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Pancreatic Neoplasms: HELP
Articles by Anthony J. Gill
Based on 59 articles published since 2010
(Why 59 articles?)
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Between 2010 and 2020, A. J. Gill wrote the following 59 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Review The Evolving Understanding of the Molecular and Therapeutic Landscape of Pancreatic Ductal Adenocarcinoma. 2018

Parkin, Ashleigh / Man, Jennifer / Chou, Angela / Nagrial, Adnan M / Samra, Jaswinder / Gill, Anthony J / Timpson, Paul / Pajic, Marina. ·The Kinghorn Cancer Centre, The Garvan Institute of Medical Research, 384 Victoria St, Darlinghurst, Sydney, NSW 2010, Australia. a.parkin@garvan.org.au. · The Kinghorn Cancer Centre, The Garvan Institute of Medical Research, 384 Victoria St, Darlinghurst, Sydney, NSW 2010, Australia. j.man@garvan.org.au. · The Kinghorn Cancer Centre, The Garvan Institute of Medical Research, 384 Victoria St, Darlinghurst, Sydney, NSW 2010, Australia. a.chou@garvan.org.au. · University of Sydney, Sydney, NSW 2006, Australia. a.chou@garvan.org.au. · The Kinghorn Cancer Centre, The Garvan Institute of Medical Research, 384 Victoria St, Darlinghurst, Sydney, NSW 2010, Australia. Adnan.Nagrial@health.nsw.gov.au. · Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, NSW 2145, Australia. Adnan.Nagrial@health.nsw.gov.au. · Department of Surgery, Royal North Shore Hospital, St Leonards, Sydney, NSW 2065, Australia. jas.samra@bigpond.com. · The Kinghorn Cancer Centre, The Garvan Institute of Medical Research, 384 Victoria St, Darlinghurst, Sydney, NSW 2010, Australia. Anthony.Gill@health.nsw.gov.au. · University of Sydney, Sydney, NSW 2006, Australia. Anthony.Gill@health.nsw.gov.au. · Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, Sydney, NSW 2065, Australia. Anthony.Gill@health.nsw.gov.au. · Cancer Diagnosis and Pathology Research Group, Kolling Institute of Medical Research, St Leonards, NSW 2065, Australia. Anthony.Gill@health.nsw.gov.au. · The Kinghorn Cancer Centre, The Garvan Institute of Medical Research, 384 Victoria St, Darlinghurst, Sydney, NSW 2010, Australia. p.timpson@garvan.org.au. · St Vincent's Clinical School, Faculty of Medicine, University of NSW, Sydney, NSW 2010, Australia. p.timpson@garvan.org.au. · The Kinghorn Cancer Centre, The Garvan Institute of Medical Research, 384 Victoria St, Darlinghurst, Sydney, NSW 2010, Australia. m.pajic@garvan.org.au. · St Vincent's Clinical School, Faculty of Medicine, University of NSW, Sydney, NSW 2010, Australia. m.pajic@garvan.org.au. ·Diseases · Pubmed #30428574.

ABSTRACT: Pancreatic cancer is the third leading cause of cancer-related deaths, characterised by poor survival, marked molecular heterogeneity and high intrinsic and acquired chemoresistance. Only 10⁻20% of pancreatic cancer patients present with surgically resectable disease and even then, 80% die within 5 years. Our increasing understanding of the genomic heterogeneity of cancer suggests that the failure of definitive clinical trials to demonstrate efficacy in the majority of cases is likely due to the low proportion of responsive molecular subtypes. As a consequence, novel treatment strategies to approach this disease are urgently needed. Significant developments in the field of precision oncology have led to increasing molecular stratification of cancers into subtypes, where individual cancers are selected for optimal therapy depending on their molecular or genomic fingerprint. This review provides an overview of the current status of clinically used and emerging treatment strategies, and discusses the advances in and the potential for the implementation of precision medicine in this highly lethal malignancy, for which there are currently no curative systemic therapies.

2 Review Understanding the Pathophysiology of Psychological Distress and Pancreatic Cancer: A Systematic Review. 2018

Bettison, Travis M / Nahm, Christopher B / Gill, Anthony J / Mittal, Anubhav / Malhi, Gin S / Samra, Jaswinder S. · ·Pancreas · Pubmed #29521940.

ABSTRACT: BACKGROUND: Psychological distress is highly prevalent in patients with pancreatic cancer (PC), yet little is known about the pathophysiology underlying the relationship between these 2 diseases. Our aim was to systematically review the evidence examining the pathophysiological mechanisms of the association between PC and psychological distress. METHODS: A systematic review of the literature was conducted using MEDLINE, Embase, PsychINFO, and CINAHL databases and reported according to the preferred reporting items for systematic reviews and meta-analyses guidelines. Studies examining the pathophysiological mechanisms between PC and psychological distress were included for analysis. RESULTS: Eight studies were identified that fulfilled inclusion criteria. Four mechanisms were identified accounting for the possible relationship between psychological distress and PC, including (1) stress-induced β-adrenergic signaling, (2) interleukin-6-mediated effects, (3) kynurenine pathway upregulation, and (4) altered cerebral glucose metabolism. CONCLUSIONS: The relationship between psychological distress and PC is complex, and our understanding of these mechanisms may have implications for holistic clinical management and oncological outcome. The evidence exploring the pathophysiology of this interaction is sparse, but most well established with regard to the stress-induced β-adrenergic signaling mechanism. Further studies in larger cohorts are required to elucidate the relationship between PC and psychological distress to be able to identify therapeutic targets for both conditions.

3 Review Ampullary cancer of intestinal origin and duodenal cancer - A logical clinical and therapeutic subgroup in periampullary cancer. 2017

Chandrasegaram, Manju D / Gill, Anthony J / Samra, Jas / Price, Tim / Chen, John / Fawcett, Jonathan / Merrett, Neil D. ·the Prince Charles Hospital, Brisbane, Queensland 4032, Australia. · Sydney Medical School, University of Sydney, New South Wales 2006, Australia. · Queen Elizabeth Hospital, Adelaide, South Australia 5011, Australia. · Flinders Medical Centre, Adelaide, South Australia 5042, Australia. · School of Medicine, University of Queensland, Queensland 4006, Australia. · Department of Upper GI Surgery, Bankstown Hospital, Sydney, New South Wales 2200, Australia. ·World J Gastrointest Oncol · Pubmed #29085567.

ABSTRACT: Periampullary cancers include pancreatic, ampullary, biliary and duodenal cancers. At presentation, the majority of periampullary tumours have grown to involve the pancreas, bile duct, ampulla and duodenum. This can result in difficulty in defining the primary site of origin in all but the smallest tumors due to anatomical proximity and architectural distortion. This has led to variation in the reported proportions of resected periampullary cancers. Pancreatic cancer is the most common cancer resected with a pancreaticoduodenectomy followed by ampullary (16%-50%), bile duct (5%-39%), and duodenal cancer (3%-17%). Patients with resected duodenal and ampullary cancers have a better reported median survival (29-47 mo and 22-54 mo) compared to pancreatic cancer (13-19 mo). The poorer survival with pancreatic cancer relates to differences in tumour characteristics such as a higher incidence of nodal, neural and vascular invasion. While small ampullary cancers can present early with biliary obstruction, pancreatic cancers need to reach a certain size before biliary obstruction ensues. This larger size at presentation contributes to a higher incidence of resection margin involvement in pancreatic cancer. Ampullary cancers can be subdivided into intestinal or pancreatobiliary subtype cancers with histomolecular staining. This avoids relying on histomorphology alone, as even some poorly differentiated cancers preserve the histomolecular profile of their mucosa of origin. Histomolecular profiling is superior to anatomic location in prognosticating survival. Ampullary cancers of intestinal subtype and duodenal cancers are similar in their intestinal origin and form a logical clinical and therapeutic subgroup of periampullary cancers. They respond to 5-FU based chemotherapeutic regimens such as capecitabine-oxaliplatin. Unlike pancreatic cancers,

4 Review Impact of perioperative fluid administration on early outcomes after pancreatoduodenectomy: A meta-analysis. 2017

Huang, Yeqian / Chua, Terence C / Gill, Anthony J / Samra, Jaswinder S. ·Department of Gastrointestinal Surgery, Royal North Shore Hospital, St Leonards, NSW, Australia; Discipline of Surgery, University of Sydney, Sydney, NSW, Australia. · Department of Gastrointestinal Surgery, Royal North Shore Hospital, St Leonards, NSW, Australia; Discipline of Surgery, University of Sydney, Sydney, NSW, Australia. Electronic address: terence.c.chua@gmail.com. · Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, St Leonards, NSW, Australia; University of Sydney, Sydney, NSW, Australia; Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, NSW, Australia. · Department of Gastrointestinal Surgery, Royal North Shore Hospital, St Leonards, NSW, Australia; Discipline of Surgery, University of Sydney, Sydney, NSW, Australia; Macquarie University Hospital, Macquarie University, NSW, Australia. ·Pancreatology · Pubmed #28285959.

ABSTRACT: BACKGROUND: Pancreatoduodenectomy (PD) remains a technically challenging surgical procedure with morbidity rates ranging between 30 and 50%. It is suggested that the liberal use of fluids is associated with a poor perioperative outcome. This review examines the impact of fluid administration on outcomes after PD. METHODS: A literature search was conducted using the MEDLINE, EMBASE and PubMed database (June 1966-June 2016). Studies identified were appraised with standard selection criteria. Data points were extracted and meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). RESULTS: Eleven studies, seven retrospective trials and four randomized control trials comprising 2842 patients were included. Seven studies were meta-analyzed. There was no difference in length of hospital stay (P = 0.25), pancreas specific complications (P = 0.20), pulmonary (P = 0.58), cardiovascular (P = 0.75), gastrointestinal (P = 0.49), hepatobiliary (P = 0.53), urogenital (P = 0.42), wound complication (P = 0.79), reoperation rate (P = 0.69), overall morbidity (P = 0.18), major morbidity (P = 0.91), 30-day mortality (P = 0.07) and 90-day mortality (P = 0.58) in low or high fluid groups. CONCLUSION: The current available data fails to demonstrate an association between the amount of perioperative intravenous fluid administration and postoperative complications in patients undergoing PD.

5 Review Systematic Review and Meta-Analysis of Enucleation Versus Standardized Resection for Small Pancreatic Lesions. 2016

Chua, Terence C / Yang, Timothy X / Gill, Anthony J / Samra, Jaswinder S. ·Department of Gastrointestinal Surgery, Royal North Shore Hospital, St Leonards, NSW, Australia. terence.c.chua@gmail.com. · Discipline of Surgery, University of Sydney, Sydney, NSW, Australia. terence.c.chua@gmail.com. · Department of Gastrointestinal Surgery, Royal North Shore Hospital, St Leonards, NSW, Australia. · Discipline of Surgery, University of Sydney, Sydney, NSW, Australia. · Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, St Leonards, NSW, Australia. · University of Sydney, Sydney, NSW, Australia. · Deparment of Anatomical Pathology, Royal North Shore Hospital, St Leonards, NSW, Australia. · Macquarie University Hospital, Macquarie University, Sydney, NSW, Australia. jas.samra@bigpond.com. · Department of Gastrointestinal Surgery, Royal North Shore Hospital, University of Sydney, Sydney, NSW, Australia. jas.samra@bigpond.com. ·Ann Surg Oncol · Pubmed #26307231.

ABSTRACT: BACKGROUND: The appropriate surgical strategy in patients with small pancreatic lesions of low malignant potential, such as pancreatic neuroendocrine tumors, remains unknown. Increasing reports suggest limited pancreatic surgery may be a safe option for parenchymal preservation. METHODS: PubMed and MEDLINE were searched in the English literature for studies from January 2000 to February 2015 examining enucleation for pancreatic lesions that were single-arm and comparative studies (versus resection). Single-arm enucleation studies were systematically reviewed. Comparative studies were included for meta-analysis. Endpoints include safety, complications, mortality, survival, and parenchymal-related outcomes. RESULTS: Thirteen studies comprising of 1101 patients undergoing enucleation were included. Seven studies were comparative studies of enucleation and standardized pancreatic resection. Enucleation was a shorter procedure (pooled mean differences (MD) = 109, 95 % confidence interval (CI) 105-114; Z = 46.37; P < 0.001) associated with less blood loss (pooled MD = 314, 95 % CI 297-330; Z = 37.47; P < 0.001). Both enucleation and resection had similar mortality and complication rates, but the rate of pancreatic fistula (all grades) (pooled odds ratio (OR) = 1.99; 95 % CI 1.2-3.4; Z = 2.57; P = 0.01] and rate of pancreatic fistula (grade B/C) (pooled OR = 1.58; 95 % CI 1.0-2.5; Z = 2.06; P = 0.04) was higher in the enucleation group. Enucleation resulted in lower rates of endocrine (pooled OR = 0.22; 95 % CI 0.1-0.5; Z = 3.21; P = 0.001) and exocrine (pooled OR = 0.07; 95 % CI 0.02-0.2; Z = 5.08; P < 0.001) insufficiency. The median 5-year survival was 95 % (range 93-98) and 84 % (range 79-90). CONCLUSIONS: Enucleation appears to be a safe procedure and achieves parenchymal preservation for small pancreatic lesions of low malignant potential. Its oncologic efficacy compared with standardized pancreatic resection with respect to long-term survival and recurrences have not been reported adequately and hence may not be concluded as being comparable.

6 Review Meta-analysis of radical resection rates and margin assessment in pancreatic cancer. 2015

Chandrasegaram, M D / Goldstein, D / Simes, J / Gebski, V / Kench, J G / Gill, A J / Samra, J S / Merrett, N D / Richardson, A J / Barbour, A P. ·National Health and Medical Research Clinical Trials Centre, University of Sydney, New South Wales, Australia. · Discipline of Surgery, University of Adelaide, Adelaide, South Australia, Australia. · Department of Surgery, Prince Charles Hospital, Queensland, Australia. · Department of Medical Oncology, Prince of Wales Hospital, Prince of Wales Clinical School University of New South Wales, New South Wales, Australia. · Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, New South Wales, Australia. · Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia. · Cancer Diagnosis and Pathology Research Group, Kolling Institute of Medical Research, University of Sydney, New South Wales, Australia. · Department of Surgery, Royal North Shore Hospital, New South Wales, Australia. · Discipline of Surgery, School of Medicine, University of Western Sydney, New South Wales, Australia. · Department of Surgery, Westmead Hospital, Westmead, New South Wales, Australia. · University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland, Australia. ·Br J Surg · Pubmed #26350029.

ABSTRACT: BACKGROUND: R0 resection rates (complete tumour removal with negative resection margins) in pancreatic cancer are 70-80 per cent when a 0-mm margin is used, declining to 15-24 per cent with a 1-mm margin. This review evaluated the R0 resection rates according to different margin definitions and techniques. METHODS: Three databases (MEDLINE from 1946, PubMed from 1946 and Embase from 1949) were searched to mid-October 2014. The search terms included 'pancreatectomy OR pancreaticoduodenectomy' and 'margin'. A meta-analysis was performed with studies in three groups: group 1, axial slicing technique (minimum 1-mm margin); group 2, other slicing techniques (minimum 1-mm margin); and group 3, studies with minimum 0-mm margin. RESULTS: The R0 rates were 29 (95 per cent c.i. 26 to 32) per cent in group 1 (8 studies; 882 patients) and 49 (47 to 52) per cent in group 2 (6 studies; 1568 patients). The combined R0 rate (groups 1 and 2) was 41 (40 to 43) per cent. The R0 rate in group 3 (7 studies; 1926 patients) with a 0-mm margin was 72 (70 to 74) per cent The survival hazard ratios (R1 resection/R0 resection) revealed a reduction in the risk of death of at least 22 per cent in group 1, 12 per cent in group 2 and 23 per cent in group 3 with an R0 compared with an R1 resection. Local recurrence occurred more frequently with an R1 resection in most studies. CONCLUSION: Margin clearance definitions affect R0 resection rates in pancreatic cancer surgery. This review collates individual studies providing an estimate of achievable R0 rates, creating a benchmark for future trials.

7 Review von Hippel-Lindau syndrome. 2013

Chou, Angela / Toon, Christopher / Pickett, Justine / Gill, Anthony J. ·Department of Anatomical Pathology, St Vincents Hospital, Darlinghurst, NSW, Australia. ·Front Horm Res · Pubmed #23652669.

ABSTRACT: von Hippel-Lindau (VHL) disease is an autosomal-dominant familial cancer syndrome associated with mutations of the VHL tumor suppressor gene (3p25-26). Its estimated incidence ranges from 1 in 36,000 to 1 in 53,000 with a penetrance of up to 95% by age 60. Genotype-phenotype correlation divides VHL into two broad clinical subtypes. Type 1 VHL is predominantly associated with large deletion or truncation mutations which result in an encoded protein with very little or no activity. It is associated with retinal and CNS hemangioblastoma and renal cell carcinoma but not pheochromocytoma. Type 2 is usually associated with missense mutations encoding a protein with limited activity and includes pheochromocytoma. It is further classified into three other subtypes (2A, 2B, 2C) based on the presence of hemangioblastoma and renal cell carcinoma. Visceral cysts in the kidney, pancreas and epididymis, nonfunctioning pancreatic neuroendocrine tumors which often show distinctive clear cell cytology, endolymphatic sac tumors and head and neck paragangliomas are well recognized but less common presenting features. Surveillance of carriers can reduce the burden of disease and is best performed in specialist referral centers with due consideration given to both the complex molecular pathogenesis and psychosocial aspects of the disease.

8 Clinical Trial Precision Medicine for Advanced Pancreas Cancer: The Individualized Molecular Pancreatic Cancer Therapy (IMPaCT) Trial. 2015

Chantrill, Lorraine A / Nagrial, Adnan M / Watson, Clare / Johns, Amber L / Martyn-Smith, Mona / Simpson, Skye / Mead, Scott / Jones, Marc D / Samra, Jaswinder S / Gill, Anthony J / Watson, Nicole / Chin, Venessa T / Humphris, Jeremy L / Chou, Angela / Brown, Belinda / Morey, Adrienne / Pajic, Marina / Grimmond, Sean M / Chang, David K / Thomas, David / Sebastian, Lucille / Sjoquist, Katrin / Yip, Sonia / Pavlakis, Nick / Asghari, Ray / Harvey, Sandra / Grimison, Peter / Simes, John / Biankin, Andrew V / Anonymous5550827 / Anonymous5560827. ·The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia. Macarthur Cancer Therapy Centre, Campbelltown, New South Wales, Australia. Sydney Catalyst Translational Cancer Research Centre, University of Sydney, Camperdown, New South Wales, Australia. andrew.biankin@glasgow.ac.uk l.chantrill@garvan.org.au. · The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia. Sydney Catalyst Translational Cancer Research Centre, University of Sydney, Camperdown, New South Wales, Australia. Crown Princess Mary Cancer Centre, Westmead, New South Wales, Australia. · The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia. · The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia. Prince of Wales Hospital, Randwick, New South Wales, Australia. · Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland. · University of Sydney, New South Wales, Australia. Macquarie University Hospital, Sydney, New South Wales, Australia. · Department of Anatomical Pathology, Royal North Shore Hospital, Sydney, New South Wales, Australia. · The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia. Sydney Catalyst Translational Cancer Research Centre, University of Sydney, Camperdown, New South Wales, Australia. · The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia. Department of Anatomical Pathology, St. Vincent's Hospital, Darlinghurst, Sydney, New South Wales, Australia. · Department of Anatomical Pathology, St. Vincent's Hospital, Darlinghurst, Sydney, New South Wales, Australia. · Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland. Department of Surgery, Bankstown Hospital, Sydney, New South Wales, Australia. South Western Sydney Clinical School, Faculty of Medicine, University of NSW, Liverpool, New South Wales, Australia. West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom. · NHMRC Clinical Trials Centre, University of Sydney, Camperdown, New South Wales, Australia. · Sydney Catalyst Translational Cancer Research Centre, University of Sydney, Camperdown, New South Wales, Australia. NHMRC Clinical Trials Centre, University of Sydney, Camperdown, New South Wales, Australia. · Northern Sydney Cancer Centre, Royal North Shore Hospital, New South Wales, Australia. · Bankstown Cancer Centre, Bankstown, New South Wales, Australia. · Sydney Catalyst Translational Cancer Research Centre, University of Sydney, Camperdown, New South Wales, Australia. Chris O'Brien Lifehouse, Camperdown, New South Wales, Australia. · Sydney Catalyst Translational Cancer Research Centre, University of Sydney, Camperdown, New South Wales, Australia. NHMRC Clinical Trials Centre, University of Sydney, Camperdown, New South Wales, Australia. Chris O'Brien Lifehouse, Camperdown, New South Wales, Australia. · The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia. Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland. Department of Surgery, Bankstown Hospital, Sydney, New South Wales, Australia. South Western Sydney Clinical School, Faculty of Medicine, University of NSW, Liverpool, New South Wales, Australia. West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom. andrew.biankin@glasgow.ac.uk l.chantrill@garvan.org.au. ·Clin Cancer Res · Pubmed #25896973.

ABSTRACT: PURPOSE: Personalized medicine strategies using genomic profiling are particularly pertinent for pancreas cancer. The Individualized Molecular Pancreatic Cancer Therapy (IMPaCT) trial was initially designed to exploit results from genome sequencing of pancreatic cancer under the auspices of the International Cancer Genome Consortium (ICGC) in Australia. Sequencing revealed small subsets of patients with aberrations in their tumor genome that could be targeted with currently available therapies. EXPERIMENTAL DESIGN: The pilot stage of the IMPaCT trial assessed the feasibility of acquiring suitable tumor specimens for molecular analysis and returning high-quality actionable genomic data within a clinically acceptable timeframe. We screened for three molecular targets: HER2 amplification; KRAS wild-type; and mutations in DNA damage repair pathways (BRCA1, BRCA2, PALB2, ATM). RESULTS: Tumor biopsy and archived tumor samples were collected from 93 patients and 76 were screened. To date 22 candidate cases have been identified: 14 KRAS wild-type, 5 cases of HER2 amplification, 2 mutations in BRCA2, and 1 ATM mutation. Median time from consent to the return of validated results was 21.5 days. An inability to obtain a biopsy or insufficient tumor content in the available specimen were common reasons for patient exclusion from molecular analysis while deteriorating performance status prohibited a number of patients from proceeding in the study. CONCLUSIONS: Documenting the feasibility of acquiring and screening biospecimens for actionable molecular targets in real time will aid other groups embarking on similar trials. Key elements include the need to better prescreen patients, screen more patients, and offer more attractive clinical trial options.

9 Clinical Trial Distal pancreatectomy, splenectomy, and celiac axis resection (DPS-CAR): common hepatic arterial stump pressure should determine the need for arterial reconstruction. 2015

Mittal, Anubhav / de Reuver, Philip R / Shanbhag, Satya / Staerkle, Ralph F / Neale, Michael / Thoo, Catherine / Hugh, Thomas J / Gill, Anthony J / Samra, Jaswinder S. ·Department of Gastrointestinal Surgery, Royal North Shore Hospital and North Shore Private Hospital, University of Sydney, Sydney, New South Wales, Australia. · Department of Surgery, University of Auckland, Auckland, New Zealand. · Department of Vascular Surgery, Royal North Shore Hospital and North Shore Private Hospital, University of Sydney, Sydney, New South Wales, Australia. · Department of Anatomical Pathology, Royal North Shore Hospital and North Shore Private Hospital, University of Sydney, Sydney, New South Wales, Australia. · Department of Gastrointestinal Surgery, Royal North Shore Hospital and North Shore Private Hospital, University of Sydney, Sydney, New South Wales, Australia; Macquarie University Hospital, Macquarie University, Sydney, New South Wales, Australia. Electronic address: jas.samra@bigpond.com. ·Surgery · Pubmed #25532436.

ABSTRACT: BACKGROUND: Tumors arising in the neck and body of the pancreas often invade the common hepatic artery and celiac axis (CA), necessitating distal pancreatectomy, splenectomy, and celiac axis resection (DPS-CAR). In these patients, the need for revascularization of the common hepatic artery (CHA) can be avoided on the basis of the pressure change in the CHA after clamping of the CA. METHODS: All patients presenting to North Shore Hospital Campus of University of Sydney with advanced pancreatic malignancy of the neck and body between 2007 and 2014 were included in the study. The pressure in the CHA was measured pre- and postclamping of the CA; a decrease of more than 25% in the mean arterial pressure necessitated vascular reconstruction of the CHA. RESULTS: Seven patients underwent a DPS-CAR between 2007 and 2014. Arterial reconstruction was required in 2 patients based on a decrease of >25% mean arterial pressure in the CHA after clamping the CA. There was no in hospital or 90-day mortality, and no patients developed ischemic hepatitis. CONCLUSION: A single-stage DPS-CAR with selective arterial reconstruction based on the CHA pressure change after clamping the CA is a safe approach.

10 Article Pancreatic resection in patients with synchronous extra-pancreatic malignancy: outcomes and complications. 2020

Mehta, Shreya / Tan, Grace I / Nahm, Christopher B / Chua, Terence C / Pearson, Andrew / Gill, Anthony J / Samra, Jaswinder S / Mittal, Anubhav. ·Upper Gastrointestinal Surgical Unit, Royal North Shore Hospital, Sydney, New South Wales, Australia. · Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia. · Department of Surgery, Logan Hospital, Metro South Health, Logan City, Queensland, Australia. · School of Medicine, Griffith University, Gold Coast, Queensland, Australia. · Cancer Diagnosis and Pathology Group, Kolling Institute, Royal North Shore Hospital, Sydney, New South Wales, Australia. · Macquarie University Hospital, Macquarie University, Sydney, New South Wales, Australia. ·ANZ J Surg · Pubmed #31943690.

ABSTRACT: BACKGROUND: Patients may present with a resectable pancreatic tumour in the context of a concurrent primary extra-pancreatic malignancy. These patients pose a dilemma regarding their suitability for surgery. We evaluated our experience with such patients who underwent pancreatic resection with curative intent and detailed their outcomes and rationale for surgical decision-making. METHODS: A retrospective review of patients with pancreatic concurrent extra-pancreatic primary malignancy who underwent pancreatic resection at our institution over a 12-year period (2005-2016) was performed. Clinical, histopathological and perioperative outcomes were reviewed. RESULTS: Ten patients with a median age of 74 years (40-85 years) were identified. Secondary primary tumours included thyroid (n = 2), gastrointestinal (n = 4), small bowel neuroendocrine (n = 1), renal (n = 1) and haematological malignancies (n = 2). Pancreatic tumours included pancreatic ductal adenocarcinomas (n = 6), solid pseudopapillary neoplasms (n = 2) and ampullary carcinomas (n = 2). After a median follow up of 41.3 months (31.3-164 months), 8 of 10 patients were still alive. Two patients died due to metastatic disease from the secondary malignancy (small bowel neuroendocrine tumour and sigmoid colon adenocarcinoma). The post-operative complication rate was 30% with no perioperative 90-day mortality. CONCLUSION: Selected patients with a pancreatic and concurrent primary extra-pancreatic malignancy may undergo curative pancreatic resection with favourable outcomes.

11 Article International validation and update of the Amsterdam model for prediction of survival after pancreatoduodenectomy for pancreatic cancer. 2019

van Roessel, Stijn / Strijker, Marin / Steyerberg, Ewout W / Groen, Jesse V / Mieog, J Sven / Groot, Vincent P / He, Jin / De Pastena, Matteo / Marchegiani, Giovanni / Bassi, Claudio / Suhool, Amal / Jang, Jin-Young / Busch, Olivier R / Halimi, Asif / Zarantonello, Laura / Groot Koerkamp, Bas / Samra, Jaswinder S / Mittal, Anubhav / Gill, Anthony J / Bolm, Louisa / van Eijck, Casper H / Abu Hilal, Mohammed / Del Chiaro, Marco / Keck, Tobias / Alseidi, Adnan / Wolfgang, Christopher L / Malleo, Giuseppe / Besselink, Marc G. ·Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, the Netherlands. · Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands. · Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands. · Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Surgery, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy. · Department of Surgery, University Hospital Southampton NHS Foundation Trust, Southampton, UK. · Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea. · Pancreatic Surgery Unit, Division of Surgery, Karolinska Institute at Center for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden. · Department of Surgery, Erasmus Medical Center, Erasmus University Rotterdam, Rotterdam, the Netherlands. · Department of Surgery, Royal North Shore Hospital, St Leonards, University of Sydney, Sydney, NSW, Australia. · Cancer Diagnosis and Pathology Group Kolling Institute of Medical Research and University of Sydney, Sydney, NSW, Australia. · Department of Surgery, Universitätsklinikum Schleswig-Holstein, Lübeck, Germany. · Division of Surgical Oncology, Department of Surgery, University of Colorado at Denver-Anschutz Medical Campus, Aurora, CO, USA. · Section of Hepato-Pancreato-Biliary & Endocrine Surgery, Virginia Mason Medical Center, Seattle, WA, USA. · Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, the Netherlands. Electronic address: m.g.besselink@amsterdamumc.nl. ·Eur J Surg Oncol · Pubmed #31924432.

ABSTRACT: BACKGROUND: The objective of this study was to validate and update the Amsterdam prediction model including tumor grade, lymph node ratio, margin status and adjuvant therapy, for prediction of overall survival (OS) after pancreatoduodenectomy for pancreatic cancer. METHODS: We included consecutive patients who underwent pancreatoduodenectomy for pancreatic cancer between 2000 and 2017 at 11 tertiary centers in 8 countries (USA, UK, Germany, Italy, Sweden, the Netherlands, Korea, Australia). Model performance for prediction of OS was evaluated by calibration statistics and Uno's C-statistic for discrimination. Validation followed the TRIPOD statement. RESULTS: Overall, 3081 patients (53% male, median age 66 years) were included with a median OS of 24 months, of whom 38% had N2 disease and 77% received adjuvant chemotherapy. Predictions of 3-year OS were fairly similar to observed OS with a calibration slope of 0.72. Statistical updating of the model resulted in an increase of the C-statistic from 0.63 to 0.65 (95% CI 0.64-0.65), ranging from 0.62 to 0.67 across different countries. The area under the curve for the prediction of 3-year OS was 0.71 after updating. Median OS was 36, 25 and 15 months for the low, intermediate and high risk group, respectively (P < 0.001). CONCLUSIONS: This large international study validated and updated the Amsterdam model for survival prediction after pancreatoduodenectomy for pancreatic cancer. The model incorporates readily available variables with a fairly accurate model performance and robustness across different countries, while novel markers may be added in the future. The risk groups and web-based calculator www.pancreascalculator.com may facilitate use in daily practice and future trials.

12 Article CAF hierarchy driven by pancreatic cancer cell p53-status creates a pro-metastatic and chemoresistant environment via perlecan. 2019

Vennin, Claire / Mélénec, Pauline / Rouet, Romain / Nobis, Max / Cazet, Aurélie S / Murphy, Kendelle J / Herrmann, David / Reed, Daniel A / Lucas, Morghan C / Warren, Sean C / Elgundi, Zehra / Pinese, Mark / Kalna, Gabriella / Roden, Daniel / Samuel, Monisha / Zaratzian, Anaiis / Grey, Shane T / Da Silva, Andrew / Leung, Wilfred / Anonymous561018 / Mathivanan, Suresh / Wang, Yingxiao / Braithwaite, Anthony W / Christ, Daniel / Benda, Ales / Parkin, Ashleigh / Phillips, Phoebe A / Whitelock, John M / Gill, Anthony J / Sansom, Owen J / Croucher, David R / Parker, Benjamin L / Pajic, Marina / Morton, Jennifer P / Cox, Thomas R / Timpson, Paul. ·The Garvan Institute of Medical Research & The Kinghorn Cancer Centre, Sydney, NSW, 2010, Australia. · St Vincent's Clinical School, Faculty of Medicine, University of New South Wales Sydney, Sydney, NSW, 2010, Australia. · Molecular Pathology department, the Netherlands Cancer Institute, Amsterdam, 1066CX, the Netherlands. · Graduate school of Biomedical Engineering, University of New South Wales Sydney, Sydney, NSW, 2052, Australia. · Cancer Research UK Beatson Institute, Glasgow Scotland, G61 BD, UK. · Department of Physiology, Anatomy and Microbiology, School of Life Sciences, La Trobe University, Bundoora, VIC, 3086, Australia. · Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA. · Department of Bioengineering, Institute of Engineering in Medicine, University of California, San Diego, CA, 92121, USA. · Children's Medical Research Institute, University of Sydney, Sydney, NSW, 2006, Australia. · Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, 9054, New Zealand. · Maurice Wilkins Centre, University of Otago, Dunedin, 9054, New Zealand. · Biomedical imaging facility, Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW, Australia. · Pancreatic Cancer Translational Research Group, Lowy Cancer Research Centre, School of Medical Sciences, University of New South Wales, Sydney, NSW, 2052, Australia. · Australian Centre for Nanomedicine, University of New South Wales, Sydney, NSW, 2052, Australia. · Sydney Medical School, University of Sydney, Sydney, NSW, 2006, Australia. · NSW Health Pathology, Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, Sydney, NSW, 2065, Australia. · Cancer Diagnosis and Pathology Research Group, Kolling Institute of Medical Research, St Leonards, NSW, 2065, Australia. · Schools of Life and Environmental Sciences, the Charles Perkin Centre, the University of Sydney, Sydney, NSW, 2006, Australia. · The Garvan Institute of Medical Research & The Kinghorn Cancer Centre, Sydney, NSW, 2010, Australia. t.cox@garvan.org.au. · St Vincent's Clinical School, Faculty of Medicine, University of New South Wales Sydney, Sydney, NSW, 2010, Australia. t.cox@garvan.org.au. · The Garvan Institute of Medical Research & The Kinghorn Cancer Centre, Sydney, NSW, 2010, Australia. p.timpson@garvan.org.au. · St Vincent's Clinical School, Faculty of Medicine, University of New South Wales Sydney, Sydney, NSW, 2010, Australia. p.timpson@garvan.org.au. ·Nat Commun · Pubmed #31406163.

ABSTRACT: Heterogeneous subtypes of cancer-associated fibroblasts (CAFs) coexist within pancreatic cancer tissues and can both promote and restrain disease progression. Here, we interrogate how cancer cells harboring distinct alterations in p53 manipulate CAFs. We reveal the existence of a p53-driven hierarchy, where cancer cells with a gain-of-function (GOF) mutant p53 educate a dominant population of CAFs that establish a pro-metastatic environment for GOF and null p53 cancer cells alike. We also demonstrate that CAFs educated by null p53 cancer cells may be reprogrammed by either GOF mutant p53 cells or their CAFs. We identify perlecan as a key component of this pro-metastatic environment. Using intravital imaging, we observe that these dominant CAFs delay cancer cell response to chemotherapy. Lastly, we reveal that depleting perlecan in the stroma combined with chemotherapy prolongs mouse survival, supporting it as a potential target for anti-stromal therapies in pancreatic cancer.

13 Article MiRNA-3653 Is a Potential Tissue Biomarker for Increased Metastatic Risk in Pancreatic Neuroendocrine Tumours. 2019

Gill, Preetjote / Kim, Edward / Chua, Terence C / Clifton-Bligh, Roderick J / Nahm, Christopher B / Mittal, Anubhav / Gill, Anthony J / Samra, Jaswinder S. ·Upper Gastrointestinal Surgical Unit, Royal North Shore Hospital, Sydney, Australia. · Sydney Medical School, University of Sydney, Sydney, Australia. · Cancer Genetics, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, Australia. · Department of Endocrinology, Royal North Shore Hospital, Sydney, NSW, 2065, Australia. · Australian Pancreatic Centre, St Leonards, Sydney, Australia. · Sydney Medical School, University of Sydney, Sydney, Australia. affgill@med.usyd.edu.au. · Australian Pancreatic Centre, St Leonards, Sydney, Australia. affgill@med.usyd.edu.au. · NSW Health Pathology, Department of Anatomical Pathology, Royal North Shore Hospital, Sydney, NSW, Australia. affgill@med.usyd.edu.au. · Cancer Diagnosis and Pathology Research Group, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, NSW, Australia. affgill@med.usyd.edu.au. · Upper Gastrointestinal Surgical Unit, Royal North Shore Hospital, Sydney, Australia. jas.samra@bigpond.com. · Sydney Medical School, University of Sydney, Sydney, Australia. jas.samra@bigpond.com. · Australian Pancreatic Centre, St Leonards, Sydney, Australia. jas.samra@bigpond.com. · Faculty of Medical and Health Sciences, Macquarie University, Sydney, Australia. jas.samra@bigpond.com. ·Endocr Pathol · Pubmed #30767148.

ABSTRACT: Pancreatic neuroendocrine tumours (PNETs) are relatively uncommon, accounting for 1-2% of all pancreatic neoplasms. Tumour grade (based on the Ki67 proliferative index and mitotic rate) is associated with metastatic risk across large cohorts; however, predicting the behaviour of individual tumours can be difficult. Therefore, any tool which could further stratify metastatic risk may be clinically beneficial. We sought to investigate microRNA (miRNA) expression as a marker of metastatic disease in PNETs. Tumours from 37 patients, comprising 23 with locoregional disease (L) and 14 with distant metastases (DM), underwent miRNA profiling. In total 506 miRNAs were differentially expressed between the L and DM groups, with four miRNAs (miR-3653 upregulated, and miR-4417, miR-574-3p and miR-664b-3p downregulated) showing statistical significance. A database search demonstrated that miRNA-3653 was associated with ATRX abnormalities. Mean survival between the two groups was correlated with mean expression of miRNA-3653; however, this did not reach statistical significance (p = 0.204). Although this is a small study, we conclude that miRNA-3653 upregulation may be associated with an increased risk of metastatic disease in PNETS, perhaps through interaction with ATRX and the alternate lengthening of telomeres pathway.

14 Article Management of post-pancreatectomy haemorrhage using resuscitative endovascular balloon occlusion of the aorta. 2019

Singh, Gurkirat / Nahm, Christopher B / Jamieson, Nigel B / Chua, Terence C / Wong, Shen / Thoo, Cathy / Mittal, Anubhav / Gill, Anthony J / Samra, Jaswinder S. ·Upper Gastrointestinal Surgical Unit, Royal North Shore Hospital, Sydney, Australia. · School of Medicine, Dentistry and Nursing, University of Glasgow, Glasgow, Scotland. · Department of Vascular Surgery, Royal North Shore Hospital, Sydney, Australia. · Australian Pancreatic Centre, St Leonards, Sydney, Australia. · Department of Anatomical Pathology, Royal North Shore Hospital, Sydney, NSW, Australia. · Cancer Diagnosis and Pathology Research Group, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia. · Upper Gastrointestinal Surgical Unit, Royal North Shore Hospital, Sydney, Australia. jas.samra@bigpond.com. · Australian Pancreatic Centre, St Leonards, Sydney, Australia. jas.samra@bigpond.com. · Faculty of Medical and Health Sciences, Macquarie University, Sydney, Australia. jas.samra@bigpond.com. ·Langenbecks Arch Surg · Pubmed #30758668.

ABSTRACT: BACKGROUND: Delayed massive post-pancreatectomy haemorrhage (PPH) is a highly lethal complication after pancreatectomy. Angiographic procedures have led to improved outcomes in the management of these patients. In the setting of an acute haemorrhage, laparotomy and packing are often required to help stablise the patient. However, re-operative surgery in the post-pancreatectomy setting is technically challenging. METHODS: A novel strategy of incorporating the resuscitative endovascular balloon occlusion of the aorta (REBOA) is described. RESULTS: Two patients where the specific application of this technique uses the REBOA were described. CONCLUSION: The REBOA serves as a useful adjunct in haemorrhage control and haemodynamic stablisation to allow successful management of delayed massive PPH.

15 Article Biomarker panel predicts survival after resection in pancreatic ductal adenocarcinoma: A multi-institutional cohort study. 2019

Nahm, Christopher B / Turchini, John / Jamieson, Nigel / Moon, Elizabeth / Sioson, Loretta / Itchins, Malinda / Arena, Jennifer / Colvin, Emily / Howell, Viive M / Pavlakis, Nick / Clarke, Stephen / Samra, Jaswinder S / Gill, Anthony J / Mittal, Anubhav. ·The University of Sydney Northern Clinical School, Sydney, NSW, Australia; Upper Gastrointestinal Surgical Unit, Royal North Shore Hospital, St. Leonards, NSW Australia; Bill Walsh Translational Cancer Research Laboratory, Kolling Institute, University of Sydney, Sydney, NSW, Australia; Sydney Vital, Kolling Institute, Sydney, NSW, Australia. · The University of Sydney Northern Clinical School, Sydney, NSW, Australia; Cancer Diagnosis and Pathology, Kolling Institute, University of Sydney, Sydney, NSW, Australia. · Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, UK. · Bill Walsh Translational Cancer Research Laboratory, Kolling Institute, University of Sydney, Sydney, NSW, Australia; Sydney Vital, Kolling Institute, Sydney, NSW, Australia. · Cancer Diagnosis and Pathology, Kolling Institute, University of Sydney, Sydney, NSW, Australia; Sydney Vital, Kolling Institute, Sydney, NSW, Australia. · The University of Sydney Northern Clinical School, Sydney, NSW, Australia; Bill Walsh Translational Cancer Research Laboratory, Kolling Institute, University of Sydney, Sydney, NSW, Australia; Department of Medical Oncology, Royal North Shore Hospital, St. Leonards, NSW, Australia; Sydney Vital, Kolling Institute, Sydney, NSW, Australia. · Department of Medical Oncology, Royal North Shore Hospital, St. Leonards, NSW, Australia; Australian Pancreatic Centre, Royal North Shore Hospital, St. Leonards, NSW, Australia. · The University of Sydney Northern Clinical School, Sydney, NSW, Australia; Bill Walsh Translational Cancer Research Laboratory, Kolling Institute, University of Sydney, Sydney, NSW, Australia; Sydney Vital, Kolling Institute, Sydney, NSW, Australia. · The University of Sydney Northern Clinical School, Sydney, NSW, Australia; Bill Walsh Translational Cancer Research Laboratory, Kolling Institute, University of Sydney, Sydney, NSW, Australia; Department of Medical Oncology, Royal North Shore Hospital, St. Leonards, NSW, Australia; Sydney Vital, Kolling Institute, Sydney, NSW, Australia; Australian Pancreatic Centre, Royal North Shore Hospital, St. Leonards, NSW, Australia. · The University of Sydney Northern Clinical School, Sydney, NSW, Australia; Upper Gastrointestinal Surgical Unit, Royal North Shore Hospital, St. Leonards, NSW Australia; Sydney Vital, Kolling Institute, Sydney, NSW, Australia; Australian Pancreatic Centre, Royal North Shore Hospital, St. Leonards, NSW, Australia; Faculty of Medical and Health Sciences, Macquarie University, Sydney, NSW, Australia. · The University of Sydney Northern Clinical School, Sydney, NSW, Australia; Cancer Diagnosis and Pathology, Kolling Institute, University of Sydney, Sydney, NSW, Australia; Australian Pancreatic Centre, Royal North Shore Hospital, St. Leonards, NSW, Australia; Faculty of Medical and Health Sciences, Macquarie University, Sydney, NSW, Australia. · The University of Sydney Northern Clinical School, Sydney, NSW, Australia; Upper Gastrointestinal Surgical Unit, Royal North Shore Hospital, St. Leonards, NSW Australia; Australian Pancreatic Centre, Royal North Shore Hospital, St. Leonards, NSW, Australia; Faculty of Medical and Health Sciences, Macquarie University, Sydney, NSW, Australia. Electronic address: anubhav.mittal@sydney.edu.au. ·Eur J Surg Oncol · Pubmed #30348604.

ABSTRACT: BACKGROUND: Up to 60% of patients who undergo curative-intent pancreatic ductal adenocarcinoma (PDAC) resection experience disease recurrence within six months. We recently published a systematic review of prognostic immunohistochemical biomarkers in PDAC and shortlisted a panel of those reported with the highest level of evidence, including p53, p16, Ca-125, S100A4, FOXC1, EGFR, mesothelin, CD24 and UPAR. This study aims to discover and validate the prognostic significance of a combinatorial panel of tumor biomarkers in patients with resected PDAC. METHODS: Patients who underwent PDAC resection were included from a single institution discovery cohort and a multi-institutional validation cohort. Tumors in the discovery cohort were stained immunohistochemically for all nine shortlisted biomarkers. Biomarkers significantly associated with overall survival (OS) were reevaluated as a combinatorial panel in both discovery and validation cohorts for its prognostic significance. RESULTS: 224 and 191 patients were included in the discovery and validation cohorts, respectively. In both cohorts, S100A4, Ca-125 and mesothelin expression were associated with shorter OS. In both cohorts, the number of these biomarkers expressed was significantly associated with OS (discovery cohort 36.8 vs. 26.4 vs 16.3 vs 12.8 months, P < 0.001; validation cohort 25.2 vs 18.3 vs 13.6 vs 11.9 months, P = 0.008 for expression of zero, one, two and three biomarkers, respectively). On multivariable analysis, expression of at least one of three biomarkers was independently associated with shorter OS. CONCLUSION: Combinations of S100A4, Ca-125 and mesothelin expression stratify survival after resection of localized PDAC. Co-expression of all three biomarkers is associated with the poorest prognostic outcome.

16 Article ROBO2 is a stroma suppressor gene in the pancreas and acts via TGF-β signalling. 2018

Pinho, Andreia V / Van Bulck, Mathias / Chantrill, Lorraine / Arshi, Mehreen / Sklyarova, Tatyana / Herrmann, David / Vennin, Claire / Gallego-Ortega, David / Mawson, Amanda / Giry-Laterriere, Marc / Magenau, Astrid / Leuckx, Gunther / Baeyens, Luc / Gill, Anthony J / Phillips, Phoebe / Timpson, Paul / Biankin, Andrew V / Wu, Jianmin / Rooman, Ilse. ·Cancer Division, The Garvan Institute of Medical Research, Sydney, Darlinghurst 2010, NSW, Australia. andreia.pinho@mq.edu.au. · Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Macquarie University 2109, NSW, Australia. andreia.pinho@mq.edu.au. · Australian Pancreatic Cancer Genome Initiative (APGI), Sydney, Darlinghurst 2010, NSW, Australia. andreia.pinho@mq.edu.au. · Oncology Research Centre, Vrije Universiteit Brussel, Brussels, 1090, Belgium. · Cancer Division, The Garvan Institute of Medical Research, Sydney, Darlinghurst 2010, NSW, Australia. · Australian Pancreatic Cancer Genome Initiative (APGI), Sydney, Darlinghurst 2010, NSW, Australia. · St. Vincent's Clinical School, UNSW, Sydney, Darlinghurst 2010, NSW, Australia. · Beta cell Neogenesis Lab, Vrije Universiteit Brussel, Brussels, 1090, Belgium. · Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, University of Sydney, Sydney, St. Leonards 2065, NSW, Australia. · Lowy Cancer Research Centre, University of New South Wales, Sydney, Sydney 2052, NSW, Australia. · Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, G61 1BD, Scotland, UK. · West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, G5 0SF, Scotland, UK. · South Western Sydney Clinical School, UNSW, Liverpool, Liverpool 2170, NSW, Australia. · Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center for Cancer Bioinformatics, Peking University Cancer Hospital & Institute, Beijing, 100142, China. · Australian Pancreatic Cancer Genome Initiative (APGI), Sydney, Darlinghurst 2010, NSW, Australia. irooman@vub.be. · Oncology Research Centre, Vrije Universiteit Brussel, Brussels, 1090, Belgium. irooman@vub.be. ·Nat Commun · Pubmed #30504844.

ABSTRACT: Whereas genomic aberrations in the SLIT-ROBO pathway are frequent in pancreatic ductal adenocarcinoma (PDAC), their function in the pancreas is unclear. Here we report that in pancreatitis and PDAC mouse models, epithelial Robo2 expression is lost while Robo1 expression becomes most prominent in the stroma. Cell cultures of mice with loss of epithelial Robo2 (Pdx1

17 Article ATRX loss is an independent predictor of poor survival in pancreatic neuroendocrine tumors. 2018

Chou, Angela / Itchins, Malinda / de Reuver, Philip R / Arena, Jennifer / Clarkson, Adele / Sheen, Amy / Sioson, Loretta / Cheung, Veronica / Perren, Aurel / Nahm, Christopher / Mittal, Anubhav / Samra, Jaswinder S / Pajic, Marina / Gill, Anthony J. ·Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, NSW 2065, Australia; University of Sydney, Sydney, NSW 2006, Australia; Department of Anatomical Pathology, SYDPATH, St Vincent's Hospital, Darlinghurst, NSW 2010, Australia; The Kinghorn Cancer Centre and Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia. · University of Sydney, Sydney, NSW 2006, Australia; Department of Medical Oncology, Royal North Shore Hospital, St Leonards, NSW 2065, Australia. · Department of Surgery, Radboud University Medical Center, Nijmegen 6525, The Netherlands; Department of Upper Gastrointestinal Surgery, Royal North Shore Hospital, St Leonards, NSW 2065, Australia. · Department of Upper Gastrointestinal Surgery, Royal North Shore Hospital, St Leonards, NSW 2065, Australia. · Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, NSW 2065, Australia; NSW Health Pathology, Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, NSW 2065, Australia. · Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, NSW 2065, Australia. · Institute of Pathology, University of Bern, Bern 3012, Switzerland. · University of Sydney, Sydney, NSW 2006, Australia; Department of Upper Gastrointestinal Surgery, Royal North Shore Hospital, St Leonards, NSW 2065, Australia. · The Kinghorn Cancer Centre and Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia. · Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, NSW 2065, Australia; University of Sydney, Sydney, NSW 2006, Australia; NSW Health Pathology, Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, NSW 2065, Australia. Electronic address: affgill@med.usyd.edu.au. ·Hum Pathol · Pubmed #30081149.

ABSTRACT: Pancreatic neuroendocrine tumors (PanNETs) are rare neoplasms accounting for 1% to 2% of all pancreatic tumors. The biological behavior of PanNETs is heterogeneous and unpredictable, adding to the difficulties of clinical management. The DAXX (death domain associated protein) and ATRX (α-thalassemia/mental retardation syndrome X-linked) genes encode proteins involved in SWI/SNF-like chromatin remodeling. Somatic inactivating mutations in DAXX and ATRX are frequent in PanNETs, mutually exclusive, and associated with telomere dysfunction, resulting in genomic instability and alternate lengthening of telomeres. We sought to assess the clinical significance of the loss of the ATRX and DAXX proteins as determined by immunohistochemistry (IHC) in patients with PanNET. From an unselected cohort of 105 patients, we found ATRX loss in 10 tumors (9.5%) and DAXX loss in 16 (15.2%). DAXX and ATRX losses were confirmed mutually exclusive and associated with other adverse clinicopathological variables and poor survival in univariate analysis. In addition, ATRX loss was also associated with higher AJCC stage and infiltrative tumor borders. However, only ATRX loss, lymphovascular invasion, and perineural spread were independent predictors of poor overall survival in multivariate analysis. In conclusion, loss of expression of ATRX as determined by IHC is a useful independent predictor of poor overall survival in PanNETs. Given its relative availability, ATRX loss as determined by IHC may have a role in routine clinical practice to refine prognostication in patients with PanNET.

18 Article Hypercalcemia in Glucagon Cell Hyperplasia and Neoplasia (Mahvash Syndrome): A New Association. 2018

Gild, Matti L / Tsang, Venessa / Samra, Jaswinder / Clifton-Bligh, Roderick J / Tacon, Lyndal / Gill, Anthony J. ·Department of Endocrinology and Diabetes, Royal North Shore Hospital, St Leonards, New South Wales, Australia. · University of Sydney, Sydney, New South Wales, Australia. · Department of Surgery, Royal North Shore Hospital, St. Leonards, New South Wales, Australia. · Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, St. Leonards, New South Wales, Australia. ·J Clin Endocrinol Metab · Pubmed #30032256.

ABSTRACT: Context: Hyperglucagonemia in the absence of glucagonomas is rare. Biallelic-inactivating mutations in the glucagon receptor gene (GCGR) cause glucagon cell hyperplasia and neoplasia (GCHN), also termed Mahvash syndrome. Here, we report the first case to our knowledge of GCHN presenting with hypercalcemia and demonstrate a unique relationship between calcium and α-cell hyperplasia. Case Description: A 47-year-old man presented with severe PTH-independent hypercalcemia, 13.95 mg/dL (3.48 mmol/L). Imaging and extensive pathology tests yielded no conclusive cause. Glucagon levels >300 times the upper limit of normal were discovered. Subtotal pancreatectomy identified α-cell hyperplasia and neoplasia with metastatic disease in lymph nodes. Genomic analysis confirmed a homozygous missense variant in GCGR (Asp63Asn). This is a previously described pathologic variant and has a known association with GCHN. Conclusions: Inactivating mutations of the glucagon receptor gene lead to nonfunctional hyperglucagonemia and are associated with GCHN. Homozygous or compound heterozygous GCGR mutations are associated with α-cell hyperplasia, a known precursor to pancreatic neuroendocrine tumors that can metastasize. Hypercalcemia is an unreported consequence of GCHN with an unclear mechanism.

19 Article Tailored first-line and second-line CDK4-targeting treatment combinations in mouse models of pancreatic cancer. 2018

Chou, Angela / Froio, Danielle / Nagrial, Adnan M / Parkin, Ashleigh / Murphy, Kendelle J / Chin, Venessa T / Wohl, Dalia / Steinmann, Angela / Stark, Rhys / Drury, Alison / Walters, Stacey N / Vennin, Claire / Burgess, Andrew / Pinese, Mark / Chantrill, Lorraine A / Cowley, Mark J / Molloy, Timothy J / Anonymous170925 / Waddell, Nicola / Johns, Amber / Grimmond, Sean M / Chang, David K / Biankin, Andrew V / Sansom, Owen J / Morton, Jennifer P / Grey, Shane T / Cox, Thomas R / Turchini, John / Samra, Jaswinder / Clarke, Stephen J / Timpson, Paul / Gill, Anthony J / Pajic, Marina. ·The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales, Australia. · Faculty of Medicine, St Vincent's Clinical School, University of NSW, Sydney, New South Wales, Australia. · Department of Anatomical Pathology, SYDPATH, Darlinghurst, Australia. · Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, New South Wales, Australia. · St. Vincent's Hospital, Darlinghurst, Australia. · St Vincent's Centre for Applied Medical Research, Darlinghurst, New South Wales, Australia. · Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Queensland, Australia. · University of Melbourne, Melbourne, Victoria, Australia. · Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, UK. · West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, UK. · Department of Surgery, Cancer Research UK, Beatson Institute, Institute of Cancer Sciences, University of Glasgow, Glasgow, UK. · Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia. · Department of Anatomical Pathology, Royal North Shore Hospital, Sydney, New South Wales, Australia. · Cancer Diagnosis and Pathology Research Group, Kolling Institute of Medical Research, New South Wales, Australia. · Department of Surgery, Royal North Shore Hospital, Sydney, New South Wales, Australia. ·Gut · Pubmed #29080858.

ABSTRACT: OBJECTIVE: Extensive molecular heterogeneity of pancreatic ductal adenocarcinoma (PDA), few effective therapies and high mortality make this disease a prime model for advancing development of tailored therapies. The p16-cyclin D-cyclin-dependent kinase 4/6-retinoblastoma (RB) protein (CDK4) pathway, regulator of cell proliferation, is deregulated in PDA. Our aim was to develop a novel personalised treatment strategy for PDA based on targeting CDK4. DESIGN: Sensitivity to potent CDK4/6 inhibitor PD-0332991 (palbociclib) was correlated to protein and genomic data in 19 primary patient-derived PDA lines to identify biomarkers of response. In vivo efficacy of PD-0332991 and combination therapies was determined in subcutaneous, intrasplenic and orthotopic tumour models derived from genome-sequenced patient specimens and genetically engineered model. Mechanistically, monotherapy and combination therapy were investigated in the context of tumour cell and extracellular matrix (ECM) signalling. Prognostic relevance of companion biomarker, RB protein, was evaluated and validated in independent PDA patient cohorts (>500 specimens). RESULTS: Subtype-specific in vivo efficacy of PD-0332991-based therapy was for the first time observed at multiple stages of PDA progression: primary tumour growth, recurrence (second-line therapy) and metastatic setting and may potentially be guided by a simple biomarker (RB protein). PD-0332991 significantly disrupted surrounding ECM organisation, leading to increased quiescence, apoptosis, improved chemosensitivity, decreased invasion, metastatic spread and PDA progression in vivo. RB protein is prevalent in primary operable and metastatic PDA and may present a promising predictive biomarker to guide this therapeutic approach. CONCLUSION: This study demonstrates the promise of CDK4 inhibition in PDA over standard therapy when applied in a molecular subtype-specific context.

20 Article Pancreatoduodenectomy in a public versus private teaching hospital is comparable with some minor variations. 2018

Chua, Terence C / Mittal, Anubhav / Nahm, Chris / Hugh, Thomas J / Arena, Jenny / Gill, Anthony J / Samra, Jaswinder S. ·Upper Gastrointestinal Surgical Unit, Royal North Shore Hospital, Sydney, New South Wales, Australia. · Discipline of Surgery, The University of Sydney, Sydney, New South Wales, Australia. · Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Sydney, New South Wales, Australia. · The University of Sydney, Sydney, New South Wales, Australia. · Department of Anatomical Pathology, Royal North Shore Hospital, Sydney, New South Wales, Australia. · Macquarie University Hospital, Macquarie University, Sydney, New South Wales, Australia. ·ANZ J Surg · Pubmed #28982221.

ABSTRACT: BACKGROUND: The impact of the public and private hospital systems on major abdominal operations that are demanding on clinical resources, such as pancreatic surgery, has not been explored in an Australian setting. This study examines the perioperative outcome of patients undergoing pancreatoduodenectomy (PD) at a major public and private hospital. METHODS: Patients undergoing PD between January 2004 and October 2015 were classified based on their health insurance status and location of where the surgery was performed. Clinical variables relating to perioperative outcome were retrieved and compared using univariate and multivariate analyses. RESULTS: Four hundred and twenty patients underwent PD of whom 232 patients (55%) were operated on in the private hospital. Overall, there was no difference in morbidity and mortality in the public versus the private hospital. However, there were variations in public versus private hospital, this included longer duration of surgery (443 min versus 372 min; P < 0.001), increased estimated blood loss (683 mL versus 506 mL; P < 0.001) and more patients requiring perioperative blood transfusion (25% versus 13%; P = 0.001). Of the 10 complications compared, post-operative bleeding was higher in the private hospital (11% versus 5%; P = 0.051) and intra-abdominal collections were more common in the public hospital (11% versus 5%; P = 0.028). Independent predictive factors for major complications were American Society of Anesthesiologists score (odds ratio (OR) = 1.91; P = 0.050), patients requiring additional visceral resection (OR = 3.36; P = 0.014) and post-operative transfusion (OR = 3.37; P < 0.001). The hospital type (public/private) was not associated with perioperative outcome. CONCLUSION: Comparable perioperative outcomes were observed between patients undergoing PD in a high-volume specialized unit in both the public and private hospital systems.

21 Article Histopathological tumour viability after neoadjuvant chemotherapy influences survival in resected pancreatic cancer: analysis of early outcome data. 2018

Townend, Phil / de Reuver, Phil R / Chua, Terence C / Mittal, Anubhav / Clark, Stephen J / Pavlakis, Nick / Gill, Anthony J / Samra, Jaswinder S. ·Department of Gastrointestinal Surgery, Royal North Shore Hospital, Sydney, New South Wales, Australia. · Discipline of Surgery, The University of Sydney, Sydney, New South Wales, Australia. · Department of Medical Oncology, Royal North Shore Hospital, Sydney, New South Wales, Australia. · Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Sydney, New South Wales, Australia. · Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia. · Deparment of Anatomical Pathology, Royal North Shore Hospital, Sydney, New South Wales, Australia. · Macquarie University Hospital, Macquarie University, Sydney, New South Wales, Australia. ·ANZ J Surg · Pubmed #28318082.

ABSTRACT: BACKGROUND: Neoadjuvant therapy is increasingly recognized as an effective strategy prior to pancreatoduodenectomy. We investigate the role of neoadjuvant chemotherapy (NAC) followed by surgery and the predictive role of viable residual tumour cells histopathologically on outcomes. METHODS: The study population comprised of 195 consecutive patients with pancreatic adenocarcinoma who were treated with either NAC or a surgery-first (SF) strategy. Histopathological viable tumour cells were examined in the NAC patients and clinicopathological factors were correlated with overall survival. RESULTS: Forty-two patients (22%) were treated with NAC and 153 patients (78%) underwent SF. NAC was associated with higher estimated blood loss during surgery (928 mL versus 615 mL; P = 0.004), fewer (<15) excised lymph nodes (37% versus 17%; P = 0.015) and lower rates of lymphovascular invasion (65% versus 45%; P = 0.044) when compared with SF. Two-year survival of patients undergoing NAC was 63% and 51% in patients undergoing SF (P = 0.048). The 2-year survival of patients who had >65% residual tumour cells was 45% and 90% in patients who had <65% residual tumour cells (P = 0.022). Favourable responders (<65% viable tumour cells) were observed to have shorter operation time (<420 min) (55% versus 13%; P = 0.038), trend towards negative lymph node status (38% versus 10%; P = 0.067) and greater lymph node harvest in node positive patients (≥4 positive lymph nodes) (77% versus 37%; P = 0.045). CONCLUSION: The improved survival of patients undergoing NAC indicates effective management of micrometastatic disease and is an effective option requiring further investigation. Histopathological viable tumour cells after NAC was a surrogate marker for survival.

22 Article Pancreatoduodenectomy and the risk of complications from perioperative fluid administration. 2018

Gill, Preetjote / Chua, Terence C / Huang, Yeqian / Mehta, Shreya / Mittal, Anubhav / Gill, Anthony J / Samra, Jaswinder S. ·Department of Upper Gastrointestinal Surgery, Royal North Shore Hospital, Sydney, New South Wales, Australia. · Discipline of Surgery, The University of Sydney, Sydney, New South Wales, Australia. · Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Sydney, New South Wales, Australia. · Deparment of Anatomical Pathology, Royal North Shore Hospital, Sydney, New South Wales, Australia. · Macquarie University Hospital, Macquarie University, Sydney, New South Wales, Australia. ·ANZ J Surg · Pubmed #28239944.

ABSTRACT: BACKGROUND: The dogma of administering sufficient intravenous fluids aggressively to avoid under-resuscitation has recently been challenged. Evidence suggests that excessive perioperative fluid administration may be associated with negative clinical outcomes in gastrointestinal surgery. This study examines the impact of fluid administration on perioperative outcomes in patients undergoing pancreatoduodenectomy (PD). METHODS: A retrospective analysis of 202 patients undergoing PD between January 2004 and August 2015 was performed. A cut-off value of 10 mL/kg/h was applied (low fluid group: <10 mL/kg/h versus high fluid group: ≥10 mL/kg/h). RESULTS: There were 76 patients in the low fluid group and 126 patients in the high fluid group. Both groups had comparable age, American Society of Anesthesiologists score and preoperative morbidity rates. Patients in the high fluid group received significantly more total fluids, crystalloids and colloids intraoperatively (P < 0.0001, P < 0.0001 and P = 0.013, respectively) without a significant difference in estimated blood loss (P = 0.586). The net fluid balance on post-operative day 0 was also significantly higher in the high fluid group (P < 0.0001). The mortality rate was 0% in the cohort. Major morbidity rate was 46.1% and 44.4% in low and high fluid groups, respectively (P = 0.836). Reoperation rate was 5.3% for the low fluid group and 1.6% for the high fluid group (P = 0.136). There were no significant differences between the groups for any of the individual complications. CONCLUSION: This study did not identify a difference in post-operative outcomes between the low and high fluid regime in patients undergoing PD.

23 Article Circulating and disseminated tumor cells in pancreatic cancer and their role in patient prognosis: a systematic review and meta-analysis. 2017

Stephenson, David / Nahm, Christopher / Chua, Terence / Gill, Anthony / Mittal, Anubhav / de Reuver, Philip / Samra, Jaswinder. ·Sydney Medical School, University of Sydney, Camperdown, Sydney, Australia. · Upper GI Surgical Unit, Department of Gastrointestinal Surgery, Royal North Shore Hospital, St. Leonards, Sydney, Australia. · Cancer Diagnosis and Pathology, Kolling Institute, Royal North Shore Hospital, St. Leonards, Sydney, Australia. · Department of Surgery, Radboud University Medical Centre, Nijmegen, The Netherlands. ·Oncotarget · Pubmed #29291024.

ABSTRACT: Background: Disseminated tumor cells (DTCs) and circulating tumor cells (CTCs) have been postulated to seed metastases and contribute to poorer patient outcomes in many types of solid cancer. To date, no systematic reviews have examined the role of both DTCs and CTCs in pancreatic cancer. We aimed to determine the prognostic value of DTCs/CTCs in pancreatic cancer using a systematic review and meta-analysis. Materials and Methods: A comprehensive literature search identified studies examining DTCs and CTCs in the bone marrow and blood of pancreatic cancer patients at diagnosis with follow-up to determine disease-free/progression-free survival (DFS/PFS) and overall survival (OS). Statistical analyses were performed to determine the hazard ratio (HR) of DTCs/CTCs on DFS/PFS and OS. Results: The literature search identified 16 articles meeting the inclusion criteria. The meta-analysis demonstrated statistically significant HR differences in DFS/PFS (HR = 1.93, 95% CI 1.19-3.11, Conclusion: The detection of DTCs/CTCs at diagnosis is associated with poorer DFS/PFS and OS in pancreatic cancer.

24 Article Retrospective cohort analysis of neoadjuvant treatment and survival in resectable and borderline resectable pancreatic ductal adenocarcinoma in a high volume referral centre. 2017

Itchins, M / Arena, J / Nahm, C B / Rabindran, J / Kim, S / Gibbs, E / Bergamin, S / Chua, T C / Gill, A J / Maher, R / Diakos, C / Wong, M / Mittal, A / Hruby, G / Kneebone, A / Pavlakis, N / Samra, J / Clarke, S. ·Department of Oncology, Royal North Shore Hospital, Sydney, NSW, Australia; Sydney Medical School (Northern), The University of Sydney, Australia. Electronic address: mitchins@gmail.com. · Department of Oncology, Royal North Shore Hospital, Sydney, NSW, Australia. · Upper GI Surgical Unit, Department of Gastrointestinal Surgery, Royal North Shore Hospital, Sydney, NSW, Australia; Sydney Medical School (Northern), The University of Sydney, Australia. · Upper GI Surgical Unit, Department of Gastrointestinal Surgery, Royal North Shore Hospital, Sydney, NSW, Australia. · National Health and Medical Research Council Clinical Trial Centre (NHMRC CTC), The University of Sydney, Australia. · Sydney Medical School (Northern), The University of Sydney, Australia; Cancer Diagnosis and Pathology, Kolling Institute, Royal North Shore Hospital, Sydney, Australia. · Department of Radiology, Royal North Shore Hospital, Australia. · Department of Oncology, Royal North Shore Hospital, Sydney, NSW, Australia; Sydney Medical School (Northern), The University of Sydney, Australia; Northern Cancer Institute, Sydney, NSW, Australia. · Department of Medical Oncology, Gosford Hospital, New South Wales, Australia. · Department of Oncology, Royal North Shore Hospital, Sydney, NSW, Australia; Sydney Medical School (Northern), The University of Sydney, Australia. ·Eur J Surg Oncol · Pubmed #28688722.

ABSTRACT: BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease. Neoadjuvant therapy (NA) with chemotherapy (NAC) and radiotherapy (RT) prior to surgery provides promise. In the absence of prospective data, well annotated clinical data from high-volume units may provide pilot data for randomised trials. METHODS: Medical records from a tertiary hospital in Sydney, Australia, were analysed to identify all patients with resectable or borderline resectable PDAC. Data regarding treatment, toxicity and survival were collected. RESULTS: Between January 1 2010 and April 1 2016, 220 sequential patients were treated: 87 with NA and 133 with upfront operation (UO). Forty-three NA patients (52%) and 5 UO patients (4%) were borderline resectable at diagnosis. Twenty-four borderline patients received NA RT, 22 sequential to NAC. The median overall survival (OS) in the NA group was 25.9 months (mo); 95% CI (21.1-43.0 mo) compared to 26.9 mo (19.7, 32.7) in the UO; HR 0.89; log-ranked p-value = 0.58. Sixty-nine NA patients (79%) were resected, mOS was 29.2 mo (22.27, not reached (NR)). Twenty-two NA (31%) versus 22 UO (17%) were node negative at operation (N0). In those managed with NAC/RT the mOS was 29.0 mo (17.3, NR). There were no post-operative deaths with NA within 90-days and three in the UO arm. DISCUSSION: This is a hypothesis generating retrospective review of a selected real-world population in a high-throughput unit. Treatment with NA was well tolerated. The long observed survival in this group may be explained by lymph node sterilisation by NA, and the achievement of R0 resection in a greater proportion of patients.

25 Article Lost in translation: returning germline genetic results in genome-scale cancer research. 2017

Johns, Amber L / McKay, Skye H / Humphris, Jeremy L / Pinese, Mark / Chantrill, Lorraine A / Mead, R Scott / Tucker, Katherine / Andrews, Lesley / Goodwin, Annabel / Leonard, Conrad / High, Hilda A / Nones, Katia / Patch, Ann-Marie / Merrett, Neil D / Pavlakis, Nick / Kassahn, Karin S / Samra, Jaswinder S / Miller, David K / Chang, David K / Pajic, Marina / Anonymous6590904 / Pearson, John V / Grimmond, Sean M / Waddell, Nicola / Zeps, Nikolajs / Gill, Anthony J / Biankin, Andrew V. ·Cancer Research Program, Garvan Institute of Medical Research, Kinghorn Cancer Centre, Sydney, Australia. · St Vincents Hospital, Darlinghurst, Australia. · Western Sydney University Clinical School, Sydney, Australia. · Genetics Department, SEALS Pathology, Prince of Wales Hospital, Randwick, Sydney, Australia. · School of Medicine, University of New South Wales, Sydney, Australia. · Hereditary Cancer Clinic, Prince of Wales Hospital, Randwick, Sydney, Australia. · Cancer Genetics Department, Royal Prince Alfred Hospital and Liverpool Hospital, Sydney, NSW, Australia. · QIMR Berghofer Medical Research Institute, Brisbane, Australia. · Sydney Cancer Genetics, Sydney, Australia. · Department of Surgery, Bankstown Hospital, Eldridge Road, Bankstown, Sydney, Australia. · Division of Surgery, School of Medicine, Western Sydney University, Sydney, Australia. · Department of Medical Oncology, Royal North Shore Hospital and Faculty of Medicine, University of Sydney, Sydney, Australia. · Genetic and Molecular Pathology, SA Pathology, Women's and Children's Hospital, North Adelaide, Adelaide, Australia. · Department of Surgery, Royal North Shore Hospital, Sydney, Australia. · Illumina Inc, 5200 Illumina Way, San Diego, CA, 92122, USA. · Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, UK. · West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, UK. · South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Liverpool, Australia. · University of Melbourne, Parkville, Australia. · St John of God Subiaco, Perth, Australia. · School of Surgery, The University of Western Australia, Perth, Australia. · Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney Australia and University of Sydney, Sydney, Australia. · Cancer Research Program, Garvan Institute of Medical Research, Kinghorn Cancer Centre, Sydney, Australia. andrew.biankin@glasgow.ac.uk. · West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, UK. andrew.biankin@glasgow.ac.uk. · South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Liverpool, Australia. andrew.biankin@glasgow.ac.uk. · Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow, UK. andrew.biankin@glasgow.ac.uk. ·Genome Med · Pubmed #28454591.

ABSTRACT: BACKGROUND: The return of research results (RoR) remains a complex and well-debated issue. Despite the debate, actual data related to the experience of giving individual results back, and the impact these results may have on clinical care and health outcomes, is sorely lacking. Through the work of the Australian Pancreatic Cancer Genome Initiative (APGI) we: (1) delineate the pathway back to the patient where actionable research data were identified; and (2) report the clinical utilisation of individual results returned. Using this experience, we discuss barriers and opportunities associated with a comprehensive process of RoR in large-scale genomic research that may be useful for others developing their own policies. METHODS: We performed whole-genome (n = 184) and exome (n = 208) sequencing of matched tumour-normal DNA pairs from 392 patients with sporadic pancreatic cancer (PC) as part of the APGI. We identified pathogenic germline mutations in candidate genes (n = 130) with established predisposition to PC or medium-high penetrance genes with well-defined cancer associated syndromes or phenotypes. Variants from candidate genes were annotated and classified according to international guidelines. Variants were considered actionable if clinical utility was established, with regard to prevention, diagnosis, prognostication and/or therapy. RESULTS: A total of 48,904 germline variants were identified, with 2356 unique variants undergoing annotation and in silico classification. Twenty cases were deemed actionable and were returned via previously described RoR framework, representing an actionable finding rate of 5.1%. Overall, 1.78% of our cohort experienced clinical benefit from RoR. CONCLUSION: Returning research results within the context of large-scale genomics research is a labour-intensive, highly variable, complex operation. Results that warrant action are not infrequent, but the prevalence of those who experience a clinical difference as a result of returning individual results is currently low.

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