Added value of EUS-B-FNA to bronchoscopy and EBUS-TBNA in diagnosing and staging of lung cancer.

Background: Bronchoscopy and EBUS are standard procedures in lung cancer work-up but have low diagnostic yield in lesions outside the central airways and hilar/mediastinal lymph nodes. Growing evidence on introducing the EBUS endoscope into the oesophagus (EUS-B) in the same session as bronchoscopy/EBUS gives access to new anatomical areas that can be safely biopsied. Objective: To summarize the current evidence of the added value of EUS-B-FNA to bronchoscopy and EBUS-TBNA in lung cancer work-up. Methods: A narrative review. Results: Few randomized trials or prospective studies are available. Prospective studies show that add-on EUS-B-FNA increases diagnostic yield when sampling abnormal mediastinal lymph nodes, para-oesophageal lung and left adrenal gland. A large retrospective series on EUS-B-FNA from retroperitoneal lymph nodes suggests high diagnostic yield without safety concerns, as do casuistic reports on EUS-B-FNA from mediastinal pleural thickening, pancreatic lesions, ascites fluid and pericardial effusions. No study has systematically assessed both diagnostic yield, safety, patient reported outcomes, adverse events and costs. Conclusion: The diagnostic value of add-on EUS-B to standard bronchoscopy and EBUS in lung cancer work-up appears very promising without safety concerns, giving the pulmonologist access to a variety of sites out of reach with other minimally invasive techniques. Little is known on patient-reported outcomes and costs. Future and prospective research should focus on effectiveness aspects to clarify whether overall benefits of add-on EUS-B sufficiently exceed overall downsides.

Using the Endoscope for Endobronchial Ultrasound in the Esophagus.

EUS-B is a procedure using the echoendobronchoscope in the esophagus and stomach. The procedure is a minimally invasive, safe, and feasible approach that pulmonologists can use to visualize and biopsy structures adjacent to the esophagus and stomach. EUS-B gives access to many structures of which some may also be reached by EBUS (mediastinal lymph nodes, lung or pleural tumors, pericardial fluid) while others cannot be reached such as retroperitoneal lymph nodes, ascites, and lesions in the liver, pancreas or left adrenal gland. The procedure is a pulmonologist- and patient- friendly version of the gastroenterologists' EUS using the thin EBUS endoscope that the pulmonologist already masters. Thus EUS-B training should be easy and a natural continuation of EBUS. With the patient under conscious sedation and in the supine position, the echoendoscope is introduced either through the nostril or mouth into the oropharynx. Then the patient is encouraged to swallow while the endoscope is slowly bent posteriorly and introduced into the esophagus and stomach. Using the ultrasonic image, the operator identifies the six landmarks by EUS-B and EUS: the left liver lobe, abdominal aorta (with the celiac trunk and superior mesenteric artery), left adrenal gland, and mediastinal lymph node stations 7, 4L, and 4R. Biopsies can be taken from suspected lesions under real-time ultrasonographic guidance- fine needle aspiration (EUS-B-FNA) using a technique similar to that used with EBUS-TBNA. The biopsy order is M1b-M1a-N3-N2-N1-T (M = metastasis, N = lymph node, T = tumor) to avoid iatrogenic upstaging. Pre- and post-procedural observation is similar to that of bronchoscopy. EUS-B is safe and feasible in the hands of experienced interventional pulmonologists and provides a significant expansion of the diagnostic possibilities in providing safe, fast, and thorough diagnosis and staging of lung cancer.

Asymptomatic lung nodules in dental professionals: A diagnostic challenge.

Dental care workers are frequently exposed to various types of volatile organic and inorganic compounds. In addition to biological materials, these compounds include silica, heavy metals, and acrylic plastics. Such exposures may cause respiratory symptoms, but the nonspecific nature of these symptoms often means that the etiology is difficult to discern. The disease severity depends on the particle size and type of the inhaled compounds, as well as the duration and intensity of exposure, which varies markedly among dental workers. Here, we present two unique cases with the same occupational exposure. Both patients showed radiological changes in the lungs that were suspicious for lung cancer. The first patient did not undergo a biopsy due to cardiac comorbidities and risk of bleeding, and the diagnosis was based on thoracic computer tomography (CT) which confirmed multiple, bilateral, solid, smooth, partly calcified lung nodules, normal positron emission tomography (PET)-CT and the relevant occupational exposure. In the second case, a CT-guided biopsy and thoracoscopic resection was done with histopathological findings consistent with granuloma. The multi-disciplinary team decision of both cases was consistent with occupational exposure related lunge disease. This is the first case study report whereby same occupational exposure related health condition is compared with two different approaches. Respiratory clinicians should be aware of this potential diagnosis, especially for asymptomatic patients with relevant exposures. Careful attention to the occupational history may help to prevent unnecessary, invasive diagnostic procedures or surgeries.

A rare clinical presentation of Waldenström Macroglobulinemia mimicking lung cancer.

Waldenström macroglobulinemia rarely presents as pulmonary symptoms, and even rarer as chylothorax. We present a patient who presented with bilateral pleural effusion and a 30 mm solid lesion in the lung. Biochemical analysis of the pleural fluid revealed chylothorax. The 18-fluorodeoxygenase positron emission tomography, bronchoscopy, endobronchial ultrasound, and cytological examination of the pleural fluid, showed no apparent cause of the chylothorax. The diagnostic breakthrough was made with flow cytometry of the pleural fluid, which revealed a small group of clonal B-cells. Biopsy from the parietal pleura and bone marrow led to the diagnosis Waldenström macroglobulinemia. This demonstrates that flow cytometry should be considered when routine diagnostics do not lead to a reach a specific diagnosis.

Learning Curves for Electromagnetic Navigation Bronchoscopy Using CUSUM Analysis.

BACKGROUND: Electromagnetic navigation bronchoscopy (ENB) is a relatively new and technically demanding procedure for the guidance of bronchoscopic biopsy to help locate small lung lesions. The results in experienced hands are well described. However, we do not know the results in unexperienced hands-in other words, we have no knowledge about how fast you can learn the procedure. AIM: The aim of this study was to draw learning curves for beginners in ENB using Cumulated Sum (CUSUM) analysis, a method for quantitative evaluation of the learning curves for clinical procedures. METHODS: Four operators from 3 centers without prior ENB experience were enrolled. The outcome of consecutive ENB procedures was assessed and classified as either diagnostic or nondiagnostic based on sample adequacy. Learning curves were drawn based on diagnostic yield. RESULTS: A total of 215 procedures were assessed. For 2 of the operators (operators 1 and 4), at least 25 to 30 procedures were necessary to obtain competency whereas operators 2 and 3 showed more horizontal learning curves indicating an overweight of diagnostic procedures from the beginning. CONCLUSION: Operators achieve competences in ENB at different paces. This must be taken in account when beginners start to learn the procedure. There is a huge need for a structured educational program and a validated test to determine competences.

[Malignant pleural effusion].

Malignant pleural effusion (MPE) is a common condition, often associated with a high level of symptoms. In this review, several palliative treatments for symptomatic MPE are summarised, including repeated thoracentesis, pleurodesis and insertion of indwelling pleural catheters. Choice of treatment depends on patient symptoms, life expectancy, pleural fluid production, expected effect of oncological treatment, whether trapped lung is suspected or not, and patient preferences. Treatment should be discussed with a pulmonary specialist with knowledge of pleural diseases.

Multimodal soft tissue markers for bridging high-resolution diagnostic imaging with therapeutic intervention.

Diagnostic imaging often outperforms the surgeon's ability to identify small structures during therapeutic procedures. Smart soft tissue markers that translate the sensitivity of diagnostic imaging into optimal therapeutic intervention are therefore highly warranted. This paper presents a unique adaptable liquid soft tissue marker system based on functionalized carbohydrates (Carbo-gel). The liquid state of these markers allows for high-precision placement under image guidance using thin needles. Based on step-by-step modifications, the image features and mechanical properties of markers can be optimized to bridge diagnostic imaging and specific therapeutic interventions. The performance of Carbo-gel is demonstrated for markers that (i) have radiographic, magnetic resonance, and ultrasound visibility; (ii) are palpable and visible; and (iii) are localizable by near-infrared fluorescence and radio guidance. The study demonstrates encouraging proof of concept for the liquid marker system as a well-tolerated multimodal imaging marker that can improve image-guided radiotherapy and surgical interventions, including robotic surgery.

Early initiated postoperative rehabilitation enhances quality of life in patients with operable lung cancer: Secondary outcomes from a randomized trial.

INTRODUCTION: Patients with lung cancer report a lower degree of Health Related Quality of Life (HRQoL) compared with other cancer patients. HRQoL reflects how patients experience the impact of their disease and its treatment on their quality of daily living. A widely used questionnaire in lung cancer patients is the Functional Assessment of Cancer Therapy - Lung (FACT-L) questionnaire. Here we report the secondary outcomes on FACT-L data from the Postoperative Rehabilitation in Operation for Lung CAncer (PROLUCA) study, which describes the effect of early (14 days) versus late initiated (14 weeks) postoperative rehabilitation. MATERIALS AND METHODS: The PROLUCA study was designed as a two-armed randomized controlled trial with an early rehabilitation group (14 days after surgery (ERG)) or a control arm with a late rehabilitation group (14 weeks after surgery (LRG)). The results for seven domain scores obtained using the FACT-L at the following time-points: baseline, 14 weeks, 26 weeks and 52 weeks after surgery are presented here. RESULTS: 119 patients were randomized to the ERG and 116 to the LRG. In the ERG, HRQoL measured by both FACT-L and FACT-G (general core instrument) showed a continuous improvement up to 26 weeks after which HRQoL decreased after further 26 weeks without structured intervention. In the LRG a non-significant deterioration was detected over the first 14 weeks after surgery. After participation in the 12 weeks rehabilitation program, an increase in HRQoL was seen, without reaching the same level as the early group. CONCLUSION: Analyses of the seven domain scores obtained using FACT-L and FACT-G reflect the importance of starting exercise early after surgery since the ERG avoid a temporary decrease in HRQoL. It is therefore recommended to start up a structured rehabilitation program 14 days after surgery, containing high intensity interval training and strength exercise twice a week for 12 weeks.

Endoscopic ultrasound-guided pleural biopsy in the hands of the pulmonologist.

The use of the endobronchial ultrasound (EBUS) endoscope in the oesophagus, the so-called EUS-B procedure, for the diagnosis and staging of thoracic malignancy is quickly gaining ground. Pleural lesions located close to the oesophagus can be inaccessible to transthoracic biopsy and endoscopic procedures can be the only option. We here present two cases demonstrating that EUS-B-guided fine needle aspiration (EUS-B-FNA) of pleural lesions is possible. The first case demonstrates a EUS-B-FNA with malignant mesothelioma of a pleural lesion in a 70-year-old patient. In the second case, EUS-B-FNA diagnosed a pleural metastasis from adenoid cystic adenocarcinoma in a 75-year-old-patient. In conclusion, we hereby demonstrate that EUS-B-FNA from pleural lesions is feasible and appears to be safe.

Early initiated postoperative rehabilitation reduces fatigue in patients with operable lung cancer: A randomized trial.

INTRODUCTION: Little is known about the optimal amount and timing of exercise strain in concern of the operation wound and with regard improvement of physical function and quality of life (QOL) after surgery for lung cancer. On this background, we decided to investigate the effect of early vs. late initiated postoperative rehabilitation in patients with operable lung cancer on exercise capacity, functional capacity, muscle strength, and QOL. METHODS: The study was designed as a two-armed randomized controlled trial with randomization to either early initiated postoperative rehabilitation (14 days after surgery (ERG)) or a control arm with late initiated postoperative rehabilitation (14 weeks after surgery (LRG)). The primary endpoint was a change in maximum oxygen consumption (VO2peak) from baseline to post intervention 26 weeks following lung resection. Fatigue was measured with EORTC QLQ C30 LC13. RESULTS: From April 2013 to June 2016, 582 patients with operable NSCLC were screened for eligibility. With 119 patients randomized in the early rehabilitation group (ERG) and 116 randomized to late rehabilitation group (LRG). There was no significant difference from baseline to 26 weeks between ERG and LRG (p = 0.926). There was a significant difference from baseline to 14 weeks between groups (p = 0.0018). There was a significant difference from 14 weeks to 26 weeks between the two groups (p < 0.001). We found no significant differences in QOL but we found a significant difference between ERG and LRG from baseline to 14 weeks in fatigue level in favour of ERG. CONCLUSION: This is the first randomized controlled trial to investigate the effects of early vs. late initiated postoperative rehabilitation in patients with lung cancer. There is no difference in the commencement (early vs. late) of a postoperative exercise program for patients with lung cancer on exercise capacity. But to reduce fatigue patients should be recommended to initiate early exercise programs.

Changes in Health-Related Quality of Life During Rehabilitation in Patients With Operable Lung Cancer: A Feasibility Study (PROLUCA).

INTRODUCTION: Surgical resection in patients with non-small cell lung cancer (NSCLC) may be associated with significant morbidity, functional limitations, and decreased quality of life. OBJECTIVES: The objective is to present health-related quality of life (HRQoL) changes over time before and 1 year after surgery in patients with NSCLC participating in a rehabilitation program. METHODS: Forty patients with NSCLC in disease stage I to IIIa, referred for surgical resection at the Department of Cardiothoracic Surgery RT, Rigshospitalet, were included in the study. The rehabilitation program comprised supervised group exercise program, 2 hours weekly for 12 weeks, combined with individual counseling. The study endpoints were self-reported HRQoL (Functional Assessment of Cancer Therapy-Lung, European Organization for Research and Treatment in Cancer-Quality of Life Questionnaire-QLQ-C30, Short-Form-36) and self-reported distress, anxiety, depression, and social support (National Comprehensive Cancer Network Distress Thermometer, Hospital Anxiety and Depression Scale, Multidimensional Scale of Perceived Social Support), measured presurgery, postintervention, 6 months, and 1 year after surgery. RESULTS: Forty patients were included, 73% of whom completed rehabilitation. Results on emotional well-being ( P < .0001), global quality of life ( P = .0032), and mental health component score ( P = .0004) showed an overall statistically significant improvement during the study. CONCLUSION: This feasibility study demonstrated that global quality of life, mental health, and emotional well-being improved significantly during the study, from time of diagnosis until 1 year after resection, in patients with NSCLC participating in rehabilitation.

Ultrasound-guided Lung Biopsy in the Hands of Respiratory Physicians: Diagnostic Yield and Complications in 215 Consecutive Patients in 3 Centers.

BACKGROUND: The aim of the study was to determine the diagnostic yield and prevalence of complications of ultrasound-guided transthoracic needle aspiration biopsies (US-TTNAB) performed by respiratory physicians after implementation of the procedure in an everyday clinical setting at 3 different centers. METHODS: Patients were included if they during the period from January 2012 to August 2014 had a registered US-TTNAB procedure code or if a US biopsy registration form had been filled out at either of the participating centers. Histology or cytology results were used as a reference test for diagnoses that could be made based on these results. Reference test for the remaining diagnoses was clinical follow-up. The diagnostic yield of US-TTNAB was defined as the proportion of patients in which the result of the US-TTNAB was consistent with the reference test. RESULTS: A total of 215 patients in which a primary US-TTNAB had been performed were identified. The most common biopsy sites were lungs and pleurae with a total of 164 (76.3%) patients and 31 patients (14.4%), respectively. US-TTNAB diagnostic yield was 76.9% (95% CI, 70.3%-83.4%) for malignant diagnoses and 47.6% (95% CI, 31.9%-63.4%) for nonmalignant diagnoses. The most common complications of US-TTNAB were pneumothorax (2.5%; 95% CI, 0.03%-4.6%) and pain at the biopsy site (2%; 95% CI, 0.04%-3.9%). No fatalities related to US-TTNAB were observed. CONCLUSION: US-TTNAB performed by respiratory physicians is a safe procedure with a low risk of complications and the diagnostic yield to establish a malignant diagnosis is acceptable.

Bronchoscopy as a supplement to computed tomography in patients with haemoptysis may be unnecessary.

BACKGROUND: Haemoptysis is a common symptom and can be an early sign of lung cancer. Careful investigation of patients with haemoptysis may lead to early diagnosis. The strategy for investigation of these patients, however, is still being debated. OBJECTIVES: We studied whether the combination of computed tomography (CT) and bronchoscopy had a higher sensitivity for malignant and non-malignant causes of haemoptysis than CT alone. METHODS: The study was a retrospective, non-randomised, two-centre study and included patients who were referred from primary care for the investigation of haemoptysis. RESULTS: A total of 326 patients were included in the study (mean age 60.5 [SD 15.3] years, 63.3% male). The most common aetiologies of haemoptysis were cryptogenic (52.5%), pneumonia (16.3%), emphysema (8.0%), bronchiectasis (5.8%) and lung cancer (4.0%). In patients diagnosed with lung cancer, bronchoscopy, CT and the combination of bronchoscopy and CT had a sensitivity of 0.61, 0.92 (p<0.05) and 0.97 (p=0.58), respectively. In patients with non-malignant causes of haemoptysis, most aetiologies were diagnosed by CT and comprised mainly pneumonia, emphysema and bronchiectasis. Bronchoscopy did not reveal these conditions and the sensitivity to these conditions was not increased by combining CT and bronchoscopy. CONCLUSIONS: CT can stand alone as a diagnostic workup for patients with haemoptysis referred to an outpatient clinic. Bronchoscopy does not identify any malignant aetiologies not already diagnosed by CT. Combining the two test modalities does not result in a significant increase in sensitivity for malignant or non-malignant causes of haemoptysis.

Results of the Randomized Danish Lung Cancer Screening Trial with Focus on High-Risk Profiling.

RATIONALE: As of April 2015, participants in the Danish Lung Cancer Screening Trial had been followed for at least 5 years since their last screening. OBJECTIVES: Mortality, causes of death, and lung cancer findings are reported to explore the effect of computed tomography (CT) screening. METHODS: A total of 4,104 participants aged 50-70 years at the time of inclusion and with a minimum 20 pack-years of smoking were randomized to have five annual low-dose CT scans (study group) or no screening (control group). MEASUREMENTS AND MAIN RESULTS: Follow-up information regarding date and cause of death, lung cancer diagnosis, cancer stage, and histology was obtained from national registries. No differences between the two groups in lung cancer mortality (hazard ratio, 1.03; 95% confidence interval, 0.66-1.6; P = 0.888) or all-cause mortality (hazard ratio, 1.02; 95% confidence interval, 0.82-1.27; P = 0.867) were observed. More cancers were found in the screening group than in the no-screening group (100 vs. 53, respectively; P < 0.001), particularly adenocarcinomas (58 vs. 18, respectively; P < 0.001). More early-stage cancers (stages I and II, 54 vs. 10, respectively; P < 0.001) and stage IIIa cancers (15 vs. 3, respectively; P = 0.009) were found in the screening group than in the control group. Stage IV cancers were nonsignificantly more frequent in the control group than in the screening group (32 vs. 23, respectively; P = 0.278). For the highest-stage cancers (T4N3M1, 21 vs. 8, respectively; P = 0.025), this difference was statistically significant, indicating an absolute stage shift. Older participants, those with chronic obstructive pulmonary disease, and those with more than 35 pack-years of smoking had a significantly increased risk of death due to lung cancer, with nonsignificantly fewer deaths in the screening group. CONCLUSIONS: No statistically significant effects of CT screening on lung cancer mortality were found, but the results of post hoc high-risk subgroup analyses showed nonsignificant trends that seem to be in good agreement with the results of the National Lung Screening Trial. Clinical trial registered with www.clinicaltrials.gov (NCT00496977).