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Background The association between socioeconomic status (SES) and lung cancer is internationally established but in Australia this relationship remains ill defined. Aims To examine the association between SES, place of residence and lung cancer outcomes in a large Australian cohort. Methods 2369 consecutive lung cancer patients managed by St Vincent's Hospital lung multidisciplinary meeting between 2001–2014 were included. Postcode data stratified participants by Socio-Economic Indexes for Areas, a validated measure of SES, and by geographical location, an important socioeconomic factor in Australia. Results There was no difference between socioeconomic groups in age (68 years), sex (63% males) or presentation (75% symptomatic). Low socioeconomic patients had increased smoking rates and a trend towards less adenocarcinoma. More low SES patients were from rural locations, had a greater frequency of earlier stage disease and curative treatment with higher overall survival even after multivariate analysis. When stratified for socioeconomic status, overall 5-year survival was significantly better in the low SES group (33% vs 24%, n = 2275, p = 0.02), although stage-stratified survival was similar in all socioeconomic groups. Conclusions Low SES patients were more frequently from rural locations and unexpectedly had earlier stage disease and higher overall survival. The excellent outcomes in rural and lower SES patients is reassuring but suggests that there is a population of these patients with advanced lung cancer who are not referred for multidisciplinary care. Further studies are required to better define this group and determine the barriers to referral to improve overall lung cancer outcomes.

Background Xenotransplantation could provide a solution to the donor shortage that is currently the major barrier to solid-organ transplantation. The ability to breed pigs with multiple genetic modifications provides a unique opportunity to explore the immunologic challenges of pulmonary xenotransplantation. Methods Explanted lungs from wild-type and 3 groups of genetically modified pigs were studied: (i) α1,3-galactosyltransferase gene knockout (GTKO); (ii) GTKO pigs expressing the human complementary regulatory proteins CD55 and CD59 (GTKO/CD55-59); and (iii) GTKO pigs expressing both CD55-59 and CD39 (GTKO/CD55-59/CD39). The physiologic, immunologic and histologic properties of porcine lungs were evaluated on an ex vivo rig after perfusion with human blood. Results Lungs from genetically modified pigs demonstrated stable pulmonary vascular resistance and better oxygenation of the perfusate, and survived longer than wild-type lungs. Physiologic function was inversely correlated with the degree of platelet sequestration into the xenograft. Despite superior physiologic profiles, lungs from genetically modified pigs still showed evidence of intravascular thrombosis and coagulopathy after perfusion with human blood. CONCLUSIONS The ability to breed pigs with multiple genetic modifications, and to evaluate lung physiology and histology in real-time on an ex vivo rig, represent significant advances toward better understanding the challenges inherent to pulmonary xenotransplantation.

Background: The association between lower socioeconomic status (SES) and lung cancer has been established internationally but not extensively in Australia. Aims: To describe a large cohort of lung cancer patients, perform survival analysis and examine differences between patients of different SES. Methods: Data was collected on 2369 consecutive lung cancer patients managed by St Vincent9s Hospital Lung Multi-disciplinary Meeting (MDM) 2001-14. Postcode data was used to stratify people by SES and geographical remoteness. Results: Mean age at diagnosis was 68 years with 63% males and 37% females. Presentation was incidental in 25%, symptomatic in 75%, and screened in Conclusion: Overall and stage-stratified survival was above average and stage-stratified survivial did not differ between different socioeconomic groups supporting referral to lung cancer MDMs based in high throughput centres.

Background Intracardiac tumors are rare neoplasms that present with clinical features of obstruction, embolization, conduction disturbances, and constitutional symptoms. Complete surgical resection under cardiopulmonary bypass offers the best prospect of disease-free survival. Methods Data of 30 consecutive patients who underwent resection of an intracardiac mass at St. Vincent’s Hospital from 1990 to 2012 were reviewed. Results The patients presented with dyspnea (33%), palpitations or arrhythmias (20%), and recurrent pulmonary edema (6%). There was a history of embolic stroke in 46%. Intracardiac masses were identified using preoperative echocardiography. Resection was performed on cardiopulmonary bypass via a modified Dubost (superior transseptal) approach in 78%, a left atriotomy in 11%, and a biatrial approach in 5%. Twenty-eight (93%) masses were identified as neoplastic, predominantly myxomas (62%). There was no mortality at 30 days. On long-term follow-up (mean 9 years, range 1–19 years) there were 5 deaths; 83% of patients were still alive. Conclusions Cardiac tumors are rare and an important differential diagnosis in the context of unexplained obstructive symptoms, emboli, and conduction abnormalities. Myxomas are the most common cardiac neoplasm. Solid tumors are more common, more likely to be associated with heart failure, and best excised in one whole part, whereas papillary tumors are more likely to be associated with neurological symptoms, and more likely to be resected by piecemeal removal. Prompt and complete resection under cardiopulmonary bypass is the safest approach.

International audience; Dust devils - convective vortices made visible by the dust and debris they entrain - are common in arid environments and have been observed on Earth and Mars. Martian dust devils have been identified both in images taken at the surface and in remote sensing observations from orbiting spacecraft. Observations from landing craft and orbiting instruments have allowed the dust devil translational forward motion (ground velocity) to be calculated, but it is unclear how these velocities relate to the local ambient wind conditions, for (i) only model wind speeds are generally available for Mars, and (ii) on Earth only anecdotal evidence exists that compares dust devil ground velocity with ambient wind velocity. If dust devil ground velocity can be reliably correlated to the ambient wind regime, observations of dust devils could provide a proxy for wind speed and direction measurements on Mars. Hence, dust devil ground velocities could be used to probe the circulation of the martian boundary layer and help constrain climate models or assess the safety of future landing sites. We present results from a field study of terrestrial dust devils performed in the southwest USA in which we measured dust devil horizontal velocity as a function of ambient wind velocity. We acquired stereo images of more than a 100 active dust devils and recorded multiple size and position measurements for each dust devil. We used these data to calculate dust devil translational velocity. The dust devils were within a study area bounded by 10 m high meteorology towers such that dust devil speed and direction could be correlated with the local ambient wind speed and direction measurements. Daily (10:00-16:00 local time) and 2-h averaged dust devil ground speeds correlate well with ambient wind speeds averaged over the same period. Unsurprisingly, individual measurements of dust devil ground speed match instantaneous measurements of ambient wind speed more poorly; a 20-min smoothing window applied to the ambient wind speed data improves the correlation. In general, dust devils travel 10-20% faster than ambient wind speed measured at 10 m height, suggesting that their ground speeds are representative of the boundary layer winds a few tens of meters above ground level. Dust devil ground motion direction closely matches the measured ambient wind direction. The link between ambient winds and dust devil ground velocity demonstrated here suggests that a similar one should apply on Mars. Determining the details of the martian relationship between dust devil ground velocity and ambient wind velocity might require new in situ or modelling studies but, if completed successfully, would provide a quantitative means of measuring wind velocities on Mars that would otherwise be impossible to obtain. (C) 2012 Elsevier Inc. All rights reserved.

The 14-channel NASA Ames Airborne Tracking Sunphotometer (AATS-14) measured solar- beam transmission on the NASA DC-8 during the second SAGE III Ozone Loss and Validation Experiment (SOLVE II). This paper presents AATS-14 results for multiwavelength aerosol optical depth (AOD), including comparisons to results from two satellite sensors and another DC-8 instrument, namely the Stratospheric Aerosol and Gas Experiment III (SAGE III), the Polar Ozone and Aerosol Measurement III (POAM III) and the Direct-beam Irradiance Airborne Spectrometer (DIAS). AATS-14 provides aerosol results at 13 wavelengths λ spanning the range of SAGE III and POAM III aerosol wavelengths. Because most AATS measurements were made at solar zenith angles (SZA) near 90°, retrieved AODs are strongly affected by uncertainties in the relative optical airmass of the aerosols and other constituents along the line of sight (LOS) between instrument and sun. To reduce dependence of the AATS-satellite comparisons on airmass, we perform the comparisons in LOS transmission and LOS optical thickness (OT) as well as in vertical OT (i.e., optical depth, OD). We also use a new airmass algorithm that validates the algorithm we previously used to within 2% for SZASZA≥90°. For 6 DC-8 flights, 19 January-2 February 2003, AATS and DIAS results for LOS aerosol OT at λ=400nm agree to ≤12% of the AATS value. Mean and root-mean-square (RMS) differences, (DIAS-AATS)/AATS, are -2.3% and 7.7%, respectively. For DC-8 altitudes, AATS-satellite comparisons are possible only for λ>440nm, because of signal depletion for shorter λ on the satellite full-limb LOS. For the 4AATS-SAGE and 4AATS-POAM near-coincidences conducted 19-31 January 2003, AATS-satellite AOD differences were ≤0.0041 for all λ>440nm. RMS differences were ≤0.0022 for SAGE-AATS and ≤0.0026 for POAM-AATS. RMS relative differences in AOD ([SAGE-AATS]/AATS) were ≤33% for λ~755nm, AATS-POAM differences were less than AATS-SAGE differences, and RMS relative differences in AOD ([AATS-POAM]/AATS) were ≤31% for all λ between 440 and 1020nm. Unexplained differences that remain are associated with transmission differences, rather than differences in gas subtraction or conversion from LOS to vertical quantities. The very small stratospheric AOD values that occurred during SOLVEII added to the challenge of the comparisons, but do not explain all the differences.

HIC1 is a zinc-finger transcriptional repressor frequently targeted for deletion and/or epigenetic gene silencing in cancer. In cancer cell lines, re-expression of HIC1 results in the downregulation of target genes thought to promote context-dependent tumor growth, including Sirt1, Atoh1, Efna1 and components of the WNT and STAT3 signalling pathway. In mouse embryonic fibroblasts, we now show that deletion of a conditional loxP allele of Hic1 results in immediate growth arrest without significant overexpression of Hic1 target genes, followed by a prolonged period of cellular quiescence. After several weeks, we then observed the spontaneous emergence of rapidly growing clones that fulfil all the criteria for transformation, associated with aneuploidy and recurrent copy number alterations. By contrast, conditional deletion of p53 using the same experimental protocol resulted in prompt immortalisation without transformation, and a stable tetraploid karyotype resembling that seen in NIH-3T3 cells. These data suggest that inactivation of Hic1 in cells undergoing replication stress in tissue culture can induce complete transformation associated with marked genomic instability. To test this hypothesis in vivo, we employed the inhaled adenoviral Cre recombinase model in order to direct loxP recombination to the airway epithelium of adult mice. As previously described by other groups, Cre activation of a conditional oncogenic KRasG12D mutant resulted in the appearance of multiple lung adenomas within 6-8 weeks following viral inhalation. By contrast, mice carrying this KRasG12D allele, as well as homozygous for the conditional Hic1lox knockout allele, developed highly aggressive adenocarcinomas with prominent pleomorphic and micropapillary histology. These data suggest a novel tumour suppressor role for HIC1 in maintaining genomic stability in replicating cells. HIC1 is known to interact with components of the SWI/SNF and PRC2 complexes, which help maintain genomic integrity by re-establishing constitutive heterochromatin following DNA replication. We therefore speculate that loss of HIC1 function may phenocopy recently described mutations in components of these chromatin-remodelling complexes such as ARID1A and BRG1. Citation Format: Anette Szczepny, Lisa McKenzie, Samantha Jayesekara, Prue Russell, Gavin Wright, Stephen B. Baylin, Fernando J. Rossello, Jason E. Cain, David N. Watkins. Conditional deletion of the tumor suppressor Hic1 results in aneuploidy and single-step transformation. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-81. doi:10.1158/1538-7445.AM2014-LB-81

Aims Non-small cell lung cancer (NSCLC) has the highest cancer-related mortality globally. Rearrangements of ALK in NSCLCs define a subgroup of patients with specific clinical, pathological and molecular characteristics and are associated with sensitivity to an ALK/MET inhibitor, with promising response rates. We aimed to assess the clinical utility of ALK translocation screening and to identify the frequency and clinicopathological features of lung adenocarcinomas harbouring ALK translocations, using immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH). Methods NSCLC tissue was obtained from patients treated at the Royal Prince Alfred Hospital and Concord Repatriation Hospital, Sydney, and St Vincent’s Hospital and Peter MacCallum Cancer Centre, Melbourne, with a total of 666 cases evaluated. Tissue microarrays were screened using ALK IHC (Clone ALK-1, Dako; Clone 5A4, Novocastra) and ALK break-apart translocation FISH (Abbott Molecular). Results ALK rearrangements were found in six cases (1%) by FISH, which is comparatively lower than other reported frequencies. The 5A4 ALK antibody identified all six ALK positive cases (100% sensitivity). One false negative resulted from the ALK-1 antibody (86% sensitivity). Conclusions We believe ALK IHC represents an effective means of routinely screening selected NSCLC patients for ALK rearrangement testing using FISH.

atypical subgroupwere found tobe significantlyolder, and presented with higher stage disease. Discussion: It is clear from the current study and previous reports that patients with atypical histopathology have different baseline characteristics, disease behavior and prognosis compared to patients with typical disease. The proposed TNM staging system appears to be applicable to patients in our surgical experience, and may offer more accurate prognostic information and assist in the management plans for individuals. doi:10.1016/j.hlc.2010.11.042 Comprehensive Adenocarcinoma Sub-typing Predicts Outcome After Lung Cancer Resection M. Daniels a,∗, G. Wrightb, P. Russell b, R. Williamsb, M. Conronb, Z. Wainer c a Alfred Health, Melbourne, Australia b St Vincent’s Hospital, Melbourne, Australia c University of Melbourne, Department of Surgery, St Vincent’s Hospital, Melbourne, Australia Background: Current lung adenocarcinoma pathological classification, published in 2004 by the World Health Organisation, has limited clinical utility. A new multidisciplinary classification has been proposed by the European Respiratory Society, the American Thoracic S o p c

Background: Radical lobectomy for early-stage Non-Small Cell Lung Cancer (NSCLC) by way of Video-assisted Thoracic Surgery (VATS) is a safe procedure with reduced post-operative morbidity. It has yet to gain world wide acceptance due to a perceived oncological inadequacy. Mediastinal Lymph Node Dissection (MLND) has a confirmed 4-year survival advantage over lymph node (LN) sampling (HR 0.78; 95% CI: 0.63–0.93). We aim to compare the quality of MLND samples from VATS and Open lobectomies. Methods: VATS lobectomies were compared with open lobectomy controls from 2000 to 2008. Retrospective pathology reviews were performed on all MLND samples. LN was counted according to each IASLC nodal zones. The number of LN per zone and in total was compared. Anatomical location of the lobectomy and the 7th ed. cTNM stage was recorded. Results: We included 132 VATS and 157 Ospen lobectomies (132:157). Stage distribution for VATS and Open were: Stage IA (64:55), State IB (64:68), Stage IIA (3:17), Stage IIB (1:14), Stage IIIA (0:3). Mean tumour diameter was 26 mm and 37 mm for VATS and Open respectively. Anatomical location of lobectomies for VATS and Open were: Right (91:100), Left (49:64). The mean number of LN dissected by VATS was higher in the upper mediastinal (Mean 7.2 vs. 4.0; p < 0.05), aorto-pulmonary (Mean 3.0 vs. 2.6), subcarinal (3.0 vs. 2.4), and hilar/interlobar zones (2.0 vs. 1.8). In total, VATS averaged 23 LN per case compared with 18 for Open (p < 0.05). Open lobe MLND performed better for the lower mediastinal zone. Conclusion: The quality of VATS MLND is often better than that of a thoracotomy, and therefore an adequate oncological procedure for early-stage NSCLC with reduced post-operative morbidity.