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Pancreatic Neoplasms: HELP
Articles by Anubhav Mittal
Based on 18 articles published since 2010
(Why 18 articles?)
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Between 2010 and 2020, Anubhav Mittal wrote the following 18 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 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.

2 Review Systematic review of peri-operative prognostic biomarkers in pancreatic ductal adenocarcinoma. 2016

Petrushnko, Wilson / Gundara, Justin S / De Reuver, Philip R / O'Grady, Greg / Samra, Jaswinder S / Mittal, Anubhav. ·Upper Gastrointestinal Surgical Unit, Royal North Shore Hospital, North Shore Private Hospital, University of Sydney, St Leonards, NSW 2065, Australia. · Department of Surgery, University of Auckland, New Zealand. · Upper Gastrointestinal Surgical Unit, Royal North Shore Hospital, North Shore Private Hospital, University of Sydney, St Leonards, NSW 2065, Australia. Electronic address: anubhav.mittal@sydney.edu.au. ·HPB (Oxford) · Pubmed #27485059.

ABSTRACT: BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) continues to be associated with a poor prognosis. This systematic review aimed to summarize the literature regarding potential prognostic biomarkers to facilitate validation studies and clinical application. METHODS: A systematic review was performed (2004-2014) according to PRISMA guidelines. Studies were ranked using REMARK criteria and the following outcomes were examined: overall/disease free survival, nodal involvement, tumour characteristics, metastasis, recurrence and resectability. RESULTS: 256 biomarkers were identified in 158 studies. 171 biomarkers were assessed with respect to overall survival: urokinase-type plasminogen activator receptor, atypical protein kinase C and HSP27 ranked the highest. 33 biomarkers were assessed for disease free survival: CD24 and S100A4 were the highest ranking. 17 biomarkers were identified for lymph node involvement: Smad4/Dpc4 and FOXC1 ranked highest. 13 biomarkers were examined for tumour grade: mesothelin and EGFR were the highest ranking biomarkers. 10 biomarkers were identified for metastasis: p16 and sCD40L were the highest ranking. 4 biomarkers were assessed resectability: sCD40L, s100a2, Ca 19-9, CEA. CONCLUSION: This review has identified and ranked specific biomarkers that should be a primary focus of ongoing validation and clinical translational work in PDAC.

3 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.

4 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.

5 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.

6 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.

7 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.

8 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.

9 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.

10 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.

11 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.

12 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.

13 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.

14 Article Pancreatic Metastasectomy-an Analysis of Survival Outcomes and Prognostic Factors. 2016

Chua, Terence C / Petrushnko, Wilson / Mittal, Anubhav / 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. · Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, NSW, Australia. · Macquarie University Hospital, Macquarie University, Sydney, NSW, Australia. ·J Gastrointest Surg · Pubmed #26892167.

ABSTRACT: BACKGROUND: The pancreas and peripancreatic region may be a site of metastasis from distant sites. Recent data suggest that pancreatic metastasectomy may achieve long-term survival. We seek to examine our experience with this metastasectomy by reporting the perioperative and survival outcomes. METHODS: Patients undergoing resection of isolated pancreatic metastasis were identified from a prospective pancreatic surgical database at the Department of Gastrointestinal Surgery, North Shore campus of the University of Sydney between January 2004 and June 2015 and selected for retrospective review. Data on operative morbidity and mortality were reported. Survival analysis was performed using the Kaplan-Meier method. RESULTS: Fifteen patients underwent pancreatic metastasectomy after a median disease-free interval of 63 months (range 0 to 199). Pancreatoduodenectomy was performed in six patients (40 %), distal pancreatectomy with or without splenectomy in three patients (20 %), and pancreatectomy with other visceral organ resection in six patients (40 %). Major complications occurred in six patients (40 %) without mortality. The median survival was 40 months (95 % CI 24.3 to 53.7), and 1-, 3-, and 5-year survival were 76, 48, and 31 % respectively. Cox proportional hazard model identified margin negative resection (hazard ratio (HR) 10.5; P = 0.044) as a predictor of improved survival. CONCLUSION: Long-term survival may be achieved in selected patients with pancreatic metastasis through pancreatic metastasectomy with acceptable morbidity. Selection of patients should be individualized and based on their primary disease origin, biological behavior of the tumor, resectability of the tumor, and the relative effectiveness of systemic or targeted therapies.

15 Article Immunoregulatory Forkhead Box Protein p3-Positive Lymphocytes Are Associated with Overall Survival in Patients with Pancreatic Neuroendocrine Tumors. 2016

de Reuver, Philip R / Mehta, Shreya / Gill, Preetjote / Andrici, Juliana / D'Urso, Lisa / Clarkson, Adele / Mittal, Anubhav / Hugh, Thomas J / Samra, Jaswinder S / Gill, Anthony J. ·Department of Gastrointestinal Surgery, Royal North Shore Hospital and North Shore Private Hospital, University of Sydney, New South Wales, Australia. Electronic address: Philipdereuver@gmail.com. · Department of Gastrointestinal Surgery, Royal North Shore Hospital and North Shore Private Hospital, University of Sydney, New South Wales, Australia. · Department of Anatomical Pathology, Royal North Shore Hospital, Cancer Diagnosis and Pathology Group Kolling Institute of Medical Research, University of Sydney, New South Wales, Australia. · Department of Gastrointestinal Surgery, Royal North Shore Hospital and North Shore Private Hospital, University of Sydney, New South Wales, Australia; Macquarie University Hospital, Macquarie University, New South Wales, Australia. ·J Am Coll Surg · Pubmed #26809747.

ABSTRACT: BACKGROUND: Forkhead box protein p3-positive (FoxP3(+)) regulatory T cells (Tregs) suppress host T-cell-mediated immune responses, limit surveillance against cancers, and have been associated with a poor prognosis. STUDY DESIGN: This study aims to identify the prognostic significance of FoxP3(+) Tregs in pancreatic neuroendocrine tumors (PNETs). Patients diagnosed with PNETs between 1992 and 2014 (n = 101) were included in this retrospective analysis. Clinical data, histopathology, and expression of FoxP3(+) Tregs and Ki-67 by immunohistochemistry were assessed. The association of these factors with survival was tested by log-rank test and in additional multivariable analysis. RESULTS: A total of 101 patients were included in this study. Mean age was 58.0 years (range 18 to 87 years) and median tumor size was 25 mm (range 8 to 160 mm). The degree of infiltration of tumor by FoxP3(+) Tregs was graded as 0 (n = 75), 1 (n = 15), or 2 (n = 11). Median follow-up was 50 months (interquartile range 123 months; Q1 = 20 months and Q3 = 123 months). In univariate analyses, patient age older than 57 years, TNM stage III or IV, tumor size >25 mm, Ki-67 labeling index >20, and a high number of FoxP3(+) tumor-infiltrating lymphocytes were significantly associated with poorer overall survival. In multivariable analyses, FoxP3(+) expression score of 2 (hazard ratio = 6.9; 95% CI 1.4-34.4) was the only statistically significant predictor for overall mortality. CONCLUSIONS: FoxP3(+) Treg expression is an independent prognostic factor in patients with PNETs, associated with statistically significant shorter overall survival. There is a role for additional research into the immune-mediated role of FoxP3(+) Tregs in PNETs.

16 Article Somatostatin Receptor SSTR-2a Expression Is a Stronger Predictor for Survival Than Ki-67 in Pancreatic Neuroendocrine Tumors. 2015

Mehta, Shreya / de Reuver, Philip R / Gill, Preetjote / Andrici, Juliana / D'Urso, Lisa / Mittal, Anubhav / Pavlakis, Nick / Clarke, Stephen / Samra, Jaswinder S / Gill, Anthony J. ·From Department of Gastrointestinal Surgery, Royal North Shore Hospital and North Shore Private Hospital, University of Sydney, New South Wales, Australia (SM, PDR, PG, AM, JSS) · Department of Medical Oncology, Royal North Shore Hospital and North Shore Private Hospital, University of Sydney, New South Wales, Australia (NP, SC) · Macquarie University Hospital, Macquarie University, New South Wales, Australia (JSS) · and Department of Anatomical Pathology Royal North Shore Hospital, Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, University of Sydney, New South Wales, Australia (JA, LDU, AJG). ·Medicine (Baltimore) · Pubmed #26447992.

ABSTRACT: Somatostatin receptors (SSTR) are commonly expressed by neuroendocrine tumors. Expression of SSTR-2a and SSTR-5 may impact symptomatic management; however, the impact on survival is unclear. The aim of this study is to correlate SSTR-2a and SSTR-5 expression in pancreatic neuroendocrine tumors (PNETs) with survival. This study is designed to determine the prognostic significance of somatostatin receptors SSTR-2a and SSTR-5 in PNETs. This retrospective cohort study included cases of resected PNETs between 1992 and 2014. Clinical data, histopathology, expression of SSTR and Ki-67 by immunohistochemistry, and long-term survival were analyzed. A total of 99 cases were included in this study. The mean age was 57.8 years (18-87 years) and median tumor size was 25 mm (range 8-160 mm). SSTR-2a and SSTR-5 expression was scored as negative (n = 19, 19.2%; n = 75, 75.8%, respectively) and positive (n = 80, 80.1%; n = 24, 24.2%). The median follow-up was 49 months. SSTR-2a expression was associated with improved overall survival, with cumulative survival rates at 1, 3, and 5 years being 97.5%, 91.5%, and 82.9%, respectively. Univariate analysis demonstrated better survival in SSTR-2a positive patients (log rank P = 0.04). SSTR-5 expression was not associated with survival outcomes (log rank P = 0.94). Multivariate analysis showed that positive SSTR-2a expression is a stronger prognostic indicator for overall survival [Hazard Ratio (HR): 0.2, 95% Confidence interval (CI): 0.1-0.8] compared to high Ki-67 (HR: 0.8, 95% CI: 0.1-5.7). Expression of SSTR-2a is an independent positive prognostic factor for survival in PNETs.

17 Article Endovascular stenting of mesenterico-portal vein stenosis to reduce blood flow through venous collaterals prior to pancreatoduodenectomy. 2015

Chua, Terence C / Wang, Frank / Maher, Richard / Gananadha, Sivakumar / Mittal, Anubhav / Samra, Jaswinder S. ·Department of Gastrointestinal Surgery, Discipline of Surgery, University of Sydney, Sydney, NSW, Australia, terence.c.chua@gmail.com. ·Langenbecks Arch Surg · Pubmed #25998372.

ABSTRACT: BACKGROUND: When the mesenterico-portal vein is stenosed due to tumor related compression, venous collaterals develop and flow occurs antegrade towards the portal vein through the collateral tributaries. Undertaking pancreatoduodenectomy for pancreatic cancer in this setting may result in significant blood loss during the process of ligation of these tributaries. DESCRIPTION OF TECHNIQUE: We describe the technique of endovascular stenting of the mesenterico-portal vein to reduce flow within these collateral tributaries and hence blood loss, to facilitate extended pancreatoduodenectomy and vein resection. CONCLUSION: Percutaneous transhepatic placement of endovascular stent into a stenotic mesentero-portal vein facilitates pancreatoduodenectomy by reducing operative time, which would otherwise be required in dealing with the extensive venous collaterals and hence also reducing blood loss.

18 Article Extended pancreatoduodenectomy as defined by the International Study Group for Pancreatic Surgery is associated with worse survival but not with increased morbidity. 2015

De Reuver, Philip R / Mittal, Anubhav / Neale, Michael / 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. Electronic address: philipdereuver@gmail.com. · Department of Gastrointestinal Surgery, Royal North Shore Hospital and North Shore Private Hospital, University of Sydney, Sydney, New South Wales, Australia. · 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. ·Surgery · Pubmed #25920909.

ABSTRACT: BACKGROUND: Recently, the International Study Group for Pancreatic Surgery presented a consensus statement on the definition of an extended pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC). Because extended resections are associated with increased morbidity and mortality, prognostic factors for outcome are mandatory to optimize patient selection. The aim of this study was to apply the new definition of an extended PD and to assess prognostic factors for short-term complications and survival in patients with PDAC. METHODS: A retrospective analysis was performed on a prospectively collected database running from 2004 to 2014. Inclusion criteria were all PD resections with histopathology-proven PDAC. Clinical data, operative results, and short- and long-term outcomes were analyzed. RESULTS: We included 177 patients who underwent PD for PDAC in this study. Sixty-six patients (37%) underwent a standard PD and 111 (63%) underwent an extended PD. No differences were found in duration of postoperative stay (median, 13 days) or overall complication rate of 35% (n = 61). Severe complications occurred in 24 patients (13%). Male sex (odds ratio, 2.4; 95% CI, 0.9-6.6) was a prognostic factor for severe complications. There was no in-hospital or 90-day mortality in either group. Multivariate survival analysis showed that poor tumor differentiation (hazard ratio [HR], 2.0; 95% CI, 1.3-3.1), lymph node metastasis (HR, 2.3; 95% CI, 1.4-3.9), neural invasion (HR, 1.9; 95% CI, 1.2-3.1), were independent prognostic factors for worse survival. An extended resection was associated with worse survival, but was not an independent prognostic factor (HR, 1.5; 95% CI, 1.0-2.3). CONCLUSION: Extended PD is associated with worse survival but not with increased morbidity.