Evaluation of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration (EBUS-TBNA) Samples from Advanced Non-Small Cell Lung Cancer for Whole Genome, Whole Exome and Comprehensive Panel Sequencing.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is often the only source of tumor tissue from patients with advanced, inoperable lung cancer. EBUS-TBNA aspirates are used for the diagnosis, staging, and genomic testing to inform therapy options. Here we extracted DNA and RNA from 220 EBUS-TBNA aspirates to evaluate their suitability for whole genome (WGS), whole exome (WES), and comprehensive panel sequencing. For a subset of 40 cases, the same nucleic acid extraction was sequenced using WGS, WES, and the TruSight Oncology 500 assay. Genomic features were compared between sequencing platforms and compared with those reported by clinical testing. A total of 204 aspirates (92.7%) had sufficient DNA (100 ng) for comprehensive panel sequencing, and 109 aspirates (49.5%) had sufficient material for WGS. Comprehensive sequencing platforms detected all seven clinically reported tier 1 actionable mutations, an additional three (7%) tier 1 mutations, six (15%) tier 2-3 mutations, and biomarkers of potential immunotherapy benefit (tumor mutation burden and microsatellite instability). As expected, WGS was more suited for the detection and discovery of emerging novel biomarkers of treatment response. WGS could be performed in half of all EBUS-TBNA aspirates, which points to the enormous potential of EBUS-TBNA as source material for large, well-curated discovery-based studies for novel and more effective predictors of treatment response. Comprehensive panel sequencing is possible in the vast majority of fresh EBUS-TBNA aspirates and enhances the detection of actionable mutations over current clinical testing.

Tracheobronchial stents: an expanding prospect.

The first dedicated tracheobronchial silicone stent was designed by the French pulmonologist Jean-Paul Dumon. The most common indications for stenting are to minimise extrinsic airway compression from mass effect, maintain airway patency due to intrinsic obstruction or treat significant nonmalignant airway narrowing or fistulae. Silicone stents require rigid bronchoscopy for insertion; however, they are more readily repositioned and removed compared with metallic stents. Metallic stents demonstrate luminal narrowing when loads are applied to their ends, therefore stents should either be reinforced at the ends or exceed the area of stenosis by a minimum of 5 mm. Nitinol, a nickel-titanium metal alloy, is currently the preferred material used for airway stents. Airway stenting provides effective palliation for patients with severe symptomatic obstruction. Drug-eluting and three-dimensional printing of airway stents present promising solutions to the challenges of the physical and anatomical constraints of the tracheobronchial tree. Biodegradable stents could also be a solution for the treatment of nonmalignant airway obstruction.

Central airway squamous metaplasia following radiation therapy mimicking local tumour recurrence.

Radiation therapy can result in injury to the lung parenchyma and central airways; the latter is less well documented in the literature. Here, we describe a 65-year-old Caucasian male, who developed focal endobronchial nodules and right main bronchial stenosis suggesting tumour recurrence, 32 months following curative intent concurrent chemoradiation therapy for Stage 3B squamous cell carcinoma of the lung. Computed tomography and positron emission tomography results are detailed. Flexible bronchoscopy with bronchial biopsies revealed squamous metaplasia rather than malignant tumour recurrence, with ongoing observation planned.

Central airway squamous metaplasia following radiation therapy mimicking local tumour recurrence.

Radiation therapy can result in injury to the lung parenchyma and central airways; the latter is less well documented in the literature. Here, we describe a 65-year-old Caucasian male, who developed focal endobronchial nodules and right main bronchial stenosis suggesting tumour recurrence, 32 months following curative intent concurrent chemoradiation therapy for Stage 3B squamous cell carcinoma of the lung. Computed tomography and positron emission tomography results are detailed. Flexible bronchoscopy with bronchial biopsies revealed squamous metaplasia rather than malignant tumour recurrence, with ongoing observation planned.

Endobronchial indocyanine green instillation to identify the intersegmental plane for successful segmentectomy.

The traditional indications for lobectomy for resectable Non-small Cell Lung Cancer (NSCLC) may be set to change. Recently, anatomical segmentectomy (AS) versus lobectomy as an approach for early-stage NSCLC has been described in phase 3 randomised controlled trials. The demand for methods to facilitate AS may increase as a consequence. We describe three cases of AS using the combination of endobronchial infiltration of indocyanine green (ICG) to identify the intersegmental plane (critical for the performance of AS), and Computed Tomography (CT) guided methylene blue injection for lesion localisation. The operations were completed successfully demonstrating satisfactory post-operative outcomes including lesion resection with clear surgical margins and acceptable length of stay. We believe that endobronchial instillation of ICG and CT-guided methylene blue injection for lesion localisation show promise as a technique to complement parenchymal sparing thoracic oncological surgery.

Vomiting and Abdominal Pain in a 5-Year-Old Male.

This case describes small bowel obstruction secondary to a Meckel's Diverticulum in a 5-year-old male patient with a chief complain of abdominal pain and vomiting. We review the pathophysiology, diagnosis, and management of Meckel's Diverticulum. This case report highlights the importance of considering a broad differential diagnosis during a clinical workup.

Cryobiopsy with radial-endobronchial ultrasound (Cryo-Radial) has comparable diagnostic yield with higher safety in comparison to computed tomography-guided transthoracic biopsy for peripheral pulmonary lesions: An exploratory randomised study.

BACKGROUND: Computed tomography-guided transthoracic biopsy (CT-TTB) is the 'gold standard' biopsy for lung nodules. Radial-endobronchial ultrasound (R-EBUS) bronchoscopy is another recommended biopsy but carries a lower diagnostic yield. Addition of cryobiopsy with R-EBUS (Cryo-Radial) has shown promising results. There are no studies comparing CT-TTB with Cryo-Radial biopsy. AIM: The co-primary aims were the diagnostic yeild and safety. The secondary aim: ability to test epidermal growth factor receptor (EGFR). METHODS: A randomised controlled, multicentre exploratory study was conducted at three tertiary hospitals. Patients with nodules >1 cm on CT of the chest were randomised to CT-TTB or Cryo-Radial. With Cryo-Radial, patients had 1-3 cryo-biopsies in addition to at least one R-EBUS biopsy through the 2.6 mm guide sheath. RESULTS: Forty-eight patients were randomised: 22 to CT-TTB and 26 to Cryo-Radial. Sixteen in the CT-TTB and 20 in the Cryo-Radial received the allocated biopsy. The diagnostic yield was CT-TTB 93.8% (15/16) versus Cryo-Radial 85% (17/20) P = 0.61 and the odds ratio was 0.37. For 5/13 (38%), a diagnosis was solely made on cryobiopsy. Eleven (78%) of 14 in CT-TTB versus 7/10 (70%) Cryo-Radial were suitable for EGFR testing P = 0.66, with odds ratio 0.63. Pneumothorax occurrence was 44% (7/16) in CT-TTB versus 4.2% (1/24) in Cryo-Radial. Two (12.5%) of 16 CT-TTB required chest drain insertion. CONCLUSION: Cryo-Radial is comparable in diagnostic yield and ability to perform EGFR testing with a significantly lower risk of pneumothorax, compared with CT-TTB. Cryo-Radial has the additional advantage of mediastinal staging during the same procedure with Linear-EBUS and is a promising first-line tool in the diagnostic method of lung cancer.

Development of a Bronchoscopy-Radiologic Skills and Task Assessment Tool (BRadSTAT): A Tool for Evaluating the Radiological Skills of Bronchoscopists with Different Experience.

BACKGROUND: Competency using radiologic images for bronchoscopic navigation is presumed during subspecialty training, but no assessments objectively measure combined knowledge of radiologic interpretation and ability to maneuver a bronchoscope into peripheral airways. OBJECTIVES: The objectives of this study were (i) to determine whether the Bronchoscopy-Radiology Skills and Tasks Assessment Tool (BRadSTAT) discriminates between bronchoscopists of various levels of experience and (ii) to improve construct validity using study findings. METHODS: BRadSTAT contains 10 questions that assess chest X-ray and CT scan interpretation using multiple images per question and 2 technical skill assessments. After administration to 33 bronchoscopists (5 Beginners, 9 Intermediates, 10 Experienced, and 9 Experts), discriminative power was strengthened using differential weighting on CT-related questions, producing the BRadSTAT-CT score. Cut points for both scores were determined via cross-validation. RESULTS: Mean BRadSTAT scores for Beginner, Intermediate, Experienced, and Expert were 74 (±13 SD), 78 (±14), 86 (±9), and 88 (±8), respectively. Statistically significant differences were noted between Expert and Beginner, Expert and Intermediate, and Experienced and Beginner (all p ≤ 0.05). Mean BRadSTAT-CT scores for Beginner, Intermediate, Experienced, and Expert were 63 (±14), 74 (±15), 82 (±13), and 90 (±9), respectively, all statistically significant (p ≤ 0.03). Cut points for BRadSTAT-CT had lower sensitivity but greater specificity and accuracy than for BRadSTAT. CONCLUSION: BRadSTAT represents the first validated assessment tool measuring knowledge and skills for bronchoscopic access to peripheral airways, which discriminates between bronchoscopists of various experience levels. Refining BRadSTAT produced the BRadSTAT-CT, which had higher discriminative power. Future studies should focus on their usefulness in competency-based bronchoscopy programs.

Reversal of collateral ventilation using endoscopic polymer foam in COPD patients undergoing endoscopic lung volume reduction with endobronchial valves: A controlled parallel group trial.

BACKGROUND AND OBJECTIVE: We have previously described reversal of collateral ventilation (CV) in a severe chronic obstructive pulmonary disease (COPD) patient with endoscopic polymer foam (EPF), prior to endoscopic lung volume reduction (ELVR) with valves. The aim of this study was to investigate the efficacy of this in a larger cohort and compare outcomes with a similar cohort with no CV. METHODS: Patients with severe COPD, with the left upper lobe (LUL) targeted for ELVR, were assessed for CV with high resolution computed tomography (HRCT). If fissure completeness was >95% they were enrolled as controls for valves alone (endobronchial valve control group [EBV-CTRL]). If fissure completeness was 80%-95%, defects were mapped to the corresponding segment, where EPF was instilled following confirmation of CV with CHARTIS. EBVs were inserted 1 month afterwards. RESULTS: Fourteen patients were enrolled into both arms. After 6 months, there were significant improvements in both groups in forced expiratory volume in 1 s (FEV1; +19.7% EPF vs. +27.7% EBV-CTRL, p < 0.05); residual volume (RV; -16.2% EPF vs. -20.1% EBV-CTRL, p = NS); SGRQ (-15.1 EPF vs. -16.6 EBV-CTRL p = NS) and 6 min walk (+25.8% EPF [77.2 m] vs. +28.4% [82.3 m] EBV-CTRL p = NS). Patients with fissural defects mapped to the lingula had better outcomes than those mapped to other segments (FEV1 +22.9% vs. +16.3% p < 0.05). There were no serious adverse reactions to EPF. CONCLUSION: EPF successfully reverses CV in severe COPD patients with a left oblique fissure that is 80%-95% complete. Following EBV, outcomes are similar to patients with complete fissures undergoing ELVR with EBV alone. EPF therapy to reverse CV potentially increases the number of COPD patients suitable for ELVR with minimal adverse reactions.

Bronchoscopy in Patients With Known or Suspected COVID-19: Results From the Global Pandemic SARS-CoV-2 Bronchoscopy Database (GPS-BD).

BACKGROUND: Amid the Coronavirus Disease 2019 (COVID-19) pandemic, the benefits and risks of bronchoscopy remain uncertain. This study was designed to characterize bronchoscopy-related practice patterns, diagnostic yields, and adverse events involving patients with known or suspected COVID-19. METHODS: An online survey tool retrospectively queried bronchoscopists about their experiences with patients with known or suspected COVID-19 between March 20 and August 20, 2020. Collected data comprised the Global Pandemic SARS-CoV-2 Bronchoscopy Database (GPS-BD). All bronchoscopists and patients were anonymous with no direct investigator-to-respondent contact. RESULTS: Bronchoscopy procedures involving 289 patients from 26 countries were analyzed. One-half of patients had known COVID-19. Most (82%) had at least 1 pre-existing comorbidity, 80% had at least 1 organ failure, 51% were critically ill, and 37% were intubated at the time of the procedure. Bronchoscopy was performed with diagnostic intent in 166 (57%) patients, yielding a diagnosis in 86 (52%). and management changes in 80 (48%). Bronchoscopy was performed with therapeutic intent in 71 (25%) patients, mostly for secretion clearance (87%). Complications attributed to bronchoscopy or significant clinical decline within 12 hours of the procedure occurred in 24 (8%) cases, with 1 death. CONCLUSION: Results from this international database provide a widely generalizable characterization of the benefits and risks of bronchoscopy in patients with known or suspected COVID-19. Bronchoscopy in this setting has reasonable clinical benefit, with diagnosis and/or management change resulting from about half of the diagnostic cases. However, it is not without risk, especially in patients with limited physiological reserve.

Gastric Desmoid Fibromatosis - Report of a Rare Mimic of Gastrointestinal Stromal Tumor.

Desmoid fibromatosis (DF) involving the gastrointestinal tract is extremely rare. Its intramural location and occasional expansile growth pattern within the bowel wall may mimic a gastrointestinal stromal tumor (GIST). Due to the different disease behaviors and management, it is important to make a correct diagnosis before further treatment. We present an extremely rare case of a gastric DF that on imaging appeared as a discrete intramural mass mimicking a GIST and that was preoperatively correctly diagnosed as a DF based on its cytomorphologic, immunohistochemical, and molecular profiles. The patient is a 71-year-old female who presented with dysphagia and unintentional weight loss. A mass was identified at the gastric fundus. Endoscopic ultrasound-guided fine-needle aspirate (FNA) and biopsy (FNB) were performed. The FNA showed a few small aggregates of cytologically bland spindle-shaped cells with elongated nuclei. The FNB yielded small fragments of tissue composed of bland spindle cells demonstrating nuclear and cytoplasmic immunostain for ß-catenin and focal stain for smooth muscle actin (SMA) and desmin. CD117, DOG1, CD34, caldesmon, S100, cytokeratin AE1/AE3, signal transducer and activator of transcription 6 (STAT6), MUC4, progesterone receptor (PR), and anaplastic lymphoma kinase (ALK) were negative, and MIB-1 showed a very low proliferation activity index. Molecular studies performed by targeted next-generation sequencing showed activating mutations in CTNNB1. These results excluded a GIST and confirmed the diagnosis of a gastric DF. Although it is very rare, DF must be included in the differential diagnosis of discrete intramural gastric spindle cell lesions. A definitive diagnosis can be made preoperatively if enough lesional material is available for appropriate immunohistochemical and molecular studies.

Interventional bronchoscopy for chronic obstructive pulmonary disease: more than a pipe dream.

Endoscopic lung volume reduction (ELVR) is recognised in both national and international expert guidelines as one of the few additive treatments to benefit patients with advanced chronic obstructive pulmonary disease (COPD) who are otherwise receiving optimal medical and supportive care. Despite these recommendations and a growing evidence base, these procedures are not widely offered across Australia and New Zealand, and general practitioner and physician awareness of this therapy can be improved. ELVR aims to mitigate the impact of hyperinflation and gas trapping on dyspnoea and exercise intolerance in COPD. Effective ELVR is of proven benefit in improving symptoms, quality of life, lung function and survival. Several endoscopic techniques to achieve ELVR have been developed, with endobronchial valve placement to collapse a single lobe being the most widely studied and commonly practised. This review describes the physiological rationale underpinning lung volume reduction, highlights the challenges of patient selection, and provides an overview of the evidence for current and investigational endoscopic interventions for COPD.

Localized tracheobronchial amyloidosis: A rare case presentation and tailored management approaches.

Localized tracheobronchial amyloidosis (TBA) is a rare manifestation of pulmonary amyloid disease, and can result in central airway obstruction. The nature of presentation is variable and there may be a delayed diagnosis. TBA has a variable prognosis and the most commonly used strategy for management is airway recanalization. Here, we describe the tailored management approach for a 64-year-old Caucasian female presenting with localized TBA of the left main bronchus. Pulmonary function testing, computed tomography and positron emission tomography results are detailed. Rigid bronchoscopy was utilized for diagnostic and therapeutic intervention, which involved debulking and stent insertion. Amyloid deposition and localized inflammation were identified through histopathology. Focal external beam radiation therapy was administered following multidisciplinary discussion and review of the literature, with no evidence of active disease at 6 months follow-up.

Human papillomavirus (HPV) vaccination and oropharyngeal HPV in ethnically diverse, sexually active adolescents: community-based cross-sectional study.

OBJECTIVES: Oropharyngeal squamous cell carcinoma is the most common human papillomavirus (HPV)-associated cancer in the UK, but little is known about the prevalence of oropharyngeal HPV in sexually active teenagers. We investigated reported HPV vaccination coverage (in females) and prevalence of oropharyngeal HPV in sexually active students attending six technical colleges in London, UK. METHODS: In 2017, we obtained mouthwash samples and questionnaires from male and female students taking part in the 'Test n Treat' chlamydia screening trial. Samples were subjected to HPV genotyping. RESULTS: Of 232 participants approached, 202 (87%) provided a mouthwash sample and questionnaire. Participants' median age was 17 years and 47% were male. Most (73%) were from black and minority ethnic groups, 64% gave a history of oral sex, 52% reported having a new sexual partner in the past 6 months, 33% smoked cigarettes, 5.9% had concurrent genitourinary Chlamydia trachomatis infection and 1.5% Neisseria gonorrhoeae and 5.0% were gay or bisexual. Only 47% (50/107) of females reported being vaccinated against HPV 16/18, of whom 74% had received ≥2 injections. HPV genotyping showed three mouthwash samples (1.5%, 95% CI 0.3% to 4.3%) were positive for possible high-risk human papillomavirus (HR-HPV), one (0.5%, 0.0% to 2.7%) for low-risk HPV 6/11, but none (0.0%, 0.0% to 1.8%) for HR-HPV. Four samples (2.0%, 0.5% to 5.0%) were positive for HPV16 using a HPV16 type-specific quantitative PCR, but these were at a very low copy number and considered essentially negative. CONCLUSIONS: Despite the high prevalence of oral sex and genitourinary chlamydia and low prevalence of HPV vaccination, the prevalence of oropharyngeal HR-HPV in these adolescents was negligible.

Cryobiopsy for Identification of Usual Interstitial Pneumonia and Other Interstitial Lung Disease Features. Further Lessons from COLDICE, a Prospective Multicenter Clinical Trial.

Rationale: Transbronchial lung cryobiopsy (TBLC) is an emerging technique for interstitial lung disease diagnosis. Good histopathologic agreement between TBLC and surgical lung biopsy (SLB) was demonstrated in the COLDICE (Cryobiopsy versus Open Lung Biopsy in the Diagnosis of Interstitial Lung Disease Alliance) study; however, diagnostic confidence was frequently lower for TBLC than SLB. Objectives: To characterize specific features of TBLC predictive of usual interstitial pneumonia (UIP) in corresponding SLB and to identify clinical indices predictive of biopsy concordance. Methods: The COLDICE study was a prospective, multicenter study investigating diagnostic agreement between TBLC and SLB. The participants underwent both procedures with blinded pathologist analysis of specimens, applying international guideline criteria. The TBLC features predictive of UIP in the paired SLB and predictive features of overall concordance were analyzed. Measurements and Main Results: A total of 65 patients (66.1 ± 9.3 yr; FVC, 84.7 ± 14.2%; DlCO, 63.4 ± 13.8%) participated in the COLDICE study. UIP was identified in 33/65 (50.8%) SLB, and 81.5% were concordant with corresponding TBLC (κ, 0.61; 95% confidence interval [CI], 0.38-0.77). The UIP guideline criteria of "predominantly subpleural or paraseptal fibrosis" was infrequently reported in TBLC (8/33, 24.2%), whereas "patchy fibrosis," "fibroblast foci," and the "absence of alternative diagnostic features" were frequently observed in TBLC. The combination of these three features strongly predicted UIP in paired SLB (odds ratio [OR], 23.4; 95% CI, 6.36-86.1; P < 0.0001). Increased numbers of TBLC samples predicted histopathologic concordance with SLB (OR, 1.8; 95% CI, 1.08-3.01; P = 0.03). The predictors of discordance included older age, family history, and radiologic asymmetry. Conclusions: Subpleural and/or paraseptal fibrosis were not essential for diagnosing UIP in TBLC, provided that other guideline criteria features were present. The diagnostic accuracy of TBLC was strengthened when increased numbers of samples were taken. Clinical trial registered with www.anzctr.org.au (ACTRN12615000718549).

Using individualized three-dimensional printed airway models to guide airway stent implantation.

Airway stents are used to manage central airway obstructions by restoring airway patency. Current manufactured stents are limited in shape and size, which pose issues in stent fenestrations needed to be manually created to allow collateral ventilation to airway branches. The precise location to place these fenestrations can be difficult to predict based on 2-dimensional computed tomography images. Inspiratory computed tomography scans were obtained from 3 patients and analysed using 3D-Slicer™, Blender™ and AutoDesk® Meshmixer™ programmes to obtain working 3D-airway models, which were 3D printed. Stent customizations were made based on 3D-model dimensions, and fenestrations into the stent were cut. The modified stents were then inserted as per usual technique. Two patients reported improved airway performance; however, stents were later removed due to symptoms related to in-stent sputum retention. In a third patient, the stent was removed a few weeks later due to the persistence of fistula leakage. The use of a 3D-printed personalized airway model allowed for more precise stent customization, optimizing stent fit and allowing for cross-ventilation of branching airways. We determine that an airway model is a beneficial tool for stent optimization but does not prevent the development of some stent-related complications such as airway secretions.