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Pancreatic Neoplasms: HELP
Articles by Dr. J Neoptolemos
Based on 104 articles published since 2008
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Between 2008 and 2019, J. Neoptolemos wrote the following 104 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5
1 Guideline Consensus statement on mandatory measurements in pancreatic cancer trials (COMM-PACT) for systemic treatment of unresectable disease. 2018

Ter Veer, Emil / van Rijssen, L Bengt / Besselink, Marc G / Mali, Rosa M A / Berlin, Jordan D / Boeck, Stefan / Bonnetain, Franck / Chau, Ian / Conroy, Thierry / Van Cutsem, Eric / Deplanque, Gael / Friess, Helmut / Glimelius, Bengt / Goldstein, David / Herrmann, Richard / Labianca, Roberto / Van Laethem, Jean-Luc / Macarulla, Teresa / van der Meer, Jonathan H M / Neoptolemos, John P / Okusaka, Takuji / O'Reilly, Eileen M / Pelzer, Uwe / Philip, Philip A / van der Poel, Marcel J / Reni, Michele / Scheithauer, Werner / Siveke, Jens T / Verslype, Chris / Busch, Olivier R / Wilmink, Johanna W / van Oijen, Martijn G H / van Laarhoven, Hanneke W M. ·Department of Medical Oncology, Cancer Center Amsterdam, Academic Medical Center, Amsterdam, Netherlands. · Department of Surgery, Cancer Center Amsterdam, Academic Medical Center, Amsterdam, Netherlands. · Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA. · Department of Internal Medicine III, Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Munich, Germany. · Methodology and Quality of Life in Oncology Unit, University Hospital of Besançon, Besançon, France. · Royal Marsden NHS Foundation Trust, London and Surrey, UK. · Department of Medical Oncology, Institut de Cancérologie de Lorraine and Lorraine University, Vandoeuvre-lès-Nancy, France. · Department of Gastroenterology and Digestive Oncology, University Hospitals Gasthuisberg Leuven and KU Leuven, Leuven, Belgium. · Department of Oncology, Hôpital Riviera-Chablais, Vevey, Switzerland. · Department of Surgery, Technical University of Munich, Klinikum rechts der Isar, Munich, Germany. · Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. · Nelune Cancer Centre, Prince of Wales Hospital, Prince of Wales Clinical School University of New South Wales, Randwick, NSW, Australia. · Department of Medical Oncology, University Hospital Basel, Basel, Switzerland. · Cancer Center, ASST Papa Giovanni XXIII, Bergamo, Italy. · Department of Gastroenterology, Gastrointestinal Cancer Unit, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium. · Vall d'Hebron University Hospital (HUVH), Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. · Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK. · Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan. · Gastrointestinal Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY, USA. · Department of Hematology, Oncology and Tumor Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany; Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany; Berlin Institute of Health, Berlin, Germany. · Department of Oncology, Karmanos Cancer Center, Wayne State University, Detroit, MI, USA. · Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy. · Department of Internal Medicine I, Medical University Vienna, Vienna, Austria. · Division of Solid Tumor Translational Oncology, West German Cancer Cancer, University Hospital Essen, Essen, Germany; German Cancer Consortium (DKTK, partner site Essen) and German Cancer Research Center, DKFZ, Heidelberg, Germany. · Department of Digestive Oncology, University Hospitals Leuven, Leuven, Belgium. · Department of Medical Oncology, Cancer Center Amsterdam, Academic Medical Center, Amsterdam, Netherlands. Electronic address: h.vanlaarhoven@amc.uva.nl. ·Lancet Oncol · Pubmed #29508762.

ABSTRACT: Variations in the reporting of potentially confounding variables in studies investigating systemic treatments for unresectable pancreatic cancer pose challenges in drawing accurate comparisons between findings. In this Review, we establish the first international consensus on mandatory baseline and prognostic characteristics in future trials for the treatment of unresectable pancreatic cancer. We did a systematic literature search to find phase 3 trials investigating first-line systemic treatment for locally advanced or metastatic pancreatic cancer to identify baseline characteristics and prognostic variables. We created a structured overview showing the reporting frequencies of baseline characteristics and the prognostic relevance of identified variables. We used a modified Delphi panel of two rounds involving an international panel of 23 leading medical oncologists in the field of pancreatic cancer to develop a consensus on the various variables identified. In total, 39 randomised controlled trials that had data on 15 863 patients were included, of which 32 baseline characteristics and 26 prognostic characteristics were identified. After two consensus rounds, 23 baseline characteristics and 12 prognostic characteristics were designated as mandatory for future pancreatic cancer trials. The COnsensus statement on Mandatory Measurements in unresectable PAncreatic Cancer Trials (COMM-PACT) identifies a mandatory set of baseline and prognostic characteristics to allow adequate comparison of outcomes between pancreatic cancer studies.

2 Guideline Guidelines for time-to-event end-point definitions in trials for pancreatic cancer. Results of the DATECAN initiative (Definition for the Assessment of Time-to-event End-points in CANcer trials). 2014

Bonnetain, Franck / Bonsing, Bert / Conroy, Thierry / Dousseau, Adelaide / Glimelius, Bengt / Haustermans, Karin / Lacaine, François / Van Laethem, Jean Luc / Aparicio, Thomas / Aust, Daniela / Bassi, Claudio / Berger, Virginie / Chamorey, Emmanuel / Chibaudel, Benoist / Dahan, Laeticia / De Gramont, Aimery / Delpero, Jean Robert / Dervenis, Christos / Ducreux, Michel / Gal, Jocelyn / Gerber, Erich / Ghaneh, Paula / Hammel, Pascal / Hendlisz, Alain / Jooste, Valérie / Labianca, Roberto / Latouche, Aurelien / Lutz, Manfred / Macarulla, Teresa / Malka, David / Mauer, Muriel / Mitry, Emmanuel / Neoptolemos, John / Pessaux, Patrick / Sauvanet, Alain / Tabernero, Josep / Taieb, Julien / van Tienhoven, Geertjan / Gourgou-Bourgade, Sophie / Bellera, Carine / Mathoulin-Pélissier, Simone / Collette, Laurence. ·Methodology and Quality of Life Unit in Cancer, EA 3181, University Hospital of Besançon and CTD-INCa Gercor, UNICNCER GERICO, Besançon, France. Electronic address: franck.bonnetain@univ-fcomte.fr. · Leiden University Medical Center, Leiden, Netherlands. · Department of Medical Oncology, Institut de Cancérologie de Lorraine, Vandoeuvre-les-Nancy, France. · Bordeaux Segalen University & CHRU, Bordeaux, France. · Department of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala, Sweden. · Department of Radiation Oncology, Leuven, Belgium. · Digestive Surgical Department, Tenon hospital, Paris, France. · Gastro Intestinal Cancer Unit Erasme Hospital Brussels, Belgium. · Gastroenterology Department, Avicenne Hospital, Paris 13, Bobigny, France. · Institute for Pathology, University Hospital Carl-Gustav-Carus, Dresden, Germany. · Surgical and Gastroenterological Department, Endocrine and Pancreatic Unit, Hospital of 'G.B.Rossi', University of Verona, Italy. · Institut de Cancérologie de l'Ouest - Centre Paul Papin Centre de Lutte Contre le Cancer (CLCC), Angers, France. · Biostatistics Unit, Centre Antoine Lacassagne, Nice, France. · Oncology Department, Hôpital Saint-Antoine & CTD-INCa GERCOR, Assistance Publique des Hôpitaux de Paris, UPMC Paris VI, Paris, France. · Gastroenterology Department, Hopital la Timone, Assitance publique des Hopitaux de Marseille, Marseille, France. · Department of Surgery, Institut Paoli Calmettes, Marseille, France. · Department of Surgery, Agia Olga Hospital, Athens, Greece. · Department of Gastroenterology, Institut Gustave Roussy, Villejuif, France. · Biostatistician, Biostatistics Unit, Centre Antoine Lacassagne, Nice, France. · Department of Radiotherapy, Institut fuer Radioonkologie, Vienna, Austria. · Department of Surgical Oncology, Royal Liverpool Hospital, United Kingdom. · Department of Gastroenterology, Beaujon Hospital, Assistance Publique des Hôpitaux de Paris, Paris, France. · Digestive Oncology and Gastro-enterology Department, Jules Bordet Institute, Brussels, Belgium. · Digestive Cancer Registry, INSERM U866, Dijon, France. · Medical Oncology Unit, Ospedali Riuniti di Bergamo, Bergame, Italy. · Inserm, Centre for Research in Epidemiology and Population Health, U1018, Biostatistics Team, Villejuif, France. · Gastroenterology Department, Caritas Hospital, Saarbrücken, Germany. · Department of the Gastrointestinal Tumors and Phase I Unit, Vall d'Hebron University Hospital, Barcelona, Spain. · Statistics Department, EORTC, Brussels, Belgium. · Department of Medical Oncology, Institut Curie, Hôpital René Huguenin, Saint-Cloud, France. · Division of Surgery and Oncology at the University of Liverpool and Royal Liverpool University Hospital, Liverpool, United Kingdom. · Department of Digestive Surgery, Universitu Hospital Strasbourg, France. · Department of Hepato-pancreatic and Biliary Surgery, Beaujon Hospital, Assistance Publique des Hôpitaux de Paris, Paris, France. · Department of Hepato-gastroenterology and Digestive Oncology, Georges Pompidou European hospital, Paris, France. · Department of Radiation Oncology, Academisch Medisch Centrum, Amsterdam, The Netherlands. · Institut Du Cancer de Montpellier, Comprehensive Cancer Centre, and Data Center for Cancer Clinical Trials, CTD-INCa, Montpellier, France. · Clinical and Epidemiological Research Unit, Institut Bergonie, Comprehensive Cancer Centre, Bordeaux, France; Data Center for Cancer Clinical Trials, CTD-INCa, Bordeaux, France; INSERM, Centre d'Investigation Clinique - Épidémiologie Clinique CIC-EC 7, F-33000 Bordeaux, France. ·Eur J Cancer · Pubmed #25256896.

ABSTRACT: BACKGROUND: Using potential surrogate end-points for overall survival (OS) such as Disease-Free- (DFS) or Progression-Free Survival (PFS) is increasingly common in randomised controlled trials (RCTs). However, end-points are too often imprecisely defined which largely contributes to a lack of homogeneity across trials, hampering comparison between them. The aim of the DATECAN (Definition for the Assessment of Time-to-event End-points in CANcer trials)-Pancreas project is to provide guidelines for standardised definition of time-to-event end-points in RCTs for pancreatic cancer. METHODS: Time-to-event end-points currently used were identified from a literature review of pancreatic RCT trials (2006-2009). Academic research groups were contacted for participation in order to select clinicians and methodologists to participate in the pilot and scoring groups (>30 experts). A consensus was built after 2 rounds of the modified Delphi formal consensus approach with the Rand scoring methodology (range: 1-9). RESULTS: For pancreatic cancer, 14 time to event end-points and 25 distinct event types applied to two settings (detectable disease and/or no detectable disease) were considered relevant and included in the questionnaire sent to 52 selected experts. Thirty experts answered both scoring rounds. A total of 204 events distributed over the 14 end-points were scored. After the first round, consensus was reached for 25 items; after the second consensus was reached for 156 items; and after the face-to-face meeting for 203 items. CONCLUSION: The formal consensus approach reached the elaboration of guidelines for standardised definitions of time-to-event end-points allowing cross-comparison of RCTs in pancreatic cancer.

3 Guideline Definition of a standard lymphadenectomy in surgery for pancreatic ductal adenocarcinoma: a consensus statement by the International Study Group on Pancreatic Surgery (ISGPS). 2014

Tol, Johanna A M G / Gouma, Dirk J / Bassi, Claudio / Dervenis, Christos / Montorsi, Marco / Adham, Mustapha / Andrén-Sandberg, Ake / Asbun, Horacio J / Bockhorn, Maximilian / Büchler, Markus W / Conlon, Kevin C / Fernández-Cruz, Laureano / Fingerhut, Abe / Friess, Helmut / Hartwig, Werner / Izbicki, Jakob R / Lillemoe, Keith D / Milicevic, Miroslav N / Neoptolemos, John P / Shrikhande, Shailesh V / Vollmer, Charles M / Yeo, Charles J / Charnley, Richard M / Anonymous3050801. ·Department of Surgery, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. · Department of Surgery, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. Electronic address: D.J.Gouma@amc.nl. · Department of Surgery and Oncology, Pancreas Institute, University of Verona, Verona, Italy. · Department of First Surgery, Agia Olga Hospital, Athens, Greece. · Department of General Surgery, Instituto Clinico Humanitas IRCCS, University of Milan, Milan, Italy. · Department of HPB Surgery, Hopital Edouard Herriot, Lyon, France. · Department of Surgery, Karolinska Institutet at Karolinska University Hospital, Huddinge, Stockholm, Sweden. · Department of General Surgery, Mayo Clinic, Jacksonville, FL. · Department of General-, Visceral- and Thoracic-Surgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany. · Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany. · Professorial Surgical Unit, University of Dublin, Trinity College, Dublin, Ireland. · Department of Surgery, Clinic Hospital of Barcelona, University of Barcelona, Barcelona, Spain. · First Department of Digestive Surgery, Hippokrateon Hospital, University of Athens, Athens, Greece; Section for Surgical Research, Department of Surgery, Medical University of Graz, Graz, Austria. · Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. · Department of Surgery, Massachusetts General Hospital and the Harvard Medical School, Boston, MA. · First Surgical Clinic, Clinical Center of Serbia, University of Belgrade, Belgrade, Serbia. · Department of Molecular and Clinical Cancer Medicine, Liverpool Cancer Research-UK Centre, University of Liverpool, Liverpool, UK. · Department of Gastrointestinal and HPB Surgical Oncology, Tata Memorial Hospital, Mumbai, India. · Department of Surgery, Penn Medicine, The University of Pennsylvania, Philadelphia, PA. · Department of Surgery, Jefferson Pancreas, Biliary and Related Cancer Center, Thomas Jefferson University, Philadelphia, PA. · Department of HPB & Transplant Surgery, Freeman Hospital, Newcastle upon Tyne, UK. ·Surgery · Pubmed #25061003.

ABSTRACT: BACKGROUND: The lymph node (Ln) status of patients with resectable pancreatic ductal adenocarcinoma is an important predictor of survival. The survival benefit of extended lymphadenectomy during pancreatectomy is, however, disputed, and there is no true definition of the optimal extent of the lymphadenectomy. The aim of this study was to formulate a definition for standard lymphadenectomy during pancreatectomy. METHODS: During a consensus meeting of the International Study Group on Pancreatic Surgery, pancreatic surgeons formulated a consensus statement based on available literature and their experience. RESULTS: The nomenclature of the Japanese Pancreas Society was accepted by all participants. Extended lymphadenectomy during pancreatoduodenectomy with resection of Ln's along the left side of the superior mesenteric artery (SMA) and around the celiac trunk, splenic artery, or left gastric artery showed no survival benefit compared with a standard lymphadenectomy. No level I evidence was available on prognostic impact of positive para-aortic Ln's. Consensus was reached on selectively removing suspected Ln's outside the resection area for frozen section. No consensus was reached on continuing or terminating resection in cases where these nodes were positive. CONCLUSION: Extended lymphadenectomy cannot be recommended. Standard lymphadenectomy for pancreatoduodenectomy should strive to resect Ln stations no. 5, 6, 8a, 12b1, 12b2, 12c, 13a, 13b, 14a, 14b, 17a, and 17b. For cancers of the body and tail of the pancreas, removal of stations 10, 11, and 18 is standard. Furthermore, lymphadenectomy is important for adequate nodal staging. Both pancreatic resection in relatively fit patients or nonresectional palliative treatment were accepted as acceptable treatment in cases of positive Ln's outside the resection plane. This consensus statement could serve as a guide for surgeons and researchers in future directives and new clinical studies.

4 Guideline Extended pancreatectomy in pancreatic ductal adenocarcinoma: definition and consensus of the International Study Group for Pancreatic Surgery (ISGPS). 2014

Hartwig, Werner / Vollmer, Charles M / Fingerhut, Abe / Yeo, Charles J / Neoptolemos, John P / Adham, Mustapha / Andrén-Sandberg, Ake / Asbun, Horacio J / Bassi, Claudio / Bockhorn, Max / Charnley, Richard / Conlon, Kevin C / Dervenis, Christos / Fernandez-Cruz, Laureano / Friess, Helmut / Gouma, Dirk J / Imrie, Clem W / Lillemoe, Keith D / Milićević, Miroslav N / Montorsi, Marco / Shrikhande, Shailesh V / Vashist, Yogesh K / Izbicki, Jakob R / Büchler, Markus W / Anonymous1520795. ·Department of Surgery, Klinikum Großhadern, University of Munich, Munich, Germany. · Department of Gastrointestinal Surgery, Penn Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA. · Department of Digestive Surgery, Centre Hospitalier Intercommunal, Poissy, France. · Department of Surgery, Jefferson Pancreas, Biliary and Related Cancer Center, Thomas Jefferson University, Philadelphia, PA. · Department of Molecular and Clinical Cancer Medicine, Liverpool Cancer Research-UK Centre, University of Liverpool, Liverpool, UK. · Department of HPB Surgery, Hopital Edouard Herriot, Lyon, France. · Department of Surgery, Karolinska Institutet at Karolinska University Hospital, Huddinge, Stockholm, Sweden. · Department of General Surgery, Mayo Clinic, Jacksonville, FL. · Department of Surgery and Oncology, Pancreas Institute, University of Verona, Verona, Italy. · Department of General-, Visceral- and Thoracic-Surgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany. · Department of HPB & Transplant Surgery, Freeman Hospital, Newcastle upon Tyne, UK. · Professorial Surgical Unit, University of Dublin, Trinity College, Dublin, Ireland. · Department of First Surgery, Agia Olga Hospital, Athens, Greece. · Department of Surgery, Clinic Hospital of Barcelona, University of Barcelona, Barcelona, Spain. · Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. · Department of Surgery, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. · Academic Unit of Surgery, University of Glasgow, Glasgow, UK. · Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA. · First Surgical Clinic, Clinical Center of Serbia, University of Belgrade, Belgrade, Serbia. · Department of General Surgery, Instituto Clinico Humanitas IRCCS, University of Milan, Milan, Italy. · Department of Gastrointestinal and HPB Surgical Oncology, Tata Memorial Hospital, Mumbai, India. · Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany. Electronic address: markus.buechler@med.uni-heidelberg.de. ·Surgery · Pubmed #24856668.

ABSTRACT: BACKGROUND: Complete macroscopic tumor resection is one of the most relevant predictors of long-term survival in pancreatic ductal adenocarcinoma. Because locally advanced pancreatic tumors can involve adjacent organs, "extended" pancreatectomy that includes the resection of additional organs may be needed to achieve this goal. Our aim was to develop a common consistent terminology to be used in centers reporting results of pancreatic resections for cancer. METHODS: An international panel of pancreatic surgeons working in well-known, high-volume centers reviewed the literature on extended pancreatectomies and worked together to establish a consensus on the definition and the role of extended pancreatectomy in pancreatic cancer. RESULTS: Macroscopic (R1) and microscopic (R0) complete tumor resection can be achieved in patients with locally advanced disease by extended pancreatectomy. Operative time, blood loss, need for blood transfusions, duration of stay in the intensive care unit, and hospital morbidity, and possibly also perioperative mortality are increased with extended resections. Long-term survival is similar compared with standard resections but appears to be better compared with bypass surgery or nonsurgical palliative chemotherapy or chemoradiotherapy. It was not possible to identify any clear prognostic criteria based on the specific additional organ resected. CONCLUSION: Despite increased perioperative morbidity, extended pancreatectomy is warranted in locally advanced disease to achieve long-term survival in pancreatic ductal adenocarcinoma if macroscopic clearance can be achieved. Definitions of extended pancreatectomies for locally advanced disease (and not distant metastatic disease) are established that are crucial for comparison of results of future trials across different practices and countries, in particular for those using neoadjuvant therapy.

5 Guideline Borderline resectable pancreatic cancer: a consensus statement by the International Study Group of Pancreatic Surgery (ISGPS). 2014

Bockhorn, Maximilian / Uzunoglu, Faik G / Adham, Mustapha / Imrie, Clem / Milicevic, Miroslav / Sandberg, Aken A / Asbun, Horacio J / Bassi, Claudio / Büchler, Markus / Charnley, Richard M / Conlon, Kevin / Cruz, Laureano Fernandez / Dervenis, Christos / Fingerhutt, Abe / Friess, Helmut / Gouma, Dirk J / Hartwig, Werner / Lillemoe, Keith D / Montorsi, Marco / Neoptolemos, John P / Shrikhande, Shailesh V / Takaori, Kyoichi / Traverso, William / Vashist, Yogesh K / Vollmer, Charles / Yeo, Charles J / Izbicki, Jakob R / Anonymous1510795. ·Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany. · Department of HPB Surgery, Hôpital Edouard Herriot, Lyon, France. · Academic Unit of Surgery, University of Glasgow, Glasgow, UK. · First Surgical Clinic, Clinical Center of Serbia, University of Belgrade, Belgrade, Serbia. · Department of Surgery, Karolinska Institutet at Karolinska University Hospital, Huddinge, Stockholm, Sweden. · Department of General Surgery, Mayo Clinic, Jacksonville, FL. · Department of Surgery and Oncology, Pancreas Institute, University of Verona, Verona, Italy. · Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany. · Department of HPB & Transplant Surgery, Freeman Hospital, Newcastle upon Tyne, UK. · Professorial Surgical Unit, University of Dublin, Trinity College, Dublin, Ireland. · Department of Surgery, Clinic Hospital of Barcelona, University of Barcelona, Barcelona, Spain. · First Department of Surgery, Agia Olga Hospital, Athens, Greece. · Department of Digestive Surgery, Centre Hospitalier Intercommunal, Poissy, France. · Department of Surgery, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany. · Department of Surgery, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. · Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA. · Department of General Surgery, Instituto Clinico Humanitas IRCCS, University of Milan, Milan, Italy. · Department of Molecular and Clinical Cancer Medicine, Liverpool Cancer Research-UK Centre, University of Liverpool, Liverpool, UK. · Department of Gastrointestinal and HPB Surgical Oncology, Tata Memorial Centre, Mumbai, India. · Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan. · St. Luke's Clinic - Center For Pancreatic and Liver Diseases, Boise, ID. · Department of Gastrointestinal Surgery, Penn Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA. · Department of Surgery, Jefferson Pancreas, Biliary and Related Cancer Center, Thomas Jefferson University, Philadelphia, PA. · Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany. Electronic address: izbicki@uke.de. ·Surgery · Pubmed #24856119.

ABSTRACT: BACKGROUND: This position statement was developed to expedite a consensus on definition and treatment for borderline resectable pancreatic ductal adenocarcinoma (BRPC) that would have worldwide acceptability. METHODS: An international panel of pancreatic surgeons from well-established, high-volume centers collaborated on a literature review and development of consensus on issues related to borderline resectable pancreatic cancer. RESULTS: The International Study Group of Pancreatic Surgery (ISGPS) supports the National Comprehensive Cancer Network criteria for the definition of BRPC. Current evidence supports operative exploration and resection in the case of involvement of the mesentericoportal venous axis; in addition, a new classification of extrahepatic mesentericoportal venous resections is proposed by the ISGPS. Suspicion of arterial involvement should lead to exploration to confirm the imaging-based findings. Formal arterial resections are not recommended; however, in exceptional circumstances, individual therapeutic approaches may be evaluated under experimental protocols. The ISGPS endorses the recommendations for specimen examination and the definition of an R1 resection (tumor within 1 mm from the margin) used by the British Royal College of Pathologists. Standard preoperative diagnostics for BRPC may include: (1) serum levels of CA19-9, because CA19-9 levels predict survival in large retrospective series; and also (2) the modified Glasgow Prognostic Score and the neutrophil/lymphocyte ratio because of the prognostic relevance of the systemic inflammatory response. Various regimens of neoadjuvant therapy are recommended only in the setting of prospective trials at high-volume centers. CONCLUSION: Current evidence justifies portomesenteric venous resection in patients with BRPC. Basic definitions were identified, that are currently lacking but that are needed to obtain further evidence and improvement for this important patient subgroup. A consensus for each topic is given.

6 Guideline New strategies and designs in pancreatic cancer research: consensus guidelines report from a European expert panel. 2012

Van Laethem, J-L / Verslype, C / Iovanna, J L / Michl, P / Conroy, T / Louvet, C / Hammel, P / Mitry, E / Ducreux, M / Maraculla, T / Uhl, W / Van Tienhoven, G / Bachet, J B / Maréchal, R / Hendlisz, A / Bali, M / Demetter, P / Ulrich, F / Aust, D / Luttges, J / Peeters, M / Mauer, M / Roth, A / Neoptolemos, J P / Lutz, M / Anonymous6430701. ·Gastrointestinal Cancer Unit, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium. jl.vanlaethem@erasme.ulb.ac.be ·Ann Oncol · Pubmed #21810728.

ABSTRACT: Although the treatment of pancreatic ductal adenocarcinoma (PDAC) remains a huge challenge, it is entering a new era with the development of new strategies and trial designs. Because there is an increasing number of novel therapeutic agents and potential combinations available to test in patients with PDAC, the identification of robust prognostic and predictive markers and of new targets and relevant pathways is a top priority as well as the design of adequate trials incorporating molecular-driven hypothesis. We presently report a consensus strategy for research in pancreatic cancer that was developed by a multidisciplinary panel of experts from different European institutions and collaborative groups involved in pancreatic cancer. The expert panel embraces the concept of exploratory early proof of concept studies, based on the prediction of response to novel agents and combinations, and randomised phase II studies permitting the selection of the best therapeutic approach to go forward into phase III, where the recommended primary end point remains overall survival. Trials should contain as many translational components as possible, relying on standardised tissue and blood processing and robust biobanking, and including dynamic imaging. Attention should not only be paid to the pancreatic cancer cells but also to microenvironmental factors and stem/stellate cells.

7 Editorial Clinical evidence does not support the use of adjuvant radiotherapy in pancreatic cancer. 2008

Neoptolemos, John P. · ·Nat Clin Pract Oncol · Pubmed #18668027.

ABSTRACT: -- No abstract --

8 Review Chemotherapy for pancreatic cancer. 2019

Springfeld, Christoph / Jäger, Dirk / Büchler, Markus W / Strobel, Oliver / Hackert, Thilo / Palmer, Daniel H / Neoptolemos, John P. ·Heidelberg University Hospital, National Center for Tumor Diseases, Department of Medical Oncology, Heidelberg, Germany. Electronic address: christoph.springfeld@med.uni-heidelberg.de. · Heidelberg University Hospital, National Center for Tumor Diseases, Department of Medical Oncology, Heidelberg, Germany. · Heidelberg University Hospital, Department of Surgery, Heidelberg, Germany. · University of Liverpool, Department of Molecular and Clinical Cancer Medicine, Liverpool, UK. ·Presse Med · Pubmed #30879894.

ABSTRACT: Chemotherapy is an important part of multimodality pancreatic cancer treatment. After curative resection, adjuvant chemotherapy can significantly improve disease free survival and overall survival. The current standard of care is six months adjuvant chemotherapy with modified folinic acid, 5-fluorouracil, irinotecan and oxaliplatin (mFOLFIRINOX) in patients fit enough for this protocol, otherwise six months of gemcitabine and capecitabine based on the European Study Group for Pancreatic Cancer (ESPAC)-4 study. In patients with metastatic disease, combination chemotherapy according to the FOLFIRINOX protocol or with gemcitabine plus nab-paclitaxel is an important improvement to gemcitabine monotherapy that was the standard for many years. Patients not fit for combination chemotherapy however may still benefit from gemcitabine. Patients with good performance status may benefit from second-line chemotherapy. Chemoradiation has long been used in locally advanced pancreatic cancer but is now tempered following the LAP07 study. This trial showed no difference in overall survival in those patients with stable disease after four months of gemcitabine (with or without erlotinib) randomized to either continuation of gemcitabine therapy or chemoradiation (54Gy with capecitabine). As an alternative to radiation, other forms local therapies including radiofrequency ablation, irreversible electroporation, high-intensity focused ultrasound, microwave ablation and local anti-KRAS therapy (using siG12D-LODER) are currently under investigation. Given the systemic nature of pancreas cancer from an early stage, the success of any local approach other than complete surgical resection (with adjuvant systemic therapy) is likely to be very limited. In patients with locally advanced, irresectable cancer, chemotherapy may offer the chance for secondary resection with a survival similar to patients with primary resectable disease. Downstaging regimens need to be evaluated in prospective randomized trials in order to make firm recommendations. Selection of patient groups for specific therapy including cytotoxics is becoming a reality using assays based on drug cellular transport and metabolism, and molecular signatures. Going forward, high throughput screening of different chemotherapy agents using molecular signatures based on patients' derived organoids holds considerable promise.

9 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.

10 Review Immunohistochemical hENT1 expression as a prognostic biomarker in patients with resected pancreatic ductal adenocarcinoma undergoing adjuvant gemcitabine-based chemotherapy. 2017

Bird, N T E / Elmasry, M / Jones, R / Psarelli, E / Dodd, J / Malik, H / Greenhalf, W / Kitteringham, N / Ghaneh, P / Neoptolemos, J P / Palmer, D. ·Liverpool University Pharmacology Unit, Institute of Translational Medicine, University of Liverpool, Crown Street, Liverpool L69 3BX, UK. ·Br J Surg · Pubmed #28199010.

ABSTRACT: BACKGROUND: Human equilibrative nucleoside transporters (hENTs) are transmembranous proteins that facilitate the uptake of nucleosides and nucleoside analogues, such as gemcitabine, into the cell. The abundance of hENT1 transporters in resected pancreatic ductal adenocarcinoma (PDAC) might make hENT1 a potential biomarker of response to adjuvant chemotherapy. The aim of this study was to see whether hENT1 expression, as determined by immunohistochemistry, was a suitable predictive marker for subsequent treatment with gemcitabine-based adjuvant chemotherapy. METHODS: A systematic review was performed, searching databases from January 1997 to January 2016. Articles pertaining to hENT1 immunohistochemical analysis in resected PDAC specimens from patients who subsequently underwent adjuvant gemcitabine-based chemotherapy were identified. Eligible studies were required to contain survival data, reporting specifically overall survival (OS) and disease-free survival (DFS) with associated hazard ratios (HRs) stratified by hENT1 status. RESULTS: Of 42 articles reviewed, eight were suitable for review, with seven selected for quantitative meta-analysis. The total number of patients included in the meta-analysis was 770 (405 hENT1-negative, 365 hENT1-positive). Immunohistochemically detected hENT1 expression was significantly associated with both prolonged DFS (HR 0·58, 95 per cent c.i. 0·42 to 0·79) and OS (HR 0·52, 0·38 to 0·72) in patients receiving adjuvant gemcitabine but not those having fluoropyrimidine-based adjuvant therapy. CONCLUSION: Expression of hENT1 is a suitable prognostic biomarker in patients undergoing adjuvant gemcitabine-based chemotherapy.

11 Review Designing a bio-inspired biomimetic in vitro system for the optimization of ex vivo studies of pancreatic cancer. 2017

Totti, Stella / Vernardis, Spyros I / Meira, Lisiane / Pérez-Mancera, Pedro A / Costello, Eithne / Greenhalf, William / Palmer, Daniel / Neoptolemos, John / Mantalaris, Athanasios / Velliou, Eirini G. ·Bioprocess and Biochemical Engineering Group (BioProChem), Department of Chemical and Process Engineering, University of Surrey, Guildford GU2 7XH, UK. · Biological Systems Engineering Laboratory (BSEL), Department of Chemical Engineering, Imperial College London, SW7 2AZ London, UK. · Department of Clinical and Experimental Medicine, University of Surrey, Guildford GU2 7XH, UK. · Department of Molecular and Clinical Cancer Medicine, University of Liverpool,Daulby Street, Liverpool L69 3GA, UK. · Department of Molecular and Clinical Cancer Medicine, University of Liverpool,Daulby Street, Liverpool L69 3GA, UK; NIHR Liverpool Pancreas Biomedical Research Unit, University of Liverpool,Daulby Street, Liverpool L69 3GA, UK. · NIHR Liverpool Pancreas Biomedical Research Unit, University of Liverpool,Daulby Street, Liverpool L69 3GA, UK. · Bioprocess and Biochemical Engineering Group (BioProChem), Department of Chemical and Process Engineering, University of Surrey, Guildford GU2 7XH, UK. Electronic address: e.velliou@surrey.ac.uk. ·Drug Discov Today · Pubmed #28153670.

ABSTRACT: Pancreatic cancer is one of the most aggressive and lethal human malignancies. Drug therapies and radiotherapy are used for treatment as adjuvants to surgery, but outcomes remain disappointing. Advances in tissue engineering suggest that 3D cultures can reflect the in vivo tumor microenvironment and can guarantee a physiological distribution of oxygen, nutrients, and drugs, making them promising low-cost tools for therapy development. Here, we review crucial structural and environmental elements that should be considered for an accurate design of an ex vivo platform for studies of pancreatic cancer. Furthermore, we propose environmental stress response biomarkers as platform readouts for the efficient control and further prediction of the pancreatic cancer response to the environmental and treatment input.

12 Review Definition and classification of chyle leak after pancreatic operation: A consensus statement by the International Study Group on Pancreatic Surgery. 2017

Besselink, Marc G / van Rijssen, L Bengt / Bassi, Claudio / Dervenis, Christos / Montorsi, Marco / Adham, Mustapha / Asbun, Horacio J / Bockhorn, Maximillian / Strobel, Oliver / Büchler, Markus W / Busch, Olivier R / Charnley, Richard M / Conlon, Kevin C / Fernández-Cruz, Laureano / Fingerhut, Abe / Friess, Helmut / Izbicki, Jakob R / Lillemoe, Keith D / Neoptolemos, John P / Sarr, Michael G / Shrikhande, Shailesh V / Sitarz, Robert / Vollmer, Charles M / Yeo, Charles J / Hartwig, Werner / Wolfgang, Christopher L / Gouma, Dirk J / Anonymous2270883. ·Department of Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. Electronic address: m.g.besselink@amc.nl. · Department of Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. · Department of Surgery and Oncology, Pancreas Institute, University of Verona, Verona, Italy. · Department of First Surgery, Agia Olga Hospital, Athens, Greece. · Department of Surgery, Humanitas Research Hospital and University, Milan, Italy. · Department of HPB Surgery, Hopital Edouard Herriot, HCL, UCBL1, Lyon, France. · Department of Surgery, Mayo Clinic, Jacksonville, FL. · Department of General-, Visceral-, and Thoracic-Surgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany. · Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany. · Department of HPB & Transplant Surgery, Freeman Hospital, Newcastle upon Tyne, UK. · Professorial Surgical Unit, University of Dublin, Trinity College, Dublin, Ireland. · Department of Surgery, Clinic Hospital of Barcelona, University of Barcelona, Barcelona, Spain. · First Department of Digestive Surgery, Hippokrateon Hospital, University of Athens, Athens, Greece; Section for Surgical Research, Department of Surgery, Medical University of Graz, Graz, Austria. · Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. · Department of Surgery, Massachusetts General Hospital and the Harvard Medical School, Boston, MA. · Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK. · Division of Subspecialty General Surgery, Mayo Clinic, Rochester, MN. · Department of GI and HPB Surgical Oncology, Tata Memorial Hospital, Mumbai, India. · Department of Surgical Oncology, Medical University in Lublin, Poland. · Department of Surgery, Penn Medicine, The University of Pennsylvania, Philadelphia, PA. · Department of Surgery, Jefferson Pancreas, Biliary and Related Cancer Center, Thomas Jefferson University, Philadelphia, PA. · Division of Pancreatic Surgery, Department of General, Visceral, and Transplantation Surgery, Ludwig Maximilians University, University of Munich, Germany. · Department of Surgery, Johns Hopkins Medicine, Baltimore, MD. ·Surgery · Pubmed #27692778.

ABSTRACT: BACKGROUND: Recent literature suggests that chyle leak may complicate up to 10% of pancreatic resections. Treatment depends on its severity, which may include chylous ascites. No international consensus definition or grading system of chyle leak currently is available. METHODS: The International Study Group on Pancreatic Surgery, an international panel of pancreatic surgeons working in well-known, high-volume centers, reviewed the literature and worked together to establish a consensus on the definition and classification of chyle leak after pancreatic operation. RESULTS: Chyle leak was defined as output of milky-colored fluid from a drain, drain site, or wound on or after postoperative day 3, with a triglyceride content ≥110 mg/dL (≥1.2 mmol/L). Three different grades of severity were defined according to the management needed: grade A, no specific intervention other than oral dietary restrictions; grade B, prolongation of hospital stay, nasoenteral nutrition with dietary restriction, total parenteral nutrition, octreotide, maintenance of surgical drains, or placement of new percutaneous drains; and grade C, need for other more invasive in-hospital treatment, intensive care unit admission, or mortality. CONCLUSION: This classification and grading system for chyle leak after pancreatic resection allows for comparison of outcomes between series. As with the other the International Study Group on Pancreatic Surgery consensus statements, this classification should facilitate communication and evaluation of different approaches to the prevention and treatment of this complication.

13 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.

14 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.

15 Review Addressing the challenges of pancreatic cancer: future directions for improving outcomes. 2015

Hidalgo, Manuel / Cascinu, Stefano / Kleeff, Jörg / Labianca, Roberto / Löhr, J-Matthias / Neoptolemos, John / Real, Francisco X / Van Laethem, Jean-Luc / Heinemann, Volker. ·Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain. Electronic address: mhidalgo@cnio.es. · Department of Medical Oncology, University of Ancona, Ancona, Italy. · Department of General Surgery, Technische Universität München, Munich, Germany. · Ospedale Papa Giovanni XXIII, Bergamo, Italy. · Department of Clinical Science, Intervention and Technology, Karolinska Institute, Stockholm, Sweden. · National Institutes of Health Research Liverpool Pancreas Biomedical Research Unit and Cancer Research UK Liverpool Clinical Trials Unit Director, University of Liverpool and Royal Liverpool University Hospital, Liverpool, UK. · Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid and Universitat Pompeu Fabra, Barcelona, Spain. · Department of Gastroenterology-GI Cancer Unit, Erasme University Hospital, Brussels, Belgium. · Comprehensive Cancer Centre Munich, Klinikum der Universität München, Munich, Germany. ·Pancreatology · Pubmed #25547205.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC), which accounts for more than 90% of all pancreatic tumours, is a devastating malignancy with an extremely poor prognosis, as shown by a 1-year survival rate of around 18% for all stages of the disease. The low survival rates associated with PDAC primarily reflect the fact that tumours progress rapidly with few specific symptoms and are thus at an advanced stage at diagnosis in most patients. As a result, there is an urgent need to develop accurate markers of pre-invasive pancreatic neoplasms in order to facilitate prediction of cancer risk and to help diagnose the disease at an earlier stage. However, screening for early diagnosis of prostate cancer remains challenging and identifying a highly accurate, low-cost screening test for early PDAC for use in clinical practice remains an important unmet need. More effective therapies are also crucial in PDAC, since progress in identifying novel therapies has been hampered by the genetic complexity of the disease and treatment remains a major challenge. Presently, the greatest step towards improved treatment efficacy has been made in the field of palliative chemotherapy by introducing FOLFIRINOX (folinic acid, 5-fluorouracil, irinotecan and oxaliplatin) and gemcitabine/nab-paclitaxel. Strategies designed to raise the profile of PDAC in research and clinical practice are a further requirement in order to ensure the best treatment for patients. This article proposes a number of approaches that may help to accelerate progress in treating patients with PDAC, which, in turn, may be expected to improve the quality of life and survival for those suffering from this devastating disease.

16 Review New biomarkers and targets in pancreatic cancer and their application to treatment. 2012

Costello, Eithne / Greenhalf, William / Neoptolemos, John P. ·National Institute for Health Research Pancreas Biomedical Research Unit and Liverpool Cancer Research UK Centre, Department of Molecular, University of Liverpool, Liverpool, L69 3GA, UK. ·Nat Rev Gastroenterol Hepatol · Pubmed #22733351.

ABSTRACT: Late diagnosis of pancreatic ductal adenocarcinoma (pancreatic cancer) and the limited response to current treatments results in an exceptionally poor prognosis. Advances in our understanding of the molecular events underpinning pancreatic cancer development and metastasis offer the hope of tangible benefits for patients. In-depth mutational analyses have shed light on the genetic abnormalities in pancreatic cancer, providing potential treatment targets. New biological studies in patients and in mouse models have advanced our knowledge of the timing of metastasis of pancreatic cancer, highlighting new directions for the way in which patients are treated. Furthermore, our increasing understanding of the molecular events in tumorigenesis is leading to the identification of biomarkers that enable us to predict response to treatment. A major drawback, however, is the general lack of an adequate systematic approach to advancing the use of biomarkers in cancer drug development, highlighted in a Cancer Biomarkers Collaborative consensus report. In this Review, we summarize the latest insights into the biology of pancreatic cancer, and their repercussions for treatment. We provide an overview of current treatments and, finally, we discuss novel therapeutic approaches, including the role of biomarkers in therapy for pancreatic cancer.

17 Review Nanotechnology advances in upper gastrointestinal, liver and pancreatic cancer. 2012

Sykes, Paul D / Neoptolemos, John P / Costello, Eithne / Halloran, Christopher M. ·Liverpool Cancer Research UK Centre, Department of Molecular and Clinical Cancer Studies, University of Liverpool, Daulby Street, Liverpool, L69 3GA, UK. ·Expert Rev Gastroenterol Hepatol · Pubmed #22646256.

ABSTRACT: Cancers of the upper GI tract, liver and pancreas have some of the poorest prognoses of any malignancies. Advances in diagnosis and treatment are sorely needed to improve the outcomes of patients. Nanotechnology offers the potential for constructing tailor-made therapies capable of targeting specific cancers. The particles themselves may be endowed with multifunctional properties that can be exploited for both diagnosis and treatment. Although development of therapies is still in the early stages, the use of nanoparticles (NPs) is widespread in diagnostic applications and will probably involve all areas of medicine in the future. Research into NPs is ongoing for upper gastrointestinal, liver and pancreatic cancers, and their use is becoming increasingly popular as contrast media for radiological investigations. Although more sophisticated technologies capable of active targeting are still in the early stages of assessment for clinical use, a small number of NP-based therapies are in clinical use.

18 Review Adjuvant treatment of pancreatic cancer. 2011

Neoptolemos, John P. ·National Institute for Health Research Pancreas Biomédical Research Unit and the Department of Molecular and Clinical Cancer Medicine, Liverpool Cancer Research UK Centre, University of Liverpool, Liverpool, United Kingdom. ·Eur J Cancer · Pubmed #21944022.

ABSTRACT: -- No abstract --

19 Review Meta-analysis of immunohistochemical prognostic markers in resected pancreatic cancer. 2011

Smith, R A / Tang, J / Tudur-Smith, C / Neoptolemos, J P / Ghaneh, P. ·Division of Surgery and Oncology, School of Cancer Studies, University of Liverpool, Royal Liverpool University Hospital, 5th Floor Duncan Building, Daulby Street, Liverpool L69 3GA, UK. ·Br J Cancer · Pubmed #21448172.

ABSTRACT: BACKGROUND: The potential prognostic value of several commonly investigated immunohistochemical markers in resected pancreatic cancer is variably reported. The objective of this study was to conduct a systematic review of literature evaluating p53, p16, smad4, bcl-2, bax, vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) expression as prognostic factors in resected pancreatic adenocarcinoma and to conduct a subsequent meta-analysis to quantify the overall prognostic effect. METHODS: Relevant literature was identified using Medline, EMBASE and ISI Web of Science. The primary end point was overall survival assessed on univariate analysis. Only studies analysing resected pancreatic adenocarcinoma were eligible for inclusion and the summary log(e) hazard ratio (logHR) and variance were pooled using an inverse variance approach. Evidence of heterogeneity was evaluated using the χ(2) test for heterogeneity and its impact on the meta-analysis was assessed by the I(2) statisic. Hazard ratios greater than one reflect adverse survival associated with positive immunostaining. RESULTS: Vascular endothelial growth factor emerged as the most potentially informative prognostic marker (11 eligible studies, n=767, HR=1.51 (95% confidence interval, CI=1.18-1.92)) with no evidence of any significant publication bias (Egger's test, P=0.269). Bcl-2 (5 eligible studies, n=314, HR=0.51 (95% CI=0.38-0.68)), bax (5 studies, n=274, HR=0.63 (95% CI=0.48-0.83)) and p16 (3 studies, n=229, HR=0.63 (95% CI=0.43-0.92)) also returned significant overall survival differences, but in smaller patient series due to a lack of evaluable literature. Neither p53 (17 studies, n=925, HR=1.22 (95% CI=0.96-1.56)), smad4 (5 studies, n=540, HR=0.88 (95% CI=0.61-1.27)) nor EGFR (4 studies, n=250, HR=1.35 (95% CI=0.80-2.27)) was found to represent significant prognostic factors when analysing the pooled patient data. There was evidence of significant heterogeneity in four of the seven study groups. CONCLUSION: These results support the case for immunohistochemical expression of VEGF representing a significant and reproducible marker of adverse prognosis in resected pancreatic cancer.

20 Review Pancreatic cancer in 2010: new insights for early intervention and detection. 2011

Costello, Eithne / Neoptolemos, John P. ·Liverpool CR-UK Centre, NIHR Pancreas Biomedical Research Unit, Department of Molecular and Clinical Cancer Medicine, Daulby Street, University of Liverpool, Liverpool, UK. ·Nat Rev Gastroenterol Hepatol · Pubmed #21293504.

ABSTRACT: Pancreatic cancer is usually detected at an advanced stage and responds poorly to treatment. In 2010 new insights were gained into understanding the complex biology of pancreatic cancer. Importantly, these insights offer novel opportunities for early diagnosis and treatment of this disease.

21 Review Pancreatic cancer: proteomic approaches to a challenging disease. 2009

Tonack, Sarah / Aspinall-O'Dea, Mark / Neoptolemos, John P / Costello, Eithne. ·Division of Surgery and Oncology, Royal Liverpool University Hospital, University of Liverpool, Liverpool, UK. ·Pancreatology · Pubmed #19657212.

ABSTRACT: PURPOSE OF REVIEW: To describe progress in the application of proteomic approaches to advance our understanding of the biology of pancreatic cancer as well as contribute potential protein biomarkers for this disease. RECENT FINDINGS: Here we review proteomic studies relating to pancreatic cancer that have been published in the past 12 months. We describe novel techniques for the simplification of complex protein samples, focusing particularly on emerging methods for reducing the complexity of blood. We provide examples, where possible, of the application of these novel technologies to pancreatic cancer research. SUMMARY: Both the range of proteomic-based approaches and their sensitivities for the detection of low-abundance proteins has increased. This provides promise that further research will yield insight into pancreatic cancer, including valuable information on proteins that may ultimately serve as biomarkers for pancreatic cancer.

22 Review Screening of high-risk families for pancreatic cancer. 2009

Greenhalf, W / Grocock, C / Harcus, M / Neoptolemos, J. ·Division of Surgery, University of Liverpool, Liverpool, UK. ·Pancreatology · Pubmed #19349734.

ABSTRACT: PURPOSE OF REVIEW: To discuss how to recognise and manage high-risk individuals. RECENT FINDINGS: Publication of initial results of screening for pancreatic cancer from US centres. Several masses and premalignant lesions have been detected, but the detection of the first pancreatic cancer through an organised study of screening has yet to be published. There has been progress in risk stratification; the role of diabetes in predisposing for cancer has been characterised and molecular modalities have been published which could be used in conjunction with imaging in a screening programme. A mutation in the palladin gene was found to segregate with the disease in a family with a clear predisposition for pancreatic cancer, though this has yet to be found in other such kindreds. SUMMARY: Significant challenges remain to be solved in screening for early pancreatic cancer. Risk stratification needs to be improved and high-risk patients included in research-based screening programmes. It will be impossible to confirm that screening can detect cancers early enough for curative treatment until the results of these prospective studies become available.

23 Review New treatment options for advanced pancreatic cancer. 2008

Middleton, Gary / Ghaneh, Paula / Costello, Eithne / Greenhalf, William / Neoptolemos, John P. ·Royal Surrey County Hospital NHS Trust, Egerton Road, Guildford, GU2 7XX, UK. gmiddleton@royalsurrey.nhs.uk ·Expert Rev Gastroenterol Hepatol · Pubmed #19072345.

ABSTRACT: Pancreatic cancer has a very high mortality rate and affects approximately 230,000 individuals worldwide. Gemcitabine has become established as the standard therapy for advanced pancreatic cancer; however, the survival advantage is small. Adjuvant chemotherapy using either 5-fluorouracil or gemcitabine is now established in pancreatic cancer as an alternative therapy. Combinations of gemcitabine with either platin agents or capecitabine may be advantageous. Anti-EGFR and anti-VEGF agents have been unsuccessful but multiple tyrosine kinase inhibitors are under investigation. Of the increasing number of immunological agents, the GV1001 antitelomerase vaccine holds some interest. Targeted agents against important mitogenic pathways, including MEK/ERK, Src, PI3K/Akt, mTOR, Hedgehog and NF-kappaB, as well as agents targeting histone deacetylase, poly(ADP-ribose) polymerase, heat shock protein 90 and other agents such as beta-lapachone, hold considerable interest for further development. However, the probability of individual success is low.

24 Review Biology and management of pancreatic cancer. 2008

Ghaneh, P / Costello, E / Neoptolemos, J P. ·Division of Surgery and Oncology, University of Liverpool, Liverpool, UK. ·Postgrad Med J · Pubmed #18940950.

ABSTRACT: -- No abstract --

25 Review Pancreatic neuroendocrine tumours. 2008

Alexakis, N / Neoptolemos, J P. ·General Surgery, University of Athens, Greece. ·Best Pract Res Clin Gastroenterol · Pubmed #18206821.

ABSTRACT: Pancreatic neuroendocrine tumours are rare tumours ( approximately 1/100,00 population/year) of which 60% are non-functioning. Except for insulinoma all types are malignant in >50% of cases. In multiple endocrine neoplasia (MEN)1, pancreatic neuroendocrine tumours occur in 40-80% of patients and are mostly non-functioning tumours or gastrinomas. Insulinomas are benign in approximately 90%, solitary in 95% of sporadic cases whilst multiple in 90% of MEN1 patients. In contrast approximately 50% gastrinomas and the majority of non-functioning pancreatic neuroendocrine tumours are malignant. Pancreatic neuroendocrine tumours occur in 10-15% of patients with Von Hippel-Lindau (VHL) and are frequently multiple (>30%). Surgical excision is a key aspect of treatment for all cases of sporadic gastrinoma and if >2.5 cm in MEN1. Insulinomas are enucleated if solitary and may require pancreatectomy if multiple. Non-functioning tumours should also be resected if sporadic and if >2 cm in MEN1 or if >2-3 cm in VHL. Tumours <1cm require yearly follow-up by CT or MRI from an early age in VHL. The local treatment for liver metastases is now well established and options include liver resection, chemoembolisation and radiofrequency ablation. Systemic therapies have also been better defined and include radionuclide therapy against somatostatin receptors or MIBG and chemotherapy especially for poorly differentiated tumours. A number of novel agents are currently in clinical development.

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