The diagnosis of peripheral pulmonary lesions (PPL) continues to present clinical challenges. Despite extensive experience with guided bronchoscopy, the diagnostic yield has not improved ...significantly. Robotic-assisted bronchoscopic platforms have been developed potentially to improve the diagnostic yield for PPL. Presently, limited data exist that evaluate the performance of robotic systems in live human subjects.
What is the safety and feasibility of robotic-assisted bronchoscopy in patients with PPLs?
This was a prospective, multicenter pilot and feasibility study that used a robotic bronchoscopic system with a mother-daughter configuration in patients with PPL 1 to 5 cm in size. The primary end points were successful lesion localization with the use of radial probe endobronchial ultrasound (R-EBUS) imaging and incidence of procedure related adverse events. Robotic bronchoscopy was performed in patients with the use of direct visualization, electromagnetic navigation, and fluoroscopy. After the use of R-EBUS imaging, transbronchial needle aspiration was performed. Rapid on-site evaluation (ROSE) was used on all cases. Transbronchial needle aspiration alone was sufficient when ROSE was diagnostic; when ROSE was not diagnostic, transbronchial biopsy was performed with the use of the robotic platform, followed by conventional guided bronchoscopic approaches at the discretion of the investigator.
Fifty-five patients were enrolled at five centers. One patient withdrew consent, which left 54 patients for data analysis. Median lesion size was 23 mm (interquartile range, 15 to 29 mm). R-EBUS images were available in 53 of 54 cases. Lesion localization was successful in 51 of 53 patients (96.2%). Pneumothorax was reported in two of 54 of the cases (3.7%); tube thoracostomy was required in one of the cases (1.9 %). No additional adverse events occurred.
This is the first, prospective, multicenter study of robotic bronchoscopy in patients with PPLs. Successful lesion localization was achieved in 96.2% of cases, with an adverse event rate comparable with conventional bronchoscopic procedures. Additional large prospective studies are warranted to evaluate procedure characteristics, such as diagnostic yield.
ClinicalTrials.gov; No.: NCT03727425; URL: www.clinicaltrials.gov.
While the complexity of flexible bronchoscopy has increased, standard options for moderate sedation medications have not changed in three decades. There is a need to improve moderate sedation while ...maintaining safety. Remimazolam was developed to address shortcomings of current sedation strategies.
A prospective, double-blind, randomized, multicenter, parallel group trial was performed at 30 US sites. The efficacy and safety of remimazolam for sedation during flexible bronchoscopy were compared with placebo and open-label midazolam.
The success rates were 80.6% in the remimazolam arm, 4.8% in the placebo arm (P < .0001), and 32.9% in the midazolam arm. Bronchoscopy was started sooner in the remimazolam arm (mean, 6.4 ± 5.82 min) compared with placebo (17.2 ± 4.15 min; P < .0001) and midazolam (16.3 ± 8.60 min). Time to full alertness after the end of bronchoscopy was significantly shorter in patients treated with remimazolam (median, 6.0 min; 95% CI, 5.2-7.1) compared with those treated with placebo (13.6 min; 95% CI, 8.1-24.0; P = .0001) and midazolam (12.0 min; 95% CI, 5.0-15.0). Remimazolam registered superior restoration of neuropsychiatric function compared with placebo and midazolam. Safety was comparable among all three arms, and 5.6% of the patients in the remimazolam group had serious treatment-emergent adverse events as compared with 6.8% in the placebo group.
Remimazolam administered under the supervision of a pulmonologist was effective and safe for moderate sedation during flexible bronchoscopy. In an exploratory analysis, it demonstrated a shorter onset of action and faster neuropsychiatric recovery than midazolam.
New technology has resulted in bronchoscopy being increasingly used for diagnosing pulmonary lesions. Reported yield from these procedures varies widely with few randomized clinical trials. This ...study compares the diagnostic yield of a thin bronchoscope and radial endobronchial ultrasound (R-EBUS) with standard bronchoscopy and fluoroscopy (SB-F) in lung lesions.
Patients presenting for diagnostic bronchoscopic evaluation at five centers were randomized to undergo SB-F or R-EBUS with a thin bronchoscope (TB-EBUS). If SB-F was nondiagnostic, crossover to the TB-EBUS arm was allowed. Data on patient demographics, radiographic features, and final pathologic or radiographic follow-up were collected. Statistical comparisons were made by Fisher exact test, χ
test, and Student t test. Bivariate and multivariate analyses were performed to determine predictors of diagnostic yield.
One hundred and ninety-seven patients were included in the final analyses. There was no difference in demographics, lesion size, or location between study arms. The average lesion size was 31.2 mm (SD, 10.8 mm). Bronchoscopy was diagnostic in 87 patients (44%). Although the diagnostic yield was higher in the TB-EBUS arm compared with the SB-F arm (49% vs 37%), this difference was not statistically significant (P = .11). Among those with nondiagnostic bronchoscopic findings in the standard arm, 87% (n = 46) crossed over to TB-EBUS, resulting in a diagnosis in seven additional patients (15% of 46).
Bronchoscopy with or without a thin scope and R-EBUS had a poor diagnostic yield for pulmonary lesions. Future work should focus on improvements in technique and technology advances that ensure a higher likelihood of obtaining a diagnosis.
Background: Bronchoscopy for the diagnosis of peripheral pulmonary lesions continues to present clinical challenges, despite increasing experience using newer guided techniques. Robotic bronchoscopic ...platforms have been developed to potentially improve diagnostic yields. Previous studies in cadaver models have demonstrated increased reach into the lung periphery using robotic systems compared to similarly sized conventional bronchoscopes, although the clinical impact of additional reach is unclear. Objectives: This study was performed to evaluate the performance of a robotic bronchoscopic system’s ability to reach and access artificial tumor targets simulating peripheral nodules in human cadaveric lungs. Methods: Artificial tumor targets sized 10–30 mm in axial diameter were implanted into 8 human cadavers. CT scans were performed prior to procedures and all cadavers were intubated and mechanically ventilated. Electromagnetic navigation, radial probe endobronchial ultrasound, and fluoroscopy were used for all procedures. Robotic-assisted bronchoscopy was performed on each cadaver by an individual bronchoscopist to localize and biopsy peripheral lesions. Results: Sixty-seven nodules were evaluated in 8 cadavers. The mean nodule size was 20.4 mm. The overall diagnostic yield was 65/67 (97%) and there was no statistical difference in diagnostic yield for lesions <20 mm compared with lesions measuring 21–30 mm, the presence of a concentric or eccentric radial ultrasound image, or relative distance from the pleura. Conclusions: The robotic bronchoscopic system was successful at biopsying 97% of peripheral pulmonary lesions 10–30 mm in size in human cadavers. These findings support further exploration of this technology in prospective clinical trials in live human subjects.
Guided bronchoscopy is increasingly used to diagnose peripheral pulmonary lesions (PPLs). A meta-analysis published in 2012 demonstrated a pooled diagnostic yield of 70%; however, recent publications ...have documented yields as low as 40% and as high as 90%.
Has the diagnostic yield of guided bronchoscopy in patients with PPLs improved over the past decade?
A comprehensive search was performed of studies evaluating the diagnostic yield of differing bronchoscopic technologies used to reach PPLs. Study quality was assessed using the Quality assessment of diagnostic accuracy of studies (QUADAS-2) assessment tool. Number of lesions, type of technology used, overall diagnostic yield, and yield by size were extracted. Adverse events were recorded. Meta-analytic techniques were used to summarize findings across all studies.
A total of 16,389 lesions from 126 studies were included. There was no significant difference in diagnostic yield prior to 2012 (39 studies; 3,052 lesions; yield 70.5%) vs after 2012 (87 studies; 13,535 lesions; yield 69.2%) (P > .05). Additionally, there was no significant difference in yield when comparing different technologies. Studies with low risk of overall bias had a lower diagnostic yield than those with high risk of bias (66% vs 71%, respectively; P = .018). Lesion size > 2 cm, presence of bronchus sign, and reports with a high prevalence of malignancy in the study population were associated with significantly higher diagnostic yield. Significant (P < .0001) between-study heterogeneity was also noted.
Despite the reported advances in bronchoscopic technology to diagnose PPLs, the diagnostic yield of guided bronchoscopy has not improved.
Conclusions.-Based on the systematic review and expert panel consensus, thoracic small specimens can be handled and processed to perform downstream testing (eg, molecular markers, immunohistochemical ...biomarkers), core needle and fine-needle techniques can provide appropriate cytologic and histologic specimens for ancillary studies, and rapid on-site cytologic evaluation remains helpful in appropriate triage, handling, and processing of specimens. (Arch Pathol Lab Med. 2020;144:933-958; doi: 10.5858/ arpa.2020-0119-CP) With the advances in minimally invasive sampling techniques, the ability to provide a diagnosis and perform multiple ancillary studies on limited-volume tissue samples, including small biopsy and cytology specimens, has been a paradigm shift in the management of pulmonary pathology. J.N.: stock options/bonds, OmniSeq, LLC (Buffalo, New York); J.V.: research grants, Abbott Molecular Inc (Des Plaines, Illinois); N.P.: consultancy, Cook Medical LLC (Bloomington, Indiana), research grants and honoraria, Olympus Corporation (Tokyo, Japan); P.I.: consultancies, AstraZeneca (Cambridge, England) and Genentech USA, Inc (South San Francisco, California), honoraria, Ventana Medical Systems, Inc (Oro Valley, Arizona); S.D.: advisory board, Bayer AG (Leverkusen, Germany) and Bristol-Myers Squibb Company (New York, New York), consultancies, AstraZeneca and Genentech USA, Inc. The majority of the EP (13 of 18 members) were assessed as having no relevant conflicts of interest. With regard to each of the specimen types of interest, what evidence is available to determine the most effective protocols for sample collection, including the immediate handling of the specimen (ie, how the needle biopsy is expelled from the needle and the selection of the appropriate media), the minimum and maximum number of passes needed to ensure that the laboratory can obtain adequate materials for diagnostic testing, and the impact of ROSE on adequacy, quality, and triage of specimens?
Bronchoscopy is commonly used to evaluate suspicious lung lesions. The yield is likely dependent on patient, radiographic, and bronchoscopic factors. Few studies have assessed these factors ...simultaneously while also including the preprocedure physician-assessed probability of cancer (pCA) when assessing yield.
This study is a secondary data analysis from a prospective multicenter trial. Diagnostic yield of standard bronchoscopy with biopsy ± fluoroscopy, endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA), electromagnetic navigation, and combination bronchoscopies was assessed. Definitions for diagnostic and nondiagnostic bronchoscopies were rigorously predefined. The association of diagnostic yield with individual variables was examined by using univariate and multivariate logistic regression analyses where appropriate.
A total of 687 patients were included from 28 sites. Overall diagnostic yield was 69%; 80% for EBUS, 55% for bronchoscopy with biopsy ± fluoroscopy, 57% for electromagnetic navigation, and 74% for combination procedures (P < .001). Patients with larger, central lesions with adenopathy were significantly more likely to undergo a diagnostic bronchoscopy. Patients with pCA < 10% and 10% to 60% had lower yields (44% and 42%, respectively), whereas pCA > 60% yielded a positive result in 77% (P < .001). In multivariate logistic regression, the use of EBUS-TBNA, larger sized lesions, and central location were significantly associated with a diagnostic bronchoscopy. Seventeen percent of those with a malignant diagnosis and 28% of those with a benign diagnosis required secondary procedures to establish a diagnosis.
This study is the first to assess the yield of bronchoscopy according to physician-assessed pCA in a large, prospective multicenter trial. The yield of bronchoscopy varied greatly according to physician suspicion that cancer is present, the patients' clinical/radiographic features, and the type of procedure performed. Of the procedures performed, EBUS-TBNA was the most likely to provide a diagnosis.
The need for appropriate specimen use for ancillary testing has become more commonplace in the practice of pathology. This, coupled with improvements in technology, often provides less invasive ...methods of testing, but presents new challenges to appropriate specimen collection and handling of these small specimens, including thoracic small biopsy and cytology samples.
To develop a clinical practice guideline including recommendations on how to obtain, handle, and process thoracic small biopsy and cytology tissue specimens for diagnostic testing and ancillary studies.
The College of American Pathologists convened an expert panel to perform a systematic review of the literature and develop recommendations. Core needle biopsy, touch preparation, fine-needle aspiration, and effusion specimens with thoracic diseases including malignancy, granulomatous process/sarcoidosis, and infection (eg, tuberculosis) were deemed within scope. Ancillary studies included immunohistochemistry and immunocytochemistry, fluorescence in situ hybridization, mutational analysis, flow cytometry, cytogenetics, and microbiologic studies routinely performed in the clinical pathology laboratory. The use of rapid on-site evaluation was also covered.
Sixteen guideline statements were developed to assist clinicians and pathologists in collecting and processing thoracic small biopsy and cytology tissue samples.
Based on the systematic review and expert panel consensus, thoracic small specimens can be handled and processed to perform downstream testing (eg, molecular markers, immunohistochemical biomarkers), core needle and fine-needle techniques can provide appropriate cytologic and histologic specimens for ancillary studies, and rapid on-site cytologic evaluation remains helpful in appropriate triage, handling, and processing of specimens.
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