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Pancreatic Neoplasms: HELP
Articles by Pippa G. Corrie
Based on 14 articles published since 2008
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Between 2008 and 2019, P. Corrie wrote the following 14 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Guideline Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours (NETs). 2012

Ramage, John K / Ahmed, A / Ardill, J / Bax, N / Breen, D J / Caplin, M E / Corrie, P / Davar, J / Davies, A H / Lewington, V / Meyer, T / Newell-Price, J / Poston, G / Reed, N / Rockall, A / Steward, W / Thakker, R V / Toubanakis, C / Valle, J / Verbeke, C / Grossman, A B / Anonymous3000709. ·Basingstoke and North Hampshire Hospital, Aldermaston Road, Basingstoke RG24 9NA, UK. john.ramage@bnhft.nhs.uk ·Gut · Pubmed #22052063.

ABSTRACT: These guidelines update previous guidance published in 2005. They have been revised by a group who are members of the UK and Ireland Neuroendocrine Tumour Society with endorsement from the clinical committees of the British Society of Gastroenterology, the Society for Endocrinology, the Association of Surgeons of Great Britain and Ireland (and its Surgical Specialty Associations), the British Society of Gastrointestinal and Abdominal Radiology and others. The authorship represents leaders of the various groups in the UK and Ireland Neuroendocrine Tumour Society, but a large amount of work has been carried out by other specialists, many of whom attended a guidelines conference in May 2009. We have attempted to represent this work in the acknowledgements section. Over the past few years, there have been advances in the management of neuroendocrine tumours, which have included clearer characterisation, more specific and therapeutically relevant diagnosis, and improved treatments. However, there remain few randomised trials in the field and the disease is uncommon, hence all evidence must be considered weak in comparison with other more common cancers.

2 Review Diagnosis and management of pancreatic cancer in adults: A summary of guidelines from the UK National Institute for Health and Care Excellence. 2018

O'Reilly, Derek / Fou, Linyun / Hasler, Elise / Hawkins, James / O'Connell, Susan / Pelone, Ferruccio / Callaway, Mark / Campbell, Fiona / Capel, Margred / Charnley, Richard / Corrie, Pippa / Elliot, Dawn / Goodburn, Lesley / Jewell, Anna / Joharchi, Suzanne / McGeeney, Laura / Mukherjee, Somnath / Oppong, Kofi / Whelan, Phil / Primrose, John / Neoptolemos, John. ·Manchester Royal Infirmary, Central Manchester NHS Foundation Trust and University of Manchester, United Kingdom. Electronic address: doreilly@doctors.org.uk. · National Institute for Health and Care Excellence, United Kingdom. · Bristol Royal Infirmary, University Hospitals Bristol NHS Foundation Trust, United Kingdom. · University of Liverpool, The Royal Liverpool & Broadgreen University Hospital NHS Trust, United Kingdom. · George Thomas Hospice, United Kingdom. · Freeman Hospital, Newcastle upon Tyne, United Kingdom. · Cambridge University Hospitals NHS Foundation Trust and University of Cambridge, United Kingdom. · Northumbria Healthcare Foundation Trust, United Kingdom. · Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Germany. · CRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford & Churchill Hospital, United Kingdom. · University of Southampton, Southampton General Hospital, United Kingdom. · University of Heidelberg, Germany. ·Pancreatology · Pubmed #30292643.

ABSTRACT: To enable standardisation of care of pancreatic cancer patients and facilitate improvement in outcome, the United Kingdom's National Institute for Health and Care Excellence (NICE) developed a clinical guideline for the diagnosis and management of pancreatic cancer in adults. Systematic literature searches, systematic review and meta-analyses were undertaken. Recommendations were drafted on the basis of the group's interpretation of the best available evidence of clinical and cost effectiveness. There was patient involvement and public consultation. Recommendations were made on: diagnosis; staging; monitoring of inherited high risk; psychological support; pain; nutrition management; and the specific management of people with resectable-, borderline-resectable- and unresectable-pancreatic cancer. The guideline committee also made recommendations for future research into neoadjuvant therapy, cachexia interventions, minimally invasive pancreatectomy, pain management and psychological support needs. These NICE guidelines aim to promote best current practice and support and stimulate research and innovation in pancreatic cancer.

3 Review Options for the treatment of gemcitabine-resistant advanced pancreatic cancer. 2010

Gounaris, Ioannis / Zaki, Kamarul / Corrie, Pippa. ·Oncology Centre, Cambridge University Hospitals NHS Trust, Cambridge, United Kingdom. ioannis.gounaris@addenbrookes.nhs.uk ·JOP · Pubmed #20208317.

ABSTRACT: CONTEXT: Pancreatic cancer is noteworthy in that the number of patients dying from the disease is roughly equal to the number diagnosed. For more than a decade, gemcitabine has constituted the standard of care for the palliative treatment of the majority of patients who present with metastatic or relapsed disease, although the survival gains are limited. Despite a median survival of less than 6 months, there is a significant proportion of advanced pancreatic cancer patients who progress on gemcitabine that remains fit and these patients are candidates for second-line treatment. METHODS: The OVID MEDLINE database was searched from 1950 to present using the MeSH terms "pancreatic neoplasms", "drug treatment" and "gemcitabine". After excluding non-relevant results, 31 published studies were identified. These results were supplemented by searching the last three (2007-2009) American Society of Clinical Oncology (ASCO) Proceedings of Annual Meetings for studies published only in abstract form and reviewing reference lists of published articles. RESULTS AND DISCUSSION: The evidence for second line treatments of metastatic pancreatic cancer consists mostly of single arm, small phase II studies. Oxaliplatin-fluoropyrimidine combinations appear promising and have shown increased survival compared to best supportive care. As the molecular pathways governing pancreatic cancer are unravelled, novel targeted therapies may offer the greatest promise for this disease either given alone, combined with one another, or with cytotoxic agents. The need for further, collaborative research is emphasised.

4 Clinical Trial HALO-109-301: a Phase III trial of PEGPH20 (with gemcitabine and nab-paclitaxel) in hyaluronic acid-high stage IV pancreatic cancer. 2018

Doherty, Gary J / Tempero, Margaret / Corrie, Pippa G. ·Department of Oncology, University of Cambridge, Box 193, Cambridge Biomedical Campus, Hills Road, Cambridge, CB2 0QQ, UK. · Department of Oncology, Cambridge University Hospitals NHS Foundation Trust, Box 193, Cambridge Biomedical Campus, Hills Road, Cambridge, CB2 0QQ, UK. · Pancreas Center, University of California, San Francisco, CA 94158, USA. ·Future Oncol · Pubmed #29235360.

ABSTRACT: The outlook for patients with advanced pancreatic cancer remains poor, despite significant advances in our understanding of pancreatic tumor biology. One emerging theme highlights the distinct composition of the pancreatic tumor microenvironment. Hyaluronic acid is a hydrophilic glycosaminoglycan whose production within the tumor leads to increased interstitial tumor pressure, thereby limiting the access of potentially effective circulating anticancer drugs via reduced tumor perfusion. PEGylated rHuPH20 is a multiply PEGylated recombinant human hyaluronidase that has shown promising efficacy in preclinical models and early phase clinical trials in pancreatic cancer patients. Here, we discuss these findings, and the rationale for the ongoing randomized Phase III trial (HALO-109-301), which seeks to definitively define the efficacy of PEGylated rHuPH20 alongside gemcitabine and nab-paclitaxel in previously untreated, hyaluronic acid-high, stage IV pancreatic cancer.

5 Clinical Trial Vandetanib plus gemcitabine versus placebo plus gemcitabine in locally advanced or metastatic pancreatic carcinoma (ViP): a prospective, randomised, double-blind, multicentre phase 2 trial. 2017

Middleton, Gary / Palmer, Daniel H / Greenhalf, William / Ghaneh, Paula / Jackson, Richard / Cox, Trevor / Evans, Anthony / Shaw, Victoria E / Wadsley, Jonathan / Valle, Juan W / Propper, David / Wasan, Harpreet / Falk, Stephen / Cunningham, David / Coxon, Fareeda / Ross, Paul / Madhusudan, Srinivasan / Wadd, Nick / Corrie, Pippa / Hickish, Tamas / Costello, Eithne / Campbell, Fiona / Rawcliffe, Charlotte / Neoptolemos, John P. ·University of Birmingham, Edgbaston, Birmingham, UK. · Liverpool Cancer Research UK Cancer Trials Unit and LCTU-GCPLabs, University of Liverpool, Liverpool, UK; Clatterbridge Cancer Centre NHS Foundation Trust, Wirral, UK. · Liverpool Cancer Research UK Cancer Trials Unit and LCTU-GCPLabs, University of Liverpool, Liverpool, UK. · Weston Park Hospital, Sheffield Teaching Hospital NHS Foundation Trust, Sheffield, UK. · Division of Molecular and Clinical Cancer Sciences, University of Manchester, Manchester, UK; Christie NHS Foundation Trust, Manchester, UK. · Centre for Cancer and Inflammation, Barts Cancer Institute, London, UK. · Hammersmith Hospital, London, UK. · Bristol Haematology and Oncology Centre, University Hospital Bristol NHS Foundation Trust, Bristol, UK. · Royal Marsden, Royal Marsden NHS Foundation Trust, London, UK. · Northern Centre for Cancer Care, Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital, Newcastle upon Tyne, UK. · Guy's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK. · Nottingham City Hospital, Nottingham University Hospitals NHS Trust, Nottingham, UK. · James Cook University Hospital, South Tees Hospitals NHS Foundation Trust, Middlesborough, UK. · Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK. · Poole Hospital NHS Foundation Trust, Bournemouth University, Poole, UK. · Liverpool Cancer Research UK Cancer Trials Unit and LCTU-GCPLabs, University of Liverpool, Liverpool, UK. Electronic address: j.p.neoptolemos@liverpool.ac.uk. ·Lancet Oncol · Pubmed #28259610.

ABSTRACT: BACKGROUND: Erlotinib is an EGFR tyrosine kinase inhibitor that has shown a significant but only marginally improved median overall survival when combined with gemcitabine in patients with locally advanced and metastatic pancreatic cancer. Vandetanib is a novel tyrosine kinase inhibitor of VEGFR2, RET, and EGFR, all of which are in involved in the pathogenesis of pancreatic cancer. We investigated the clinical efficacy of vandetanib when used in combination with gemcitabine in patients with advanced pancreatic cancer. METHODS: The Vandetanib in Pancreatic Cancer (ViP) trial was a phase 2 double-blind, multicentre, randomised placebo-controlled trial in previously untreated adult patients (aged ≥18 years) diagnosed with locally advanced or metastatic carcinoma of the pancreas confirmed by cytology or histology. Patients had to have an Eastern Cooperative Oncology Group (ECOG) score of 0-2 and a documented life expectancy of at least 3 months. Patients were randomly assigned 1:1 to receive vandetanib plus gemcitabine (vandetanib group) or placebo plus gemcitabine (placebo group) according to pre-generated sequences produced on the principle of randomly permuted blocks with variable block sizes of two and four. Patients were stratified at randomisation by disease stage and ECOG performance status. All patients received gemcitabine 1000 mg/m FINDINGS: Patients were screened and enrolled between Oct 24, 2011, and Oct 7, 2013. Of 381 patients screened, 142 eligible patients were randomly assigned to treatment (72 to the vandetanib group and 70 to the placebo group). At database lock on July 15, 2015, at a median follow-up of 24·9 months (IQR 24·3 to not attainable), 131 patients had died: 70 (97%) of 72 in the vandetanib group and 61 (87%) of 70 in the placebo group. The median overall survival was 8·83 months (95% CI 7·11-11·58) in the vandetanib group and 8·95 months (6·55-11·74) in the placebo group (hazard ratio 1·21, 80·8% CI 0·95-1·53; log rank χ INTERPRETATION: The addition of vandetanib to gemcitabine monotherapy did not improve overall survival in advanced pancreatic cancer. Tyrosine kinase inhibitors might still have potential in the treatment of pancreatic cancer but further development requires the identification of biomarkers to specifically identify responsive cancer subtypes. FUNDING: Cancer Research UK and AstraZeneca.

6 Clinical Trial Gemcitabine and capecitabine with or without telomerase peptide vaccine GV1001 in patients with locally advanced or metastatic pancreatic cancer (TeloVac): an open-label, randomised, phase 3 trial. 2014

Middleton, Gary / Silcocks, Paul / Cox, Trevor / Valle, Juan / Wadsley, Jonathan / Propper, David / Coxon, Fareeda / Ross, Paul / Madhusudan, Srinivasan / Roques, Tom / Cunningham, David / Falk, Stephen / Wadd, Nick / Harrison, Mark / Corrie, Pippa / Iveson, Tim / Robinson, Angus / McAdam, Karen / Eatock, Martin / Evans, Jeff / Archer, Caroline / Hickish, Tamas / Garcia-Alonso, Angel / Nicolson, Marianne / Steward, William / Anthoney, Alan / Greenhalf, William / Shaw, Victoria / Costello, Eithne / Naisbitt, Dean / Rawcliffe, Charlotte / Nanson, Gemma / Neoptolemos, John. ·University of Birmingham, Edgbaston, Birmingham, UK. · Liverpool Cancer Research UK Cancer Trials Unit and GCLP Facility, University of Liverpool, Liverpool, UK. · Manchester Academic Health Sciences Centre, Christie Hospital NHS Foundation Trust and University of Manchester, Manchester UK. · Weston Park Hospital, Sheffield Teaching Hospital NHS Foundation Trust, Sheffield, UK. · St Bartholomew's Hospital, Barts Health NHS Trust, West Smithfield, London, UK. · Northern Centre for Cancer Care, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital, Newcastle upon Tyne, UK. · Guy's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK. · Nottingham City Hospital, Nottingham University Hospitals NHS Trust, Nottingham, UK. · Norfolk and Norwich University Hospital, Norfolk and Norwich University Hospital NHS Foundation Trust, Norwich, UK. · The Royal Marsden, The Royal Marsden NHS Foundation Trust, London, UK. · Bristol Haematology And Oncology Centre, University Hospital Bristol NHS Foundation Trust, Bristol, UK. · The James Cook University Hospital, South Tees Hospitals NHS Foundation Trust, Middleborough, UK. · Mount Vernon Hospital, The Hillingdon Hospitals NHS Foundation Trust, Northwood, UK. · Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK. · Southampton General Hospital, University Hospital Southampton NHS Foundation Trust, Southampton, Hampshire, UK. · Conquest Hospital, East Sussex Healthcare NHS Trust, The Ridge, St Leonards-on-Sea, East Sussex, UK. · Peterborough City Hospital, Peterborough and Stamford Hospitals NHS Foundation Trust, Edith, Cavell Campus, Peterborough, UK. · Belfast City Hospital, Belfast Health and Social Care Trust, Belfast, UK. · University of Glasgow, Beatson West of Scotland Cancer Centre, Glasgow, UK. · Queen Alexandra Hospital, Portsmouth Hospitals NHS Trust, Cosham, Portsmouth, UK. · Royal Bournemouth Hospital, The Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust, Bournemouth, UK. · Glan Clwyd Hospital, University Health Board, Rhyl, Denbighshire, UK. · Abderdeen Royal Infirmary, NHS Grampian, Aberdeen, UK. · Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust, Leicester, UK. · St James University Hospital, The Leeds Teaching Hospital Trust, Beckett Street, Leeds, UK. · Liverpool Cancer Research UK Cancer Trials Unit and GCLP Facility, University of Liverpool, Liverpool, UK. Electronic address: j.p.neoptolemos@liverpool.ac.uk. ·Lancet Oncol · Pubmed #24954781.

ABSTRACT: BACKGROUND: We aimed to assess the efficacy and safety of sequential or simultaneous telomerase vaccination (GV1001) in combination with chemotherapy in patients with locally advanced or metastatic pancreatic cancer. METHODS: TeloVac was a three-group, open-label, randomised phase 3 trial. We recruited patients from 51 UK hospitals. Eligible patients were treatment naive, aged older than 18 years, with locally advanced or metastatic pancreatic ductal adenocarcinoma, and Eastern Cooperative Oncology Group performance status of 0-2. Patients were randomly assigned (1:1:1) to receive either chemotherapy alone, chemotherapy with sequential GV1001 (sequential chemoimmunotherapy), or chemotherapy with concurrent GV1001 (concurrent chemoimmunotherapy). Treatments were allocated with equal probability by means of computer-generated random permuted blocks of sizes 3 and 6 in equal proportion. Chemotherapy included six cycles of gemcitabine (1000 mg/m(2), 30 min intravenous infusion, at days 1, 8, and 15) and capecitabine (830 mg/m(2) orally twice daily for 21 days, repeated every 28 days). Sequential chemoimmunotherapy included two cycles of combination chemotherapy, then an intradermal lower abdominal injection of granulocyte-macrophage colony-stimulating factor (GM-CSF; 75 μg) and GV1001 (0·56 mg; days 1, 3, and 5, once on weeks 2-4, and six monthly thereafter). Concurrent chemoimmunotherapy included giving GV1001 from the start of chemotherapy with GM-CSF as an adjuvant. The primary endpoint was overall survival; analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN4382138. FINDINGS: The first patient was randomly assigned to treatment on March 29, 2007, and the trial was terminated on March 27, 2011. Of 1572 patients screened, 1062 were randomly assigned to treatment (358 patients were allocated to the chemotherapy group, 350 to the sequential chemoimmunotherapy group, and 354 to the concurrent chemoimmunotherapy group). We recorded 772 deaths; the 290 patients still alive were followed up for a median of 6·0 months (IQR 2·4-12·2). Median overall survival was not significantly different in the chemotherapy group than in the sequential chemoimmunotherapy group (7·9 months [95% CI 7·1-8·8] vs 6·9 months [6·4-7·6]; hazard ratio [HR] 1·19, 98·25% CI 0·97-1·48, p=0·05), or in the concurrent chemoimmunotherapy group (8·4 months [95% CI 7·3-9·7], HR 1·05, 98·25% CI 0·85-1·29, p=0·64; overall log-rank of χ(2)2df=4·3; p=0·11). The commonest grade 3-4 toxic effects were neutropenia (68 [19%] patients in the chemotherapy group, 58 [17%] patients in the sequential chemoimmunotherapy group, and 79 [22%] patients in the concurrent chemoimmunotherapy group; fatigue (27 [8%] in the chemotherapy group, 35 [10%] in the sequential chemoimmunotherapy group, and 44 [12%] in the concurrent chemoimmunotherapy group); and pain (34 [9%] patients in the chemotherapy group, 39 [11%] in the sequential chemoimmunotherapy group, and 41 [12%] in the concurrent chemoimmunotherapy group). INTERPRETATION: Adding GV1001 vaccination to chemotherapy did not improve overall survival. New strategies to enhance the immune response effect of telomerase vaccination during chemotherapy are required for clinical efficacy. FUNDING: Cancer Research UK and KAEL-GemVax.

7 Article Safety and Efficacy of Modified FOLFIRINOX for Advanced Pancreatic Adenocarcinoma: A UK Single-Centre Experience. 2015

Ghorani, Ehsan / Wong, Han Hsi / Hewitt, Carole / Calder, Joanna / Corrie, Pippa / Basu, Bristi. ·Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK. ·Oncology · Pubmed #26372905.

ABSTRACT: OBJECTIVES: The combination of 5-fluorouracil (5-FU), irinotecan and oxaliplatin (FOLFIRINOX) is considered the first-line chemotherapy for fit patients with advanced pancreatic ductal adenocarcinoma (PDAC) but carries an unfavourable adverse event (AE) profile. We retrospectively evaluated the tolerability and efficacy of a modified FOLFIRINOX (mFOLFIRINOX) regimen: intravenous oxaliplatin 85 mg/m2, irinotecan 135 mg/m2, folinic acid 400 mg/m2 and 5-FU infusion 2,400 mg/m2 over 46 h, with routine subcutaneous filgrastim on a 14-day cycle. METHODS: Records of 18 patients with advanced PDAC who received treatment with mFOLFIRINOX were reviewed. Imaging of measurable disease was assessed for response, and survival was measured from the date of commencing chemotherapy to disease progression and/or death. RESULTS: Grade 3 or 4 AEs (n; %) included vomiting (5; 28), nausea (4; 22), diarrhoea (3; 17) and non-neutropaenic fever (3; 17). For patients with stage IV disease, 12/15 (80%) achieved at least stable disease as the best radiological response, with 7/15 (47%) objective responses. In this subgroup, median overall and progression-free survival were 9.3 months (95% CI 8.3-10.4) and 7.2 months (95% CI 4.7-9.6), respectively. CONCLUSION: Compared to full-dose FOLFIRINOX, our modified regimen resulted in lower haematological but only marginally improved non-haematological toxicity rates, with comparable efficacy outcomes. Prospective studies are required to validate these findings.

8 Article Salvage pancreaticoduodenectomy after complete response to chemoradiotherapy for a previously unresectable pancreatic adenosquamous carcinoma: a case report. 2015

Elias, Anne / Chatzizacharias, Nikolaos A / Xanthis, Athanasios / Corrie, Pippa / Davies, Susan / Brais, Rebecca J / Jamieson, Neville V / Praseedom, Raaj K / Huguet, Emmanuel / Harper, Simon J F / Jah, Asif. ·From the Department of HPB and Transplant Surgery (AE, NAC, AX, NVJ, RKP, EH, SJFH, AJ) · Department of Oncology (PC) · and Department of Histopathology (SD, RJB), Addenbrooke's Hospital, Cambridge, UK. ·Medicine (Baltimore) · Pubmed #25674740.

ABSTRACT: Pancreatic cancer is known for its typically late presentation and poor survival rates, with overall 5-year survival of less than 5%. The role of chemotherapy alone or with radiotherapy in the management of locally advanced tumors continues to be an area of debate.We report a case of locally advanced, pancreatic adenosquamous carcinoma that was initially deemed unresectable intraoperatively. Nonetheless, the tumor was resected after radiological response to gemcitabine-capecitabine chemoradiotherapy regimen similar to the Selective Chemoradiation in Advanced LOcalised Pancreatic cancer trial. Histological examination revealed complete pathological response with extensive fibrosis (ypT0 N0). On 12-month follow-up CT, a single liver lesion in the left lateral segment was identified and confirmed to be a metastasis with cytological diagnosis via EUS and FNA. The disease remained stable and confined to the solitary hepatic metastasis after further gemcitabine chemotherapy. Therefore, a further successful resection was performed.The 2 main strategies for the management of locally advanced unresectable pancreatic cancer are chemotherapy induction followed by consolidation chemoradiotherapy or chemotherapy alone, with conflicting published evidence. Evidence for the optimal management of the rare histological type of adenosquamous carcinoma is scant. We present a case of such tumor with a complete pathological response to chemoradiotherapy. The results of future studies in the area are eagerly awaited.

9 Article Endothelin-1 and endothelin B receptor expression in pancreatic adenocarcinoma. 2015

Cook, N / Brais, R / Qian, W / Hak, C Chan Wah / Corrie, P G. ·Oncology Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK CRUK Cancer Research Institute, University of Cambridge, Cambridge, UK. · Department of Pathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK. · Cambridge Cancer Trials Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK. · School of Clinical Medicine, University of Cambridge, Cambridge, UK. · Oncology Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK. ·J Clin Pathol · Pubmed #25572612.

ABSTRACT: BACKGROUND: Endothelin-1 (ET-1) acting through endothelin A and B receptors (ETAR and ETBR) has been implicated in the development of cancer. The endothelin axis has not previously been characterised in human pancreatic adenocarcinoma (PAC). METHODS: Expression of ET-1, ETAR, ETBR, vascular endothelial growth factor and microvessel density (MVD) was determined by immunohistochemistry in 45 surgically resected human PACs and 15 non-cancer human pancreas samples. RESULTS: PAC had the highest staining intensity for ET-1 and ETBR: 38% PAC samples scored 2+ or more compared with 7% non-cancer sample in ET-1; 58% PAC samples scored 2+ compared with 0% non-cancer samples in ETBR. MVD was significantly lower in PAC compared with non-cancer tissue (p<0.0001). CONCLUSIONS: PAC was characterised by greater expression of ET-1 and ETBR compared with normal pancreas.

10 Article "It can't be very important because it comes and goes"--patients' accounts of intermittent symptoms preceding a pancreatic cancer diagnosis: a qualitative study. 2014

Evans, Julie / Chapple, Alison / Salisbury, Helen / Corrie, Pippa / Ziebland, Sue. ·Health Experiences Research Group, Department of Primary Care Health Sciences, University of Oxford, Oxford, UK. ·BMJ Open · Pubmed #24549161.

ABSTRACT: OBJECTIVE: This article explores how people with pancreatic cancer interpreted prediagnostic signs and symptoms, and what triggered them to seek medical help for symptoms that occurred intermittently. DESIGN: Thematic analysis of prediagnostic symptom descriptions drawn from a qualitative interview study of people with experiences of pancreatic cancer. PARTICIPANTS: 40 people affected by pancreatic cancer (32 patients and 8 relatives of people who had died). Age at interview ranged from 35 to 84 years; 55% were men; and 57.5% of patients had been offered potentially curative surgery. SETTING: Respondents interviewed at home were recruited from different parts of the UK during 2009/2010. RESULTS: Analysis of the interviews suggested that intermittent symptoms were not uncommon in the months, or even years, before diagnosis but that the fact that the symptom did not persist was often taken by the patient as a reassuring indicator that it could not be 'very important'. Such symptoms were rarely acted upon until a pattern became apparent, the frequency of symptom episodes increased, there was a change in the nature of the intermittent symptoms or additional symptom(s) appeared. These findings build on social science theories of consultation behaviour. CONCLUSIONS: Our study-the largest reported collection of qualitative interviews with people with pancreatic cancer-reports for the first time that symptoms of an intermittent nature may precede a pancreatic cancer diagnosis. Patients (and potentially their doctors as well) may be falsely reassured by symptoms that come and go. Pancreatic cancer might be identified at a stage where curative treatment is more likely if there were greater awareness that intermittent gastrointestinal symptoms can have a serious cause, and if patients with intermittent pancreatitis-like symptoms were investigated more readily.

11 Article Capecitabine and streptozocin ± cisplatin in advanced gastroenteropancreatic neuroendocrine tumours. 2014

Meyer, Tim / Qian, Wendi / Caplin, Martyn E / Armstrong, Graham / Lao-Sirieix, Si-Houy / Hardy, Richard / Valle, Juan W / Talbot, Denis C / Cunningham, David / Reed, Nick / Shaw, Ashley / Navalkissoor, Shaunak / Luong, Tu-Vinh / Corrie, Pippa G. ·Neuroendocrine Tumour Unit, The Royal Free Hospital, Pond Street, London, UK; UCL Cancer Institute, London, UK. · Cambridge Cancer Trials Centre, Cambridge Clinical Trials Unit - Cancer Theme, Addenbrooke's Hospital, Cambridge, UK; Medical Research Council Biostatistics Unit Hub for Trials Methodology, Cambridge, UK. · Neuroendocrine Tumour Unit, The Royal Free Hospital, Pond Street, London, UK. · Cambridge Cancer Trials Centre, Cambridge Clinical Trials Unit - Cancer Theme, Addenbrooke's Hospital, Cambridge, UK. · Department of Medical Oncology, The Christie, Manchester, UK. · Oxford Neuroendocrine Tumour Centre, Churchill Hospital, Oxford, UK. · Gastrointestinal Unit, The Royal Marsden, London, UK. · Beatson Oncology Centre, Glasgow, UK. · Oncology Centre, Addenbrooke's Hospital, Cambridge, UK. · Cambridge Cancer Trials Centre, Cambridge Clinical Trials Unit - Cancer Theme, Addenbrooke's Hospital, Cambridge, UK; Oncology Centre, Addenbrooke's Hospital, Cambridge, UK. Electronic address: pippa.corrie@addenbrookes.nhs.uk. ·Eur J Cancer · Pubmed #24445147.

ABSTRACT: BACKGROUND: Cytotoxic chemotherapy is widely used for advanced, unresectable pancreatic and other gastrointestinal foregut neuroendocrine tumours (NETs) and the most commonly used regimen combines 5-fluorouracil with streptozocin. The NET01 trial was designed to investigate whether capecitabine combined with streptozocin was an acceptable regimen with or without adding cisplatin. METHODS: Patients with advanced, unresectable NETs of pancreatic, gastrointestinal foregut or unknown primary site were randomised to receive three-weekly capecitabine (Cap) 625 mg/m(2) twice daily orally, streptozocin (Strep) 1.0 g/m(2) intravenously on day 1, with or without cisplatin (Cis) 70 mg/m(2) intravenously on day 1. The primary outcome measure was objective response. Secondary outcome measures included progression-free and overall survival, quality of life, toxicity and biochemical response. RESULTS: 86 (44 CapStrep, 42 CapStrepCis) patients were randomised. Best objective response rate was 12% (95% confidence interval (CI)=2-22%) with CapStrep and 16% (95% CI=4-27.4%) with CapStrepCis. Disease-control rate was 80% with CapStrep and 74% with CapStrepCis. The estimated median progression-free and overall survival were 10.2 and 26.7 months for CapStrep and 9.7 and 27.5 months for CapStrepCis. 44% of CapStrep and 68% of CapStrepCis patients experienced grade ≥3 adverse events. INTERPRETATION: The efficacies of the novel CapStrep±Cis regimens were very similar. CapStrep was better tolerated than CapStrepCis. The trial was registered as EudraCT: 2004-005202-71 and ISRCTN: 35124268.

12 Article The effects of gemcitabine and capecitabine combination chemotherapy and of low-dose adjuvant GM-CSF on the levels of myeloid-derived suppressor cells in patients with advanced pancreatic cancer. 2014

Annels, Nicola E / Shaw, Victoria E / Gabitass, Rachel F / Billingham, Lucinda / Corrie, Pippa / Eatock, Martin / Valle, Juan / Smith, David / Wadsley, Jonathan / Cunningham, David / Pandha, Hardev / Neoptolemos, John P / Middleton, Gary. ·University of Surrey, Guildford, UK, n.annels@surrey.ac.uk. ·Cancer Immunol Immunother · Pubmed #24292263.

ABSTRACT: In pre-clinical models, the only two chemotherapy drugs which have been demonstrated to directly reduce the number of myeloid-derived suppressor cells (MDSCs) are gemcitabine and 5-fluorouracil. Here we analyze the dynamics of MDSCs, phenotyped as Lin-DR-CD11b+, in patients with advanced pancreatic cancer receiving the combination of gemcitabine and capecitabine, a 5-FU pro-drug. We found no evidence that gemcitabine and capecitabine directly reduce MDSC% in patients. Gemcitabine and capecitabine reduced MDSCs in 42% of patients (n = 19) and MDSC% fell in only 3/9 patients with above-median baseline MDSCs. In 5/8 patients with minimal tumour volume change on treatment, the MDSC% went up: increases in MDSC% in these patients appeared to correlate with sustained cancer-related inflammatory cytokine upregulation. In a separate cohort of 21 patients treated with gemcitabine and capecitabine together with concurrently administered GV1001 vaccine with adjuvant GM-CSF, the MDSC% fell in 18/21 patients and there was a significant difference in the trajectory of MDSCs between those receiving GV1001 and GM-CSF in combination with chemotherapy and those receiving chemotherapy alone. Thus, there was no evidence that the addition of low-dose adjuvant GM-CSF increased Lin-DR-CD11b+ MDSC in patients receiving combination chemoimmunotherapy. 9/21 patients developed an immune response to GV1001 and the MDSCs fell in 8 of these 9 patients, 6 of whom had above-median pre-vaccination MDSC levels. A high pre-vaccination MDSC% does not preclude the development of immunity to a tumour-associated antigen.

13 Article Direct histological processing of EUS biopsies enables rapid molecular biomarker analysis for interventional pancreatic cancer trials. 2012

Brais, Rebecca J / Davies, Susan E / O'Donovan, Maria / Simpson, Ben W / Cook, Natalie / Darbonne, Walter C / Chilcott, Sian / Lolkema, Martijn P / Neesse, Albrecht / Lockley, Michelle / Corrie, Pippa G / Jodrell, Duncan I / Praseedom, Raaj K / Huguet, Emmanuel L / Jah, Asif / Jamieson, Neville V / de Sauvage, Frederic J / Tuveson, David A / Carroll, Nicholas R. ·Department of Histopathology, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, United Kingdom. ·Pancreatology · Pubmed #22487467.

ABSTRACT: OBJECTIVE: Current practice to diagnose pancreatic cancer is accomplished by endoscopic ultrasound guided fine needle aspiration (EUS-FNA) using a cytological approach. This method is time consuming and often fails to provide suitable specimens for modern molecular analyses. Here, we compare the cytological approach with direct formalin fixation of pancreatic EUS-FNA micro-cores and evaluate the potential to perform molecular biomarker analysis on these specimen. METHODS: 130 specimens obtained by EUS-FNA with a 22G needle were processed by the standard cytological approach and compared to a separate cohort of 130 specimens that were immediately formalin fixed to preserve micro-cores of tissue prior to routine histological processing. RESULTS: We found that direct formalin fixation significantly shortened the time required for diagnosis from 3.6 days to 2.9 days (p<0.05) by reducing the average time (140 vs 33 min/case) and number of slides (9.65 vs 4.67 slides/case) for histopathological processing. Specificity and sensitivity yielded comparable results between the two approaches (82.3% vs 77% and 90.9% vs 100%). Importantly, EUS-FNA histology preserved the tumour tissue architecture with neoplastic glands embedded in stroma in 67.89% of diagnostic cases compared to 27.55% with the standard cytological approach (p < 0.001). Furthermore, micro-core samples were suitable for molecular studies including the immunohistochemical detection of intranuclear Hes1 in malignant cells, and the laser-capture microdissection-mediated measurement of Gli-1 mRNA in tumour stromal myofibroblasts. CONCLUSIONS: Direct formalin fixation of pancreatic EUS-FNA micro-cores demonstrates superiority regarding diagnostic delay, costs, and specimen suitability for molecular studies. We advocate this approach for future investigational trials in pancreatic cancer patients.

14 Minor Inspired to improve outcomes in pancreatic cancer. Interviewed by Natasha Galukande. 2013

Corrie, Pippa. · ·Future Oncol · Pubmed #23718296.

ABSTRACT: -- No abstract --