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Pancreatic Neoplasms: HELP
Articles by Colin D. Johnson
Based on 11 articles published since 2009
(Why 11 articles?)
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Between 2009 and 2019, Colin Johnson wrote the following 11 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Review Pancreatic cancer. 2016

Kleeff, Jorg / Korc, Murray / Apte, Minoti / La Vecchia, Carlo / Johnson, Colin D / Biankin, Andrew V / Neale, Rachel E / Tempero, Margaret / Tuveson, David A / Hruban, Ralph H / Neoptolemos, John P. ·NIHR Pancreas Biomedical Research Unit, Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Duncan Building, Daulby Street, Liverpool L69 3GA, UK. · Department of General, Visceral and Pediatric Surgery, University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany. · Departments of Medicine, and Biochemistry and Molecular Biology, Indiana University School of Medicine, the Melvin and Bren Simon Cancer Center, and the Pancreatic Cancer Signature Center, Indianapolis, Indiana, USA. · SWS Clinical School, University of New South Wales, and Ingham Institute for Applied Medical Research, Sydney, New South Wales, Australia. · Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy. · University Surgical Unit, University Hospital Southampton, Southampton, UK. · Institute of Cancer Sciences, Wolfson Wohl Cancer Research Centre, University of Glasgow, Garscube Estate, Bearsden, Glasgow, Scotland, UK. · QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. · UCSF Pancreas Center, University of California San Francisco - Mission Bay Campus/Mission Hall, San Francisco, California, USA. · Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, New York, USA. · The Sol Goldman Pancreatic Cancer Research Center, Departments of Pathology and Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. ·Nat Rev Dis Primers · Pubmed #27158978.

ABSTRACT: Pancreatic cancer is a major cause of cancer-associated mortality, with a dismal overall prognosis that has remained virtually unchanged for many decades. Currently, prevention or early diagnosis at a curable stage is exceedingly difficult; patients rarely exhibit symptoms and tumours do not display sensitive and specific markers to aid detection. Pancreatic cancers also have few prevalent genetic mutations; the most commonly mutated genes are KRAS, CDKN2A (encoding p16), TP53 and SMAD4 - none of which are currently druggable. Indeed, therapeutic options are limited and progress in drug development is impeded because most pancreatic cancers are complex at the genomic, epigenetic and metabolic levels, with multiple activated pathways and crosstalk evident. Furthermore, the multilayered interplay between neoplastic and stromal cells in the tumour microenvironment challenges medical treatment. Fewer than 20% of patients have surgically resectable disease; however, neoadjuvant therapies might shift tumours towards resectability. Although newer drug combinations and multimodal regimens in this setting, as well as the adjuvant setting, appreciably extend survival, ∼80% of patients will relapse after surgery and ultimately die of their disease. Thus, consideration of quality of life and overall survival is important. In this Primer, we summarize the current understanding of the salient pathophysiological, molecular, translational and clinical aspects of this disease. In addition, we present an outline of potential future directions for pancreatic cancer research and patient management.

2 Review International Association of Pancreatology (IAP)/European Pancreatic Club (EPC) consensus review of guidelines for the treatment of pancreatic cancer. 2016

Takaori, Kyoichi / Bassi, Claudio / Biankin, Andrew / Brunner, Thomas B / Cataldo, Ivana / Campbell, Fiona / Cunningham, David / Falconi, Massimo / Frampton, Adam E / Furuse, Junji / Giovannini, Marc / Jackson, Richard / Nakamura, Akira / Nealon, William / Neoptolemos, John P / Real, Francisco X / Scarpa, Aldo / Sclafani, Francesco / Windsor, John A / Yamaguchi, Koji / Wolfgang, Christopher / Johnson, Colin D / Anonymous480853. ·Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan. Electronic address: takaori@kuhp.kyoto-u.ac.jp. · Department of Surgery and Oncology, Pancreas Institute, University of Verona, Verona, Italy. · Academic Unit of Surgery, University of Glasgow, Glasgow, United Kingdom. · Department of Radiation Oncology, University Hospitals Freiburg, Germany. · Department of Pathology and Diagnostics, University of Verona, Verona, Italy. · Department of Pathology, Royal Liverpool University Hospital, Liverpool, United Kingdom. · Department of Medicine, The Royal Marsden NHS Foundation Trust, London and Surrey, United Kingdom. · Pancreatic Surgery Unit, Università Vita e Salute, Milano, Italy. · HPB Surgical Unit, Department of Surgery and Cancer, Imperial College, Hammersmith Hospital, London, United Kingdom. · Department of Medical Oncology, Kyorin University School of Medicine, Tokyo, Japan. · Endoscopic Unit, Paoli-Calmettes Institute, Marseille, France. · NIHR Pancreas Biomedical Research Unit, Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, United Kingdom. · Department of Radiation Oncology and Image-applied Therapy, Kyoto University Hospital, Kyoto, Japan. · Division of General Surgery, Yale University, New Haven, CT, United States of America. · Epithelial Carcinogenesis Group, CNIO-Spanish National Cancer Research Centre, Madrid, Spain. · Department of Surgery, University of Auckland, HBP/Upper GI Unit, Auckland City Hospital, Auckland, New Zealand. · Department of Advanced Treatment of Pancreatic Disease, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan. · Department of Surgery, The Johns Hopkins University, Baltimore, MD, United States of America. · University Surgical Unit, Southampton General Hospital, Southampton, United Kingdom. ·Pancreatology · Pubmed #26699808.

ABSTRACT: BACKGROUND: Pancreatic cancer is one of the most devastating diseases with an extremely high mortality. Medical organizations and scientific societies have published a number of guidelines to address active treatment of pancreatic cancer. The aim of this consensus review was to identify where there is agreement or disagreement among the existing guidelines and to help define the gaps for future studies. METHODS: A panel of expert pancreatologists gathered at the 46th European Pancreatic Club Meeting combined with the 18th International Association of Pancreatology Meeting and collaborated on critical reviews of eight English language guidelines for the clinical management of pancreatic cancer. Clinical questions (CQs) of interest were proposed by specialists in each of nine areas. The recommendations for the CQs in existing guidelines, as well as the evidence on which these were based, were reviewed and compared. The evidence was graded as sufficient, mediocre or poor/absent. RESULTS: Only 4 of the 36 CQs, had sufficient evidence for agreement. There was also agreement in five additional CQs despite the lack of sufficient evidence. In 22 CQs, there was disagreement regardless of the presence or absence of evidence. There were five CQs that were not addressed adequately by existing guidelines. CONCLUSION: The existing guidelines provide both evidence- and consensus-based recommendations. There is also considerable disagreement about the recommendations in part due to the lack of high level evidence. Improving the clinical management of patients with pancreatic cancer, will require continuing efforts to undertake research that will provide sufficient evidence to allow agreement.

3 Clinical Trial Health-Related Quality of Life in SCALOP, a Randomized Phase 2 Trial Comparing Chemoradiation Therapy Regimens in Locally Advanced Pancreatic Cancer. 2015

Hurt, Christopher N / Mukherjee, Somnath / Bridgewater, John / Falk, Stephen / Crosby, Tom / McDonald, Alec / Joseph, George / Staffurth, John / Abrams, Ross A / Blazeby, Jane M / Bridges, Sarah / Dutton, Peter / Griffiths, Gareth / Maughan, Tim / Johnson, Colin. ·Wales Cancer Trials Unit, College of Biomedical and Life Sciences, Cardiff University, Cardiff, Wales, United Kingdom. Electronic address: hurtcn@cardiff.ac.uk. · Cancer Research UK/MRC Oxford Institute for Radiation Oncology, Oxford University, NIHR Biomedical Research, Oxford, United Kingdom. · UCL Cancer Institute, London, United Kingdom. · Bristol Haematology and Oncology Centre, Bristol, United Kingdom. · Velindre Cancer Centre, Velindre Hospital, Cardiff, Wales, United Kingdom. · Beatson West of Scotland Cancer Centre, Glasgow, Scotland, United Kingdom. · Institute of Cancer and Genetics, Cardiff University, Cardiff, Wales, United Kingdom. · Department of Radiation Oncology, Rush University Medical Center, Chicago, Illinois. · Division of Surgery, Head and Neck, University Hospitals Bristol National Health Service Foundation Trust, Bristol and School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom. · Wales Cancer Trials Unit, College of Biomedical and Life Sciences, Cardiff University, Cardiff, Wales, United Kingdom. · Centre for Statistics in Medicine, University of Oxford, Oxford, United Kingdom. · Southampton Clinical Trials Unit, Faculty of Medicine, Southampton University, Southampton General Hospital, Southampton, United Kingdom. · University Surgical Unit, Faculty of Medicine, University Hospital Southampton, Southampton, United Kingdom. ·Int J Radiat Oncol Biol Phys · Pubmed #26530749.

ABSTRACT: PURPOSE: Chemoradiation therapy (CRT) for patients with locally advanced pancreatic cancer (LAPC) provides survival benefits but may result in considerable toxicity. Health-related quality of life (HRQL) measurements during CRT have not been widely reported. This paper reports HRQL data from the Selective Chemoradiation in Advanced Localised Pancreatic Cancer (SCALOP) trial, including validation of the QLQ-PAN26 tool in CRT. METHODS AND MATERIALS: Patients with locally advanced, inoperable, nonmetastatic carcinoma of the pancreas were eligible. Following 12 weeks of induction gemcitabine plus capecitabine (GEMCAP) chemotherapy, patients with stable and responding disease were randomized to a further cycle of GEMCAP followed by capecitabine- or gemcitabine-based CRT. HRQL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the EORTC Pancreatic Cancer module (PAN26). RESULTS: A total of 114 patients from 28 UK centers were registered and 74 patients randomized. There was improvement in the majority of HRQL scales during induction chemotherapy. Patients with significant deterioration in fatigue, appetite loss, and gastrointestinal symptoms during CRT recovered within 3 weeks following CRT. Differences in changes in HRQL scores between trial arms rarely reached statistical significance; however, where they did, they favored capecitabine therapy. PAN26 scales had good internal consistency and were able to distinguish between subgroups of patients experiencing toxicity. CONCLUSIONS: Although there is deterioration in HRQL following CRT, this resolves within 3 weeks. HRQL data support the use of capecitabine- over gemcitabine-based chemoradiation. The QLQ-PAN26 is a reliable and valid tool for use in patients receiving CRT.

4 Clinical Trial Stereotactic body radiation therapy with concurrent full-dose gemcitabine for locally advanced pancreatic cancer: a pilot trial demonstrating safety. 2013

Gurka, Marie K / Collins, Sean P / Slack, Rebecca / Tse, Gary / Charabaty, Aline / Ley, Lisa / Berzcel, Liam / Lei, Siyuan / Suy, Simeng / Haddad, Nadim / Jha, Reena / Johnson, Colin D / Jackson, Patrick / Marshall, John L / Pishvaian, Michael J. ·Department of Radiation Oncology, Georgetown University Hospital, Washington, DC 20007, USA. ·Radiat Oncol · Pubmed #23452509.

ABSTRACT: BACKGROUND: Concurrent chemoradiation is a standard option for locally advanced pancreatic cancer (LAPC). Concurrent conventional radiation with full-dose gemcitabine has significant toxicity. Stereotactic body radiation therapy (SBRT) may provide the opportunity to administer radiation in a shorter time frame with similar efficacy and reduced toxicity. This Pilot study assessed the safety of concurrent full-dose gemcitabine with SBRT for LAPC. METHODS: Patients received gemcitabine, 1000 mg/m2 for 6 cycles. During week 4 of cycle 1, patients received SBRT (25 Gy delivered in five consecutive daily fractions of 5 Gy prescribed to the 75-83% isodose line). Acute and late toxicities were assessed using NIH CTCAE v3. Tumor response was assessed by RECIST. Patients underwent an esophagogastroduodenoscopy at baseline, 2, and 6 months to assess the duodenal mucosa. Quality of life (QoL) data was collected before and after treatment using the QLQ-C30 and QLQ-PAN26 questionnaires. RESULTS: Between September 2009 and February 2011, 11 patients enrolled with one withdrawal during radiation therapy. Patients had grade 1 to 2 gastrointestinal toxicity from the start of SBRT to 2 weeks after treatment. There were no grade 3 or greater radiation-related toxicities or delays for cycle 2 of gemcitabine. On endoscopy, there were no grade 2 or higher mucosal toxicities. Two patients had a partial response. The median progression free and overall survival were 6.8 and 12.2 months, respectively. Global QoL did not change between baseline and immediately after radiation treatment. CONCLUSIONS: SBRT with concurrent full dose gemcitabine is safe when administered to patients with LAPC. There is no delay in administration of radiation or chemotherapy, and radiation is completed with minimal toxicity.

5 Article PET-PANC: multicentre prospective diagnostic accuracy and health economic analysis study of the impact of combined modality 18fluorine-2-fluoro-2-deoxy-d-glucose positron emission tomography with computed tomography scanning in the diagnosis and management of pancreatic cancer. 2018

Ghaneh, Paula / Hanson, Robert / Titman, Andrew / Lancaster, Gill / Plumpton, Catrin / Lloyd-Williams, Huw / Yeo, Seow Tien / Edwards, Rhiannon Tudor / Johnson, Colin / Abu Hilal, Mohammed / Higginson, Antony P / Armstrong, Tom / Smith, Andrew / Scarsbrook, Andrew / McKay, Colin / Carter, Ross / Sutcliffe, Robert P / Bramhall, Simon / Kocher, Hemant M / Cunningham, David / Pereira, Stephen P / Davidson, Brian / Chang, David / Khan, Saboor / Zealley, Ian / Sarker, Debashis / Al Sarireh, Bilal / Charnley, Richard / Lobo, Dileep / Nicolson, Marianne / Halloran, Christopher / Raraty, Michael / Sutton, Robert / Vinjamuri, Sobhan / Evans, Jonathan / Campbell, Fiona / Deeks, Jon / Sanghera, Bal / Wong, Wai-Lup / Neoptolemos, John P. ·Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK. · Liverpool Cancer Research UK Cancer Trials Unit, University of Liverpool, Liverpool, UK. · Department of Mathematics and Statistics, Lancaster University, Lancaster, UK. · Centre for Health Economics and Medicines Evaluation, Bangor University, Bangor, UK. · Faculty of Medicine, University of Southampton, Southampton, UK. · Department of Surgery, University Hospital Southampton NHS Foundation Trust, Southampton, UK. · Department of Radiology, Portsmouth Hospitals NHS Trust, Portsmouth, UK. · Department of Gastrointestinal Surgery, Leeds Teaching Hospitals NHS Trust, Leeds, UK. · Department of Radiology, Leeds Teaching Hospitals NHS Trust, Leeds, UK. · Department of Surgery, Glasgow Royal Infirmary, NHS Greater Glasgow and Clyde, Glasgow, UK. · Department of Surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK. · Department of General Surgery, Wye Valley NHS Trust, Hereford, UK. · Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, London, UK. · Gastrointestinal and Lymphoma Unit, Royal Marsden NHS Foundation Trust, London, UK. · Institute for Liver and Digestive Health, University College London Hospitals NHS Foundation Trust, London, UK. · Department of Surgery, Royal Free London NHS Foundation Trust, London, UK. · Department of Surgery, Royal Blackburn Hospital, East Lancashire Hospitals NHS Trust, Blackburn, UK. · Department of Surgery, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK. · Department of Surgery, Ninewells Hospital and Medical School, NHS Tayside, Dundee, UK. · Department of Oncology, King's College Hospital NHS Foundation Trust, London, UK. · Department of Surgery, Morriston Hospital, Abertawe Bro Morgannwg University Health Board, Swansea, UK. · Department of Surgery, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK. · Faculty of Medicine and Life Sciences, University of Nottingham, Nottingham, UK. · Department of Oncology, Aberdeen Royal Infirmary, NHS Grampian, Aberdeen, UK. · Department of Surgery, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK. · Department of Nuclear Medicine, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK. · Department of Radiology, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK. · Department of Pathology, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK. · Institute of Applied Health Research, University of Birmingham, Birmingham, UK. · Paul Strickland Scanner Centre, Mount Vernon Hospital, Middlesex, UK. ·Health Technol Assess · Pubmed #29402376.

ABSTRACT: BACKGROUND: Pancreatic cancer diagnosis and staging can be difficult in 10-20% of patients. Positron emission tomography (PET)/computed tomography (CT) adds precise anatomical localisation to functional data. The use of PET/CT may add further value to the diagnosis and staging of pancreatic cancer. OBJECTIVE: To determine the incremental diagnostic accuracy and impact of PET/CT in addition to standard diagnostic work-up in patients with suspected pancreatic cancer. DESIGN: A multicentre prospective diagnostic accuracy and clinical value study of PET/CT in suspected pancreatic malignancy. PARTICIPANTS: Patients with suspected pancreatic malignancy. INTERVENTIONS: All patients to undergo PET/CT following standard diagnostic work-up. MAIN OUTCOME MEASURES: The primary outcome was the incremental diagnostic value of PET/CT in addition to standard diagnostic work-up with multidetector computed tomography (MDCT). Secondary outcomes were (1) changes in patients' diagnosis, staging and management as a result of PET/CT; (2) changes in the costs and effectiveness of patient management as a result of PET/CT; (3) the incremental diagnostic value of PET/CT in chronic pancreatitis; (4) the identification of groups of patients who would benefit most from PET/CT; and (5) the incremental diagnostic value of PET/CT in other pancreatic tumours. RESULTS: Between 2011 and 2013, 589 patients with suspected pancreatic cancer underwent MDCT and PET/CT, with 550 patients having complete data and in-range PET/CT. Sensitivity and specificity for the diagnosis of pancreatic cancer were 88.5% and 70.6%, respectively, for MDCT and 92.7% and 75.8%, respectively, for PET/CT. The maximum standardised uptake value (SUV CONCLUSION: PET/CT provided a significant incremental diagnostic benefit in the diagnosis of pancreatic cancer and significantly influenced the staging and management of patients. PET/CT had limited utility in chronic pancreatitis and other pancreatic tumours. PET/CT is likely to be cost-effective at current reimbursement rates for PET/CT to the UK NHS. This was not a randomised controlled trial and therefore we do not have any information from patients who would have undergone MDCT only for comparison. In addition, there were issues in estimating costs for PET/CT. Future work should evaluate the role of PET/CT in intraductal papillary mucinous neoplasm and prognosis and response to therapy in patients with pancreatic cancer. STUDY REGISTRATION: Current Controlled Trials ISRCTN73852054 and UKCRN 8166. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

6 Article Health-related Quality of Life and Functional Outcomes in 5-year Survivors After Pancreaticoduodenectomy. 2017

Fong, Zhi Ven / Alvino, Donna M / Castillo, Carlos Fernández-Del / Nipp, Ryan D / Traeger, Lara N / Ruddy, Margaret / Lubitz, Carrie C / Johnson, Colin D / Chang, David C / Warshaw, Andrew L / Lillemoe, Keith D / Ferrone, Cristina R. ·*Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA †Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA ‡Department of Psychology, Massachusetts General Hospital, Harvard Medical School, Boston, MA §Department of Surgery, University of Southampton, Southampton, UK. ·Ann Surg · Pubmed #28657944.

ABSTRACT: OBJECTIVE: Our aim was to assess quality of life (QOL) and functionality in a large cohort of patients ≥5-years after pancreaticoduodenectomy (PD). BACKGROUND: Long-term QOL outcomes after PD for benign or malignant disease are largely undocumented. METHODS: We administered the EORTC QLQ-C30 questionnaire to patients who underwent PD for neoplasms from 1998 to 2011 and compared their scores with an age- and sex-matched normal population. Clinical relevance (CR) of differences was scored as small (5-10), moderate (10-20), or large (>20) based on validated interpretation of clinically important differences. RESULTS: Of 305 PD survivors, 245 (80.3%) responded, of whom 157 (64.1%) underwent PD for nonmalignant lesions. Median follow-up was 9.1 years (range 5.1 -21.2 yrs). New-onset diabetes developed in 10.6%; 50.4% reported taking pancreatic enzymes; 54.6% reported needing antacids. Compared with the age- and sex-adjusted controls, PD survivors demonstrated higher global QOL (78.7 vs 69.7, CR small, P < 0.001), physical (86.7 vs 77.9, CR small, P < 0.001) and role-functioning scores (86.3 vs 74.1, CR medium, P < 0.001). Using linear regression and adjusting for socioeconomic variables, there were no differences in QOL or functional scores in the benign versus malignant subgroups. Older age at operation was associated with worse physical-functioning (-0.4/yr, P = 0.008). Taking pancrelipase (-6.8, P = 0.035) or antacids (-6.3, P = 0.044) were both associated with lower social-functioning scores. CONCLUSIONS: Patients who had a PD demonstrated better global QOL, physical- and role-functioning scores at 5-years when compared with age- and sex-matched controls. Approximately half of the patients required pancreatic enzyme replacement, while only 11% developed new-onset diabetes.

7 Article Pro-migratory and TGF-β-activating functions of αvβ6 integrin in pancreatic cancer are differentially regulated via an Eps8-dependent GTPase switch. 2017

Tod, Jo / Hanley, Christopher J / Morgan, Mark R / Rucka, Marta / Mellows, Toby / Lopez, Maria-Antoinette / Kiely, Philip / Moutasim, Karwan A / Frampton, Steven J / Sabnis, Durgagauri / Fine, David R / Johnson, Colin / Marshall, John F / Scita, Giorgio / Jenei, Veronika / Thomas, Gareth J. ·Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Tremona Road, Southampton, UK. · Institute of Translational Medicine, University of Liverpool, Crown Street, Liverpool, UK. · Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Tremona Road, Southampton, UK. · Barts Cancer Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, UK. · IFOM FOM Foundation, Institute FIRC of Molecular Oncology and University of Milan, School of Medicine, Department of Oncology and Hemato-Oncology-DIPO, Via Adamello, Milan, Italy. ·J Pathol · Pubmed #28608476.

ABSTRACT: The integrin αvβ6 is up-regulated in numerous carcinomas, where expression commonly correlates with poor prognosis. αvβ6 promotes tumour invasion, partly through regulation of proteases and cell migration, and is also the principal mechanism by which epithelial cells activate TGF-β1; this latter function complicates therapeutic targeting of αvβ6, since TGF-β1 has both tumour-promoting and -suppressive effects. It is unclear how these different αvβ6 functions are linked; both require actin cytoskeletal reorganization, and it is suggested that tractive forces generated during cell migration activate TGF-β1 by exerting mechanical tension on the ECM-bound latent complex. We examined the functional relationship between cell invasion and TGF-β1 activation in pancreatic ductal adenocarcinoma (PDAC) cells, and confirmed that both processes are αvβ6-dependent. Surprisingly, we found that cellular functions could be biased towards either motility or TGF-β1 activation depending on the presence or absence of epidermal growth factor receptor pathway substrate 8 (Eps8), a regulator of actin remodelling, endocytosis, and GTPase activation. Similar to αvβ6, we found that Eps8 was up-regulated in >70% of PDACs. In complex with Abi1/Sos1, Eps8 regulated αvβ6-dependent cell migration through activation of Rac1. Down-regulation of Eps8, Sos1 or Rac1 suppressed cell movement, while simultaneously increasing αvβ6-dependent TGF-β1 activation. This latter effect was modulated through increased cell tension, regulated by Rho activation. Thus, the Eps8/Abi1/Sos1 tricomplex acts as a key molecular switch altering the balance between Rac1 and Rho activation; its presence or absence in PDAC cells modulates αvβ6-dependent functions, resulting in a pro-migratory (Rac1-dependent) or a pro-TGF-β1 activation (Rho-dependent) functional phenotype, respectively. © 2017 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

8 Article Laparoscopic versus open distal pancreatectomy: a clinical and cost-effectiveness study. 2012

Abu Hilal, Mohammad / Hamdan, Mohammed / Di Fabio, Francesco / Pearce, Neil W / Johnson, Colin D. ·Hepatobiliary-Pancreatic and Laparoscopic Surgical Unit, Southampton University Hospitals NHS Foundation Trust, Southampton, UK. abu_hlal@yahoo.com ·Surg Endosc · Pubmed #22179475.

ABSTRACT: BACKGROUND: Laparoscopic distal pancreatectomy (LDP) is being increasingly performed with some concerns regarding the cost of the minimally invasive approach. The purpose of this study was to assess the cost-effectiveness of LDP versus open distal pancreatectomy (ODP). METHODS: A retrospective clinical and cost-comparison analysis was performed for patients who underwent LDP vs. OPD between 2005 and 2011. Data considered for the comparison analysis were: operative costs (surgical procedure, operative time, blood transfusions), postoperative costs (laboratory testing, hospital stay, complication management, readmissions), and overall costs. RESULTS: Fifty-one distal pancreatectomies (laparoscopic = 35, open = 16) were performed during the study period. The median operative time was 200 (range, 120-420) min for LDP vs. 225 (range, 120-460) min for ODP (p = 0.93). Median blood loss was 200 (range, 50-900) mL for LDP vs. 394 (range, 75-2000) mL for ODP (p = 0.038). Median hospital stay was 7 (range, 3-25) days in the laparoscopic group vs. 11 (range, 5-46) days in the open group (p = 0.007). Complication rate was 40% for LDP vs. 69% in ODP (p = 0.075). Postoperative intervention was required in 11% of patients after LDP vs. 31% after ODP (p = 0.12). The average operative, postoperative, and overall cost was £6039 (range, £4276-£9500), £4547 (range, £1299-£13937), £10587 (range, £6508-£20303) vs. £5231 (range, £3409-£9330), £10094 (range, £2665-£39291), £15324 (range, £7209-£47484) for the LDP and ODP groups, respectively (p = 0.033; p = 0.006; p = 0.197). CONCLUSIONS: We showed that LDP is feasible and safe without having a negative impact on cost. Extensive experience in pancreatic and laparoscopic surgery is required to optimize surgical outcomes.

9 Article Management of median arcuate ligament syndrome in patients who require pancreaticoduodenectomy. 2011

Whistance, Robert N / Shah, Vallari / Grist, Emily R / Shearman, Clifford P / Pearce, Neil W / Odurny, Allan / Stedman, Brian / Johnson, Colin D. ·Department of Hepatobiliary and Pancreatic Surgery, Southampton General Hospital, UK. robert.whistance@hotmail.co.uk ·Ann R Coll Surg Engl · Pubmed #21944786.

ABSTRACT: Pancreaticoduodenectomy is the standard treatment for localised neoplasms of the pancreatic head. The operation can be performed safely in specialist units but good outcome is compromised if postoperative blood flow to the liver and biliary tree is inadequate. Coeliac artery occlusion with blood supply to the liver arising from the superior mesenteric artery via the gastroduodenal artery is difficult to recognise, especially intraoperatively. Recognition of absent hepatic artery pulsation after occlusion of the gastroduodenal artery opens a dilemma: should the resection be abandoned or should vascular reconstruction be undertaken, adding risk to an already complex procedure? We describe two cases with a resectable pancreatic endocrine tumour in which coeliac artery occlusion caused by median arcuate ligament compression was identified from cross-sectional imaging and reconstructions. We highlight two different strategies to correct the vascular insufficiency and allow safe pancreatic resection.

10 Article An open randomized comparison of clinical effectiveness of protocol-driven opioid analgesia, celiac plexus block or thoracoscopic splanchnicectomy for pain management in patients with pancreatic and other abdominal malignancies. 2009

Johnson, Colin D / Berry, D P / Harris, S / Pickering, R M / Davis, C / George, S / Imrie, C W / Neoptolemos, J P / Sutton, R. ·University Surgical Unit (816), Southampton General Hospital, Southampton, UK. c.d.johnson@soton.ac.uk ·Pancreatology · Pubmed #20090396.

ABSTRACT: METHODS: Patients with confirmed irresectable malignancy of the pancreas or upper abdominal viscera who required opioid analgesia were randomized to MM alone, MM+CPB, or MM+TS. Randomization was stratified by treatment centre, tumour type and previous opioid medication. The primary endpoint was pain relief at 2 months. RESULTS: 65 patients (58 pancreas cancer) were randomized, 18 withdrew or died within 2 months. Effective pain relief was achieved in only one third of subjects at 2 weeks, and just under half at 2 months (MM: 6/19 and 5/12 evaluable patients; CPB: 5/14 and 5/9; TS 4/14 and 4/11). There were no significant differences between the groups in pain scores or opioid consumption, and there was no correlation between continued use of opioids and effective pain relief. DISCUSSION: Previous randomized studies have shown small differences in pain scores, but no difference in opioid consumption and quality of life. The absence of any benefit from interventions in the present study questions their value.

11 Article Aggressive multi-visceral pancreatic resections for locally advanced neuroendocrine tumours. Is it worth it? 2009

Abu Hilal, Mohammed / McPhail, Mark J W / Zeidan, Bashar A / Jones, Ceri E / Johnson, Colin D / Pearce, Neil W. ·University Surgical Unit, Southampton General Hospital, Southampton, United Kingdom. abuhlal@yahoo.com ·JOP · Pubmed #19454819.

ABSTRACT: CONTEXT: Traditional surgical principles state that pancreatic resection should not be contemplated when malignancies arise in the pancreas and involve other organs. While this is logic for ductal adenocarcinoma and other tumours with aggressive biological behavior; for even large neuroendocrine tumours, aggressive multivisceral resection may achieve useful palliation and excellent survival. DESIGN: Case records were retrospectively analyzed. PATIENTS AND INTERVENTIONS: Twelve consecutive patients (7 males, 5 females; median age 57 years, range: 37-79 years) underwent multi-visceral en bloc resections for neuroendocrine tumour arising in the pancreas between 1994 and 2008. RESULTS: Three patients underwent pancreaticoduodenectomy; 9 patients had left sided pancreatic resections for neuroendocrine tumour of median diameter 9.5 cm (5-25 cm). They had a median of 3 (range: 1-4) additional organs resected. There were no post-operative deaths or late mortality with median follow up of 24 months. Five patients experienced a complication (major in 3 patients). Median disease free survival was not attained and 3 patients experienced recurrent disease mostly in the liver and may be candidates for further resection. CONCLUSION: Aggressive multi-visceral resection for locally advanced neuroendocrine tumour involving the pancreas is technically feasible and in selected patients can be achieved with low mortality and acceptable morbidity, offering good disease free and overall survival. However this complex surgery should be only performed in specialist centers.