Ultrasound in the Diagnosis of Non-Expandable Lung: A Prospective Observational Study of M-Mode, B-Mode, and 2D-Shear Wave Elastography.

BACKGROUND: Non-expandable lung (NEL) has severe implications for patient symptoms and impaired lung function, as well as crucial implications for the management of malignant pleural effusion (MPE). Indwelling pleural catheters have shown good symptom relief for patients with NEL; hence, identifying patients early in their disease is vital. With the inability of the lung to achieve pleural apposition following thoracentesis and the formation of a hydropneumothorax, traditionally, chest X-ray and clinical symptoms have been used to make the diagnosis following thoracentesis. It is our aim to investigate whether ultrasound measurement of lung movement during respiration can predict NEL before thoracentesis, thereby aiding clinicians in their planning for the optimal treatment of affected patients. METHODS: A total of 49 patients were consecutively included in a single-centre trial performed at a pleural clinic. Patients underwent protocolled ultrasound assessment pre-thoracentesis with measurements of lung and diaphragm movement and shear wave elastography measurements of the pleura and pleural effusion at the planned site of thoracentesis. RESULTS: M-mode measurements of lung movement provided the best diagnostic ROC-curve results, with an AUC of 0.81. Internal validity showed good results utilising the calibration belt test and Brier test. CONCLUSION: M-mode measurement of lung movement shows promise in diagnosing NEL before thoracentesis in patients with known or suspected MPE. A validation cohort is needed to confirm the results.

Safety and feasibility of oesophageal ultrasound for the work-up of thoracic malignancy in patients with respiratory impairment.

Biopsying lung tumours with endobronchial access in patients with respiratory impairment is challenging. However, fine needle aspiration with the endobronchial ultrasound-endoscope via the oesophagus (EUS-B-FNA) makes it possible to obtain tissue samples without entering the airways. Safety of EUS-B-FNA in these patients has not earlier been investigated prospectively. Therefore, this study aimed at assessing feasibility and safety of EUS-B-FNA from centrally located tumours suspected of thoracic malignancy in patients with respiratory insufficiency. The study is a prospective observational study. Patients with indication of EUS-B-FNA of centrally located tumours and respiratory impairment defined as modified Medical Research Council (mMRC) dyspnoea scale score of ≥3, saturation ≤90% or need of continuous oxygen supply were included prospectively in three centres. Any adverse events (AEs) were recorded during procedure and 1-hour recovery. AEs were defined as hypoxemia (saturation <90% or need for increased oxygen supply) or any kind of events needing intervention. Late procedure-related events were recorded during 30-day follow-up. Between April 1, 2020 and January 30, 2021, 16 patients were included. No severe AEs (SAEs) occurred, but AEs were seen in 50% (n=8) and 13% (n=2) of the patients during procedure and recovery respectively. AEs included hypoxemia corrected with increased oxygen supply and in two cases reversal of sedation. Late procedure-related events were seen in 13% (n=2) and included prolonged need of oxygen and one infection treated with oral antibiotics. In this cohort, EUS-B-FNA of centrally located tumours was safe and feasible in patients with respiratory impairment, when examined in the bronchoscopy suite. A variety of mostly mild and manageable complications may occur, a few even up to 30 days post-procedure.

Is it okay to choose to receive bad news by telephone? An observational study on psychosocial consequences of diagnostic workup for lung cancer suspicion.

BACKGROUND: In-person meeting is considered the gold standard in current communication protocols regarding sensitive information, yet one size may not fit all, and patients increasingly demand or are offered disclosure of bad news by, e.g., telephone. It is unknown how patients' active preference for communication modality affect psychosocial consequences of receiving potentially bad news. AIM: To explore psychosocial consequences in patients, who themselves chose to have results of lung cancer workup delivered either in-person or by telephone compared with patients randomly assigned to either delivery in a recently published randomised controlled trial (RCT). METHODS: An observational study prospectively including patients referred for invasive workup for suspected lung cancer stratified in those declining (Patient's Own Choice, POC group) and those participating in the RCT. On the day of invasive workup and five weeks later, patients completed a validated, nine-dimension, condition-specific questionnaire, Consequences of Screening in Lung Cancer (COS-LC). Primary outcome: difference in change in COS-LC dimensions between POC and RCT groups. RESULTS: In total, 151 patients were included in the POC group versus 255 in the RCT. Most (70%) in the POC group chose to have results by telephone. Baseline characteristics and diagnostic outcomes were comparable between POC and RCT groups, and in telephone and in-person subgroups too. We observed no statistically significant between-groups differences in any COS-LC score between POC and RCT groups, or between telephone and in-person subgroups in the POC group. CONCLUSION: Continually informed patients' choice between in-person or telephone disclosure of results of lung cancer workup is not associated with differences in psychosocial outcomes. The present article supports further use of a simple model for how to prepare the patient for potential bad news.

Breaking potentially bad news of cancer workup to well-informed patients by telephone versus in-person: A randomised controlled trial on psychosocial consequences.

BACKGROUND: The use of telephone in delivering cancer care increases, but not in cancer workup. Current protocols for breaking bad news assume a single in-person meeting. Cancer workup involves multiple opportunities for patient information. We investigated the psychosocial consequences in gradually informed patients of receiving lung cancer workup results by telephone versus in-person. METHODS: A randomised, controlled, open-label, assessor-blinded, single-centre trial including patients referred for invasive workup for suspected malignancy (clinical trials no. NCT04315207). Patients were informed on probable cancer at referral, after imaging, and on the day of invasive workup (Baseline visit). Primary endpoint: change (Δ) from baseline to follow-up (4 weeks after receiving workup results) in scores of a validated, sensitive, condition-specific questionnaire (COS-LC) assessing consequences on anxiety, behaviour, dejection and sleep. RESULTS: Of 492 eligible patients, we randomised 255 patients (mean age: 68 years; female: 38%; malignancy diagnosed: 68%) to the telephone (n = 129) or in-person (n = 126) group. Groups were comparable at baseline and follow-up, and no between-groups difference in ΔCOS-LC was observed in the intention-to-treat population, or in subgroups diagnosed with or without malignancy. CONCLUSION: Breaking final result of cancer workup by telephone is not associated with adverse psychosocial consequences compared to in-person conversation in well-informed patients.

Characterization of Lung Tumors that the Pulmonologist can Biopsy from the Esophagus with Endosonography (EUS-B-FNA).

BACKGROUND: According to guidelines, it is possible to biopsy lung tumors "immediately adjacent to the esophagus" with EUS-B-FNA. However, it is unknown what "immediately adjacent" exactly means. OBJECTIVE: to investigate the possibility of achieving EUS-B-FNA biopsies from a lung tumor depending on the distance from the esophagus and to establish the maximal allowable distance between the tumor and the esophagus. METHODS: In a prospective observational study, we included patients with a lung tumor located maximum 6 cm from the esophagus and indication of EUS-B-FNA from the tumor. The tumors were of different sizes. In a plot presenting the tumor size-distance relationship in cases with (biopsy) versus without (non-biopsy) successful EUS-B-FNA, a separation line representing the threshold between the groups were identified and a biopsy-index equation established. The maximal tumor-size corrected distance (TSCD) was calculated using the residuals to the separation line. RESULTS: In total, 70 patients were included. EUS-B-FNA from the lung tumor was possible in 46 patients. All tumors with a distance from the esophagus below 19 mm could be biopsied. The maximal allowable esophagus-tumor distance depended on tumor size. From the separation line, a biopsy-index equation was established with the sensitivity of 93.5%, a specificity of 100%, and total accuracy of 95.7%. The TSCD was 31 mm (sensitivity: 95.7%, specificity 75.0%, and accuracy: 88.6%). CONCLUSION: We established a biopsy-index equation to predict the achievability of a lung tumor using EUS-B-FNA depending on distance to esophagus and tumor size. A general maximal TSCD was 31 mm.

[The use of one single echoendoscope in both the trachea and the oesophagus in diagnosing and staging of lung cancer].

The use of one single ultrasound echoendoscope in both the trachea (EBUS) and the oesophagus (EUS-B) gives a fast, safe and precise diagnosis and stage of the patient with suspected lung cancer. There is solid evidence for simulator-based training in EBUS concerning safety and diagnostic outcome, but this is currently not an option in EUS-B and needs development. In this review, we recommend evidence-based simulator training and certification in EBUS and when available also in EUS-B before practicing on patients.

Re-biopsy after first line treatment in advanced NSCLC can reveal changes in PD-L1 expression.

OBJECTIVES: Re-biopsy in progressive advanced Non-Small-Cell Lung Cancer (NSCLC) after first line treatment may reveal information about evolving tumor biology during treatment. Our study aims to investigate the feasibility, risk of complications, and clinical relevance of performing re-biopsy systematically. MATERIALS AND METHODS: NSCLC patients with advanced, non-targetable disease, receiving first line systemic treatment, were included in a prospective single-centre study (NCT03512847). A diagnostic biopsy was performed at baseline and repeated at time of progression, preferentially from the progressive lesions as determined by CT or PET/CT. The primary endpoint was feasibility, including complication rate to re-biopsy. Secondary endpoints were clinical relevance, defined as a potential of changing treatment or follow-up, due to new histological evidence, specifically a change in PD-L1 Tumor Proportion Score (TPS). RESULTS: Fifty-one patients with progressive advanced NSCLC had re-biopsy performed. Median time from patients' acceptance to biopsy was seven days (range: 0-31). Complication rate was 6% (n = 3) represented by pneumothorax, hydro-pneumothorax and pneumonia, respectively. No severe or chronic complications occurred. Sufficient material for PD-L1 analyses was obtained in 46 of 51 patients: the remaining five cases had insufficient tissue for analyses, no malignant cells/only suspected malignant cells, questioning whether progression was real. PD-L1 TPS change was observed in 33% of patients (n = 15) and 17% (n = 8) had potentially clinically relevant changes. A significantly higher chance of PD-L1 TPS change was observed in chemotherapy-treated patients. CONCLUSION: Our study showed that re-biopsy is feasible, with low risk of complications, and can be clinically relevant in patients with suspected progression in advanced NSCLC.

Pleural epithelioid hemangioendothelioma mimicking pleural empyema: A case report.

Malignant pleural effusion is an important and difficult differential diagnosis to pleural empyema. Epithelioid hemangioendothelioma is an uncommon vascular tumor, which typically occurs in liver, lung or bone. We present an extremely rare case of primary pleural epithelioid hemangioendothelioma mimicking pleural empyema. We conclude, that pleural epithelioid hemangioendothelioma should be kept in mind as a differential diagnosis in patients suspected of empyema.

Aspiration of Pericardial Effusion Performed with EUS-B-FNA in Suspected Lung Cancer.

Ultrasound-guided needle aspiration via the esophagus using the endobronchial endoscope (EUS-B-FNA) is increasingly being performed by the pulmonologist for the diagnosis of lung cancer, but we have little experience and data available in the literature especially with respect to staging of the disease. We present 2 cases of EUS-B-guided aspiration of malignant pericardial effusion performed in the same setting as bronchoscopy and endobronchial ultrasound. No complications were observed. We conclude that EUS-B-FNA may be safe and efficacious in the evaluation of pericardial effusion during lung cancer workup. Thus, EUS-B-FNA may save time in the diagnostic workup, improve cancer staging, and prevent transthoracic pericardiocentesis.

EUS-B for suspected left adrenal metastasis in lung cancer.

BACKGROUND: Several studies have reported the efficacy of esophageal ultrasound-guided fine needle aspiration (EUS-FNA) for the detection of metastases in the left adrenal gland (LAG) in patients with lung cancer. Currently we have only limited evidence based on small studies on the usefulness of EUS-B [endobronchial ultrasound (EBUS) scope into the esophagus] to provide tissue proof of suspected LAG metastases. The objectives of this study are to investigate feasibility, safety and diagnostic yield of EUS-B-FNA in LAG analysis in patients with proven or suspected lung cancer. METHODS: In two Danish hospitals, a systematic search in the electronic database for patients who underwent EUS-B-FNA of the LAG for suspected or proven lung cancer was performed retrospectively between January 1st, 2015 and December 31st, 2017. Computed tomography (CT), positron emission tomography-CT, endoscopy, pathology and follow-up data were acquired. RESULTS: One hundred and thirty-five patients were included; the prevalence of biopsy proven LAG malignancy was 30% (40/135). A total of 87% (117/135) of EUS-B-FNA samples were adequate (i.e., containing adrenal or malignant cells). No complications were observed. CONCLUSIONS: We present the largest cohort of patients ever reported showing that EUS-B-FNA of the LAG is a safe and feasible procedure and should therefore be used for staging purposes in patients with lung cancer and a suspicious LAG.

Fluoroscopy guided percutaneous biopsy in combination with bronchoscopy and endobronchial ultrasound in the diagnosis of suspicious lung lesions - the triple approach.

Flexible bronchoscopy and endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) are the pulmonologists´ basic procedures for the biopsy of suspicious lung lesions. If inconclusive, other guiding-modalities for tissue sampling are needed, computed tomography performed by a radiologist, or - if available - radial EBUS or electromagnetic navigation biopsy. We wanted to investigate if same-day X-ray fluoroscopy-guided transthoracic fine-needle aspiration biopsy (F-TTNAB) performed by the pulmonologist immediately after bronchoscopy and EBUS is a feasible alternative. We retrospectively identified consecutive patients in whom F-TTNAB followed a bronchoscopy and EBUS in the same séance. Patients in whom the suspicion of malignancy was invalidated after complete work up were followed for six months to identify false-negative cases. In total 125 patients underwent triple approach (bronchoscopy, EBUS and F-TTNAB) during the same séance. Malignancy was diagnosed in 86 (69%), and 77 of these (90%) were primary lung cancers. The diagnostic yield of F-TTNAB for malignancy was 77%, and sensitivity was 90%. Pneumothorax occurred in 35 (28%) patients, and was administered with pleural drainage in 22 (18% of all patients). No cases of prolonged haemoptysis were observed. The risk of pneumothorax differed insignificantly with lesion size ≤2.0 cm (27%) versus >2.0 cm (29%). We conclude that it is feasible for pulmonologist to perform F-TTNAB immediately after endoscopy as a combined triple approach in a fast-track workup of suspected lung cancer.

EUS-B-FNA for Diagnosing Liver and Celiac Metastases in Lung Cancer Patients.

BACKGROUND: In patients with suspected or proven lung cancer, assessment of regional nodal and distant metastases is key before treatment planning. By introducing the endobronchial ultrasound (EBUS)-guided scope into the esophagus and stomach (EUS-B), liver lesions and celiac nodes can be visualized. To date, the utility of EUS-B in diagnosing liver lesions and retroperitoneal lymph nodes is unknown. OBJECTIVES: To assess the feasibility, safety, and diagnostic yield of sampling of liver lesions and retroperitoneal nodes by EUS-B fine-needle aspiration (FNA) in a lung cancer staging setting. METHOD: Consecutive patients suspected of lung cancer in 2 Danish centers between 1 January 2015 and 31 December 2017 were included retrospectively when a lesion in the liver or a retroperitoneal lymph node was visualized and biopsied with EUS-B-FNA. RESULTS: 23 left liver lobe lesions and 19 retroperitoneal lymph nodes were sampled by EUS-B-FNA. Sensitivity and diagnostic yield of sampled liver lesions were 86 and 83%, respectively. In 19/23 patients, there was a cytopathological diagnosis of malignancy. Sensitivity and diagnostic yield from retroperitoneal lymph node samples were 83 and 63%, respectively. In 10/19 patients, the diagnosis was malignancy. No complications were observed. CONCLUSION: EUS-B-FNA enables safe sampling of left liver lobe lesions and retroperitoneal lymph nodes. EUS-B should be considered as a minimally invasive technique to provide tissue proof of distant metastases lung cancer patients.

Endoscopic Ultrasound with Bronchoscope-Guided Fine Needle Aspiration for the Diagnosis of Paraesophageally Located Lung Lesions.

BACKGROUND: Diagnosing centrally located lung tumors without endobronchial abnormalities and not located near the major airways is a diagnostic challenge. Tumors near or adjacent to the esophagus can be aspirated and detected with esophageal ultrasound (EUS) using gastrointestinal endoscopes. OBJECTIVE: To assess the feasibility and diagnostic yield of endoscopic ultrasound with bronchoscope-guided fine needle aspiration (EUS-B-FNA) in paraesophageally located lung tumors and its added value to bronchoscopy and endobronchial ultrasound (EBUS). METHODS: Retrospective, multicenter international study (from January 1, 2015 until January 1, 2018) of patients with suspected lung cancer, undergoing bronchoscopy, EBUS, and endoscopic ultrasound bronchoscopy (EUS-B) in one session by a single operator (pulmonologist), in whom the primary lung tumor was detected and aspirated by EUS-B. In the absence of malignancy following endoscopy, transthoracic ultrasound needle aspiration, clinical and radiological follow-up of at least 6 months was performed. The yield and sensitivity of EUS-B-FNA and its added value to bronchoscopy and EBUS was assessed. RESULTS: 58 patients were identified with the following diagnosis: non-small-cell lung cancer (n = 43), small-cell lung cancer (n = 6), mesothelioma (n = 2), metastasis (n = 1), nonmalignant (n = 6). The yield and sensitivity of EUS-B-FNA for detecting lung cancer was 90%. In 26 patients (45%), the intrapulmonary tumor was exclusively detected by EUS-B. Adding EUS-B to conventional bronchoscopy and EBUS increased the diagnostic yield for diagnosing lung cancer in para-esophageally located lung tumors from 51 to 91%. No EUS-B-related complications were observed. CONCLUSION: EUS-B-FNA is a feasible and safe technique for diagnosing centrally located intrapulmonary tumors that are located near or adjacent to the esophagus. EUS-B should be considered in the same endoscopy session following nondiagnostic bronchoscopy and EBUS.

Accuracy and consequences of same-day, invasive lung cancer workup - a retrospective study in patients treated with surgical resection.

BACKGROUND: Though widely used, little is known about accuracy and efficacy of same-day, invasive workup of suspected lung cancer. OBJECTIVE: To evaluate the accuracy and efficacy of same-day, invasive lung cancer workup (diagnosis and mediastinal staging), and to identify differences between patients without (Group A) or with (Group B) need for resampling. METHODS: A retrospective study was performed on all consecutive patients referred for surgical treatment for localised lung cancer after invasive diagnostic and staging workup at our unit. Data were extracted from electronic medical files. Surgical specimens served as gold standard for correct diagnosis and stage. RESULTS: A total of 129 patients (peripheral lesion: 84%; mediastinal staging: 97%) were included. After same-day, invasive workup, 71% had no need for further invasive workup (Group A), while 29% had (Group B). Group A differed significantly from Group B in fewer invasive tests, fewer days from referral to surgery, and lower pneumothorax incidence, while no differences were observed in diagnostic accuracy, cancer subtype, tumour size, tumour stage, peripheral lesion, nodal involvement, gender, or presence of chronic obstructive pulmonary disease. Tumour located in right upper lobe was associated with need for resampling. DISCUSSION: Our retrospective study suggests that same-day, invasive workup for lung cancer is safe, accurate, and efficacious in reducing time to therapy, even in patients with small lesions and low tumour burden.

Multimodality approach to mediastinal staging in non-small cell lung cancer. Faults and benefits of PET-CT: a randomised trial.

BACKGROUND: Correct mediastinal staging is a cornerstone in the treatment of patients with non-small cell lung cancer. A large range of methods is available for this purpose, making the process of adequate staging complex. The objective of this study was to describe faults and benefits of positron emission tomography (PET)-CT in multimodality mediastinal staging. METHODS: A randomised clinical trial was conducted including patients with a verified diagnosis of non-small cell lung cancer, who were considered operable. Patients were assigned to staging with PET-CT (PET-CT group) followed by invasive staging (mediastinoscopy and/or endoscopic ultrasound with fine needle aspiration (EUS-FNA)) or invasive staging without prior PET-CT (conventional work up (CWU) group). Mediastinal involvement (dichotomising N stage into N0-1 versus N2-3) was described according to CT, PET-CT, mediastinoscopy, EUS-FNA and consensus (based on all available information), and compared with the final N stage as verified by thoracotomy or a conclusive invasive diagnostic procedure. RESULTS: A total of 189 patients were recruited, 98 in the PET-CT group and 91 in the CWU group. In an intention-to-treat analysis the overall accuracy of the consensus N stage was not significantly higher in the PET-CT group than in the CWU group (90% (95% confidence interval 82% to 95%) vs 85% (95% CI 77% to 91%)). Excluding the patients in whom PET-CT was not performed (n=14) the difference was significant (95% (95% CI 88% to 98%) vs 85% (95% CI 77% to 91%), p=0.034). This was mainly based on a higher sensitivity of the staging approach including PET-CT. CONCLUSION: An approach to lung cancer staging with PET-CT improves discrimination between N0-1 and N2-3. In those without enlarged lymph nodes and a PET-negative mediastinum the patient may proceed directly to surgery. However, enlarged lymph nodes on CT needs confirmation independent of PET findings and a positive finding on PET-CT needs confirmation before a decision on surgery is made. CLINICAL TRIAL NUMBER: NCT00867412.

Ambulatory blood pressure monitoring after 1 year on valsartan or amlodipine-based treatment: a VALUE substudy.

OBJECTIVE: The ambulatory blood pressure (ABP) monitoring substudy of the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial was carried out in a subset of patients from USA, Italy and Denmark. ABP was measured after 1 year in the trial, with the aim of evaluating comparability of ABP levels on valsartan (VAL) and amlodipine (AML)-based regimens. METHODS: ABP was measured every 20 min during a 25-h period after morning administration of medicine; 659 patients were available for intention-to-treat analysis. RESULTS: Office blood pressure (BP) differences were smaller than in the main study and mean ABP levels also showed only minor differences between the two regimens (VAL, 132.5/74.8 mmHg; AML, 131.5/75.2 mmHg). However, during the first 7 h after dosing, ABP was lower on VAL, whereas AML exerted a significantly stronger effect during the last 4 h of the dosing interval--possibly influencing the differences in office BP found in the main study. Mean heart rate (HR) was higher on AML (72.3 bpm) than on VAL (70.5 bpm) (P = 0.013), suggesting a sustained difference in sympathetic activation. Correlation analysis showed a close relationship between treated ABP levels and the occurrence of combined cardiovascular endpoints--superior to the relationship to office BP. CONCLUSIONS: In these elderly high-risk patients, diastolic ABP levels tended to be less predictive than systolic, and daytime less predictive than night-time for all cardiovascular endpoints. The findings underline the importance of ABP substudies in comparative trials for elucidating significant differences in pharmacodynamics, and stresses the superior predictive power of ABP.

A multicenter, randomized, double-blind, placebo-controlled, 6-month trial of bupropion hydrochloride sustained-release tablets as an aid to smoking cessation in hospital employees.

Despite changes in smoking behavior, one-third of the Danish population continues to smoke. Many of these smokers are hospital employees. This 6-month, multicenter, parallel group, randomized, double-blind, placebo-controlled study evaluated treatment with bupropion hydrochloride sustained release (Zyban) compared with placebo as an aid to smoking cessation in health care workers. A total of 336 hospital employees who smoked at least 10 cigarettes daily were randomized (2:1) to 7 weeks of treatment with bupropion (n=222) or placebo (n=114). All participants were motivated to quit smoking and received behavioral counseling. Continuous smoking abstinence during weeks 4-7 was the primary endpoint, and long-term smoking abstinence was among the secondary endpoints. Of the original participants, 212 completed the 6-month trial. Continuous smoking abstinence at week 7 was achieved by 43% in the bupropion group and 18% in the placebo group, p<.001. After 26 weeks, 18% and 7%, respectively, were continuously abstinent, p=.008. Side-effects were frequent but simple and reversible in both groups, and generally consistent with the findings of previous studies. Dizziness, insomnia, and pruritus appeared more frequently in the bupropion group than in the placebo group. Bupropion was effective as an aid to smoking cessation in a broad group of hospital employees in Denmark.