Anatomy and Neuroscience - Research Publications
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ItemA randomised controlled trial comparing high-flow nasal oxygen with standard management for conscious sedation during bronchoscopy(WILEY, 2018-02)Traditional conscious sedation for endobronchial ultrasound procedures places patients at risk of desaturation, and high-flow nasal oxygen may reduce the risk. We designed a parallel-group randomised controlled trial of high-flow nasal oxygen at a flow rate of 30-70 l.min-1 via nasal cannulae, compared with standard oxygen therapy at 10 l.min-1 via a bite block in adults planned for conscious sedation for endobronchial ultrasound. The primary outcome was the proportion of patients experiencing desaturation (defined as SpO2 < 90%). Secondary outcomes included oxygen saturation after pre-oxygenation, lowest oxygen saturation during procedure, number of hypoxic episodes, duration of hypoxia, end-procedure end-tidal CO2 , satisfaction scores and complications. Thirty participants were allocated to each group. Baseline patient characteristics, procedure time and anaesthetic agents used were similar between the groups. Desaturation occurred in 4 out of 30 patients allocated to the high-flow nasal oxygen group, compared with 10 out of 30 allocated to the standard oxygenation group, a non-significant difference (p = 0.07) with intention to treat analysis. The difference was significant (p = 0.047) when using a per-protocol analysis. Oxygen saturation after pre-oxygenation and the lowest oxygen saturation during procedure were significantly higher in the high-flow nasal oxygen group compared with the standard oxygenation group; median (IQR [range] 100 (99-100 [93-100]) vs. 98 (97-99 [94-100]), p = 0.0001 and 97.5 (94-99 [77-100]) vs. 92 (88-95 [79-98]), p < 0.001, respectively. There were no differences in other secondary outcomes. Although high-flow nasal oxygen may prevent desaturation due to some causes, it does not protect against hypoxaemia in all circumstances.
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ItemDiagnostic yield of pleural fluid cytology in malignant effusions: an Australian tertiary centre experience(WILEY, 2018-11)BACKGROUND: Timely diagnosis of malignant pleural effusions is critical to guide prognosis and management decisions. Cytological analysis of pleural fluid has been the first-line diagnostic test for many decades, with highly variable reported sensitivities of 40-90%. Its diagnostic accuracy in modern practice in Australia needs to be understood. AIMS: To determine the diagnostic yield of pleural fluid cytology for the detection of malignant pleural effusions and to determine the aetiologies of pleural effusions at our centre. METHODS: The study involved the retrospective chart review of all pleural fluid samples submitted for cytological analysis at a tertiary referral centre in Melbourne, Australia, over a 12-month period. Aetiology of all effusions was determined, and sensitivity, specificity, negative predictive value and diagnostic accuracy for the detection of malignant pleural effusions were calculated. We also examined diagnostic yield based on tumour cell type. RESULTS: Of the 153 cases analysed, 61 (39.9%) were malignant. Lung cancers accounted for 44.3% of malignant effusions, followed by mesothelioma (18%), ovarian carcinoma (11.5%) and lymphoma (8.2%). The commonest single causes of a benign effusion were cardiac (16.3%) and parapneumonic (13%). Sensitivity for diagnosis of malignant effusions was 67.2% overall, but 87.9% for adenocarcinomas and only 45.5% for mesothelioma. CONCLUSION: Tumour type is an important determinant of pleural fluid cytology diagnostic yield. Cytology has good sensitivity and specificity for the diagnosis of adenocarcinoma, but if another tumour type is suspected, particularly mesothelioma, clinicians should be aware of the limitations.
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ItemLow rates of eligibility for lung cancer screening in patients undergoing computed tomography coronary angiography(WILEY, 2018-10)Incidental findings, including pulmonary nodules, on computed tomography coronary angiography (CTCA) are common. Previous authors have suggested CTCA could allow opportunistic screening for lung cancer, though the lung cancer risk profile of this patient group has not previously been established. Smoking histories of 229 patients undergoing CTCA at two tertiary hospitals were reviewed and only 25% were current or former smokers aged 55-80 years old. Less than half of this group were eligible for screening based on the PLCOm2012 risk model. We conclude that routine screening in the form of full thoracic field imaging, of individuals undergoing CTCA is not appropriate as it would likely result in net harm.
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ItemOutcomes following resection of non-small cell lung cancer in octogenarians(WILEY, 2018-12)BACKGROUND: The treatment of choice for early stage non-small cell lung cancer (NSCLC) is surgical resection. Little is known about the short- and long-term outcomes among very elderly patients. We sought to determine predictors of short- and long-term survival among octogenarians undergoing curative-intent resection for NSCLC in Victoria, Australia. METHODS: We retrospectively reviewed data from all patients aged ≥80 years who underwent curative-intent resection for NSCLC over 12 years (January 2005-December 2016) across five tertiary centres. We examined effect of age, stage of disease, extent of surgery and lung function on short- and long-term survival. RESULTS: Two hundred patients aged ≥80 years underwent curative-intent resections. Mortality at 30 and 120 days was 2.9% and 5.9%, respectively. Increased early mortality was observed among those ≥83 years, at 30 days (6.8% versus 0.8%, P = 0.044) and 120 days (12.2% versus 2.3%, P = 0.0096). Early mortality was highest among patients ≥83 years requiring lobectomy, compared to sub-lobar resection at 120 days (17% versus 3.8%, P = 0.019). Long-term survival was predicted by age and stage of disease. Among patients with Stage I disease aged <83 years, lobectomy was associated with superior 5-year survival, compared to sub-lobar resection (83% versus 61%, P = 0.02). CONCLUSION: In carefully selected elderly patients undergoing curative-intent resection of early stage NSCLC, both short- and long-term outcomes appear consistent with younger historical cohorts. Early mortality was associated with lobectomy in those with advanced age. Older patients undergoing lobectomy appeared to be at highest risk for early mortality, while younger patients with Stage I disease undergoing at least lobectomy appear to have the best long-term survival.
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ItemParasternal intercostal muscle ultrasound in chronic obstructive pulmonary disease correlates with spirometric severity(NATURE PUBLISHING GROUP, 2018-10-15)In chronic obstructive pulmonary disease (COPD), loss of computed tomography (CT)-measured intercostal mass correlates with spirometric severity. Intercostal muscle ultrasound offers a repeatable and radiation-free alternative, however requires validation. We aimed to determine the reliability of parasternal intercostal muscle ultrasound, and the concurrent validity of parasternal ultrasound with clinicometric parameters. Twenty stable COPD patients underwent ultrasound measurement of thickness and echogenicity of 2nd and 3rd parasternal intercostal muscles, dominant pectoralis major and quadriceps, and diaphragm thickness; spirometry; and chest CT. Intra-rater intraclass correlation (ICC) for ultrasound intercostal thickness was 0.87-0.97 depending on site, with echogenicity ICC 0.63-0.91. Inter-rater ICC was fair to excellent. Ultrasound intercostal thickness moderately correlated with FEV1% predicted (r = 0.33) and quadriceps thickness (r = 0.31). Echogenicity correlated negatively with FEV1% predicted (r = -0.32). CT-measured lateral intercostal mass correlate negatively with parasternal ultrasound intercostal thickness. These data confirm ultrasound of parasternal intercostal musculature is reproducible. Lower intercostal muscle quantity and quality reflects greater COPD spirometric severity. This novel tool may have biomarker potential for both the systemic effects of COPD on muscle as well as local disruption of respiratory mechanics. The negative correlation between CT and ultrasound measurements may reflect complex site-dependent interactions between respiratory muscles and the chest wall.
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ItemUltralow dose CT for follow-up of solid pulmonary nodules A pilot single-center study using Bland-Altman analysis(LIPPINCOTT WILLIAMS & WILKINS, 2018-08)Solid pulmonary nodules are a common finding requiring serial computed tomography (CT) imaging. We sought to explore the detection and measurement accuracy of an ultralow-dose CT (ULDCT) protocol compared with our standard low-dose CT (LDCT) nodule follow-up protocol.In this pragmatic single-center pilot prospective cohort study, patients scheduled for clinically indicated CT surveillance of 1 or more known solid pulmonary nodules >2 mm underwent ULDCT immediately after routine LDCT. The Bland-Altman 95% limits of agreement for diameter and volumetry were calculated.In all, 57 patients underwent 60 imaging episodes, with 170 evaluable nodules. ULDCT detected all known solid pulmonary nodules >2 mm. Bland-Altman analyses demonstrated clinically agreement for both nodule diameter and volume, both of which fell within prespecified limits.This single-center pilot study suggests that ULDCT may be of use in surveillance of known solid pulmonary nodules >2 mm.
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ItemNo Preview AvailableSystematic endobronchial ultrasound-guided transbronchial needle aspiration improves radiotherapy planning in non-small cell lung cancer(European Respiratory Society, 2019-07)Objectives: Patients suitable for radical chemoradiotherapy for lung cancer routinely have radiotherapy (planning) volumes based on positron emission tomography (PET)-computed tomography (CT) imaging alone. Endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) can identify PET-occult malignancy and benign PET-avid regions. We investigated the impact of EBUS-TBNA on curative-intent radiotherapy in non-small cell lung cancer (NSCLC). Methods: A prospective multicentre trial was undertaken, investigating the impact of systematic EBUS-TBNA in addition to PET-CT for patients considered for radical chemoradiotherapy with NSCLC. A subset analysis of patients with discordant findings between PET-CT and EBUS-TBNA was performed. Radiotherapy plans investigated tumour coverage and dose to critical organs at risk (OARs) using PET-CT alone in comparison to PET-CT and EBUS-TBNA. Results: Of 30 patients enrolled, 10 had discordant findings between PET-CT and EBUS-TBNA. EBUS-TBNA-derived plans allowed for reduction in dose to OARs in patients downstaged by EBUS-TBNA, and reduced the risk of geographic miss in treating PET-occult disease in four patients where EBUS-TBNA identified malignant involvement of PET-negative lymphadenopathy. With the addition of EBUS-TBNA to radiotherapy planning, reductions were noted of 5.7%, 3.7% and 12.5% for the risks of symptomatic pneumonitis, mean heart dose and mean oesophageal dose, respectively. Conclusions: This study demonstrates for the first time that systematic EBUS-TBNA prior to radical-intent radiotherapy significantly improves coverage of subclinical disease through detection of PET-occult metastases. Identification of false-positive lymph node involvement in highly selected cases may reduce radiation dose to critical structures, and risk of organ toxicity.
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ItemDeep multi-region whole-genome sequencing reveals heterogeneity and gene-by-environment interactions in treatment-naive, metastatic lung cancer(SPRINGERNATURE, 2019-03-07)Our understanding of genomic heterogeneity in lung cancer is largely based on the analysis of early-stage surgical specimens. Here we used endoscopic sampling of paired primary and intrathoracic metastatic tumors from 11 lung cancer patients to map genomic heterogeneity inoperable lung cancer with deep whole-genome sequencing. Intra-patient heterogeneity in driver or targetable mutations was predominantly in the form of copy number gain. Private mutation signatures, including patterns consistent with defects in homologous recombination, were highly variable both within and between patients. Irrespective of histotype, we observed a smaller than expected number of private mutations, suggesting that ancestral clones accumulated large mutation burdens immediately prior to metastasis. Single-region whole-genome sequencing of from 20 patients showed that tumors in ever-smokers with the strongest tobacco signatures were associated with germline variants in genes implicated in the repair of cigarette-induced DNA damage. Our results suggest that lung cancer precursors in ever-smokers accumulate large numbers of mutations prior to the formation of frank malignancy followed by rapid metastatic spread. In advanced lung cancer, germline variants in DNA repair genes may interact with the airway environment to influence the pattern of founder mutations, whereas similar interactions with the tumor microenvironment may play a role in the acquisition of mutations following metastasis.