasound in the Intensive Care Unit.

Spreading beyond the realm of tertiary academic medical centers, point-of-care ultrasound in the intensive care unit is an important diagnostic tool. The real-time feedback garnered can lead to critical and clinically relevant changes in management and decrease potential complications. Bedside ultrasound evaluation in the intensive care setting with a small, portable equipment is well-suited for placement of central lines, lumbar puncture, thoracentesis or other bedside ICU procedures and in the evaluation of cardiac activity, pleural and abdominal cavity and the overall fluid volume. Formalized curriculums centering on point-of-care ultrasound are emerging that will enhance its applicability and relevance.

Endobronchial lipoma

ABSTRACT Endobronchial lipomas are rare benign lung tumors that can cause bronchial obstruction and parenchymal damage. While an uncommon etiology, they are often misdiagnosed due to a clinical presentation similar to obstructive pulmonary pathologies such as COPD and asthma. Upon review of English-language literature, under 50 cases of endobronchial lipomas were documented in the prior 10 years (2011-2021). There are no clear guidelines regarding the management of this particular entity, but typically interventional debulking is the treatment of choice. Here we present another unique case of endobronchial lipoma along with our diagnostic and therapeutic methodology. The patient underwent bronchoscopic debulking via a cryotherapy probe. Based on the histopathologic analysis, a diagnosis of endobronchial lipoma was made. Endobronchial lipomas must remain in any clinician's differential when a patient presents with dyspnea. We report the unique location of this lipoma based on our literature review and the importance of investigating endobronchial lesions due to a possible diagnosis of endobronchial lipoma.

Use of a removable endobronchial valve for the treatment of bronchopleural fistula.

We report the case of a patient with a prolonged bronchopleural fistula and empyema that were successfully treated by the placement of a removable, unidirectional endobronchial valve. This is the first report of the use of such a device for this indication.

Mediastinal and Hilar Lymph Node Measurements. Comparison of Multidetector-Row Computed Tomography and Endobronchial Ultrasound.

RATIONALE: Multidetector-row chest computed tomography scan is a common initial imaging modality and endobronchial ultrasound is a minimally invasive diagnostic tool used to evaluate enlarged lymph nodes, but comparisons of imaging results are lacking. OBJECTIVES: To determine the size of thoracic lymph nodes and the strength of agreement between each measurement from coronal plane computed tomography and static endobronchial ultrasound images. METHODS: A retrospective review of consecutive patients who underwent endobronchial ultrasound-transbronchial needle aspiration of their lymph nodes because of clinical suspicion of benign or malignant thoracic disease. MEASUREMENTS AND MAIN RESULTS: One hundred and twenty-four lymph nodes from the mediastinal (74.2%) and hilar (25.8%) stations were measured in 59 patients (mean age, 64.5 yr; 33 males). The mean (standard deviation) short-axis diameter on computed tomography was 14.1 (6.7) mm compared with 12.6 (6.6) mm on endobronchial ultrasound. Benign lymph nodes (n = 42) were larger on computed tomography than on endobronchial ultrasound (14.1 [6.2] vs. 11.5 [6.2] mm). Malignant lymph nodes (n = 35) were larger on endobronchial ultrasound than on computed tomography (17.3 [6.4] vs. 16.2 [6.7] mm). Sixty-five percent of the lymph nodes that were initially interpreted as not enlarged on axial computed tomography images measured greater than 10 mm on each imaging modality (12.5 [5.9] mm on computed tomography and 10.5 [5.6] mm on endobronchial ultrasound) and 24% of the sampled lymph nodes from this group contained malignant cells. Random-effects maximal likelihood linear regression showed a statistically significant difference between endobronchial ultrasound and the computed tomography method for measuring short-axis diameter in all 124 lymph nodes. There was a weak agreement (intraclass correlation, rho: 0.44 [95% confidence interval, 0.31-0.59]) between short-axis diameter measurements from each imaging modality. CONCLUSIONS: Our single-center study shows that there was poor correlation between computed tomography and endobronchial ultrasound for the measurement of mediastinal and hilar lymph nodes. Malignant cells were recovered by ultrasound-guided needle aspiration from a substantial fraction of lymph nodes that were initially interpreted as normal in size. If these findings are confirmed, new criteria may be needed for lymph node measurement on computed tomography that will guide selection of lymph nodes for endobronchial ultrasound-transbronchial needle aspiration.

A Translational, Pharmacodynamic, and Pharmacokinetic Phase IB Clinical Study of Everolimus in Resectable Non-Small Cell Lung Cancer.

PURPOSE: The altered PI3K/mTOR pathway is implicated in lung cancer, but mTOR inhibitors have failed to demonstrate efficacy in advanced lung cancer. We studied the pharmacodynamic effects of everolimus in resectable non-small cell lung cancer (NSCLC) to inform further development of these agents in lung cancer. EXPERIMENTAL DESIGN: We enrolled 33 patients and obtained baseline tumor biopsy and 2[18F]fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) imaging followed by everolimus treatment (5 or 10 mg daily, up to 28 days), or without intervening treatment for controls. Target modulation by everolimus was quantified in vivo and ex vivo by comparing metabolic activity on paired PET scans and expression of active phosphorylated forms of mTOR, Akt, S6, eIF4e, p70S6K, 4EBP1, and total Bim protein between pretreatment and posttreatment tissue samples. RESULTS: There were 23 patients on the treatment arm and 10 controls; median age 64 years; 22 tumors (67%) were adenocarcinomas. There was a dose-dependent reduction in metabolic activity (SUVmax: 29.0%, -21%, -24%; P = 0.014), tumor size (10.1%, 5.8%, -11.6%; P = 0.047), and modulation of S6 (-36.1, -13.7, -77.0; P = 0.071) and pS6 (-41.25, -61.57, -47.21; P = 0.063) in patients treated in the control, 5-mg, and 10-mg cohorts, respectively. Targeted DNA sequencing in all patients along with exome and whole transcriptome RNA-seq in an index patient with hypersensitive tumor was employed to further elucidate the mechanism of everolimus activity. CONCLUSIONS: This "window-of-opportunity" study demonstrated measurable, dose-dependent, biologic, metabolic, and antitumor activity of everolimus in early-stage NSCLC.

Safety of pacemakers and defibrillators in electromagnetic navigation bronchoscopy.

BACKGROUND: Electromagnetic Navigation Bronchoscopy (ENB) (InReach iLogic system; superDimension Inc) is a relatively new discipline, with promising diagnostic and therapeutic applications in patients with lung lesions. Navigation is performed in a magnetic field and, therefore, has been considered relatively contraindicated in patients with pacemakers and automated implantable cardioverter-defibrillators (AICDs). Potential risks include altering the function and shutting off the device, device damage, lead displacement, and potential overheating. Over the past decade, there has been extensive literature about the safety of pacemakers in either the 1.5-T or 3-T magnetic fields used in current MRI scanners. Although the magnetic field used in ENB is significantly weaker, 0.0001 T or approximately equal to the earth's gravity, its safety in patients with pacemakers is yet to be elucidated. We present our initial experience with ENB in patients with cardiac implanted electrical devices. METHODS: Twenty-four procedures in 24 patients with lung lesions and permanent pacemakers were performed. A cardiac electrophysiologist and programmer were present during the procedure. At baseline, the pacers were interrogated, and ECG was recorded. Continuous cardiac monitoring was performed during the procedure, and at the end, the pacer settings and function were reinterrogated to check for any changes. RESULTS: The procedures were all successfully concluded. None of the patients suffered any arrhythmias or disruption to their pacemakers' function. CONCLUSION: ENB appears to be safe when performed in patients with pacemakers and AICDs. Larger multicenter studies are needed to prove the final safety in this patient population.