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Aortitis is found in 2-12% of thoracic aortic aneurysm repair/replacement surgeries. Yet little is known about such patients' post-operative outcomes or the role of post-operative corticosteroids. The study was undertaken across three tertiary referral hospitals in Sydney, Australia. Prospectively collected data for all thoracic aortic repair/replacement patients between 2004 and 2018 was accessed from a national surgical registry and analysed. Histopathology records identified cases of inflammatory aortitis which were subclassified as clinically isolated aortitis (CIA), giant cell arteritis (GCA), Takayasu (TAK) or other aortitis. Between-group outcomes were compared utilising logistic and median regression analyses. Between 2004 and 2018, a total of 1119 thoracic aortic surgeries were performed of which 41 (3.7%) were inflammatory aortitis cases (66% CIA, 27% GCA, 5% TAK, 2% other). Eight out of 41 (20%) aortitis patients received post-operative corticosteroids. Compared to non-aortitis patients, the aortitis group was predominantly female (53.7% vs. 28.1%, p 0.05) between aortitis and non-aortitis groups for 30-day mortality (7.3% vs 6.5%), significant morbidity (14.6% vs. 22.4%), or infection (9.8% vs. 6.4%). Outcomes were similar for the non-corticosteroid-treated aortitis subgroup. Histologic evidence of inflammatory thoracic aortitis following surgery did not affect post-operative mortality or morbidity. Withholding corticosteroids did not adversely affect patient outcomes. These findings will assist rheumatologists and surgeons in the post-operative management of aortitis.

There is uncertainty on how multiparametric MRI (mpMRI) and MRI-targeted biopsy (MRI-TB) can be best used to manage low-risk prostate cancer patients on Active Surveillance (AS). We performed a scoping review to evaluate the benefits and harm associated with four different biopsy scenarios in which mpMRI can be implemented in AS. Medline, Embase and Cochrane Library databases (1 January 2013–18 September 2020) were searched. Included studies were on men with low-risk prostate cancer enrolled in AS, who had mpMRI ± MRI-TB and standard prostate biopsy (systematic transrectal ultrasound or transperineal saturation biopsy), at confirmatory or follow-up biopsy. Primary outcomes were the number of Gleason score upgrades and biopsies avoided. Eight confirmatory biopsy studies and three follow-up biopsy studies were included. Compared to the benchmark of using standard biopsy (SB) for all men, the addition of MRI-TB increased the detection of Gleason score upgrades at both confirmatory (6/8 studies) and follow-up biopsy (3/3 studies), with increments of 1.7–11.8 upgrades per 100 men. 6/7 studies suggested that the use of a positive mpMRI to triage men for MRI-TB or SB alone would detect fewer Gleason score upgrades than benchmark at confirmatory biopsy, but the combination of MRI-TB and SB would detect more upgrades than the benchmark. For follow-up biopsy, the evidence on mpMRI triage biopsy scenarios was inconclusive due to the small number of included studies. The addition of MRI-TB to benchmark (SB for all men) maximises the detection of Gleason score upgrades at confirmatory and follow-up biopsy. When the use of mpMRI to triage men for a biopsy is desired, the combination of MRI-TB and SB should be considered for men with positive mpMRI at confirmatory biopsy. The evidence on mpMRI triage scenarios was inconclusive in the follow-up biopsy setting.

Contains fulltext : 245166.pdf (Publisher’s version ) (Open Access) AIMS: Current guidelines for pathology reporting on pancreatic cancer differ in certain aspects, resulting in divergent reporting practices and a lack of comparability of data. Here, we report on a new international dataset for pathology reporting on resection specimens with cancer of the exocrine pancreas (ductal adenocarcinoma and acinar cell carcinoma). The dataset was produced under the auspices of the International Collaboration on Cancer Reporting (ICCR), which is a global alliance of major (inter)national pathology and cancer organisations. METHODS AND RESULTS: According to the ICCR's rigorous process for dataset development, an international expert panel consisting of pancreatic pathologists, a pancreatic surgeon and an oncologist produced a set of core and non-core data items based on a critical review and discussion of current evidence. Commentary was provided for each data item to explain the rationale for selecting it as a core or non-core element and its clinical relevance, and to highlight potential areas of disagreement or lack of evidence, in which case a consensus position was formulated. Following international public consultation, the document was finalised and ratified, and the dataset, which includes a synoptic reporting guide, was published on the ICCR website. CONCLUSIONS: This first international dataset for cancer of the exocrine pancreas is intended to promote high-quality, standardised pathology reporting. Its widespread adoption will improve the consistency of reporting, facilitate multidisciplinary communication, and enhance the comparability of data, all of which will help to improve the management of pancreatic cancer patients.

BackgroundEvidence-based clinical practice guidelines recommend discussion by a multidisciplinary team (MDT) to review and plan the management of patients for a variety of cancers. However, not all patients diagnosed with cancer are presented at an MDT.Objectives(1) To identify the factors (barriers and enablers) influencing presentation of all patients to, and the perceived value of, MDT meetings in the management of patients with pancreatic cancer and; (2) to identify potential interventions that could overcome modifiable barriers and enhance enablers using the theoretical domains framework (TDF).MethodsSemistructured interviews were conducted with radiologists, surgeons, medical and radiation oncologists, gastroenterologists, palliative care specialists and nurse specialists based in New South Wales and Victoria, Australia. Interviews were conducted either in person or via videoconferencing. All interviews were recorded, transcribed verbatim, deidentified and data were thematically coded according to the 12 domains explored within the TDF. Common belief statements were generated to compare the variation between participant responses.ResultsIn total, 29 specialists were interviewed over a 4-month period. Twenty-two themes and 40 belief statements relevant to all the TDF domains were generated. Key enablers influencing MDT practices included a strong organisational focus (social/professional role and identity), beliefs about the benefits of an MDT discussion (beliefs about consequences), the use of technology, for example, videoconferencing (environmental context and resources), the motivation to provide good quality care (motivation and goals) and collegiality (social influences). Barriers included: absence of palliative care representation (skills), the number of MDT meetings (environmental context and resources), the cumulative cost of staff time (beliefs about consequences), the lack of capacity to discuss all patients within the allotted time (beliefs about capabilities) and reduced confidence to participate in discussions (social influences).ConclusionsThe internal and external organisational structures surrounding MDT meetings ideally need to be strengthened with the development of agreed evidence-based protocols and referral pathways, a focus on resource allocation and capabilities, and a culture that fosters widespread collaboration for all stages of pancreatic cancer.

Background and purpose Cone Beam Computed Tomography (CBCT) is routinely used in radiotherapy to identify the position of the target volume. The aim of this study was to determine whether the CBCT dose, when followed by the treatment, influences the therapeutic outcomes as determined by in-vitro clonogenic cell survival in a radiobiological experiment. Materials and methods Human cell lines, four cancer and one normal, were exposed to a 6 MV photon beam, produced by a linear accelerator. For half of each sample, a prior imaging dose was delivered using the on-board CBCT. A sample size of n = 103 was used to achieve statistical power. Results The experimental group of cell lines exposed to CBCT imaging prior to treatment exhibited a reduction in mean cancer cell survival of ~17 times (p = 0.02) greater than predicted from the average dose response and equivalent to more than 5% of the therapeutic dose, compared to 11 times greater than predicted for normal cells (n.s.). Conclusion The greater than predicted reduction in survival resulting from the additional CBCT dose is consistent with radiation-induced bystander effects.

Background: Recent developments in the design of needle tips used for fine needle biopsy via endoscopic ultrasound (EUS) allows for the procurement of core tissue for histological assessment in addition to cytology. Core tissue provides tissue architecture as well as the ability to perform molecular profiling investigations. We present a single centre study of experience with a new EUS needle with a Franseen tip (AcquireTM; Boston Scientific, Natick, MA, USA). The aim of the study was to assess the diagnostic yield of biopsies from solid lesions throughout the gastrointestinal tract. Methods: We performed a retrospective study of consecutive patients undergoing EUS biopsy between January 2017 and November 2018. Cystic lesions with no solid component were excluded or if samples were not sent for both cytology and histology. Rapid onsite evaluation (ROSE) was performed and the core tissue obtained was sent for histology. Results: Forty-six patients underwent EUS biopsy of solid lesions with specimens sent for both cytology and histology. Lesions included solid pancreatic masses (n = 31), lymph node (n = 3), gastric subepithelial lesion (n = 3), other (n = 9). The mean number of passes per lesion was 1.9 (range 1–4). In 43/46 (93%) of cases, a core specimen was obtained. Tissue obtained by EUS biopsy was adequate for evaluation by ROSE in 39/46 cases (85%). Histological diagnosis was confirmed in 41/46 (89%) cases compared to 31/46 (67%) cases with cytology (P = 0.011). Subgroup analysis of pancreatic lesions showed histological diagnosis was superior to cytology (90% vs 61%, P = 0.007). There were no adverse events. Conclusion: Histological analysis of specimens obtained via EUS biopsy was superior to cytology, particularly in assessment of solid pancreatic lesions

Background: Stroke results in impairment of cerebral autoregulation. Systemic blood pressure (BP), whether low or high, may affect cerebral blood flow and cause damage to brain tissue, so is important in the context of stroke. Effective management of BP may result in less severe strokes and better outcomes for patients. Methods: A literature search was performed to answer the research question, using the CINAHL Complete and MEDLINE Complete databases. Inclusion and exclusion criteria were applied. Full texts were reviewed for eligibility and 15 quantitative articles were selected and discussed. Results: Fifteen international quantitative primary research articles were selected and grouped into four themes: admission blood pressure; BP indexes/BP variability; active treatment of BP; and prehospital care. The articles were randomised controlled trials, cohort studies and one post-hoc analysis. Conclusion: In patients with acute ischaemic stroke (AIS), systolic BP in the 140–160 mmHg range on admission to hospital is associated with higher rates of positive outcome and lower stroke severity. BP-lowering therapy in AIS is safe and does not affect stroke severity, but also does not alter patient outcome. In the context of intracerebral haemorrhage (ICH), intensive BP-lowering therapy to a target of 140 mmHg and maintenance of this value for 7 days produces high rates of positive long-term outcomes in terms of quality of life and Modified Rankin Scale scores. Furthermore, early initiation of BP management, namely in the prehospital environment, is beneficial. These results provide evidence that antihypertensive treatment should be provided in the prehospital environment, and support early administration of treatment to reduce systolic BP to a target of 140 mmHg, which is a beneficial value for patients experiencing ICH and AIS.

Prostate cancer is characterised by significant global disparity; mortality rates in Sub-Saharan Africa are double to quadruple those in Eurasia1. Hypothesising unknown interplay between genetic and non-genetic factors, tumour genome profiling envisages contributing mutational processes2,3. Through whole-genome sequencing of treatment-naïve prostate cancer from 183 ethnically/globally distinct patients (African versus European), we generate the largest cancer genomics resource for Sub-Saharan Africa. Identifying ~2 million somatic variants, Africans carried the greatest burden. We describe a new molecular taxonomy using all mutational types and ethno-geographic identifiers, including Asian. Defined as Global Mutational Subtypes (GMS) A–D, although Africans presented within all subtypes, we found GMS-B to be ‘African-specific’ and GMS-D ‘African-predominant’, including Admixed and European Africans. Conversely, Europeans from Australia, Africa and Brazil predominated within ‘mutationally-quiet’ and ethnically/globally ‘universal’ GMS-A, while European Australians shared a higher mutational burden with Africans in GMS-C. GMS predicts clinical outcomes; reconstructing cancer timelines suggests four evolutionary trajectories with different mutation rates (GMS-A, low 0.968/year versus D, highest 1.315/year). Our data suggest both common genetic factors across extant populations and regional environmental factors contributing to carcinogenesis, analogous to gene-environment interaction defined here as a different effect of an environmental surrounding in persons with different ancestries or vice versa. We anticipate GMS acting as a proxy to intrinsic and extrinsic mutational processes in cancers, promoting global inclusion in landmark studies.

Malignant mesothelioma with EWSR1-ATF1 fusion is a rare malignancy described in young adults without exposure to asbestos. To our knowledge, outcomes to local and systemic therapies for this subtype of malignant mesothelioma have not been described. This case report describes the clinical course of a 19-year old male, diagnosed with malignant peritoneal mesothelioma with EWSR1-ATF1 fusion localised to the abdomen. His disease followed an aggressive course and resulted in limited survival (18 months). There was treatment resistance to several lines of conventional local and systemic treatments for peritoneal mesothelioma as well as biologically targeted MET-inhibition with crizotinib. More research is required in this rare subtype of peritoneal mesothelioma.

We have read with interest the recent debate between Drs Varma and Epstein regarding the grading of intraductal carcinoma of the prostate.$^{1}$ Unfortunately, the arguments as presented do little to abate the confusion surrounding this so-called diagnostic entity.

Background and study aims Diagnostic sensitivity for indeterminate biliary lesions remains suboptimal. Cytology techniques may mitigate the impediment of small cholangioscopic specimens. Our primary aim was to compare cell block cytology (CB) with standard histology for foregut SpyBite (SB) specimens. Our secondary aim was to assess CB in biliary SB biopsies. Patients and methods This was a two-phase prospective pilot study. In phase one, a prospective pilot study, foregut SB specimens from three sites (4 per site per patient per processing technique) were allocated to CB or histology, and assessed by a single, blinded pathologist. The gold standard comprised two standard forceps (CFB) histological specimens per site per patient. Specimen ease of processing, size and number, adequacy for diagnosis and artefact were evaluated. In phase two, CB was used for consecutive patients with indeterminate biliary lesions, and compared with phase one CB results. Results In phase one, 240 SB foregut biopsies were performed in 10 patients, 227 specimens recorded by pathologist. Specimen origin was identified in 100 % and 97 % of histology and CB batches respectively. Specimens were significantly larger in the histology group (2.02 mm vs 1.49 mm, P Conclusions In this pilot study, cell block cytology showed similar results as histological analysis of SpyBite specimens in the analysis of biliary stricture.

Background After radical prostatectomy (RP) for prostate cancer (PC), p53 alterations predict biochemical relapse (BCR), however, recent evidence suggests that metastatic relapse (MR) not BCR is a surrogate for PC specific mortality (PCSM). This updated analysis of a previously published study investigated the association between p53 aberrations, MR and PCSM in men with localised PC. Methods Two hundred and seventy-one men with localised PC treated with RP were included. RP specimens stained for p53 by immunohistochemistry were scored as (a) percentage of p53-positive tumour nuclei; and (b) clustering, where ≥12 p53-positive cells within a ×200 power field was deemed ‘cluster positive’. Associations between p53 status and clinical outcomes (BCR, MR and PCSM) were evaluated. Results Increasing percentage of p53-positive nuclei was significantly associated with shorter time to BCR, MR and PCSM (All p

Despite advances in antiviral therapy, molecular drivers of Hepatitis C Virus (HCV)-related liver disease remain poorly characterised. Chronic infection with HCV genotypes (1 and 3) differ in presentation of liver steatosis and virological response to therapies, both to interferon and direct acting antivirals. To understand what drives these clinically important differences, liver expression profiles of patients with HCV Genotype 1 or 3 infection (n = 26 and 33), alcoholic liver disease (n = 8), and no liver disease (n = 10) were analysed using transcriptome-wide microarrays. In progressive liver disease, HCV genotype was the major contributor to altered liver gene expression with 2151 genes differentially expressed >1.5-fold between HCV Genotype 1 and 3. In contrast, only 6 genes were altered between the HCV genotypes in advanced liver disease. Induction of lipogenic, lipolytic, and interferon stimulated gene pathways were enriched in Genotype 1 injury whilst a broad range of immune-associated pathways were associated with Genotype 3 injury. The results are consistent with greater lipid turnover in HCV Genotype 1 patients. Moreover, the lower activity in inflammatory pathways associated with HCV genotype 1 is consistent with relative resistance to interferon-based therapy. This data provides a molecular framework to explain the clinical manifestations of HCV-associated liver disease.

The International Collaboration on Cancer Reporting (ICCR) was formed in 2011 to harmonise the datasets, protocols and checklists for pathological reporting of various cancers and develop internationally agreed upon, evidence-based datasets. A dataset for prostate cancer in radical prostatectomy specimens was developed in 2011-2012 as part of a pilot project; however, it required substantial revision following the ISUP Consensus Conference on Gleason Grading in 2014, the publication of the World Health Organisation (WHO) Classification of Tumours of the Urinary System and Male Genital Organs in 2016, and the 8th edition of the Tumour-Node-Metastasis (TNM) staging system in late 2016. This article presents the up-to-date, evidence-based ICCR dataset and associated commentary for reporting prostate cancer in radical prostatectomy specimens. PubMed and Google search engines were used to review the published literature on the subject, and the dataset was developed in line with the previously published ICCR framework for the development of cancer datasets. Substantial changes have been incorporated into the second edition of the ICCR prostate cancer (radical prostatectomy) dataset. These include revisions to prostate cancer grading, reporting of intraductal carcinoma of prostate and surgical margins, among others. Up-to-date cancer datasets underpin structured reporting and facilitate the production of consistent and accurate pathological data for patient care as well as comparisons between different cohorts and populations internationally.

Introduction The aim of this work is to report diagnostic reference levels (DRLs) for hybrid positron emission tomography and x-ray computed tomography (PET/CT) exams in Australia (AU) for Queensland (QLD) and Western Australia (WA) (AU QLD/WA) and New Zealand (NZ). Methods Two-structured booklets were designed to collect dose information, patient demographics, equipment details and acquisition protocols for fluoride-18 fluorodeoxyglucose (18 F-FDG) PET/CT procedures, and any additional diagnostic CT routinely performed as part of 18 F-FDG whole-body examination. The DRL was reported based on the 75th percentile and achievable dose for 18 F-FDG, CT dose index volume (CTDIvol ) and dose length product (DLP). The effective dose and total effective dose was reported for 18 F-FDG whole-body PET/CT examination. Also, the effective dose was reported separately for identified additional diagnostic CT. Results The findings of this study show that the current DRL for 18 F-FDG in AU QLD/WA and NZ was 333.75 MBq and 332.87 MBq, respectively. The reported AU QLD/WA CTDIvol and DLP associated with 18 F-FDG whole-body PET/CT examinations from vertex to thigh (VT) was 4.41 mGy and 474 mGy.cm. In NZ, the reported VT CTDIvol and DLP was 13.07 mGy and 1319.05 mGy.cm. The effective dose for 18 F-FDG and CT component was 5.6 mSv and 4.7 mSv for AU QLD/WA. For NZ, the effective dose was 5.7 mSv and 10.9 mSv for 18 F-FDG and CT component. The total effective dose delivered from the 18 F-FDG whole-body scan from the AU QLD/WA PET/CT centres (10.44 mSv) were lower than the radiation doses delivered from the NZ (16.65 mSv). Conclusions The current DRLs were proposed for AU QLD/WA and NZ for 18 F-FDG whole-body PET/CT examinations. Variations existed in the current practice of AU QLD/WA and NZ PET/CT examinations. There is a need to optimize the radiation doses delivered from PET/CT examinations.

Background Pancreatic cancer (PC) remains a highly fatal disease. There is a gap in the literature on the of quality care on survival in a real-world population. Objectives This study: (1) assessed compliance with a consensus set of quality indicators (QIs); and (2) evaluated the association between compliance with these QIs and survival. Methods Data were collected on a core set of quality indicators by the Upper Gastrointestinal Cancer Registry (UGICR) for patients diagnosed with PC between 1 January 2016 and 31 December 2019. Univariable and multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs for the association between survival and patient characteristics, hospital characteristics and QIs, stratified by resectability. A multivariable analysis tested the relationship between significant patient and hospital characteristics, patient cluster effects within hospitals and survival. Results 1061 patients were eligible for this study with 52% male, 71% over the age of 65, 23% potentially resectable and 51% with metastatic disease at diagnosis. 52% received some form of cancer directed treatment. Significant association with improved survival were: (1) in the potentially resectable group having adjuvant chemotherapy administered following surgery or a reason documented (HR, 0.29; 95 CI, 0.19-0.46); (2) in the locally advanced group included having chemotherapy ± chemoradiation, or a reason documented for not undergoing treatment (HR, 0.38; 95 CI, 0.25-0.58) and (3) in the metastatic disease group included having documented ECOG at presentation and/or American society of Anaesthesiologists (ASA) performance status at a diagnostic procedure (HR, 0.65; 95 CI, 0.47-0.89), being seen by a medical oncologist and/or a radiation oncologist in the absence of treatment (HR, 0.48; 95 CI, 0.31-0.77), and having disease management discussed at an MDT meeting (HR, 0.79; 95 CI, 0.64-0.96). Conclusion Capture of a concise data set has enabled quality of care to be assessed and an analysis of factors associated with improved survival identified.

Generative adversarial networks (GANs) can be trained to generate three-dimensional (3D) image data, which are useful for design optimization. However, this conventionally requires 3D training data, which are challenging to obtain. Two-dimensional (2D) imaging techniques tend to be faster, higher resolution, better at phase identification and more widely available. Here we introduce a GAN architecture, SliceGAN, that is able to synthesize high-fidelity 3D datasets using a single representative 2D image. This is especially relevant for the task of material microstructure generation, as a cross-sectional micrograph can contain sufficient information to statistically reconstruct 3D samples. Our architecture implements the concept of uniform information density, which ensures both that generated volumes are equally high quality at all points in space and that arbitrarily large volumes can be generated. SliceGAN has been successfully trained on a diverse set of materials, demonstrating the widespread applicability of this tool. The quality of generated micrographs is shown through a statistical comparison of synthetic and real datasets of a battery electrode in terms of key microstructural metrics. Finally, we find that the generation time for a 108 voxel volume is on the order of a few seconds, yielding a path for future studies into high-throughput microstructural optimization. A generative approach called SliceGAN is demonstrated that can construct complex three-dimensional (3D) images from representative two-dimensional (2D) image examples. This is a promising approach in particular for studying microstructured materials where acquiring good-quality 3D data is challenging; 3D datasets can be created with SliceGAN, making use of high-quality 2D imaging techniques that are widely available.

Patient portals are websites or apps that provide patients with tools to manage healthcare appointments, access their health records, and communicate with clinicians. Patient portals have been demonstrated to be beneficial for improving communication between patients/carers and their healthcare team in a range of health settings. However, there is limited research on the barriers and enablers for implementing patient portals from the perspective of health professionals and healthcare teams, particularly in a paediatric setting. This study aimed to understand healthcare teams’ experiences of using a patient portal and, using the Unified Theory of Acceptance and Use of Technology (UTAUT) framework, explore the barriers and enablers to ongoing use. Participants were 11 health professionals participating in the pilot of a patient portal for patients/carers in paediatric care. Data were collected using semi-structured interviews. Analysis of the interview data identified nine themes about implementing a patient portal in paediatric care, all of which aligned with the four constructs of the UTAUT. This study identified that barriers and enablers of the uptake of a patient portal by health professionals in a paediatric context aligned with the UTAUT framework. Value for the patient, improved workflow, and adequate technical and implementation support were highlighted by participants.

Intraductal carcinoma of the prostate (IDC-P) has been recently recognized by the World Health Organization classification of prostatic tumors as a distinct entity, most often occurring concurrently with invasive prostatic adenocarcinoma (PCa). Whether documented admixed with PCa or in its rare pure form, numerous studies associate this entity with clinical aggressiveness. Despite increasing clinical experience and requirement of IDC-P documentation in protocols for synoptic reporting, the specifics of its potential contribution to assessment of grade group (GG) and cancer quantitation of PCa in both needle biopsies (NBx) and radical prostatectomy (RP) specimens remain unclear. Moreover, there are no standard guidelines for incorporating basal cell marker immunohistochemistry (IHC) in the diagnosis of IDC-P, either alone or as part of a cocktail with AMACR/racemase. An online survey containing 26 questions regarding diagnosis, reporting practices, and IHC resource utilization, focusing on IDC-P, was undertaken by 42 genitourinary subspecialists from 9 countries. The degree of agreement or disagreement regarding approaches to individual questions was classified as significant majority (>75%), majority (51% to 75%), minority (26% to 50%) and significant minority (≤25%). IDC-P with or without invasive cancer is considered a contraindication for active surveillance by the significant majority (95%) of respondents, although a majority (66%) also agreed that the clinical significance/behavior of IDC-P on NBx or RP with PCa required further study. The majority do not upgrade PCa based on comedonecrosis seen only in the intraductal component in NBx (62%) or RP (69%) specimens. Similarly, recognizable IDC-P with GG1 PCa was not a factor in upgrading in NBx (78%) or RP (71%) specimens. The majority (60%) of respondents include readily recognizable IDC-P in assessment of linear extent of PCa at NBx. A significant majority (78%) would use IHC to confirm or exclude intraductal carcinoma if other biopsies showed no PCa, while 60% would use it to confirm IDC-P with invasive PCa in NBx if it would change the overall GG assignment. Nearly half (48%, a minority) would use IHC to confirm IDC-P for accurate Gleason pattern 4 quantitation. A majority (57%) report the percentage of IDC-P when present, in RP specimens. When obvious Gleason pattern 4 or 5 PCa is present in RP or NBx, IHC is rarely to almost never used to confirm the presence of IDC-P by the significant majority (88% and 90%, respectively). Most genitourinary pathologists consider IDC-P to be an adverse prognostic feature independent of the PCa grade, although recommendations for standardization are needed to guide reporting of IDC-P vis a vis tumor quantitation and final GG assessment. The use of IHC varies widely and is performed for a multitude of indications, although it is used most frequently in scenarios where confirmation of IDC-P would impact the GG assigned. Further study and best practices recommendations are needed to provide guidance with regards to the most appropriate indications for IHC use in scenarios regarding IDC-P.

Purpose To investigate the possibility of reducing the injected activity for whole-body [18F]FDG-PET/CT studies of paediatric oncology patients and to assess the usefulness of time-of-flight (TOF) acquisition on PET image quality at reduced count levels. Procedures Twenty-nine paediatric oncology patients (12F/17M, 3–18 years old (median age 13y), weight 45±20 kg, BMI 19±4 kg/m2), who underwent routine whole-body PET/CT examinations on a Siemens Biograph mCT TrueV system with TOF capability (555ps) were included in this study. The mean injected activity was 156 ± 45 MBq (3.8 ± 0.8 kg/MBq) and scaled to patient weight. The raw data was collected in listmode (LM) format and pre-processed to simulate reduced levels of [18F]FDG activity (75, 50, 35, 20 and 10% of the original counts) by randomly removing events from the original LM data. All data were reconstructed using the vendor-specific e7-tools with standard OSEM only, with OSEM plus resolution recovery (PSF). The reconstructions were repeated with added TOF (TOF) and PSF+TOF. The benefit of TOF together with the reduced count levels was evaluated by calculating the gains in signal-to-noise ratio (SNR) in the liver and contrast-to-noise ratio (CNR) in all PET-positive lesions before and after TOF employed at every simulated reduced count level. Finally, the PSF+TOF images at 50, 75 and 100% of counts were evaluated clinically on a 5-point scale by three nuclear medicine physicians. Results The visual inspection of the reconstructed images did not reveal significant differences in image quality between 75 and 100% count levels for PSF+TOF. The improvements in SNR and CNR were the greatest for TOF reconstruction and PSF combined. Both SNR and CNR gains did increase linearly with the patients BMI for both OSEM only and PSF reconstruction. These benefits were observed until reducing the counts to 50 and 35% for SNR and CNR, respectively. Conclusions The benefit of using TOF was noticeable when using 50% or greater of the counts when evaluating the CNR and SNR. For [18F]FDG-PET/CT, whole-body paediatric imaging the injected activity can be reduced to 75% of the original dose without compromising PET image quality.

IntroductionWith almost 50% of cases preventable and the Australian National Bowel Cancer Screening Program in place, colorectal cancer (CRC) is a prime candidate for investment to reduce the cancer burden. The challenge is determining effective ways to reduce morbidity and mortality and their implementation through policy and practice. Pathways-Bowel is a multistage programme that aims to identify best-value investment in CRC control by integrating expert and end-user engagement; relevant evidence; modelled interventions to guide future investment; and policy-driven implementation of interventions using evidence-based methods.Methods and analysisPathways-Bowel is an iterative work programme incorporating a calibrated and validated CRC natural history model for Australia (Policy1-Bowel) and assessing the health and cost outcomes and resource use of targeted interventions. Experts help identify and prioritise modelled evaluations of changing trends and interventions and critically assess results to advise on their real-world applicability. Where appropriate the results are used to support public policy change and make the case for optimal investment in specific CRC control interventions. Fourteen high-priority evaluations have been modelled or planned, including evaluations of CRC outcomes from the changing prevalence of modifiable exposures, including smoking and body fatness; potential benefits of daily aspirin intake as chemoprevention; increasing CRC incidence in people aged Pathways-Bowel is a unique, comprehensive approach to evaluating CRC control; no prior body of work has assessed the relative benefits of a variety of interventions across CRC development and progression to produce a list of best-value investments.Ethics and disseminationEthics approval was not required as human participants were not involved. Findings are reported in a series of papers in peer-reviewed journals and presented at fora to engage the community and policymakers.

The International Society of Urological Pathology (ISUP) hosts a reference image database supervised by experts with the purpose of establishing an international standard in prostate cancer grading. Here, we aimed to identify areas of grading difficulties and compare the results with those obtained from an artificial intelligence system trained in grading. In a series of 87 needle biopsies of cancers selected to include problematic cases, experts failed to reach a 2/3 consensus in 41.4% (36/87). Among consensus and non-consensus cases, the weighted kappa was 0.77 (range 0.68–0.84) and 0.50 (range 0.40–0.57), respectively. Among the non-consensus cases, four main causes of disagreement were identified: the distinction between Gleason score 3 + 3 with tangential cutting artifacts vs. Gleason score 3 + 4 with poorly formed or fused glands (13 cases), Gleason score 3 + 4 vs. 4 + 3 (7 cases), Gleason score 4 + 3 vs. 4 + 4 (8 cases) and the identification of a small component of Gleason pattern 5 (6 cases). The AI system obtained a weighted kappa value of 0.53 among the non-consensus cases, placing it as the observer with the sixth best reproducibility out of a total of 24. AI may serve as a decision support and decrease inter-observer variability by its ability to make consistent decisions. The grading of these cancer patterns that best predicts outcome and guides treatment warrants further clinical and genetic studies. Results of such investigations should be used to improve calibration of AI systems.

In developed countries, it is projected that there will be a 70% increase in the number of adults living with Cystic Fibrosis (CF) between 2010 and 2025. This shift in demographics highlights the importance of high-quality transition programmes with developmentally appropriate integrated health care services as the individual moves through adolescence to adulthood. Adolescents living with CF face additional and unique challenges that may have long-term impacts on their health, quality of life and life-expectancy. CF specific issues around socially challenging symptoms, body image, reproductive health and treatment burden differentiate people with CF from their peers and require clinicians to identify and address these issues during the transition process. This review provides an overview of the health, developmental and psychosocial challenges faced by individuals with CF, their guardians and health care teams considering the fundamental components and tools that are required to build a transition programme that can be tailored to suit individual CF clinics.

Purpose The purpose of this study was to investigate the effect of increasing iterative reconstruction (IR) algorithm strength at different tube voltages in coronary computed tomography angiography (CCTA) protocols using a three‐dimensional (3D)‐printed and Catphan® 500 phantoms. Methods A 3D‐printed cardiac insert and Catphan 500 phantoms were scanned using CCTA protocols at 120 and 100 kVp tube voltages. All CT acquisitions were reconstructed using filtered back projection (FBP) and Adaptive Statistical Iterative Reconstruction (ASIR) algorithm at 40% and 60% strengths. Image quality characteristics such as image noise, signal–noise ratio (SNR), contrast–noise ratio (CNR), high spatial resolution, and low contrast resolution were analyzed. Results There was no significant difference (P > 0.05) between 120 and 100 kVp measures for image noise for FBP vs ASIR 60% (16.6 ± 3.8 vs 16.7 ± 4.8), SNR of ASIR 40% vs ASIR 60% (27.3 ± 5.4 vs 26.4 ± 4.8), and CNR of FBP vs ASIR 40% (31.3 ± 3.9 vs 30.1 ± 4.3), respectively. Based on the Modulation Transfer Function (MTF) analysis, there was a minimal change of image quality for each tube voltage but increases when higher strengths of ASIR were used. The best measure of low contrast detectability was observed at ASIR 60% at 120 kVp. Conclusions Changing the IR strength has yielded different image quality noise characteristics. In this study, the use of 100 kVp and ASIR 60% yielded comparable image quality noise characteristics to the standard CCTA protocols using 120 kVp of ASIR 40%. A combination of 3D‐printed and Catphan® 500 phantoms could be used to perform CT dose optimization protocols.

Objective We aimed to define preoperative clinical and molecular characteristics that would allow better patient selection for operative resection. Background Although we use molecular selection methods for systemic targeted therapies, these principles are not applied to surgical oncology. Improving patient selection is of vital importance for the operative treatment of pancreatic cancer (pancreatic ductal adenocarcinoma). Although surgery is the only chance of long-term survival, 80% still succumb to the disease and approximately 30% die within 1 year, often sooner than those that have unresected local disease. Method In 3 independent pancreatic ductal adenocarcinoma cohorts (total participants = 1184) the relationship between aberrant expression of prometastatic proteins S100A2 and S100A4 and survival was assessed. A preoperative nomogram based on clinical variables available before surgery and expression of these proteins was constructed and compared to traditional measures, and a postoperative nomogram. Results High expression of either S100A2 or S100A4 was independent poor prognostic factors in a training cohort of 518 participants. These results were validated in 2 independent patient cohorts (Glasgow, n = 198; Germany, n = 468). Aberrant biomarker expression stratified the cohorts into 3 distinct prognostic groups. A preoperative nomogram incorporating S100A2 and S100A4 expression predicted survival and nomograms derived using postoperative clinicopathological variables. Conclusions Of those patients with a poor preoperative nomogram score, approximately 50% of patients died within a year of resection. Nomograms have the potential to improve selection for surgery and neoadjuvant therapy, avoiding surgery in aggressive disease, and justifying more extensive resections in biologically favorable disease.

A plethora of individual candidate biomarkers for predicting biochemical relapse in localized prostate cancer (PCa) have been proposed. Combined biomarkers may improve prognostication, and ensuring validation against more clinically relevant endpoints are required. The Australian PCa Research Centre NSW has contributed to numerous studies of molecular biomarkers associated with biochemical relapse. In the current study, these biomarkers were re-analyzed for biochemical relapse, metastatic relapse and PCa death with extended follow-up. Biomarkers of significance were then used to develop a combined prognostic model for clinical outcomes and validated in a large independent cohort. The discovery cohort (n = 324) was based on 12 biomarkers with a median follow-up of 16 years. Seven biomarkers were significantly associated with biochemical relapse. Three biomarkers were associated with metastases: AZGP1, Ki67 and PML. Only AZGP1 was associated with PCa death. In their individual and combinational forms, AZGP1 and Ki67 as a dual BM signature was the most robust predictor of metastatic relapse (AUC 0.762). The AZPG1 and Ki67 signature was validated in an independent cohort of 347 PCa patients. The dual BM signature of AZGP1 and Ki67 predicted metastasis in the univariable (HR 7.2, 95% CI, 1.6-32; p = 0.01) and multivariable analysis (HR 5.4, 95% CI, 1.2-25; p = 0.03). The dual biomarker signature marginally improved risk prediction compared to AZGP1 alone (AUC 0.758 versus 0.738, p < 0.001). Our findings indicate that biochemical relapse is not an adequate surrogate for metastasis or PCa death. The dual biomarker signature of AZGP1 and Ki67 offers a small benefit in predicting metastasis over AZGP1 alone.

The urgent unmet need for hepatocellular carcinoma (HCC) therapies is addressed here by characterising a novel mouse model of HCC in the context of ongoing liver damage and overnutrition. Male C57Bl/6J mice were treated with diethylnitrosamine (DEN) and thioacetamide (TAA), and some were provided with an atherogenic high fat diet (HFD). Inflammation, steatosis, fibrosis, 87 genes, liver lesions and intratumoural leukocyte subsets were quantified up to 24 weeks of age. Adding HFD to DEN/TAA increased fibrosis, steatosis and inflammation, and the incidence of both HCC and non-HCC dysplastic lesions. All lesions contained α-SMA positive fibroblasts. Macrophage marker F4/80 was not significantly different between treatment groups, but the macrophage-associated genes Arg-1 and Cd47 were differentially expressed. Fibrosis, cancer and cell death associated genes were upregulated in DEN/TAA/HFD livers. Fewer Kupffer cells and plasmacytoid dendritic cells were in tumours compared to control liver. In conclusion, combining a hepatotoxin with an atherogenic diet produced more intrahepatic tumours, dysplastic lesions and fibrosis compared to hepatotoxin alone. This new HCC model provides a relatively rapid means of examining primary HCC and potential therapies in the context of multiple hepatotoxins including those derived from overnutrition.

Long-term outcomes from large cohorts are not yet available upon which to base recommended follow-up protocols after prostate focal therapy. This is an updated summary of a 2015 SIU-ICUD review of the best available current evidence and expert consensus on guidelines for surveillance after prostate focal therapy. We performed a systematic search of the PubMed, Cochrane and Embase databases to identify studies where primary prostate focal therapy was performed to treat prostate cancer. Multiparametric magnetic resonance imaging (mpMRI) should be performed at 3–6 months, 12–24 months and at 5 years after focal therapy. Targeted biopsy of the treated zone should be performed at 3–6 months and fusion biopsy of any suspicious lesion seen on mpMRI. Additionally, a systematic biopsy should be performed at 12–24 months and again at 5 years. In histological diagnosis, characteristic changes of each treatment modality should be noted and in indeterminate situations various immunohistochemical molecular markers can be helpful. Small volume 3 + 3 (Prognostic grade group [PGG] 1) or very small volume (

In November, 2014, 65 prostate cancer pathology experts, along with 17 clinicians including urologists, radiation oncologists, and medical oncologists from 19 different countries gathered in a consensus conference to update the grading of prostate cancer, last revised in 2005. The major conclusions were: (1) Cribriform glands should be assigned a Gleason pattern 4, regardless of morphology; (2) Glomeruloid glands should be assigned a Gleason pattern 4, regardless of morphology; (3) Grading of mucinous carcinoma of the prostate should be based on its underlying growth pattern rather than grading them all as pattern 4; and (4) Intraductal carcinoma of the prostate without invasive carcinoma should not be assigned a Gleason grade and a comment as to its invariable association with aggressive prostate cancer should be made. Regarding morphologies of Gleason patterns, there was clear consensus on: (1) Gleason pattern 4 includes cribriform, fused, and poorly formed glands; (2) The term hypernephromatoid cancer should not be used; (3) For a diagnosis of Gleason pattern 4, it needs to be seen at 10x lens magnification; (4) Occasional/seemingly poorly formed or fused glands between well-formed glands is insufficient for a diagnosis of pattern 4; (5) In cases with borderline morphology between Gleason pattern 3 and pattern 4 and crush artifacts, the lower grade should be favored; (6) Branched glands are allowed in Gleason pattern 3; (7) Small solid cylinders represent Gleason pattern 5; (8) Solid medium to large nests with rosette-like spaces should be considered to represent Gleason pattern 5; and (9) Presence of unequivocal comedonecrosis, even if focal is indicative of Gleason pattern 5. It was recognized by both pathologists and clinicians that despite the above changes, there were deficiencies with the Gleason system. The Gleason grading system ranges from 2 to 10, yet 6 is the lowest score currently assigned. When patients are told that they have a Gleason score 6 out of 10, it implies that their prognosis is intermediate and contributes to their fear of having a more aggressive cancer. Also, in the literature and for therapeutic purposes, various scores have been incorrectly grouped together with the assumption that they have a similar prognosis. For example, many classification systems consider Gleason score 7 as a single score without distinguishing 3+4 versus 4+3, despite studies showing significantly worse prognosis for the latter. The basis for a new grading system was proposed in 2013 by one of the authors (J.I.E.) based on data from Johns Hopkins Hospital resulting in 5 prognostically distinct Grade Groups. This new system was validated in a multi-institutional study of over 20,000 radical prostatectomy specimens, over 16,000 needle biopsy specimens, and over 5,000 biopsies followed by radiation therapy. There was broad (90%) consensus for the adoption of this new prostate cancer Grading system in the 2014 consensus conference based on: (1) the new classification provided more accurate stratification of tumors than the current system; (2) the classification simplified the number of grading categories from Gleason scores 2 to 10, with even more permutations based on different pattern combinations, to Grade Groups 1 to 5; (3) the lowest grade is 1 not 6 as in Gleason, with the potential to reduce overtreatment of indolent cancer; and (4) the current modified Gleason grading, which forms the basis for the new grade groups, bears little resemblance to the original Gleason system. The new grades would, for the foreseeable future, be used in conjunction with the Gleason system [ie. Gleason score 3+3=6 (Grade Group 1)]. The new grading system and the terminology Grade Groups 1-5 have also been accepted by the World Health Organization for the 2016 edition of Pathology and Genetics: Tumours of the Urinary System and Male Genital Organs.

Background Docetaxel, the standard chemotherapy for metastatic castration-resistant prostate cancer (CRPC) also enhances the survival of patients with metastatic castration-sensitive prostate cancer (CSPC) when combined with androgen-deprivation therapy. Focal Adhesion Kinase (FAK) activation is a mediator of docetaxel resistance in prostate cancer cells. The aim of this study was to investigate the effect of the second generation FAK inhibitor VS-6063 on docetaxel efficacy in pre-clinical CRPC and CSPC models. Methods Docetaxel-resistant CRPC cells, mice with PC3 xenografts, and ex vivo cultures of patient-derived primary prostate tumors were treated with VS-6063 and/or docetaxel, or vehicle control. Cell counting, immunoblotting, and immunohistochemistry techniques were used to evaluate the treatment effects. Results Docetaxel and VS-6063 co-treatment caused a greater decrease in the viability of docetaxel-resistant CRPC cells, and a greater inhibition in PC3 xenograft growth compared to either monotherapy. FAK expression in human primary prostate cancer was positively associated with advanced tumor stage. Patient-derived prostate tumor explants cultured with both docetaxel and VS-6063 displayed a higher percentage of apoptosis in cancer cells, than monotherapy treatment. Conclusions Our findings suggest that co-administration of the FAK inhibitor, VS-6063, with docetaxel represents a potential therapeutic strategy to overcome docetaxel resistance in prostate cancer.

Post-natal growth in surgical lung conditions, such as congenital diaphragmatic hernia and oesophageal atresia with tracheo-oesophageal fistula, is often sub-optimal in the early years of life when lung growth is occurring. Whilst constitutional, behavioural and mechanical factors may contribute to poor feeding and weight gain, there is a common path of management with greater caloric supplementation that may change growth trajectories and potentially lead to better respiratory, anthropometric and cognitive outcomes. We provide simple, single page, feeding supplementation sheets in three age groups: 0-6months, 6-12months and 12-24months that have proven useful for enhancing weight gain in our patients.

Background Prostate cancers (PCs) with similar characteristics at the time of diagnosis can have very different disease outcomes. Conventional biomarkers of PC still lack precision in identifying individuals at high risk of PC recurrence. While many candidate biomarkers are proposed in the literature, few are in clinical practice as they lack rigorous validation. This study prospectively enrolled an independent phase III cohort to evaluate the clinical utility of zinc-alpha 2-glycoprotein (AZGP1) as a prognostic biomarker in localized PC. Patients and methods In our multicentre, prospective phase III study, AZGP1 status in 347 radical prostatectomy specimens was assayed by immunohistochemistry in a NATA-accredited laboratory. The AZGP1 score was assessed in a multivariable model incorporating established prognostic factors. We also report extended outcomes from our previous phase II study. The primary endpoint was biochemical relapse-free survival (BRFS). Secondary endpoints were metastasis-free survival (MFS) and PC-specific survival (PCSS). Results In the phase II cohort, with a median follow-up of 15.8 years, low/absent AZGP1 expression was an independent predictor of poor BRFS (HR, 1.4; 95% CI, 1.1–1.9; P = 0.03), MFS (HR, 2.8; 95% CI, 1.2–6.6;P = 0.02) and PCSS (HR, 3.8; 95% CI, 1.5–9.5;P = 0.005). These results were validated in our prospective phase III cohort. Low/absent AZGP1 expression independently predicted for BRFS (HR, 1.9; 95% CI, 1.1–3.3;P = 0.02), with shorter MFS (HR, 2.0; 95% CI, 1.1–3.4;P = 0.02). AZGP1 improved the discriminatory value when incorporated into existing prognostic risk models. Conclusion Our study provides prospective phase III validation that absent/low AZGP1 expression provides independent prognostic value in PC. This study provides robust evidence for the incorporation of this biomarker into clinical practice.

Cardiac computed tomography angiography (CCTA) is a commonly used diagnostic tool for cardiovascular disease. Despite constant improvements to imaging technologies, the radiation dose to patients from CCTA remains a concern when using this procedure. There remains a need for optimisation of CCTA procedures and accurate dose monitoring to reduce the potential risk of cancer. Establishing diagnostic reference levels (DRLs) allows for the assessment of radiation dose variations, enabling strategies aimed at standardising doses across radiological centres. This systematic review explores the literature on CCTA methodologies that have been used to establish DRLs. A search was carried out using the Web of Science, SCOPUS, Medline, CINAHL and EMBASE databases. Reference lists of published articles were also assessed to identify further articles. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology was employed to evaluate articles for relevance. Articles were included if they assessed DRLs in CCTA. The search resulted in 448 articles, of which, six were included after a thorough screening process. The literature demonstrates a wide dose variation in reported CCTA DRLs ranging from 671 to 1510 mGy cm in DLP. Where reported, CTDIvol DRLs ranged from 26 to 70 mGy. Differences were found in the methodologies used for establishing CCTA DRLs, including the sampling methodology used for identifying suitable patients and scanning protocols. This current review emphasises the need for an international standardisation for DRLs establishment methods, to provide a more comparable global measurement of dose variations across CT sites.

Infiltration of the prostatic ducts by prostatic adenocarcinoma occurs relatively frequently, being most commonly associated with high grade disease. It is now recognised that intraductal carcinoma of the prostate (IDCP) has an associated poor prognosis and this is reflected in its histological, molecular and immunohistochemical features. The current recommendation of the World Health Organization is that IDCP not be taken into consideration when grading prostate adenocarcinoma. It is apparent that Gleason did not differentiate between IDCP and stromal invasive carcinoma when developing and validating his grading system, and recent studies suggest that the incorporation of IDCP grading into the overall grading of the specimen provides additional prognostic information.

Historically in New Zealand, coastal environments were viewed as amenities for subdivision to be incorporated into town structure plans with little regard for hazards and scientific investigation. This subdivision of coastal land has led to the proliferation of developments that are increasingly vulnerable to the slow landward creep of sea level rise and increasing extreme storm events. Planning and management of vulnerable coastal communities and infrastructure could benefit from an emphasis on sustainable and resilient adaptation through managed retreat away from coastal hazards. However, it is not at all clear exactly how managed retreat can be accomplished. This chapter explores methods for analysing the interactions and manifestations of complex intersecting environmental and economic systems that are implicit in a managed retreat from coastal hazards. These complex systems can be quantifiably analysed using the principles of evolutionary economics, which enables identification of knowledge structures and information flows that can inform institutional decision-making and planning. The chapter aims to explore how policy planning, implemented through the lens of evolutionary economics, can inform sustainable land-use management and development through managed retreat in the coastal environment. It discusses Systems Thinking approaches to aid the decision-making process in order to reveal effective policy outcomes and financial mechanisms that enable resilient coastal management. Specific consideration is given to System Dynamics modelling, economic impact analysis and Robust Decision Making.

To guide the design of interactive image annotation systems that generalize to new domains and applications, we need ways to evaluate the capabilities of new annotation tools across a range of different types of image, content, and task domains. In this work, we introduce Corsica, a test harness for image an- notation tools that uses calibration images to evaluate a tool's capabilities on general image properties and task requirements. Corsica is comprised of sets of three key components: 1) synthesized images with visual elements that are not domain- specific, 2) target microtasks that connects the visual elements and tools for evaluation, and 3) ground truth data for each mi- crotask and visual element pair. By introducing a specification for calibration images and microtasks, we aim to create an evolving repository that allows the community to propose new evaluation challenges. Our work aims to help facilitate the robust verification of image annotation tools and techniques.

Current pharmacokinetic models, such as the linear parametric neurotransmitter PET (lp-ntPET) model have been developed to detect and quantify transient changes in receptor occupancy caused by variations in the concentration of endogenous neurotransmitters. However, it often performs poorly when applied at the voxel level due to high statistical noise. In this paper, we propose a new method to detect transient changes in neurotransmitter concentration in dynamic PET data using deep learning. Activation onset time and response magnitude of neurotransmitter were directly estimated using a convolution neural network (CNN) and compared to the lpntPET model. Computer simulations, as well as realistic GATE simulations were used to generate dynamic PET data, representing a [11C]raclopride study, with a known range of activation onset times and response magnitudes, across a wide range of noise levels. Results showed that the proposed neural network had better quantitative performance in estimating activation onset time and response magnitude than the conventional lp-ntPET method, especially where noise is high.

PurposeThe Upper Gastrointestinal Cancer Registry (UGICR) was developed to monitor and improve the quality of care provided to patients with upper gastrointestinal cancers in Australia.ParticipantsIt supports four cancer modules: pancreatic, oesophagogastric, biliary and primary liver cancer. The pancreatic cancer (PC) module was the first module to be implemented, with others being established in a staged approach. Individuals are recruited to the registry if they are aged 18 years or older, have received care for their cancer at a participating public/private hospital or private clinic in Australia and do not opt out of participation.Findings to dateThe UGICR is governed by a multidisciplinary steering committee that provides clinical governance and oversees clinical working parties. The role of the working parties is to develop quality indicators based on best practice for each registry module, develop the minimum datasets and provide guidance in analysing and reporting of results. Data are captured from existing data sources (population-based cancer incidence registries, pathology databases and hospital-coded data) and manually from clinical records. Data collectors directly enter information into a secure web-based Research Electronic Data Capture (REDCap) data collection platform. The PC module began with a pilot phase, and subsequently, we used a formal modified Delphi consensus process to establish a core set of quality indicators for PC. The second module developed was the oesophagogastric cancer (OGC) module. Results of the 1 year pilot phases for PC and OGC modules are included in this cohort profile.Future plansThe UGICR will provide regular reports of risk-adjusted, benchmarked performance on a range of quality indicators that will highlight variations in care and clinical outcomes at a health service level. The registry has also been developed with the view to collect patient-reported outcomes (PROs), which will further add to our understanding of the care of patients with these cancers.

While combination therapy with nab-paclitaxel/gemcitabine (nab-gem) is effective in pancreatic ductal adenocarcinoma (PDAC), its efficacy as perioperative chemotherapy is unknown. The primary objective of this multicenter, prospective, single-arm, phase II study was to determine whether neoadjuvant therapy with nab-gem was associated with higher complete resection rates (R0) in resectable PDAC, while the secondary objectives were to determine the utility of radiological assessment of response to preoperative chemotherapy and the safety and efficacy of nab-gem as perioperative therapy.Patients were recruited from eight Australian sites, and 42 patients with radiologically defined resectable PDAC and an Eastern Cooperative Oncology Group performance status of 0-2 were enrolled. Participants received two cycles of preoperative nab-paclitaxel 125 mg/mPreoperative nab-gem was completed by 93% of participants, but only 63% postoperatively. Thirty-six patients had surgery: 6 (17%) were unresectable, 15 (52%) had R0 (≥ 1 mm) resections, 14 (48%) had R1 ( 1 mm) resections, and 1 patient did not have PDAC. Median progression-free survival was 12.3 months and median overall survival (OS) was 23.5 months: R0 patients had an OS of 35 months versus 25.6 months for R1 patients after surgery. Seven patients had not progressed after 43 months.The GAP trial demonstrated that perioperative nab-gem was tolerable. Although the primary endpoint of an 85% R0 rate was not met, the R0 rate was similar to trials using a 1 mm R0 resection definition, and survival rates were comparable with recent adjuvant studies.

Summary Background An increasing volume of prostate biopsies and a worldwide shortage of urological pathologists puts a strain on pathology departments. Additionally, the high intra-observer and inter-observer variability in grading can result in overtreatment and undertreatment of prostate cancer. To alleviate these problems, we aimed to develop an artificial intelligence (AI) system with clinically acceptable accuracy for prostate cancer detection, localisation, and Gleason grading. Methods We digitised 6682 slides from needle core biopsies from 976 randomly selected participants aged 50–69 in the Swedish prospective and population-based STHLM3 diagnostic study done between May 28, 2012, and Dec 30, 2014 (ISRCTN84445406), and another 271 from 93 men from outside the study. The resulting images were used to train deep neural networks for assessment of prostate biopsies. The networks were evaluated by predicting the presence, extent, and Gleason grade of malignant tissue for an independent test dataset comprising 1631 biopsies from 246 men from STHLM3 and an external validation dataset of 330 biopsies from 73 men. We also evaluated grading performance on 87 biopsies individually graded by 23 experienced urological pathologists from the International Society of Urological Pathology. We assessed discriminatory performance by receiver operating characteristics and tumour extent predictions by correlating predicted cancer length against measurements by the reporting pathologist. We quantified the concordance between grades assigned by the AI system and the expert urological pathologists using Cohen's kappa. Findings The AI achieved an area under the receiver operating characteristics curve of 0·997 (95% CI 0·994–0·999) for distinguishing between benign (n=910) and malignant (n=721) biopsy cores on the independent test dataset and 0·986 (0·972–0·996) on the external validation dataset (benign n=108, malignant n=222). The correlation between cancer length predicted by the AI and assigned by the reporting pathologist was 0·96 (95% CI 0·95–0·97) for the independent test dataset and 0·87 (0·84–0·90) for the external validation dataset. For assigning Gleason grades, the AI achieved a mean pairwise kappa of 0·62, which was within the range of the corresponding values for the expert pathologists (0·60–0·73). Interpretation An AI system can be trained to detect and grade cancer in prostate needle biopsy samples at a ranking comparable to that of international experts in prostate pathology. Clinical application could reduce pathology workload by reducing the assessment of benign biopsies and by automating the task of measuring cancer length in positive biopsy cores. An AI system with expert-level grading performance might contribute a second opinion, aid in standardising grading, and provide pathology expertise in parts of the world where it does not exist. Funding Swedish Research Council, Swedish Cancer Society, Swedish eScience Research Center, EIT Health.

Background Lynch syndrome (LS) is an inherited, cancer predisposition syndrome associated with an increased risk of colorectal, endometrial and other cancer types. Identifying individuals with LS allows access to cancer risk management strategies proven to reduce cancer incidence and improve survival. However, LS is underdiagnosed and genetic referral rates are poor. Improving LS referral is complex, and requires multisystem behaviour change. Although barriers have been identified, evidence-based strategies to facilitate behaviour change are lacking. The aim of this study is to compare the effectiveness of a theory-based implementation approach against a non-theory based approach for improving detection of LS amongst Australian patients with colorectal cancer (CRC). Methods A two-arm parallel cluster randomised trial design will be used to compare two identical, structured implementation approaches, distinguished only by the use of theory to identify barriers and design targeted intervention strategies, to improve LS referral practices in eight large Australian hospital networks. Each hospital network will be randomly allocated to a trial arm, with stratification by state. A trained healthcare professional will lead the following phases at each site: (1) undertake baseline clinical practice audits, (2) form multidisciplinary Implementation Teams, (3) identify target behaviours for practice change, (4) identify barriers to change, (5) generate intervention strategies, (6) support staff to implement interventions and (7) evaluate the effectiveness of the intervention using post-implementation clinical data. The theoretical and non-theoretical components of each trial arm will be distinguished in phases 4–5. Study outcomes include a LS referral process map for each hospital network, with evaluation of the proportion of patients with risk-appropriate completion of the LS referral pathway within 2 months of CRC resection pre and post implementation. Discussion This trial will determine the more effective approach for improving the detection of LS amongst patients with CRC, whilst also advancing understanding of the impact of theory-based implementation approaches in complex health systems and the feasibility of training healthcare professionals to use them. Insights gained will guide the development of future interventions to improve LS identification on a larger scale and across different contexts, as well as efforts to address the gap between evidence and practice in the rapidly evolving field of genomic research. Trial registration ANZCTR, ACTRN12618001072202. Registered on 27 June 2018. Electronic supplementary material The online version of this article (10.1186/s13063-019-3457-6) contains supplementary material, which is available to authorized users.

Summary Background Dietary intervention in cystic fibrosis (CF) has historically focused on high-energy diets to address malnutrition, with little attention on diet quality. With increased survival, CF complications such as impaired glucose tolerance (IGT) and cystic fibrosis related diabetes (CFRD) have increased in prevalence. In the absence of consensus on the management of IGT, the role of dietary intake, specifically carbohydrate quality, requires consideration. Aims The aims of this study were to: 1) determine nutritional quality of dietary intake at an adult CF clinic and compare this to the Australian Dietary Guidelines 2) explore relationships between dietary intake, including glycaemic index (GI) and glycaemic load (GL), and glucose response variables using continuous glucose monitoring (CGM). Methods Adults attending a Sydney hospital were recruited to undergo CGM for five-seven days and record dietary intake using a food record over the CGM period. The relationship between variables of dietary intake, including GI and GL and variables of glycaemic response, including mean amplitude of glycaemic excursions (MAGE), percentage of time in hyperglycaemic and euglycaemic range, were determined. Results Eighteen participants completed the study with 87 full days of dietary and CGM data. Dietary intake was higher than recommendations in the Australian Dietary Guidelines in relation to grains and protein foods and only slightly higher in saturated fat. Bivariate correlations showed dietary GI was significantly positively associated with percentage of time in hyperglycaemic range. Dietary GL was significantly associated with SD, MAGE and percentage of time in euglycaemic range on CGM. Results remained significant when controlled for energy intake in partial correlation analyses. Conclusions This study suggests GI and GL may be important dietary factors influencing glucose metabolism in CF. Further studies exploring low GI or GL diets as a dietary intervention in CF are the next step.