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Pancreatic Neoplasms: HELP
Articles by Kevin C. Conlon
Based on 24 articles published since 2010
(Why 24 articles?)
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Between 2010 and 2020, K. Conlon wrote the following 24 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 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 / Anonymous471156. ·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.

2 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 / Anonymous1001108. ·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.

3 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 / Anonymous991108. ·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.

4 Review Physical function in patients with resectable cancer of the pancreas and liver-a systematic review. 2020

O'Neill, Linda / Reynolds, Sophie / Sheill, Gráinne / Guinan, Emer / Mockler, David / Geoghegan, Justin / Conlon, Kevin / Reynolds, John V / Hussey, Juliette. ·Discipline of Physiotherapy, School of Medicine, Trinity College Dublin, the University of Dublin, Dublin, Ireland. oneilll8@tcd.ie. · School of Medicine, Trinity College Dublin, the University of Dublin, Dublin, Ireland. · Discipline of Physiotherapy, School of Medicine, Trinity College Dublin, the University of Dublin, Dublin, Ireland. · John Stearne Library, Trinity Centre for Health Sciences, Dublin, Ireland. · Department of Surgery, St Vincent's University Hospital, Dublin, Ireland. · Department of Surgery, Tallaght University Hospital, Dublin, Ireland. · Department of Surgery, Trinity College Dublin, the University of Dublin, Dublin, Ireland. · Department of Surgery, St James's Hospital, Dublin, Ireland. ·J Cancer Surviv · Pubmed #32221811.

ABSTRACT: PURPOSE: Surgery is the only potentially curative treatment for pancreatic and liver cancer. However, even in high-volume centres, surgical resection is associated with significant morbidity with resultant physical decline. This systematic review explored physical function and its' implications in the management of resectable cancer of the pancreas and liver. METHODS: EMBASE, Medline OVID, CINAHL, Cochrane Library and Web of Science were searched up to June 2019 using a predefined search strategy. Screening of titles, abstracts, and full texts, data extraction, and risk of bias assessment was performed independently by two reviewers. A third reviewer resolved disagreements by consensus. RESULTS: Sixteen studies with a total of 1224 participants were included. Heterogeneity of the literature prevented a meta-analysis. Physical function across the pancreatic/liver cancer trajectory has been under investigated. The relationship between physical function and pancreatic/liver cancer resection outcome remains unclear, although anaerobic threshold appears the strongest predictor of postoperative outcomes. Conclusions regarding the impact of rehabilitative interventions on physical function were limited due to risk of bias concerns. CONCLUSIONS: High-quality evidence regarding the implications of physical function in resectable pancreatic and liver cancers is lacking. Well-designed trials are required to examine physical function across the pancreatic/liver cancer continuum and to measure the impact of rehabilitation on physical function. IMPLICATIONS FOR CANCER SURVIVORS: As survival rates for pancreatic and liver cancer slowly improve a greater understanding of the impact of these cancers and their treatments on physical function, and the potential impact of rehabilitative interventions for survivors is required.

5 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 / Anonymous1010883. ·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.

6 Review Quality assessment of the guidelines on cystic neoplasms of the pancreas. 2015

Falconi, Massimo / Crippa, Stefano / Chari, Suresh / Conlon, Kevin / Kim, Sun-Whe / Levy, Philippe / Tanaka, Masao / Werner, Jens / Wolfgang, Christopher L / Pezzilli, Raffaele / Castillo, Carlos Fernandez-Del. ·Division of Pancreatic Surgery, Università Politecnica delle Marche, Ospedali Riuniti, Ancona, Italy. · Pancreas Interest Group, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA. · Department of Surgery, Trinity College, Dublin, Ireland. · Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea. · Pôle des Maladies de l'Appareil Digestif, Service de Gastroentérologie-Pancréatologie, Hospital Beaujon, APHP, Clichy Cedex, Faculté Denis Diderot, DHU Unity, France. · Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. · Department of Surgery, Ludwig-Maximilian University of Munich, Munich, Germany. · Department of Surgery and The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, MD, USA. · Pancreas Unit, Department of Digestive System, Sant'Orsola-Malpighi Hospital, Via Massarenti 9, 40138 Bologna, Italy. Electronic address: raffaele.pezzilli@aosp.bo.it. · Pancreas and Biliary Program, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. ·Pancreatology · Pubmed #26100659.

ABSTRACT: BACKGROUND: Though cystic pancreatic neoplasms (CPNs) are being increasingly detected, their evaluation and management are still debated and have lead to publication of multiple guidelines for diagnostic work-up, indications for resection, and non-operative management with follow-up strategies of CPNs. AIMS: To analyze available guidelines in order to evaluate their overall quality and clinical applicability, indications for surgical resection and its extent, modalities and timing of follow-up when non-operative management is indicated. METHODS: After a systematic search of the English literature, we selected eight guidelines for assessment according to the Appraisal of Guidelines, Research and Evaluation in Europe (AGREE) II instrument. RESULTS: One guideline received the lower AGREE score regarding the "scope and purpose", "rigor of development" and "clarity and presentation" domains, whereas one received the best score for "stakeholder involvement" domain. No differences were found among different guidelines regarding the "applicability". The overall quality assessment score showed that only two guidelines were significantly lower than the others. According to the practical utilization recommendation score, four guidelines were considered as having full applicability in clinical practice. CONCLUSION: Existing guidelines provide adequate guidance, at least with the present knowledge, for the management of cystic pancreatic lesions; however, not any one was satisfactory to all aspects related to the management of CPN. An update of the existing guidelines should be considered if and when more evidence-based data are available.

7 Review Pancreatectomy for metastatic disease: a systematic review. 2014

Adler, H / Redmond, C E / Heneghan, H M / Swan, N / Maguire, D / Traynor, O / Hoti, E / Geoghegan, J G / Conlon, K C. ·National Surgical Centre for Pancreatic Cancer, St Vincent's University Hospital, Elm Park, Dublin, Ireland. Electronic address: hugh.adler@gmail.com. · National Surgical Centre for Pancreatic Cancer, St Vincent's University Hospital, Elm Park, Dublin, Ireland. ·Eur J Surg Oncol · Pubmed #24462547.

ABSTRACT: AIM: Tumours rarely metastasise to the pancreas. While surgical resection of such metastases is believed to confer a survival benefit, there is limited data to support such management. We present a systematic review of case series of pancreatic metastasectomy and analysis of survival outcomes. METHODS: A literature search was performed using the PubMed and Cochrane databases and the reference lists of relevant articles, searching for sizeable case series of pancreatic metastasectomy with curative intent. Data extracted included basic demographics, histological primary tumour, presentation, operative management, complications and survival, while the MINORS index was used to assess study quality. RESULTS: 18 studies were found which met our inclusion criteria, involving 399 patients. Renal cell carcinoma (RCC) was the commonest malignancy metastasising to the pancreas, responsible for 62.6% of cases, followed by sarcoma (7.2%) and colorectal carcinoma (6.2%). While survival data was not uniformly reported, the median survival post-metastasectomy was 50.2 months, with a one-year survival of 86.81% and five-year survival of 50.02%. Median survival for RCC was 71.7 months with 70.4% five-year survival. Median survival was similar in patients with synchronous and metachronous pancreatic metastases, but patients with additional extrapancreatic metastases had a significantly shorter survival than patients with isolated pancreatic metastases (26 versus 45 months). Study quality was poor, with a median MINORS score of 10/16. CONCLUSIONS: Within the limitations of a review of non-randomised case series, it would appear that pancreatic metastasectomy confers a survival benefit in selected patients. Better evidence is required, but may prove difficult to acquire.

8 Clinical Trial Effect of pemetrexed on innate immune killer cells and adaptive immune T cells in subjects with adenocarcinoma of the pancreas. 2012

Davis, Marcherie / Conlon, Kevin / Bohac, Gerald C / Barcenas, John / Leslie, William / Watkins, LaTanja / Lamzabi, Ihab / Deng, Youping / Li, Yan / Plate, Janet M D. ·Division of Oncology, Hematology and Stem Cell Transplantation, Rush University Medical Center, 1725 West Harrison St, Chicago, IL 60612, USA. ·J Immunother · Pubmed #22996369.

ABSTRACT: Baseline levels of innate and adaptive immune cell functions were studied in patients with pancreatic cancer. The effects of pemetrexed were measured at 7 and 14 days after initial therapy then 14 days after combination therapy with gemcitabine. Pretherapy levels of absolute numbers of natural killer (NK) cells positively correlated with survival. Cytolytic units of NK activity correlated positively with NK cell numbers. Pemetrexed decreased NK cytolytic units to significance when combined with gemcitabine. Pemetrexed increased intracellular accumulation of interferon gamma (IFNγ) in NK cells that correlated negatively with survival. Addition of gemcitabine decreased IFNγ-producing NK cells to baseline. Memory (CD45RO*) T cells enumerated at baseline correlated negatively with survival but were decreased by pemetrexed therapy. Memory T cells were increased in subjects with greater B7-H3 expression in tumor tissue, whereas OX40*-activated total T cells and helper T-cell subset were decreased. FoxP3*, CD8* T cells correlated positively with progression-free interval and survival. In conclusion, innate NK-cell immunity and FoxP3*, CD8* T cells seemed beneficial to pancreatic cancer patients. Higher levels of B7-H3 expression in pancreatic tumors were detrimental to effective immunity. Although pemetrexed therapy increased activation of a subset of NK cells to produce IFNγ, addition of gemcitabine abated those responses, decreasing IFNγ-producing NK cells, whereas NK cells producing interleukin-2 without IFNγ at this timepoint positively correlated with survival. Innate immunity and adaptive immunity thus are important in defense against pancreatic cancer. Progression-free interval and survival were longer than observed in a phase III trial where gemcitabine preceded pemetrexed suggesting that a larger trial of pemetrexed preceding gemcitabine is warranted.

9 Article Rehabilitation strategies following oesophagogastric and Hepatopancreaticobiliary cancer (ReStOre II): a protocol for a randomized controlled trial. 2020

O'Neill, Linda / Guinan, Emer / Doyle, Suzanne / Connolly, Deirdre / O'Sullivan, Jacintha / Bennett, Annemarie / Sheill, Grainne / Segurado, Ricardo / Knapp, Peter / Fairman, Ciaran / Normand, Charles / Geoghegan, Justin / Conlon, Kevin / Reynolds, John V / Hussey, Juliette. ·Discipline of Physiotherapy, School of Medicine, Trinity College, the University of Dublin, Dublin, Ireland. oneilll8@tcd.ie. · School of Medicine, Trinity College, the University of Dublin, Dublin, Ireland. · School of Biological and Health Sciences, Technological University Dublin, Dublin, Ireland. · Discipline of Occupational Therapy, School of Medicine, Trinity College, the University of Dublin, Dublin, Ireland. · Department of Surgery, Trinity Translational Medicine Institute, Trinity College, the University of Dublin and St. James's Hospital, Dublin, Ireland. · Department of Clinical Medicine, Trinity College, the University of Dublin, Dublin, Ireland. · Discipline of Physiotherapy, School of Medicine, Trinity College, the University of Dublin, Dublin, Ireland. · Centre for Support and Training in Analysis and Research, and School of Public Health, Physiotherapy and Sports Sciences, University College Dublin, Dublin, Ireland. · Department of Health Sciences and the Hull York Medical School, University of York, York, UK. · Exercise Medicine Research Institute, School of Medical and Health Sciences, Edith Cowan University, Joondalup, Australia. · Centre for Health Policy and Management, Trinity College, the University of Dublin, Dublin, Ireland. · Department of Surgery, St Vincent's University Hospital, Dublin, Ireland. · Department of Surgery, Tallaght University Hospital, Dublin, Ireland. · Department of Surgery, Trinity College, the University of Dublin, Dublin, Ireland. ·BMC Cancer · Pubmed #32404096.

ABSTRACT: BACKGROUND: Curative treatment for upper gastrointestinal (UGI) and hepatopancreaticobiliary (HPB) cancers, involves complex surgical resection often in combination with neoadjuvant/adjuvant chemo/chemoradiotherapy. With advancing survival rates, there is an emergent cohort of UGI and HPB cancer survivors with physical and nutritional deficits, resultant from both the cancer and its treatments. Therefore, rehabilitation to counteract these impairments is required to maximise health related quality of life (HRQOL) in survivorship. The initial feasibility of a multidisciplinary rehabilitation programme for UGI survivors was established in the Rehabilitation Strategies following Oesophago-gastric Cancer (ReStOre) feasibility study and pilot randomised controlled trial (RCT). ReStOre II will now further investigate the efficacy of that programme as it applies to a wider cohort of UGI and HPB cancer survivors, namely survivors of cancer of the oesophagus, stomach, pancreas, and liver. METHODS: The ReStOre II RCT will compare a 12-week multidisciplinary rehabilitation programme of supervised and self-managed exercise, dietary counselling, and education to standard survivorship care in a cohort of UGI and HPB cancer survivors who are > 3-months post-oesophagectomy/ gastrectomy/ pancreaticoduodenectomy, or major liver resection. One hundred twenty participants (60 per study arm) will be recruited to establish a mean increase in the primary outcome (cardiorespiratory fitness) of 3.5 ml/min/kg with 90% power, 5% significance allowing for 20% drop out. Study outcomes of physical function, body composition, nutritional status, HRQOL, and fatigue will be measured at baseline (T0), post-intervention (T1), and 3-months follow-up (T2). At 1-year follow-up (T3), HRQOL alone will be measured. The impact of ReStOre II on well-being will be examined qualitatively with focus groups/interviews (T1, T2). Bio-samples will be collected from T0-T2 to establish a national UGI and HPB cancer survivorship biobank. The cost effectiveness of ReStOre II will also be analysed. DISCUSSION: This RCT will investigate the efficacy of a 12-week multidisciplinary rehabilitation programme for survivors of UGI and HPB cancer compared to standard survivorship care. If effective, ReStOre II will provide an exemplar model of rehabilitation for UGI and HPB cancer survivors. TRIAL REGISTRATION: The study is registered with ClinicalTrials.gov, registration number: NCT03958019, date registered: 21/05/2019.

10 Article Establishment and Characterisation by Expression Microarray of Patient-Derived Xenograft Panel of Human Pancreatic Adenocarcinoma Patients. 2020

Roche, Sandra / O'Neill, Fiona / Murphy, Jean / Swan, Niall / Meiller, Justine / Conlon, Neil T / Geoghegan, Justin / Conlon, Kevin / McDermott, Ray / Rahman, Rozana / Toomey, Sinead / Straubinger, Ninfa L / Straubinger, Robert M / O'Connor, Robert / McVey, Gerard / Moriarty, Michael / Clynes, Martin. ·National Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland. · St. Vincent's University Hospital, Dublin 4, Ireland. · Trinity College Dublin, College Green, Dublin 2, Ireland. · Department of Molecular Medicine, Beaumont Hospital, Royal College of Surgeons in Ireland, Dublin 9, Ireland. · Department of Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY 14214, USA. · St Luke's Radiation Oncology Network, Dublin 6, Ireland. ·Int J Mol Sci · Pubmed #32024004.

ABSTRACT: Pancreatic cancer remains among the most lethal cancers worldwide, with poor early detection rates and poor survival rates. Patient-derived xenograft (PDX) models have increasingly been used in preclinical and clinical research of solid cancers to fulfil unmet need. Fresh tumour samples from human pancreatic adenocarcinoma patients were implanted in severe combined immunodeficiency (SCID) mice. Samples from 78% of treatment-naïve pancreatic ductal adenocarcinoma patients grew as PDX tumours and were confirmed by histopathology. Frozen samples from F1 PDX tumours could be later successfully passaged in SCID mice to F2 PDX tumours. The human origin of the PDX was confirmed using human-specific antibodies; however, the stromal component was replaced by murine cells. Cell lines were successfully developed from three PDX tumours. RNA was extracted from eight PDX tumours and where possible, corresponding primary tumour (T) and adjacent normal tissues (N). mRNA profiles of tumour vs. F1 PDX and normal vs. tumour were compared by Affymetrix microarray analysis. Differential gene expression showed over 5000 genes changed across the N vs. T and T vs. PDX samples. Gene ontology analysis of a subset of genes demonstrated genes upregulated in normal vs. tumour vs. PDX were linked with cell cycle, cycles cell process and mitotic cell cycle. Amongst the mRNA candidates elevated in the PDX and tumour vs. normal were

11 Article Characterising the impact of body composition change during neoadjuvant chemotherapy for pancreatic cancer. 2019

Griffin, Oonagh M / Duggan, Sinead N / Ryan, Ronan / McDermott, Raymond / Geoghegan, Justin / Conlon, Kevin C. ·Professorial Surgical Unit, Trinity College Dublin, Trinity Centre for Health Science, Tallaght, Dublin 24, Ireland; National Surgical Centre for Pancreatic Cancer, St Vincent's University Hospital, Dublin 24, Ireland. Electronic address: griffino@tcd.ie. · Professorial Surgical Unit, Trinity College Dublin, Trinity Centre for Health Science, Tallaght, Dublin 24, Ireland. · Department of Radiology, St Vincent's University Hospital, Dublin 24, Ireland. · Department of Medical Oncology, St Vincent's University Hospital, Dublin 24, Ireland. · National Surgical Centre for Pancreatic Cancer, St Vincent's University Hospital, Dublin 24, Ireland. · Professorial Surgical Unit, Trinity College Dublin, Trinity Centre for Health Science, Tallaght, Dublin 24, Ireland; National Surgical Centre for Pancreatic Cancer, St Vincent's University Hospital, Dublin 24, Ireland. ·Pancreatology · Pubmed #31362865.

ABSTRACT: BACKGROUND: Pancreatic Cancer remains a lethal disease for the majority of patients. New chemotherapy agents such as Folfirinox offer therapeutic potential for patients who present with Borderline Resectable disease (BRPC). However, results to date are inconsistent, with factors such as malnutrition limiting successful drug delivery. We sought to determine the prevalence of sarcopenia in BRPC patients at diagnosis, and to quantify body composition change during chemotherapy. METHODS: The diagnostic/restaging CT scans of BRPC patients were analysed. Body composition was measured at L3 using Tomovision Slice-O-Matic™. Total muscle and adipose tissue mass were estimated using validated regression equations. Sarcopenia was defined as per gender- and body mass index (BMI)-specific lumbar skeletal muscle index (LSMI) and muscle attenuation reference values. RESULTS: Seventy-eight patients received neo-adjuvant chemotherapy, and 67 patients underwent restaging CT, at which point a third were deemed resectable. Half were sarcopenic at diagnosis, and sarcopenia was equally prevalent across all BMI categories.. Skeletal muscle and adipose tissue (intra-muscular, visceral and sub-cutaneous) area decreased during chemotherapy (p < 0.0001). Low muscle attenuation was observed in half of patients at diagnosis, and was associated with increased mortality risk. Loss of lean tissue parameters during chemotherapy was associated with an increased mortality risk; specifically fat-free mass, HR 1.1 (95% CI 1.03-1.17, p = 0.003) and skeletal muscle mass, HR 1.21 (95%CI 1.08-1.35, p = 0.001). CONCLUSIONS: Sarcopenia was prevalent in half of patients at the time of diagnosis with BRPC. Low muscle attenuation at diagnosis, coupled with lean tissue loss during chemotherapy, independently increased mortality risk.

12 Article The Role of Staging Laparoscopy in Resectable and Borderline Resectable Pancreatic Cancer: A Systematic Review and Meta-Analysis. 2019

Ta, Robert / O'Connor, Donal B / Sulistijo, Andrew / Chung, Benjamin / Conlon, Kevin C. ·Professorial Surgical Unit, Department of Surgery, Trinity College Dublin, Centre for Pancreatico-Biliary Diseases, Trinity Centre for Health Sciences, Tallaght Hospital, Dublin, Ireland. · Professorial Surgical Unit, Department of Surgery, Trinity College Dublin, Centre for Pancreatico-Biliary Diseases, Trinity Centre for Health Sciences, Tallaght Hospital, Dublin, Ireland, oconnd15@tcd.ie. ·Dig Surg · Pubmed #29649825.

ABSTRACT: AIM: The study aimed to determine the additional value of staging laparoscopy in patients with pancreatic cancer deemed potentially resectable based on computed tomography imaging. METHODS: A systematic literature search was performed using MEDLINE and the Cochrane Register of Controlled Trials (January 1995 to June 2017). Primary outcome measures were the overall yield and sensitivity to detect non-resectable disease. Quality of studies was assessed with the Newcastle-Ottawa Scale. RESULTS: From 156 records, 15 studies including 2,776 patients met the inclusion criteria. In 12 studies, reporting outcomes on 1,756 patients with resectable disease after standard imaging, 350 (20%, range 14-38%) cases of non-resectable cancer were detected with staging laparoscopy. In 3 studies on 242 patients with locally advanced disease after standard imaging, staging laparoscopy detected metastases in 86 patients (36%). The failure rate of staging laparoscopy to detect non-resectable disease was 5% (64 of 1,406). CONCLUSION: Staging laparoscopy reduces the non-therapeutic laparotomy rate, and in locally advanced or borderline resectable disease, staging laparoscopy could more accurately select patients for neoadjuvant protocols.

13 Article A Comparative Quantitative LC-MS/MS Profiling Analysis of Human Pancreatic Adenocarcinoma, Adjacent-Normal Tissue, and Patient-Derived Tumour Xenografts. 2018

Coleman, Orla / Henry, Michael / O'Neill, Fiona / Roche, Sandra / Swan, Niall / Boyle, Lorraine / Murphy, Jean / Meiller, Justine / Conlon, Neil T / Geoghegan, Justin / Conlon, Kevin C / Lynch, Vincent / Straubinger, Ninfa L / Straubinger, Robert M / McVey, Gerard / Moriarty, Michael / Meleady, Paula / Clynes, Martin. ·National Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland. orla.coleman2@mail.dcu.ie. · National Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland. michael.henry@dcu.ie. · National Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland. fiona.oneill@dcu.ie. · National Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland. sandra.roche@dcu.ie. · St. Vincent's University Hospital, Dublin 4, Ireland. nswan@svhg.ie. · St. Vincent's University Hospital, Dublin 4, Ireland. L.Boyle@st-vincents.ie. · St. Vincent's University Hospital, Dublin 4, Ireland. J.Murphy@st-vincents.ie. · National Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland. justine.meiller@dcu.ie. · National Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland. neil.conlon4@mail.dcu.ie. · St. Vincent's University Hospital, Dublin 4, Ireland. geoghegj@indigo.ie. · St. Vincent's University Hospital, Dublin 4, Ireland. conlonk@tcd.ie. · Trinity College Dublin, College Green, Dublin 2, Ireland. conlonk@tcd.ie. · National Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland. glynch96@gmail.com. · St. Vincent's University Hospital, Dublin 4, Ireland. glynch96@gmail.com. · Department of Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY 14214, USA. Nls2@buffalo.edu. · Department of Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY 14214, USA. Rms@buffalo.edu. · St. Vincent's University Hospital, Dublin 4, Ireland. gerard.mcvey@slh.ie. · St. Luke's Hospital, Highfield Road, Rathgar, Dublin 6, Ireland. gerard.mcvey@slh.ie. · National Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland. michaelmoriartyirl@gmail.com. · St. Luke's Hospital, Highfield Road, Rathgar, Dublin 6, Ireland. michaelmoriartyirl@gmail.com. · National Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland. paula.meleady@dcu.ie. · National Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland. martin.clynes@dcu.ie. ·Proteomes · Pubmed #30404163.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers worldwide; it develops in a relatively symptom-free manner, leading to rapid disease progression and metastasis, leading to a 5-year survival rate of less than 5%. A lack of dependable diagnostic markers and rapid development of resistance to conventional therapies are among the problems associated with management of the disease. A better understanding of pancreatic tumour biology and discovery of new potential therapeutic targets are important goals in pancreatic cancer research. This study describes the comparative quantitative LC-MS/MS proteomic analysis of the membrane-enriched proteome of 10 human pancreatic ductal adenocarcinomas, 9 matched adjacent-normal pancreas and patient-derived xenografts (PDXs) in mice (10 at F1 generation and 10 F2). Quantitative label-free LC-MS/MS data analysis identified 129 proteins upregulated, and 109 downregulated, in PDAC, compared to adjacent-normal tissue. In this study, analysing peptide MS/MS data from the xenografts, great care was taken to distinguish species-specific peptides definitively derived from human sequences, or from mice, which could not be distinguished. The human-only peptides from the PDXs are of particular value, since only human tumour cells survive, and stromal cells are replaced during engraftment in the mouse; this list is, therefore, enriched in tumour-associated proteins, some of which might be potential therapeutic or diagnostic targets. Using human-specific sequences, 32 proteins were found to be upregulated, and 113 downregulated in PDX F1 tumours, compared to primary PDAC. Differential expression of CD55 between PDAC and normal pancreas, and expression across PDX generations, was confirmed by Western blotting. These data indicate the value of using PDX models in PDAC research. This study is the first comparative proteomic analysis of PDAC which employs PDX models to identify patient tumour cell-associated proteins, in an effort to find robust targets for therapeutic treatment of PDAC.

14 Article Sarcopenia-A New Frontier in the Management Care of Patients With Borderline Resectable Pancreatic Cancer. 2018

Griffin, Oonagh / Conlon, Kevin C. ·Professorial Surgical Unit, Department of Surgery, Trinity College Dublin, Trinity Centre for Health Sciences, Dublin, Ireland. ·JAMA Surg · Pubmed #29801035.

ABSTRACT: -- No abstract --

15 Article Preoperative CT in patients with surgically resectable pancreatic adenocarcinoma: does the time interval between CT and surgery affect survival? 2018

Healy, Gerard M / Redmond, C E / Murphy, S / Fleming, H / Haughey, A / Kavanagh, R / Swan, N / Conlon, K C / Malone, D E / Ryan, E R. ·Department of Radiology, National Surgical Centre for Pancreatic Cancer, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland. ger.healy@svuh.ie. · Department of Radiology, National Surgical Centre for Pancreatic Cancer, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland. · Department of Histopathology, National Surgical Centre for Pancreatic Cancer, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland. · Department of Pancreatic Surgery, National Surgical Centre for Pancreatic Cancer, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland. · School of Medicine, Trinity College Dublin, Dublin 2, Ireland. ·Abdom Radiol (NY) · Pubmed #28695235.

ABSTRACT: PURPOSE: The preoperative imaging-to-surgery time interval (ISI) influences the risk of unexpected progression (UP) found at surgery for pancreatic adenocarcinoma. We aimed to assess whether ISI influences disease recurrence and/or survival. METHODS AND MATERIALS: A single-institution, ethics board-approved retrospective analysis of all patients who underwent attempted resection of pancreatic (PDAC) or periampullary adenocarcinoma (AmpAC) between 1st January 2010 and 31st December 2015 was performed. All patients underwent preoperative abdominal computed tomography (CT). Exclusion criteria were borderline resectable disease and neoadjuvant chemo/radiotherapy. Patients were followed up until 30th June 2016. The population was divided into ISI ≥/<25 days. Kaplan-Meier and Cox regression survival analyses were performed. RESULTS: 239 patients underwent surgical exploration. UP was found in 29 (12.1%) and these patients had longer ISI (median 46 vs. 29 days, p < 0.05). When intention-to-treat analysis was performed, there was no difference in overall survival (OS) between patients with ISI ≥/<25. In those who underwent resection, ISI did not influence disease-free survival (DFS) or OS for PDAC (n = 174). For AmpAC (n = 36), ISI ≥ 25 days was associated with longer OS (p < 0.05) but did not influence DFS. Longer ISI was independently associated with improved OS on regression analysis for AmpAC. CONCLUSION: Performing surgery for resectable pancreatic adenocarcinoma within 25 days of abdominal CT reduces the chance of UP but does not confer a survival benefit. For those who undergo resection of AmpAC, a longer ISI was associated with longer OS. This probably represents a more biologically indolent disease in this cohort.

16 Article Osteoclastic-Type Giant Cell Tumours of the Pancreas: A Homogenous Series of Rare Tumours Diagnosed by Endoscopic Ultrasound. 2016

Lahiff, Conor / Swan, Niall / Conlon, Kevin / Malone, Dermot / Maguire, Donal / Hoti, Emir / Geoghegan, Justin / McEntee, Gerry / O'Toole, Dermot. ·Department of Gastroenterology, St. James's Hospital, Dublin, Ireland. ·Dig Surg · Pubmed #27160213.

ABSTRACT: BACKGROUND: Giant cell tumors (GCT) of the pancreas are a rare form of pancreatic cancer. Although data are limited, clinical outcomes appear to depend largely on histological subtype with osteoclastic tumors carrying a better prognosis. We report on a homogenous series of patients with osteoclastic-type GCTs of the pancreas presenting to a national pancreatico-biliary gastrointestinal oncology center. METHODS: Patients underwent endoscopic, radiological and histopathological assessments. Data were collected in relation to consecutive patients presenting with osteoclastic-type tumors of the pancreas and analyzed with survival as a primary end point. RESULTS: Four patients were treated over a 4-year period. Median age was 77 years with equal gender distribution. Median tumor size was 42 mm. Histology was osteoclast-type giant cells in all 4 patients. Two patients underwent surgery with curative intent. Median overall survival was 13.1 months. CONCLUSION: This is the largest reported series of osteoclast-type histology in GCTs of the pancreas.

17 Article Pancreatic metastasectomy: experience of the Irish National Surgical Centre for Pancreatic Cancer. 2014

Redmond, C E / Adler, H / Heneghan, H M / Kelly, R / Swan, N / Cantwell, C P / Maguire, D / Traynor, O / Hoti, E / Geoghegan, J G / Conlon, K C. ·National Surgical Centre for Pancreatic Cancer, St. Vincent's University Hospital, Elm Park, Dublin, Ireland, ciaranredmond1@gmail.com. ·Ir J Med Sci · Pubmed #25056586.

ABSTRACT: BACKGROUND: Metastatic tumours of the pancreas are rare and the optimal management of these tumours remains unclear, given the paucity of data existing in the literature. We report our experience of pancreatic metastasectomy. METHODS: Data were reviewed on all patients who underwent pancreatic resection for pathologically confirmed metastatic lesions over a consecutive 7-year period. RESULTS: Seven patients (two men and five women) underwent a pancreatectomy for a metastatic pancreatic tumour. The primary tumours were renal cell carcinoma (n = 3), colorectal carcinoma (n = 2) and leiomyosarcoma (n = 2). There was no operative mortality. Postoperative morbidities occurred in two patients. The median follow-up was 49 months (range 17-76). Overall 1- and 2-year survivals were 100 and 86 %, respectively, with a 2-year disease-free survival of 72 %. CONCLUSIONS: Our series further supports that pancreatic metastasectomy can be performed safely and achieves acceptable survival outcomes.

18 Article When to perform a pancreatoduodenectomy in the absence of positive histology? A consensus statement by the International Study Group of Pancreatic Surgery. 2014

Asbun, Horacio J / Conlon, Kevin / Fernandez-Cruz, Laureano / Friess, Helmut / Shrikhande, Shailesh V / Adham, Mustapha / Bassi, Claudio / Bockhorn, Maximilian / Büchler, Markus / Charnley, Richard M / Dervenis, Christos / Fingerhutt, Abe / Gouma, Dirk J / Hartwig, Werner / Imrie, Clem / Izbicki, Jakob R / Lillemoe, Keith D / Milicevic, Miroslav / Montorsi, Marco / Neoptolemos, John P / Sandberg, Aken A / Sarr, Michael / Vollmer, Charles / Yeo, Charles J / Traverso, L William / Anonymous521108. ·Department of General Surgery, Mayo Clinic, Jacksonville, FL. Electronic address: Asbun.Horacio@mayo.edu. · Professorial Surgical Unit, University of Dublin, Trinity College, Dublin, Ireland. · 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 Surgical Oncology, Tata Memorial Centre, Mumbai, India. · Department of HPB Surgery, Hopital Edouard Herriot, Lyon, France. · 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 General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany. · Department of HPB & Transplant Surgery, Freeman Hospital, Newcastle upon Tyne, UK. · Department of First Surgery, Agia Olga Hospital, Athens, Greece. · Department of Digestive Surgery, Centre Hospitalier Intercommunal, Poissy, France. · Department of Surgery, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. · Acacdemic Unit of Surgery, Univesity 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 Molecular and Clinical Cancer Medicine, Liverpool Cancer Research-UK Centre, University of Liverpool, Liverpool, UK. · Department of Surgery, Karolinska Institutet at Karolinska University Hospital, Huddinge, Stockholm, Sweden. · Department of Gastroenterologic and General Surgery, Mayo Clinic, Rochester, MN. · 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. · St. Luke's Clinic - Center For Pancreatic and Liver Diseases, Boise, ID. ·Surgery · Pubmed #24661765.

ABSTRACT: BACKGROUND: Pancreatoduodenectomy (PD) provides the best chance for cure in the treatment of patients with localized pancreatic head cancer. In patients with a suspected, clinically resectable pancreatic head malignancy, the need for histologic confirmation before proceeding with PD has not historically been required, but remains controversial. METHODS: An international panel of pancreatic surgeons working in well-known, high-volume centers reviewed the literature and worked together to establish a consensus on when to perform a PD in the absence of positive histology. RESULTS: The incidence of benign disease after PD for a presumed malignancy is 5-13%. Diagnosis by endoscopic cholangiopancreatography brushings and percutaneous fine-needle aspiration are highly specific, but poorly sensitive. Aspiration biopsy guided by endoscopic ultrasonography (EUS) has greater sensitivity, but it is highly operator dependent and increases expense. The incidence of autoimmune pancreatitis (AIP) in the benign resected specimens is 30-43%. EUS-guided Trucut biopsy, serum levels of immunoglobulin G4, and HISORt (Histology, Imaging, Serology, Other organ involvement, and Response to therapy) are used for diagnosis. If AIP is suspected but not confirmed, the response to a short course of steroids is helpful for diagnosis. CONCLUSION: In the presence of a solid mass suspicious for malignancy, consensus was reached that biopsy proof is not required before proceeding with resection. Confirmation of malignancy, however, is mandatory for patients with borderline resectable disease to be treated with neoadjuvant therapy before exploration for resection. When a diagnosis of AIP is highly suspected, a biopsy is recommended, and a short course of steroid treatment should be considered if the biopsy does not reveal features suspicious for malignancy.

19 Article Prognostic role of neutrophil-to-lymphocyte ratio in advanced pancreatic ductal adenocarcinoma: impact of baseline fluctuation and changes during chemotherapy. 2013

Teo, MinYuen / Mohd Sharial, Mohd Syahizul Nuhairy / McDonnell, Felicity / Conlon, Kevin C / Ridgway, Paul F / McDermott, Ray S. · ·Tumori · Pubmed #24326841.

ABSTRACT: AIMS AND BACKGROUND: Inflammation has been implicated in carcinogenesis and progression of pancreatic cancer. The neutrophil-to-lymphocyte ratio is an index of systemic inflammation. We examined the prognostic role of the neutrophil-to-lymphocyte ratio at baseline and the significance of intrapersonal variability of the ratio before and during chemotherapy. METHODS AND STUDY DESIGN: Advanced pancreatic adenocarcinoma patients who had received chemotherapy were included. Baseline clinical and biochemical parameters, including the neutrophil-to-lymphocyte ratio, were extracted and analyzed. The neutrophil-to-lymphocyte ratio threshold was determined via recursive partitioning and assessed at diagnosis, prior to chemotherapy and during treatment. Overall survival was estimated via the Kaplan-Meier method and compared between groups with the logrank test. RESULTS: Between 2005 and 2011, 85 patients with locally advanced (n = 38) and metastatic disease were identified: 68% with a neutrophil-to-lymphocyte ratio >3 had shorter median overall survival than patients with a neutrophil-to-lymphocyte ratio <3 (3.4 vs 9.4 months, P = 0.001). Pretreatment, 35% of repeat neutrophil-to-lymphocyte ratios crossed the threshold of 3. A persistently elevated neutrophil-to-lymphocyte ratio >3 suggested a worse overall survival than in patients with a decreasing, increasing or persistently low neutrophil-to-lymphocyte ratio (1.9 vs 8.2, 12.3 and 11.7 months, respectively, P <0.001). Twenty-three percent of patients had a >50% decrease in neutrophil-to-lymphocyte ratio following 4 weeks of chemotherapy, with a trend towards improvement in overall survival (12.5 vs 5.0 mo, P = 0.068). CONCLUSIONS: The baseline neutrophil-to-lymphocyte ratio is a validated marker for a poor prognosis. Multiple assessments of the pre-treatment neutrophil-to-lymphocyte ratio might be required. Reduction in the neutrophil-to-lymphocyte ratio during chemotherapy may be associated with improved survival.

20 Article Identification of distinct phenotypes of locally advanced pancreatic adenocarcinoma. 2013

Teo, Minyuen / Crotty, Grace F / O'Súilleabháin, Criostóir / Ridgway, Paul F / Conlon, Kevin C / Power, Derek G / McDermott, Ray S. ·Department of Medical Oncology, Adelaide & Meath Hospital incorporating National Children's Hospital, Tallaght, Dublin, Ireland. neuy924@gmail.com ·J Gastrointest Cancer · Pubmed #22829058.

ABSTRACT: BACKGROUND: A significant number of pancreatic ductal adenocarcinoma present as locally advanced disease. Optimal treatment remains controversial. We sought to analyze the clinical course of locally advanced pancreatic adenocarcinoma (LAPC) in order to identify potential distinct clinical phenotypes. METHODS: Patients (pts) diagnosed with LAPC who survived >2 months were identified from institutional databases. Clinical details were collected. Sequential re-staging scans were reviewed. Progression-free survival (PFS), time from progression to death (TTD), and overall survival (OS) were estimated with Kaplan-Meier method and compared with log-rank test. RESULTS: Between 2005 and 2011, 40 pts were identified. Median age was 66 yrs (range, 43-74) and 60 % (n=24) were male. All pts received chemotherapy. Median OS was 11.3 months. Twenty patients (50 %) had local progression only (LP) and 16 (40 %) had metastatic progression (MP) at first documentation of progression, while four patients (10 %) had stable disease. PFS was 4.0 vs 5.6 months (hazard ratio (HR) 0.97; 95 % CI 0.49-1.93, p=0.94) for LP and MP, respectively. Three of the patients with LP (15 %) eventually developed metastatic disease after a median of 4.2 months (3.7-9.6). For MP patients, five had concurrent local progression. Sites of disease were lung (eight), peritoneum (five), liver (three), and bone (one). TTD for LP and MP was 5.6 vs 1.4 months (HR 0.62; 95 % CI 0.28-1.39, p=0.24) and OS was 13.2 vs 8.0 months (HR 0.59; 95 % CI 0.28-1.25, p=0.017), respectively. CONCLUSIONS: We identified two subgroups of LAPC with distinctive behavior, one local dominant progression with low predilection for metastases and another with rapid metastatic development and worse survival. Early recognition of these phenotypes might allow a more tailored treatment approach to improve outcome.

21 Article Invasive markers identified by gene expression profiling in pancreatic cancer. 2012

Rogers, A / Smith, M J / Doolan, P / Clarke, C / Clynes, M / Murphy, J F / McDermott, A / Swan, N / Crotty, P / Ridgway, P F / Conlon, K C. ·Department of Surgery, Trinity College Dublin, The Adelaide and Meath Hospital Incorporating the National Children's Hospital, Tallaght, Dublin 24, Ireland. ·Pancreatology · Pubmed #22487523.

ABSTRACT: BACKGROUND: Molecular profiling has proven utility as a diagnostic and predictive tool in clinical oncology. However, a clinically relevant gene expression profile in pancreatic cancer remains elusive. METHODS: Primary and metastatic pancreatic cancer cell lines (BxPC-3 and AsPC-1), were stimulated with phorbol-12-myristate 13-acetate (PMA), a known inducer of cell invasion. Affymetrix gene expression microarray analysis was performed, comparing gene expression to unstimulated controls. Differential expression was identified using ArrayAssist, and confirmed using quantitative real-time PCR. Bioinformatic analysis was performed using Pathway Studio and GOstat. The derived gene expression was further validated in fresh frozen pancreatic tumour samples. The ability of the derived 3 gene expression markersto differentiate between pancreatic adenocarcinoma (PDAC) and other neoplasms, and its association with clinicopathological variables was examined. RESULTS: PMA-induced significant changes in cell line gene expression, from which distinctive 3 potential invasive markers were derived. Expression of these genes, uPA, MMP-1 and IL1-R1 was confirmed in human pancreatic tumours, and was found to differentiate PDAC from other pancreatic neoplasms. The expression of IL1-R1 in PDAC is a novel finding. We found that the expression of MMP-1 was associated with high-grade PDAC (p = 0.035, Wilcoxon rank sum). CONCLUSION: We have identified three potential invasive markers, uPA, MMP-1 and IL1-R1, whose gene expression may differentiate PDAC from other pancreatic neoplasms, and potentially reflect a more invasive phenotype.

22 Article RNAi knockdown of Hop (Hsp70/Hsp90 organising protein) decreases invasion via MMP-2 down regulation. 2011

Walsh, Naomi / Larkin, AnneMarie / Swan, Niall / Conlon, Kevin / Dowling, Paul / McDermott, Ray / Clynes, Martin. ·National Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland. Naomi.walsh@dcu.ie ·Cancer Lett · Pubmed #21470770.

ABSTRACT: We previously identified Hop as over expressed in invasive pancreatic cancer cell lines and malignant tissues of pancreatic cancer patients, suggesting an important role for Hop in the biology of invasive pancreatic cancer. Hop is a co-chaperone protein that binds to both Hsp70/Hsp90. We hypothesised that by targeting Hop, signalling pathways modulating invasion and client protein stabilisation involving Hsp90-dependent complexes may be altered. In this study, we show that Hop knockdown by small interfering (si)RNA reduces the invasion of pancreatic cancer cells, resulting in decreased expression of the downstream target gene, matrix metalloproteinases-2 (MMP-2). Hop in conditioned media co-immunoprecipitates with MMP-2, implicating a possible extracellular function for Hop. Knockdown of Hop expression also reduced expression levels of Hsp90 client proteins, HER2, Bcr-Abl, c-MET and v-Src. Furthermore, Hop is strongly expressed in high grade PanINs compared to lower PanIN grades, displaying differential localisation in invasive ductal pancreatic cancer, indicating that the localisation of Hop is an important factor in pancreatic tumours. Our data suggests that the attenuation of Hop expression inactivates key signal transduction proteins which may decrease the invasiveness of pancreatic cancer cells possibly through the modulation of Hsp90 activity. Therefore, targeting Hop in pancreatic cancer may constitute a viable strategy for targeted cancer therapy.

23 Article Vascular endothelial growth factor and not cyclooxygenase 2 promotes endothelial cell viability in the pancreatic tumor microenvironment. 2010

Toomey, Desmond P / Manahan, Ellen / McKeown, Ciara / Rogers, Annamarie / McMillan, Helen / Geary, Michael / Conlon, Kevin C / Murphy, Joseph F. ·Professorial Surgical Unit, University of Dublin, Trinity College, Dublin, Ireland. ·Pancreas · Pubmed #20118820.

ABSTRACT: OBJECTIVES: Cyclooxygenase 2 (COX-2) and vascular endothelial growth factor (VEGF), often coexpressed in cancer, are associated with poor prognosis. However, results from pancreatic cancer trials of their inhibitors were disappointing. This study delineated the role of COX-2 and nonsteroidal anti-inflammatory drugs in angiogenesis and VEGF regulation. METHODS: AsPC-1 and BxPC-3 pancreatic cancer cells were cocultured with human umbilical vein endothelial cells (HUVECs). NS398 or VEGF-neutralizing antibody was added, and HUVEC viability assayed. Prostaglandin E2 and VEGF were quantified. Tumor cells were treated with NS398 or celecoxib, and VEGF quantified. RESULTS: In cocultures, HUVEC viability in AsPC-1 was 60% that of BxPC-3 controls (P < 0.05). Prostaglandin E2 and VEGF from BxPC-3 were double that of AsPC-1 (P < 0.05). NS398 reduced prostaglandin E2 to undetectable levels (P < 0.05) but had no effect on HUVEC viability. Vascular endothelial growth factor-neutralizing antibody reduced HUVEC viability in BxPC-3 wells to that of AsPC-1 (P < 0.05). NS398 had no effect on VEGF. Celecoxib increased VEGF in a concentration-dependent manner in each cell line up to 4-fold (P < 0.05). CONCLUSIONS: Cyclooxygenase 2 does not regulate VEGF in pancreatic cancer, and celecoxib upregulates VEGF in pancreatic cancer. It is VEGF, and not COX-2, inhibitors that reduce tumor-stimulated endothelial cell viability. Future pancreatic cancer trials should consider lower-dose nonsteroidal anti-inflammatory drugs in combination with VEGF inhibitors.

24 Unspecified The Practical Management of Chronic Pancreatitis: A Multidisciplinary Symposium Held at the Annual Meeting of the Pancreatic Society of Great Britain and Ireland, Manchester 2016. 2019

Jegatheeswaran, Santhalingam / Puleston, Joanne M / Duggan, Sinead / Hart, Andrew / Conlon, Kevin C / Siriwardena, Ajith K. ·Hepato-Pancreato-Biliary Unit, Manchester, United Kingdom. · Department of Gastroenterology Manchester Royal Infirmary, Manchester, United Kingdom. · Department of Surgery, Trinity College, Dublin, Ireland. · Department of Gastroenterology, Norfolk and Norwich University Hospital and University of East Anglia, Dublin, Ireland. · Hepato-Pancreato-Biliary Unit, Manchester, United Kingdomajith.siriwardena@cmft.nhs.uk. ·Dig Surg · Pubmed #29339657.

ABSTRACT: AIM: This study is about a questionnaire survey of delegates attending the chronic pancreatitis symposium at the 2016 meeting of the Pancreatic Society of Great Britain and Ireland and seeks a multidisciplinary "snapshot" overview of practice. METHODS: A questionnaire was developed with multidisciplinary input. Questions on access to specialist care, methods of diagnosis and treatment including specific scenarios were incorporated. Eighty-three (66%) of 125 delegates effectively participated in this survey. RESULTS: Twenty-four (29%) had neither a chronic pancreatitis MDT in their hospital nor a chronic pancreatitis referral MDT. Most frequently utilised diagnostic modalities were CT, MR and EUS with no respondents utilising duodenal intubation tests. Initial treatment was provided through non-opiate analgesia by 69 (93%), through the use of opiates by 56 (76%) and through the use of co-analgesics by 49 (66%). Fifty two (68%) routinely referred patients with alcohol-related disease for counselling. Preferred treatment for large duct disease without mass was endoscopic therapy. In older patients with a mass, pancreaticoduodenectomy was preferred. CONCLUSION: This is a small study likely to be skewed by sampling bias but is thought to be the first multidisciplinary survey of the management of chronic pancreatitis in the United Kingdom and Ireland. The results show a need for comprehensive access to specialist pancreatitis MDT care and there remains substantial variation in management.