Anatomy and Neuroscience - Research Publications

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    Diagnostic performance of 19-gauge endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in suspected lymphoma: A prospective cohort study
    Lim, CE ; Steinfort, DP ; Irving, LB (WILEY, 2020-09)
    Introduction Endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) represents a minimally invasive approach in the evaluation of mediastinal/hilar lymphadenopathy. Diagnostic performance of EBUS‐TBNA in lymphoma using standard 22‐gauge (22G) needle is limited by sample volumes that are often inadequate for histopathological assessment. Objectives To evaluate the diagnostic utility of 19‐gauge (19G) EBUS‐TBNA needle in the evaluation of suspected lymphoma. Methods We prospectively collected clinical and procedural information for patients undergoing EBUS‐TBNA with 19G needle at Royal Melbourne Hospital for investigation of mediastinal/hilar lymphadenopathy, where lymphoma was considered in the differential diagnosis. All consecutive patients between June 15, 2016 and July 10, 2019 were included. If definitive diagnosis was not achieved on EBUS‐TBNA, final diagnosis was determined through subsequent investigation or a minimum of 6 months radiologic surveillance. Results Thirty‐nine patients underwent EBUS‐TBNA using 19G needle for evaluation of suspected lymphoma. Thirteen patients had a prior diagnosis of lymphoma (33%). Lymphoma was ultimately diagnosed in 23 patients (59%). Of these, 10 had a prior diagnosis of lymphoma (43%). 19G EBUS‐TBNA demonstrated lymphoma in 19 patients, with a sensitivity of 83% (95% CI 66‐93) for detection of lymphoma. Four patients required surgical biopsy to definitively characterise lymphoma subtype. Therefore, sensitivity of 19G EBUS‐TBNA for definitive diagnosis of lymphoma was 65% (95% CI 45‐81). In patients with a prior diagnosis of lymphoma, sensitivity for definitive diagnosis of lymphoma was 80% (95% CI 48‐95). Conclusion Diagnostic performance of 19G EBUS‐TBNA appears similar to standard 22G needle in detection and definitive diagnosis of lymphoma. Further invasive testing remains necessary following non‐diagnostic EBUS‐TBNA procedures.
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    Adequate tumour cellularity is essential for accurate PD-L1 immunohistochemistry assessment on cytology cell-block specimens
    Hendry, S ; Byrne, DJ ; Christie, M ; Steinfort, DP ; Irving, LB ; Wagner, C-A ; Ellwood, T ; Cooper, WA ; Fox, SB (WILEY, 2020-03)
    OBJECTIVES: PD-L1 immunohistochemistry (IHC) is an essential predictive biomarker for patients with non-small cell lung cancer (NSCLC), required to inform treatment decisions regarding anti-PD-1 immune checkpoint inhibitor therapy. This study aims to investigate the concordance between PD-L1 IHC assessed on NSCLC cytology and histology specimens and to determine the impactce of tumour cellularity. METHODS: Matched cytology and histology NSCLC specimens were retrieved from the archives of the Royal Melbourne Hospital and the Royal Prince Alfred Hospital. PD-L1 IHC was performed concurrently on both specimens at the Peter MacCallum Cancer Centre using the SP263 assay kit on the Ventana Benchmark Ultra staining platform and scored by two experienced pathologists. RESULTS: Overall agreement between matched cytology and histology specimens was good (intraclass correlation coefficient = 0.653, n = 58); however, markedly increased when the analysis was limited to cell-blocks with >100 tumour cells (intraclass correlation coefficient = 0.957, n = 29). Specificity at both 1% and 50% cut-offs was high regardless of cellularity; however, sensitivity decreased in samples with <100 tumour cells. CONCLUSIONS: PD-L1 IHC on cytology cell-block specimens in NSCLC is an acceptable alternative to histological specimens, provided adequate tumour cells are present. Clinicians and pathologists should be mindful of the risk of false negative PD-L1 IHC in samples with low tumour cellularity, to avoid excluding patients from potentially beneficial treatment.
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    Reduction of COPD Hyperinflation by Endobronchial Valves Improves Intercostal Muscle Morphology on Ultrasound
    Wallbridge, P ; Hew, M ; Parry, SM ; Irving, L ; Steinfort, D (DOVE MEDICAL PRESS LTD, 2020)
    BACKGROUND AND OBJECTIVES: Parasternal intercostal ultrasound morphology reflects spirometric COPD severity. Whether this relates to the systemic nature of COPD or occurs in response to hyperinflation is unknown. We aimed to assess changes in ultrasound parasternal intercostal muscle quantity and quality (echogenicity) in response to relief of hyperinflation. We hypothesised that reduction in hyperinflation following endobronchial valve (EBV) insertion would increase ultrasound parasternal thickness and decrease echogenicity. METHODS: In this prospective cohort study, eight patients with severe COPD underwent evaluation of health-related quality of life, lung function, and sonographic thickness of 2nd parasternal intercostal muscles and diaphragm thickness, both before and after EBV insertion. Relationships between physiological and radiographic lung volumes, quality of life and ultrasound parameters were determined. RESULTS: Baseline FEV1 was 1.02L (SD 0.37) and residual volume (RV) was 202% predicted (SD 41%). Median SGRQ was 63.26 (range 20-70.6). Change in RV (-0.51 ± 0.9L) following EBV-insertion showed a strong negative correlation with change in parasternal thickness (r = -0.883) ipsilateral to EBV insertion, as did change in target lobe volume (-0.89 ± 0.6L) (r = -0.771). Parasternal muscle echogenicity, diaphragm thickness and diaphragm excursion did not significantly change. CONCLUSIONS: Dynamic changes in intercostal muscle thickness on ultrasound measurement occur in response to relief of hyperinflation. We demonstrate linear relationships between intercostal thickness and change in hyperinflation following endobronchial valve insertion. This demonstrates the deleterious effect of hyperinflation on intrinsic inspiratory muscles and provides an additional mechanism for symptomatic response to EBVs.
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    Safe performance of diagnostic bronchoscopy/EBUS during the SARS-CoV-2 pandemic
    Steinfort, DP ; Herth, FJF ; Irving, LB ; Nguyen, PT (WILEY, 2020-07)
    The SARS-CoV-2 pandemic is unprecedented in our professional lives and much effort and resources will be devoted to care of patients (and HCW) affected by this illness. We must also continue to aim for the same standard of care for our non-COVID respiratory patients, while minimizing risks of infection transmission to our colleagues. This commentary addresses the key paired issues of minimizing performance of diagnostic/staging bronchoscopy in patients with suspected/known lung cancer while maximizing the safety of the procedure with respect to HCW transmission of COVID-19.
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    Bronchial Rheoplasty for Treatment of Chronic Bronchitis Twelve-Month Results from a Multicenter Clinical Trial
    Valipour, A ; Fernandez-Bussy, S ; Ing, AJ ; Steinfort, DP ; Snell, G ; Williamson, JP ; Saghaie, T ; Irving, LB ; Dabscheck, EJ ; Krimsky, WS ; Waldstreicher, J (AMER THORACIC SOC, 2020-09-01)
    Rationale: Chronic bronchitis (CB) is characterized by productive cough with excessive mucus production, resulting in quality-of-life impairment and increased exacerbation risk. Bronchial rheoplasty uses an endobronchial catheter to apply nonthermal pulsed electrical fields to the airways. Preclinical studies have demonstrated epithelial ablation followed by regeneration of normalized epithelium.Objectives: To evaluate the feasibility, safety, and initial outcomes of bronchial rheoplasty in patients with CB.Methods: Pooled analysis of two separate studies enrolling 30 patients undergoing bilateral bronchial rheoplasty was conducted. Follow-up through 6 months (primary outcome) and 12 months included assessment of adverse events, airway histology, and changes in symptoms using the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test and St. George's Respiratory Questionnaire (SGRQ).Measurements and Main Results: Bronchial rheoplasty was performed in all 30 patients (63% male; mean [SD] age, 67 [7.4]; mean [SD] postbronchodilator FEV1, 65% [21%]; mean [SD] COPD Assessment Test score 25.6 [7.1]; mean [SD] SGRQ score, 59.6 [15.3]). There were no device-related and four procedure-related serious adverse events through 6 months, and there were none thereafter through 12 months. The most frequent nonserious, device- and/or procedure-related event through 6 months was mild hemoptysis in 47% (14 of 30) patients. Histologically, the mean goblet cell hyperplasia score was reduced by a statistically significant amount (P < 0.001). Significant changes from baseline to 6 months in COPD Assessment Test (mean, -7.9; median, -8.0; P = 0.0002) and SGRQ (mean, -14.6; median, -7.2; P = 0.0002) scores were observed, with similar observations through 12 months.Conclusions: This study provides the first clinical evidence of the feasibility, safety, and initial outcomes of bronchial rheoplasty in symptomatic patients with CB.Clinical trial registered with www.anzctr.org.au (ACTRN 12617000330347) and clinicaltrials.gov (NCT03107494).
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    Correlation of positron emission tomography ventilation-perfusion matching with CT densitometry in severe emphysema
    Bonney, A ; Wagner, C-A ; Siva, S ; Callahan, J ; Le Roux, P-Y ; Pascoe, DM ; Irving, L ; Hofman, MS ; Steinfort, DP (SPRINGER, 2020-07-28)
    BACKGROUND: Emphysema severity is frequently measured on CT via densitometry. Correlation with scintigraphic and spirometric functional measures of ventilation or perfusion varies widely, and no prior study has evaluated correlation between densitometry and lobar ventilation/perfusion in patients with severe emphysema. The aim of this study was to evaluate the utility and findings of gallium-68 (68Ga) ventilation/perfusion positron emission tomography-CT (68Ga-VQ/PET-CT) in severe emphysema assessment. METHODS: Fourteen consecutive patients undergoing evaluation for bronchoscopic lung volume reduction between March 2015 and March 2018 underwent 68Ga-VQ/PET-CT assessment for lobar functional lung mapping, in addition to CT densitometry. Correlations between CT densitometry and 68Ga-VQ/PET-CT parameters for individual lobar lung function were sought. RESULTS: CT densitometry assessment of emphysema correlated only weakly (R2 = 0.13) with lobar perfusion and was not correlated with ventilation (R2 = 0.04). Densitometry was moderately (R2 = 0.67) correlated with V/Q units in upper lobes, though poorly reflected physiological function in lower lobes (R2 = 0.19). Emphysema severity, as measured by CT densitometry, was moderately correlated with proportion of normal V/Q units and matched V/Q defects in individual lobes. CONCLUSIONS: Assessment of lobar pulmonary function by 68Ga-VQ/PET-CT provides physiologic information not evident on CT densitometry such as ventilation and perfusion specifics and matched defects. Further research is needed to see if the discordant findings on 68Ga-VQ/PET-CT provide prognostic information or can be used to modify patient management and improve outcomes.