BackgroundWith the need for "actionable histology" in the current era of targeted cancer treatment, and the increasing practice of upfront thoracoscopy (without a prior diagnostic thoracentesis) or a ..."biopsy first" approach in suspected malignant pleural effusions (MPEs), we sought to prospectively evaluate the diagnostic accuracy, including full molecular profiling of cancer, and safety of medical thoracoscopy (MT) at a tertiary referral hospital.MethodsPatients with MT performed for an undiagnosed pleural effusion between January 2020 and December 2022 were included in this observational cohort study. All procedures were performed with a semirigid thoracoscope under conscious sedation. Clinical outcomes and adverse events were recorded prospectively.ResultsWe evaluated 141 patients, with a mean age of 67±12 years. Talc poudrage was performed in 67 (47.5%) patients with a median of 2 interquartile range (IQR), 1-4 hospitalisation days after MT. Upfront thoracoscopy was performed in approximately half (55.3%) of patients. The overall diagnostic accuracy of MT was 95.7% in our cohort. A final diagnosis of cancer was made in 116 (82.3%) patients, with lung (67.2%) and breast cancer (8.6%) the most common. The diagnostic sensitivity of MT for malignancy was 94.8%, and molecular profiling of relevant cancer types for oncogenic mutations was achieved in all patients with malignancy seen on histopathology. The most common non-malignant diagnosis was tuberculous pleuritis in 14 patients (9.9%). Major complications occurred in 3 (2.1%) patients. Two patients had re-expansion pulmonary edema that resolved with low flow oxygen supplementation in the general ward, and one patient required intensive care unit admission for cardiac tamponade from a malignant pericardial effusion. There were no cases of mortality, bleeding complications or persistent air leaks.ConclusionsMT is a well-tolerated and effective option for the evaluation of undiagnosed pleural effusions. With expanding utility and expertise with MT and other pleural interventions, the challenge for respiratory physicians is integrating these into expeditious diagnostic and effective therapeutic pathways, individualised to patients' needs.
Summary The efficacy and technical aspects of endobronchial ultrasound (EBUS) are reviewed because this technology promises to revolutionise bronchoscopy. EBUS extends the endoscopist's view beyond ...the mucosal surface of the large airways to peri-bronchial structures and peripheral lung lesions. Guided biopsies and real-time transbronchial needle aspirations (TBNA) have been shown to increase the diagnostic yield over conventional bronchoscopic techniques. The technology is available in two forms: radial EBUS probes and linear EBUS–TBNA bronchoscopes. Radial EBUS utilizes higher frequencies and the transducer is inserted via a standard flexible bronchoscope. The higher ultrasound frequencies improve image resolution to <1 mm. Radial EBUS is used to assess airway walls, guide TBNA (diagnostic yield: 72–86%) and diagnose peripheral lung lesions (diagnostic yield: 61–80%). Linear EBUS–TBNA transducers are built into dedicated bronchoscopes to produce sector view images and permit real-time TBNA. The pooled sensitivity of real-time EBUS–TBNA in lung cancer is 90% but the false negative rate is 20%. Therefore, EBUS–TBNA is a viable alternative to cervical mediastinoscopy in the diagnosis and staging of mediastinal lymphadenopathy. However, negative results need either further confirmatory testing or adequate clinical follow-up. Complications are rare with either EBUS modality and are usually related to the underlying biopsy procedure rather than the use of ultrasound. Procedure duration is short enough to be incorporated into an outpatient setting and can performed under moderate sedation. Clear training standards are emerging to facilitate credentialing as EBUS is rapidly evolving to become a part of standard diagnostic bronchoscopy.
Despite the established role of EGFR tyrosine kinase inhibitors (TKIs) in
-mutated NSCLC, drug resistance inevitably ensues, with a paucity of treatment options especially in
-negative resistance.
We ...performed whole-exome and transcriptome analysis of 59 patients with first- and second-generation EGFR TKI-resistant metastatic
-mutated NSCLC to characterize and compare molecular alterations mediating resistance in T790M-positive (T790M
) and -negative (T790M
) disease.
Transcriptomic analysis revealed ubiquitous loss of adenocarcinoma lineage gene expression in T790M
tumors, orthogonally validated using multiplex IHC. There was enrichment of genomic features such as
alterations, 3q chromosomal amplifications, whole-genome doubling and nonaging mutational signatures in T790M
tumors. Almost half of resistant tumors were further classified as immune
, with clinical outcomes conditional on immune cell-infiltration state and T790M status. Finally, using a Bayesian statistical approach, we explored how T790M
and T790M
disease might be predicted using comprehensive genomic and transcriptomic profiles of treatment-naïve patients.
Our results illustrate the interplay between genetic alterations, cell lineage plasticity, and immune microenvironment in shaping divergent TKI resistance and outcome trajectories in
-mutated NSCLC. Genomic and transcriptomic profiling may facilitate the design of bespoke therapeutic approaches tailored to a tumor's adaptive potential.
ObjectivesWe compared 2 sociocultural cohorts with different duration of exposure to graphic health warning labels (GHWL), to investigate a possible desensitisation to their use. We further studied ...how a differing awareness and emotional impact of smoking-associated risks could be used to prevent this.SettingStructured interviews of patients from the general respiratory department were undertaken between 2012 and 2013 in 2 tertiary hospitals in Singapore and London.Participants266 participants were studied, 163 Londoners (35% smokers, 54% male, age 52±18 years) and 103 Singaporeans (53% smokers, p=0.003; 78% male, p<0.001; age 58±15 years, p=0.012).Main outcomes and measures50 items assessed demographics, smoking history, knowledge and the deterring impact of smoking-associated risks. After showing 10 GHWL, the impact on emotional response, cognitive processing and intended smoking behaviour was recorded.ResultsSingaporeans scored lower than the Londoners across all label processing constructs, and this was consistent for the smoking and non-smoking groups. Londoners experienced more ‘disgust’ and felt GHWL were more effective at preventing initiation of, or quitting, smoking. Singaporeans had a lower awareness of lung cancer (82% vs 96%, p<0.001), despite ranking it as the most deterring consequence of smoking. Overall, ‘blindness’ was the least known potential risk (28%), despite being ranked as more deterring than ‘stroke’ and ‘oral cancer’ in all participants.ConclusionsThe length of exposure to GHWL impacts on the effectiveness. However, acknowledging the different levels of awareness and emotional impact of smoking-associated risks within different sociocultural cohorts could be used to maintain their impact.
Stereotactic radiosurgery (Cyberknife; Accuray Incorporated; Sunnyvale, CA) is a treatment option for patients who are medically unfit to undergo lung tumor resection. For precise tumor ablation, the ...Cyberknife requires fiducial marker placement in or near the target tumor. Fiducial placement under transthoracic CT guidance is associated with a high risk of iatrogenic pneumothorax. Electromagnetic navigation bronchoscopy (ENB) may offer a less morbid alternative to accurately deploy fiducials to bronchoscopically invisible peripheral lung lesions.
Open-label, feasibility study to assess fiducial placement in peripheral lung tumors by ENB.
Consecutive patients with peripheral lung tumors and who were evaluated to be nonsurgical candidates underwent fiducial placement under ENB. This procedure was considered successful if fiducials were placed in or near the tumors and remained in place without migration for radiosurgery to proceed. The need for alternative or additional intrathoracic fiducial placement was documented as procedure failure.
A total of 39 fiducials markers were successfully deployed in eight of nine patients (89%). Of these eight successful cases, seven had fiducials placed directly within the tumor (88%). At Cyberknife planning, 7 to 10 days after fiducial placement, 35 of 39 fiducial markers (90%) were still in place and were adequate to allow radiosurgery to proceed. No immediate bronchoscopic complications were observed. One patient had a COPD exacerbation. Another patient returned within 1 day with transient, self-limiting fever.
ENB can be used to deploy fiducial markers for Cyberknife radiosurgery of lung tumors safely and accurately without the complications associated with transthoracic placement.
BackgroundIn advanced esophageal carcinoma (EC), there is limited data on risk factors predicting tracheobronchoesophageal fistula (TEF) formation and survival among patients who required airway ...interventions. MethodsA retrospective analysis of consecutive patients with EC, who had airway involvement requiring intervention, was conducted from 1998 to 2018. Demographics, clinical progress, disease stage, treatment and survival outcomes were recorded. Patients were followed up till death or until completion of the study. Survival was estimated with the Kaplan-Meier method and curves compared by log-rank test. Multivariate analyses of risk factors were performed using Cox proportional hazard regression. ResultsA total of 122 patients were included. The median (IQR) survival from time of airway intervention was 3.30 (1.57-6.88) months, while the median (IQR) survival from time of histological diagnosis was 8.90 (4.91-14.45) months. Tumour location within 20 mm of the carina, prior radiotherapy and/or esophageal stenting were significantly associated with formation of TEF. Mid EC adjusted hazard ratio (HR) 1.9; 95% confidence interval (CI): 1.1-3.2 or presence of TEF (adjusted HR 1.8; 95% CI: 1.0-3.2) were associated with lower survival. Patients receiving chemotherapy (adjusted HR 0.46; 95% CI: 0.25-0.84), or esophageal stenting whether before or after airway intervention (adjusted HR 0.32; 95% CI: 0.15-0.68 and adjusted HR 0.51; 95% CI: 0.29-0.90) were associated with increased survival. ConclusionsFactors associated with TEF formation include airway location, radiotherapy and prior esophageal stenting, and the development of TEF was associated with poorer survival. An algorithmic approach towards tracheobronchial involvement in EC is proposed based on these findings and a review of the literature.
Accurate diagnosis is critical to both therapeutic decisions and prognostication in interstitial lung diseases (ILD). However, surgical lung biopsies carry high complication rates. Fibred confocal ...fluorescence microscopy (FCFM) offers an alternative as it can visualize lung tissue
at the cellular level with minimal adverse events. We wanted to investigate the diagnostic utility, and safety of using FCFM for patients with ILD.
In patients with suspected ILD, FCFM images were obtained from multiple bronchopulmonary segments using a miniprobe inserted through the working channel of a flexible bronchoscope. The procedure was performed under moderate sedation in an outpatient setting. Morphometric measurements and fibre pattern analyses were co-related with computed tomography (CT) findings and patients' final diagnoses based on multi-disciplinary consensus.
One hundred and eighty four segments were imaged in 27 patients (18 males) with a median age of 67 years (range, 24-79 years). They were grouped into chronic fibrosing interstitial pneumonia (16 patients) and other ILDs. Six distinct FCFM patterns were observed: normal, increased fibres, densely packed fibres, hypercellular, thickened fibres and others/non-specific. The pattern resembling densely packed fibres was seen in at least one segment in 68.8% patients with chronic fibrosing interstitial pneumonia, but only 36.4% in other ILD (P=0.097). An association between inflammatory patterns on CT and a hypercellular pattern on FCFM was also found (P<0.001).
Our study shows the potential of FCFM in classifying ILD, but its role in further diagnosis remains limited.
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