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Chronic thromboembolic pulmonary disease (CTEPD) with or without pulmonary hypertension (PH) is an important potential consequence of venous thromboembolic disease. Untreated CTEPD with pulmonary hypertension (CTEPH) is associated with high rates of morbidity and mortality. Several treatment options are now available for patients with CTEPD and CTEPH, including pulmonary endarterectomy (PEA), balloon pulmonary angioplasty, medical therapy or a combination of therapies. Choice of treatment depends on the location of the thromboembolic disease burden, presence and severity of PH and patient factors, including frailty, parenchymal lung disease and other comorbidities. PEA is a complex surgery that can result in excellent outcomes and resolution of disease, but also comes with the risk of serious perioperative complications. This manuscript examines the history of PEA and its place in Australasia, and reports on outcomes from the main Australasian CTEPH expert centre. It provides a summary of up-to-date guidance on how PEA should be utilised in the overall management of these patients and describes opportunities and challenges for the future diagnosis and management of this disease, particularly in the Australasian setting.
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BACKGROUND: Systematic mediastinal lymph node staging by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) improves accuracy of staging in patients with early-stage non-small-cell lung cancer (NSCLC). However, patients with locally advanced NSCLC commonly undergo only selective lymph node sampling. This study aimed to determine the proportion of patients with locally advanced NSCLC in whom systematic endoscopic mediastinal staging identified PET-occult lymph node metastases, and to describe the consequences of PET-occult disease on radiotherapy planning. METHODS: This prospective, international, multicentre, single-arm, international study was conducted at seven tertiary lung cancer centres in four countries (Australia, Canada, the Netherlands, and the USA). Patients aged 18 years or older with suspected or known locally advanced NSCLC underwent systematic endoscopic mediastinal lymph node staging before combination chemoradiotherapy or high-dose palliative radiotherapy. The primary endpoint was the proportion of participants with PET-occult mediastinal lymph node metastases shown following systematic endoscopic staging. The study was prospectively registered with Australian New Zealand Clinical Trials Registry, ACTRN12617000333314. FINDINGS: From Jan 30, 2018, to March 23, 2022, 155 patients underwent systematic endoscopic mediastinal lymph node staging and were eligible for analysis. 58 (37%) of patients were female and 97 (63%) were male. Discrepancy in extent of mediastinal disease identified by PET and EBUS-TBNA was observed in 57 (37% [95% CI 29-44]) patients. PET-occult lymph node metastases were identified in 18 (12% [7-17]) participants, including 16 (13% [7-19]) of 123 participants with clinical stage IIIA or cN2 NSCLC. Contralateral PET-occult N3 disease was identified in nine (7% [2-12]) of 128 participants staged cN0, cN1, or cN2. Identification of PET-occult disease resulted in clinically significant changes to treatment in all 18 patients. In silico dosimetry studies showed the median volume of PET-occult lymph nodes receiving the prescription dose of 60 Gy was only 10·1% (IQR 0·1-52·3). No serious adverse events following endoscopic staging were reported. INTERPRETATION: Our findings suggests that systematic endoscopic mediastinal staging in patients with locally advanced or unresectable NSCLC is more accurate than PET alone in defining extent of mediastinal involvement. Standard guideline-recommended PET-based radiotherapy planning results in suboptimal tumour coverage. Our findings indicate that systematic endoscopic staging should be routinely performed in patients with locally advanced NSCLC being considered for radiotherapy to accurately inform radiation planning and treatment decision making in patients with locally advanced NSCLC. FUNDING: None.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Metástase Linfática , Mediastino , Estadiamento de Neoplasias , Humanos , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Masculino , Feminino , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/diagnóstico por imagem , Pessoa de Meia-Idade , Idoso , Estudos Prospectivos , Mediastino/patologia , Metástase Linfática/radioterapia , Austrália , Países Baixos , Linfonodos/patologia , Linfonodos/diagnóstico por imagem , Canadá , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Estados Unidos , Tomografia por Emissão de Pósitrons/métodosRESUMO
BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is established as the preferred method of mediastinal lymph node (LN) staging in non-small cell lung cancer (NSCLC). Selective (targeted) LN sampling is most commonly performed however studies in early stage NSCLC and locally advanced NSCLC confirm systematic EBUS-TBNA evaluation improves accuracy of mediastinal staging. This study aims to establish the rate of detection of positron emission tomography (PET)-occult LN metastases following systematic LN staging by EBUS-TBNA, and to determine the utility of systematic mediastinal staging for accurate delineation of radiation treatment fields in patients with locally advanced NSCLC. METHODS: Consecutive patients undergoing EBUS-TBNA for diagnosis/staging of locally advanced NSCLC will be enrolled in this international multi-centre single arm study. Systematic mediastinal LN evaluation will be performed, with all LN exceeding 6 mm to be sampled by TBNA. Where feasible, endoscopic ultrasound staging (EUS-B) may also be performed. Results of minimally invasive staging will be compared to FDG-PET. The primary end-point is proportion of patients in whom systematic LN staging identified PET-occult NSCLC metastases. Secondary outcome measures include (i) rate of nodal upstaging, (ii) false positive rate of PET for mediastinal LN assessment, (iii) analysis of clinicoradiologic risk factors for presence of PET-occult LN metastases, (iv) impact of systematic LN staging in patients with discrepant findings on PET and EBUS-TBNA on target coverage and dose to organs at risk (OAR) in patients undergoing radiotherapy. DISCUSSION: With specificity of PET of 90%, guidelines recommend tissue confirmation of positive mediastinal LN to ensure potentially early stage patients are not erroneously denied potentially curative resection. However, while confirmation of pathologic LN is routinely sought, the exact extent of mediastinal LN involvement in NSCLC in patient with Stage III NSCLC is rarely established. Studies examining systematic LN staging in early stage NSCLC report a significant discordance between PET and EBUS-TBNA. In patients with locally advanced disease this has significant implications for radiation field planning, with risk of geographic miss in the event of PET-occult mediastinal LN metastases. The SEISMIC study will examine both diagnostic outcomes following systematic LN staging with EBUS-TBNA, and impact on radiation treatment planning. TRIAL REGISTRATION: ACTRN12617000333314, ANZCTR, Registered on 3 March 2017.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Endossonografia/métodos , Fluordesoxiglucose F18 , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/radioterapia , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Metástase Linfática/patologia , Mediastino/diagnóstico por imagem , Mediastino/patologia , Estudos Multicêntricos como Assunto , Estadiamento de Neoplasias , Estudos ProspectivosRESUMO
Pulmonary arterial hypertension is associated with tyrosine kinase inhibitors used in the treatment of chronic myeloid leukemia. Dasatinib is a known cause of drug-induced pulmonary arterial hypertension. There have been case reports linking Bosutinib with deterioration of pre-existing pulmonary arterial hypertension. Here, we present a case of a 37-year-old woman with chronic myeloid leukemia treated with Bosutinib who was diagnosed with pulmonary arterial hypertension. Prior to Bosutinib, she had received Dasatinib without documented cardiopulmonary toxicity. Withdrawal of Bosutinib led to partial reversal of pulmonary arterial hypertension, and with the addition of pulmonary arterial hypertension-targeted treatment, there was near normalization of hemodynamics.
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Obstructive sleep apnea may occur throughout the lifespan, with peak occurrences in early childhood and during middle and older age. Onset in childhood is overwhelmingly due to adeno-tonsillar hypertrophy, while in adulthood, contributors include risk factors, such as obesity, male sex, and aging. More recently, there has been a precipitous increase in the prevalence of obstructive sleep apnea in youth. Drivers of this phenomenon include both increasing obesity and the survival of children with complex medical conditions into adulthood. Appropriate treatment and long-term management of obstructive sleep apnea is critical to ensure that these youth maintain well-being unfettered by secondary comorbidities. To this end, patient engagement and seamless transition of care from pediatric to adult health care systems is of paramount importance. To date, this is an unacknowledged and unmet need in most sleep programs. This article highlights the need for guideline-driven sleep disorder transition processes and illustrates the authors' experience with the development of a program for sleep apnea.
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BACKGROUND: Heart transplant patients constitute a unique patient cohort with multiple risk factors predictive of poor surgical outcome. The Alfred Hospital offers the only heart transplant service in Victoria, Australia. This article presents The Alfred Hospital's experience with outcomes of abdominal operations in the heart transplant patient population. METHODS: The statewide cardiothoracic registry was cross-referenced with The Alfred Hospital's electronic hospital database to identify heart transplant patients who had undergone abdominal surgery from 2002 to November 2012. Patients who met the inclusion criteria were evaluated in two groups: elective and emergency surgical settings. In the emergency group, risk factors recorded for poor surgical outcome were high-dose immunosuppression therapy, diabetes and other conventional vascular risk factors. Outcome measures assessed in both groups were length of stay, readmission within 30 days and 1-year mortality. RESULTS: Twelve patients were identified who underwent 13 abdominal operations. Eight were elective cases and five were emergent abdominal operations. The mean length of stay was shorter in the elective group than the emergency group (2.5 days versus 21.3 days). There was one readmission within 30 days, and no mortality at 1 year following elective surgery. In the emergency surgery group, two patients were readmitted within 30 days post-operatively, and there were two deaths observed in this group. CONCLUSION: The Alfred Hospital experience demonstrates that elective abdominal surgery following heart transplantation can be performed safely. Emergent surgery in this group of patients, however, is associated with poorer outcomes.