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Pancreatic Neoplasms: HELP
Articles from Austria
Based on 160 articles published since 2008
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These are the 160 published articles about Pancreatic Neoplasms that originated from Austria during 2008-2019.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7
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 Editorial Pancreatic diseases. 2014

Schöfl, Rainer. ·4. Interne Abteilung für Gastroenterologie & Hepatologie, Stoffwechsel- & Ernährungsmedizin, Endokrinologie, Krankenhaus der Elisabethinen Linz, Fadingerstraße 1, 4020, Linz, Austria, rainer.schoefl@elisabethinen.or.at. ·Wien Med Wochenschr · Pubmed #24619470.

ABSTRACT: -- No abstract --

5 Review Isolated pancreatic metastases from renal cell carcinoma: an outcome of a special metastatic pathway or of specific tumor cell selection? 2018

Sellner, Franz. ·Surgical Department, Kaiser Franz Josef Hospital, Kundratstraße 3, A 1100, Vienna, Austria. sellner.franz@aon.at. ·Clin Exp Metastasis · Pubmed #29948649.

ABSTRACT: Isolated pancreatic metastases (isPM) are a rare metastasizing pattern in the natural history of renal cell cancer. Their clinical hallmark is that they are confined to a single organ, the pancreas, while all other organs are unaffected for a long time. Almost all workers in the field suggested that mechanical tumor cell propagation to the pancreas may be the mechanism underlying this metastasizing pattern. In 2006 our group, by contrast, proposed an alternative mechanism, i.e. a special affinity of the tumor cells for the pancreas. In the present study an attempt was made to shed more light on the settlement of isPM by reviewing recent literature data. 666 observations of isPM reported in the literature were reviewed. The analyses showed that local lymphatic spread does not play a major role because the lymphatic system is, in general, rarely involved in isPM. This also applies to a local venous spread, because the site of pancreatic metastases is independent of the side affected by the primary renal cancer. But the results are compatible with a systemic metastatic pathway. That metastases in other organs, which would be expected given a systemic spread, are absent can plausibly be explained by a seed and soil mechanism: only the pancreas offers the tumor cell emboli an environment which is conducive to the growth of clinically manifest metastases, while settlement of metastatic tumor cells is prevented in all other organs.

6 Review Challenges and Perspectives for Immunotherapy in Adenocarcinoma of the Pancreas: The Cancer Immunity Cycle. 2018

Kieler, Markus / Unseld, Matthias / Bianconi, Daniela / Prager, Gerald. ·From the Department of Medicine I, Division of Oncology, Comprehensive Cancer Center, Medical University Vienna, Austria. ·Pancreas · Pubmed #29346215.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with a devastating 5-year overall survival of only approximately 7%. Although just 4% of all malignant diseases are accounted to PDAC, it will become the second leading cause of cancer-related deaths before 2030. Immunotherapy has proven to be a promising therapeutic option in various malignancies such as melanoma, non-small cell lung cancer (NSCLC), microsatellite instability-high gastrointestinal cancer, urinary tract cancer, kidney cancer, and others. In this review, we summarize recent findings about immunological aspects of PDAC with the focus on the proposed model of the "cancer immunity cycle". By this model, a deeper understanding of the underlying mechanism in achieving a T-cell response against cancer cells is provided. There is currently great interest in the field around designing novel immunotherapy combination studies for PDAC based on a sound understanding of the underlying immunobiology.

7 Review Intraductal tubulopapillary neoplasm (ITPN) of the pancreas associated with an invasive component: a case report with review of the literature. 2017

Kuscher, Stefanie / Steinle, Hartmut / Soleiman, Afschin / Öfner, Dietmar / Schneeberger, Stefan / Oberhuber, Georg. ·Department of Visceral, Transplant and Thoracic Surgery, Center of Operative Medicine, Medical University of Innsbruck, Innsbruck, Austria. Stefanie.Kuscher@i-med.ac.at. · Department of Internal Medicine I, Gastroenterology and Hepatology, Medical University of Innsbruck, Innsbruck, Austria. · Pathology Department of the General Hospital of Innsbruck, Innsbruck, Austria. · Department of Visceral, Transplant and Thoracic Surgery, Center of Operative Medicine, Medical University of Innsbruck, Innsbruck, Austria. ·World J Surg Oncol · Pubmed #29145864.

ABSTRACT: BACKGROUND: Intraductal tubulopapillary neoplasm (ITPN) depicts a distinct entity in the subgroup of premalignant epithelial tumors of the pancreas. Although the histomorphological and immunophenotypical characterization of ITPN has been described by several authors in terms of report of case series in the past, the rarity of that tumor subtype and similarity to other entities still makes identification of ITPN a challenge for radiologists and pathologists. To date, little is known about tubulopapillary carcinoma that can evolve from ITPN. CASE PRESENTATION: In the present work, we analyze one case of ITPN associated with an invasive component and discuss the results involving the current literature. Collected patient data included medical history, clinical symptoms, laboratory tests, radiological imaging, reports of interventions and operation, and histopathological and immunohistochemical examinations. The patient initially presented with acute pancreatitis. A solid tumor obstructing the main pancreatic duct and sticking out of the papilla of Vater was detected and caught via endoscopic intervention. Histopathological examination of the specimen revealed mainly tubular growth pattern with back to back tubular glands. Immunohistochemically, the tumor was strongly positive for keratin 7 (CK7) and pankeratin AE1/AE3, and alpha 1 antichymotrypsin; negative for synaptophysin and chromogranin A, CDx2, CK20, S100, carcinoembryonic antigen (CEA), MUC 2, MUC5AC, and somatostatin; and in part positive for CA19-9. Extended pancreatoduodenectomy was performed, the final diagnosis was tubulopapillary carcinoma grown in an ITPN. CONCLUSION: The identification of an ITPN of the pancreas can be a challenging task. Endoscopic retrograde cholangiopancreaticography is an excellent tool to directly see and indirectly visualize the intraductal solid tumor and to take a biopsy for histopathological evaluation at the same time. Together with a thorough immunohistochemical workup, differential diagnoses can be ruled out quickly. To date, reports of ITPN are rare and little is known about the potential for malignant transformation and the prognosis of tubulopapillary carcinoma grown from an ITPN. Radical surgical resection following oncologic criteria is recommended; however, more data will be needed to assess an adequate treatment and follow-up standard.

8 Review New Diagnostic and Therapeutic Aspects of Pancreatic Ductal Adenocarcinoma. 2017

Mangge, Harald / Niedrist, Tobias / Renner, Wilfried / Lyer, Stefan / Alexiou, Christoph / Haybaeck, Johannes. ·Clinical Institute of Medical and Chemical Laboratory Diagnosis, Medical University of Graz, Auenbruggerplatz 30, 8036 Graz. Austria. · Clinical Institute of Medical and Chemical Laboratory Diagnosis, Medical University of Graz, Graz. Austria. · Department of Otorhinolaryngology - Head and Neck Surgery, Section of Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftungsprofessur, Universitätsklinikum Erlangen, Friedrich- Alexander-Universität Erlangen-Nürnberg, Erlangen. Germany. · Department of Pathology, Otto-von- Guericke University of Magdeburg, Magdeburg. Germany. ·Curr Med Chem · Pubmed #28494747.

ABSTRACT: BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is devastating. Because of its silent nature, the disease is often only diagnosed once it has reached an advanced, frequently inoperable stage. To date, we have no biomarkers that facilitate earlier diagnosis, leaving sufficient time for curative therapy that effectively lowers the very high mortality rate of this cancer entity. Because of this, the life expectancy of patients with PDAC is low (i.e. ≤ 6% five-year survival rates). New data, including particular genetic signatures and features of the stromal architecture of PDAC tumors, may better explain their aggressiveness, their relatively long-lasting painless expansion, and why chemotherapy so frequently fails. The typical tumor-induced stromal desmoplasia is characterized by cancer-associated fibroblasts (CAFs), decreased immune surveillance, cancer-associated neural remodeling, and a very low vascular density. This stromal microenvironment generates hypoxia, nutrient deficiency, immune suppression, and chemoresistance. The combination of factors results in a vicious disease that begins with the long-lasting, asymptomatic development of a large tumor mass, followed by a delayed diagnosis with a high percentage of inoperable states, exhibiting a poor response to all conservative therapeutic options, including radiation, and which ends with metastasis resulting in a rapid fatal outcome. OBJECTIVE: In this article, we review coherences on genetic, cellular, immunological, Nano medical and stromal characteristics of PDAC tissue, and discuss metabolic abnormalities associated with and/or preceding the tumor progression rate. CONCLUSION: A more comprehensive understanding of the underlying mechanisms can improve the diagnostic and therapeutic management of patients suffering from this devastating type of cancer.

9 Review [Hereditary gastric and pancreatic cancer]. 2017

Langner, C. ·Institut für Pathologie, Medizinische Universität Graz, Auenbruggerplatz 25, 8036, Graz, Österreich. cord.langner@medunigraz.at. ·Pathologe · Pubmed #28484856.

ABSTRACT: Most cases of gastric and pancreatic cancer are sporadic, but familial clustering can be observed in approximately 10% of cases. Hereditary gastric cancer accounts for a very low percentage of cases (1-3%) and two syndromes have been characterized: hereditary diffuse gastric cancer (HDGC) and gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS). Gastric and pancreatic cancer can develop in the setting of other hereditary cancer syndromes, such as hereditary breast and ovarian cancer syndrome (HBOC), Li-Fraumeni syndrome, Lynch syndrome, familial adenomatous polyposis (FAP), or various hamartomatous polyposis syndromes, including juvenile polyposis and Peutz-Jeghers syndrome. Patients with hereditary pancreatitis carry an increased risk of cancer (40-55%).

10 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.

11 Review Systematic review reveals lack of quality in reporting health-related quality of life in patients with gastroenteropancreatic neuroendocrine tumours. 2016

Martini, Caroline / Gamper, Eva-Maria / Wintner, Lisa / Nilica, Bernhard / Sperner-Unterweger, Barbara / Holzner, Bernhard / Virgolini, Irene. ·Department for Psychiatry, Psychotherapy and Psychosomatics, Medical University of Innsbruck, Anichstraße 35, 6020, Innsbruck, Austria. · Department for Psychiatry, Psychotherapy and Psychosomatics, Medical University of Innsbruck, Anichstraße 35, 6020, Innsbruck, Austria. eva.gamper@tirol-kliniken.at. · Department for Nuclear Medicine, Medical University of Innsbruck, Anichstraße 35, 6020, Innsbruck, Austria. eva.gamper@tirol-kliniken.at. · Department for Nuclear Medicine, Medical University of Innsbruck, Anichstraße 35, 6020, Innsbruck, Austria. ·Health Qual Life Outcomes · Pubmed #27614762.

ABSTRACT: BACKGROUND: Gastroenteropancreatic neuroendocrine tumours (GEP-NET) are often slow-growing and patients may live for years with metastasised disease. Hence, along with increasing overall and progression-free survival, treatments aim at preserving patients' well-being and health-related quality of life (HRQoL). However, studies on systematic HRQoL assessment in patients with GEP-NET are scarce. Therefore, the purpose of the current review is to systematically evaluate the methodological quality of the identified studies. METHODS: A targeted database search was performed in PubMed, EMBASE, and CENTRAL. Data extraction was conducted by two independent researchers according to predefined criteria. For study evaluation, the Minimum Standard Checklist for Evaluating HRQoL Outcomes in Cancer Clinical Trials and the CONSORT Patient-Reported Outcome extension were adapted. RESULTS: The database search yielded 48 eligible studies. We found the awareness for the need of HRQoL measurement to be growing and application of cancer-specific instruments gaining acceptance. Overall, studies were too heterogeneous in terms of patient characteristics and treatment interventions to draw clear conclusions for clinical practice. More importantly, a range of methodological shortcomings has been identified which were mainly related to the assessment and statistical analysis, as well as the reporting and interpretation of HRQoL data. CONCLUSION: Despite an increasing interest in HRQoL in GEP-NET patients, there is still a lack of knowledge on this issue. A transfer of HRQoL results into clinical practice is hindered not only by the scarceness of studies, but also by the often limited quality of HRQoL processing and reporting.

12 Review Current knowledge on the sensitivity of the (68)Ga-somatostatin receptor positron emission tomography and the SUVmax reference range for management of pancreatic neuroendocrine tumours. 2016

Virgolini, Irene / Gabriel, Michael / Kroiss, Alexander / von Guggenberg, Elisabeth / Prommegger, Rupert / Warwitz, Boris / Nilica, Bernhard / Roig, Llanos Geraldo / Rodrigues, Margarida / Uprimny, Christian. ·Department of Nuclear Medicine, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria. irene.virgolini@i-med.ac.at. · Department of Nuclear Medicine, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria. ·Eur J Nucl Med Mol Imaging · Pubmed #27174220.

ABSTRACT: Physiologically increased pancreatic uptake at the head/uncinate process is observed in more than one-third of patients after injection of one of the three (68)Ga-labelled octreotide-based peptides used for somatostatin (sst) receptor (r) imaging. There are minor differences between these (68)Ga-sstr-binding peptides in the imaging setting. On (68)Ga-sstr-imaging the physiological uptake can be diffuse or focal and usually remains stable over time. Differences in the maximal standardised uptake values (SUVmax) reported for the normal pancreas as well as for pancreatic neuroendocrine tumour (PNET) lesions may be related to several factors, including (a) differences in the peptide binding affinities as well as differences in sstr subtype expression of pancreatic α- and β-cells, and heterogeneity / density of tumour cells, (b) differences in scanner resolution, image reconstruction techniques and acquisition protocols, (c) mostly retrospective study designs, (d) mixed patient populations, or (e) interference with medications such as treatment with long-acting sst analogues. The major limitation in most of the studies lies in the lack of histopathological confirmation of abnormal findings. There is a significant overlap between the calculated SUVmax-values for physiological pancreas and PNET-lesions of the head/uncinate process that do not favour the use of quantitative parameters in the clinical setting. Anecdotal long-term follow-up studies have even indicated that increased uptake in the head/uncinate process still can turn out to be malignant over years of follow up. SUVmax-data for the pancreatic body and tail are limited. Therefore, any visible focal tracer uptake in the pancreas must be considered as suspicious for malignancy irrespective of quantitative parameters. In general, sstr-PET/CT has significant implications for the management of NET patients leading to a change in treatment decision in about one-third of patients. Therefore, follow-up with (68)Ga-sstr-PET/CT is mandatory in the clinical setting if uptake in the head/uncinate process is observed.

13 Review FOLFIRINOX for locally advanced pancreatic cancer: a systematic review and patient-level meta-analysis. 2016

Suker, Mustafa / Beumer, Berend R / Sadot, Eran / Marthey, Lysiane / Faris, Jason E / Mellon, Eric A / El-Rayes, Bassel F / Wang-Gillam, Andrea / Lacy, Jill / Hosein, Peter J / Moorcraft, Sing Yu / Conroy, Thierry / Hohla, Florian / Allen, Peter / Taieb, Julien / Hong, Theodore S / Shridhar, Ravi / Chau, Ian / van Eijck, Casper H / Koerkamp, Bas Groot. ·Department of Surgery, Erasmus University Medical Centre, Rotterdam, Netherlands. · Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Department of Hepatogastroenterology, Antoine Beclère Hospital, Assistance publique-Hôpitaux de Paris, Paris Sud University, Clamart, France. · Department of Hematology-Oncology, Massachusetts General Hospital, Boston, MA, USA. · Department of Radiation Oncology, H Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA. · Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, USA. · Department of Medicine, Washington University School of Medicine, Saint Louis, MO, USA. · Department of Medicine, Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA. · Department of Medicine, Division of Medical Oncology, University of Kentucky-Markey Cancer Center, Lexington, KY, USA. · Department of Medicine, The Royal Marsden National Health Service Foundation Trust, London and Surrey, UK. · Department of Medical Oncology, Institut de Cancérologie de Lorraine and Lorraine University, Vandoeuvre-lès-Nancy, France. · Department of Hematology, Medical Oncology, Hemostasis, Rheumatology and Infectious Diseases, Paracelsus Medical University of Salzburg, Salzburg, Austria. · Department of Gastroenterology and Digestive Oncology, Georges Pompidou European Hospital, Assistance publique-Hôpitaux de Paris, Sorbonne Paris Cité, Paris Descartes University, Cancer Research Personalized Medicine (CARPEM), Paris, France. · Department of Radiation Oncology, Florida Hospital Cancer Institute, Orlando, FL, USA. · Department of Surgery, Erasmus University Medical Centre, Rotterdam, Netherlands. Electronic address: b.grootkoerkamp@erasmusmc.nl. ·Lancet Oncol · Pubmed #27160474.

ABSTRACT: BACKGROUND: 35% of patients with pancreatic cancer have unresectable locally advanced disease at diagnosis. Several studies have examined systemic chemotherapy with FOLFIRINOX (leucovorin and fluorouracil plus irinotecan and oxaliplatin) in patients with locally advanced pancreatic cancer. We aimed to assess the effectiveness of FOLFIRINOX as first-line treatment in this patient population. METHODS: We systematically searched Embase, MEDLINE (OvidSP), Web of Science, Scopus, PubMed Publisher, Cochrane, and Google Scholar from July 1, 1994, to July 2, 2015, for studies of treatment-naive patients of any age who received FOLFIRINOX as first-line treatment of locally advanced pancreatic cancer. Our primary outcome was overall survival. Secondary outcomes were progression-free survival; rates of grade 3 or 4 adverse events; and the proportion of patients who underwent radiotherapy or chemoradiotherapy, surgical resection after FOLFIRINOX, and R0 resection. We evaluated survival outcomes with the Kaplan-Meier method with patient-level data. Grade 3 or 4 adverse events, and the proportion of patients who underwent subsequent radiotherapy or chemoradiotherapy or resection, were pooled in a random-effects model. FINDINGS: We included 13 studies comprising 689 patients, of whom 355 (52%) patients had locally advanced pancreatic cancer. 11 studies, comprising 315 patients with locally advanced disease, reported survival outcomes and were eligible for patient-level meta-analysis. Median overall survival from the start of FOLFIRINOX ranged from 10·0 months (95% CI 4·0-16·0) to 32·7 months (23·1-42·3) across studies with a pooled patient-level median overall survival of 24·2 months (95% CI 21·7-26·8). Median progression-free survival ranged from 3·0 months (95% CI not calculable) to 20·4 months (6·5-34·3) across studies with a patient-level median progression-free survival of 15·0 months (95% 13·8-16·2). In ten studies comprising 490 patients, 296 grade 3 or 4 adverse events were reported (60·4 events per 100 patients). No deaths were attributed to FOLFIRINOX toxicity. The proportion of patients who underwent radiotherapy or chemoradiotherapy ranged from 31% to 100% across studies. In eight studies, 154 (57%) of 271 patients received radiotherapy or chemoradiotherapy after FOLFIRINOX. The pooled proportion of patients who received any radiotherapy treatment was 63·5% (95% CI 43·3-81·6, I(2) 90%). The proportion of patients who underwent surgical resection for locally advanced pancreatic cancer ranged from 0% to 43%. The proportion of patients who had R0 resection of those who underwent resection ranged from 50% to 100% across studies. In 12 studies, 91 (28%) of 325 patients underwent resection after FOLFIRINOX. The pooled proportion of patients who had resection was 25·9% (95% CI 20·2-31·9, I(2) 24%). R0 resection was reported in 60 (74%) of 81 patients. The pooled proportion of patients who had R0 resection was 78·4% (95% CI 60·2-92·2, I(2) 64%). INTERPRETATION: Patients with locally advanced pancreatic cancer treated with FOLFIRINOX had a median overall survival of 24·2 months-longer than that reported with gemcitabine (6-13 months). Future research should assess these promising results in a randomised controlled trial, and should establish which patients might benefit from radiotherapy or chemoradiotherapy or resection after FOLFIRINOX. FUNDING: None.

14 Review Non-coding RNAs in pancreatic cancer: challenges and opportunities for clinical application. 2016

Taucher, V / Mangge, H / Haybaeck, J. ·Institute of Pathology, Medical University Graz, Auenbruggerplatz 25, A-8036, Graz, Austria. · Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University Graz, Auenbruggerplatz 25, A-8036, Graz, Austria. · Institute of Pathology, Medical University Graz, Auenbruggerplatz 25, A-8036, Graz, Austria. johannes.haybaeck@medunigraz.at. ·Cell Oncol (Dordr) · Pubmed #27060060.

ABSTRACT: BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with a dismal prognosis for which new therapeutic strategies are desperately needed. Non-coding RNAs (ncRNAs), especially microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), may yield new therapeutic concepts for the treatment of PDAC. A vast number of miRNAs, including the well-studied miR-21, miR-155 and miR-34, has been shown to regulate PDAC growth, invasion and metastasis in vitro and in vivo by targeting members of key signaling pathways. In addition, other miRNAs and lncRNAs, such as HOTTIP and MALAT-1, have been shown to influence the malignant behavior of PDAC cells. METHODS: Here, we discuss several ncRNAs that may be used either as new therapeutic agents or as targets of new therapeutic agents. Furthermore, we discuss the problem of proper delivery of nucleotide-based agents and novel methods that may be used to circumvent this problem. CONCLUSIONS: Although the number of reports addressing the role of ncRNAs in PDAC virtually grows by the day, there are still many steps to be taken before the application of ncRNA-based therapies will become reality in clinical practice.

15 Review Endocrine tumours in the guinea pig. 2015

Künzel, Frank / Mayer, Jörg. ·Clinical Department of Small Animals and Horses, University of Veterinary Medicine Vienna, Veterinaerplatz 1, 1210 Vienna, Austria. Electronic address: Frank.Kuenzel@vetmeduni.ac.at. · Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA. ·Vet J · Pubmed #26542368.

ABSTRACT: Functional endocrine tumours have long been thought to be rare in guinea pigs, although conditions such as hyperthyroidism and hyperadrenocorticism have been documented with increasing frequency so the prevalence of hormonal disorders may have been underestimated. Both the clinical signs and diagnosis of hyperthyroidism in guinea pigs appear to be very similar to those described in feline hyperthyroidism, and methimazole has been proven to be a practical therapy option. Hyperadrenocorticism has been confirmed in several guinea pigs with an adrenocorticotropic hormone stimulation test using saliva as a non-invasive sample matrix; trilostane has been successfully used to treat a guinea pig with hyperadrenocorticism. Insulinomas have only rarely been documented in guinea pigs and one animal was effectively treated with diazoxide.

16 Review Intraductal papillary mucinous neoplasms. 2015

Sahora, Klaus / Fernández-del Castillo, Carlos. ·aDepartment of Surgery, Medical University Vienna, Vienna, Austria bDepartment of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, USA. ·Curr Opin Gastroenterol · Pubmed #26125316.

ABSTRACT: PURPOSE OF REVIEW: Our understanding of intraductal papillary mucinous neoplasm (IPMN) of the pancreas has remarkably grown within the last decade; nonetheless there is still an ongoing controversy if the majority of these potentially malignant neoplasms need to be resected or if observation in a subset is well tolerated. RECENT FINDINGS: Novel cyst fluid biomarkers, like Gnas mutations or mab DAS-1, could play a pivotal role in the distinction of IPMN vs. other cystic lesions, in the sub-classification of IPMN and in the detection of IPMN with high-grade dysplasia or invasive cancer. Other recent studies focused on natural history of minimal- and extensive-mixed IPMN and the safety of the 2012 AIP guidelines. Small series also described that observation can be an option in selected frail patients with MD-IPMN. Further, data from a large European multicenter study analysis indicated that patients with IPMN do not have an increased frequency of extrapancreatic malignancies. SUMMARY: Increasing knowledge about the nature of IPMN and their subtypes has resulted in an individualized approach in diagnosis and treatment. Owing to the availability of accurate diagnostic instruments, timing and indication for pancreatic resection have become more selective, sparing patients with harmless IPMN from major surgery.

17 Review Therapeutic vaccines for cancer: an overview of clinical trials. 2014

Melero, Ignacio / Gaudernack, Gustav / Gerritsen, Winald / Huber, Christoph / Parmiani, Giorgio / Scholl, Suzy / Thatcher, Nicholas / Wagstaff, John / Zielinski, Christoph / Faulkner, Ian / Mellstedt, Håkan. ·Centro de Investigación Medica Aplicada (CIMA) and Clínica Universitaria (CUN), Universidad de Navarra, Spain. · Department of Immunology, The Norwegian Radium Hospital, Cancer Research Institute, University of Oslo, Norway. · Department of Medical Oncology, VUmc Cancer Center Amsterdam, 1081 HV Amsterdam, Netherlands. · Department of Haematology/Oncology, Johannes Gutenberg University, Germany. · San Raffaele Foundation Scientific Institute, Italy. · Department of Medical Oncology, Institut Curie, France. · CRC Department of Medical Oncology, Christie Hospital NHS Trust, UK. · South West Wales Cancer Institute, Singleton Hospital, UK. · Clinical Division of Oncology, Department of Medicine I, Comprehensive Cancer Centre Vienna, Medical University Vienna, Austria. · International Medical Press, UK. · Cancer Centre Karolinska, Department of Oncology, Karolinska University Hospital, SE-171 76 Stockholm, Sweden. ·Nat Rev Clin Oncol · Pubmed #25001465.

ABSTRACT: The therapeutic potential of host-specific and tumour-specific immune responses is well recognized and, after many years, active immunotherapies directed at inducing or augmenting these responses are entering clinical practice. Antitumour immunization is a complex, multi-component task, and the optimal combinations of antigens, adjuvants, delivery vehicles and routes of administration are not yet identified. Active immunotherapy must also address the immunosuppressive and tolerogenic mechanisms deployed by tumours. This Review provides an overview of new results from clinical studies of therapeutic cancer vaccines directed against tumour-associated antigens and discusses their implications for the use of active immunotherapy.

18 Review Epigenetics and pancreatic cancer: pathophysiology and novel treatment aspects. 2014

Neureiter, Daniel / Jäger, Tarkan / Ocker, Matthias / Kiesslich, Tobias. ·Daniel Neureiter, Institute of Pathology, Paracelsus Medical University/Salzburger Landeskliniken (SALK), 5020 Salzburg, Austria. ·World J Gastroenterol · Pubmed #24976721.

ABSTRACT: An improvement in pancreatic cancer treatment represents an urgent medical goal. Late diagnosis and high intrinsic resistance to conventional chemotherapy has led to a dismal overall prognosis that has remained unchanged during the past decades. Increasing knowledge about the molecular pathogenesis of the disease has shown that genetic alterations, such as mutations of K-ras, and especially epigenetic dysregulation of tumor-associated genes, such as silencing of the tumor suppressor p16(ink4a), are hallmarks of pancreatic cancer. Here, we describe genes that are commonly affected by epigenetic dysregulation in pancreatic cancer via DNA methylation, histone acetylation or miRNA (microRNA) expression, and review the implications on pancreatic cancer biology such as epithelial-mesenchymal transition, morphological pattern formation, or cancer stem cell regulation during carcinogenesis from PanIN (pancreatic intraepithelial lesions) to invasive cancer and resistance development. Epigenetic drugs, such as DNA methyltransferases or histone deactylase inhibitors, have shown promising preclinical results in pancreatic cancer and are currently in early phases of clinical development. Combinations of epigenetic drugs with established cytotoxic drugs or targeted therapies are promising approaches to improve the poor response and survival rate of pancreatic cancer patients.

19 Review Clinical approach to the patient with a solid pancreatic mass. 2014

Függer, Reinhold / Gangl, Odo / Fröschl, Uwe. ·Dept of Surgery, Krankenhaus der Elisabethinen, Fadingerstrasse 1, 4020, Linz, Austria, reinhold.fuegger@elisabethinen.or.at. ·Wien Med Wochenschr · Pubmed #24577681.

ABSTRACT: Diagnosis and clinical work-up of a solid pancreatic mass is a challenging problem. Patients' history, laboratory parameters, computed tomography magnetic resonance imaging, and endosonography are the cornerstones in diagnosis. Biopsy is indicated in selected patients. The main goal of surgical indication is to select patients with suspected malignancy who are resectable, but avoid unnecessary resections. About 5 % of patients resected due to suspicion of malignancy finally present with a benign histology. Autoimmune pancreatitis is the most frequent cause of such unnecessary resections.

20 Review Molecularly targeted therapies in metastatic pancreatic cancer: a systematic review. 2013

Zagouri, Flora / Sergentanis, Theodoros N / Chrysikos, Dimosthenis / Zografos, Constantine G / Papadimitriou, Christos A / Dimopoulos, Meletios-Athanassios / Filipits, Martin / Bartsch, Rupert. ·Comprehensive Cancer Center Vienna, Department of Medicine I, Medical University of Vienna, Vienna, Austria. florazagouri@yahoo.co.uk ·Pancreas · Pubmed #23774698.

ABSTRACT: Pancreatic cancer is the fourth leading cause of cancer-related death. Most patients present with an advanced stage of disease that has a dismal outcome, with a median survival of approximately 6 months. Evidently, there is a clear need for the development of new agents with novel mechanisms of action in this disease. A number of biological agents modulating different signal transduction pathways are currently in clinical development, inhibiting angiogenesis and targeting epidermal growth factor receptor, cell cycle, matrix metalloproteinases, cyclooxygenase-2, mammalian target of rapamycin, or proteasome. This is the first systematic review of the literature to synthesize all available data coming from trials and evaluate the efficacy and safety of molecular targeted drugs in unresectable and metastatic pancreatic cancer. However, it should be stressed that although multiple agents have been tested, only 9 phase 3 trials have been conducted and one agent (erlotinib) has been approved by the Food and Drug Administration for use in clinical practice. As knowledge accumulates on the molecular mechanisms underlying carcinogenesis in the pancreas, the anticipated development and assessment of molecularly targeted agents may offer a promising perspective for a disease which, to date, remains incurable.

21 Review Diarrhea caused by circulating agents. 2012

Fabian, Elisabeth / Kump, Patrizia / Krejs, Guenter J. ·Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria. ·Gastroenterol Clin North Am · Pubmed #22917166.

ABSTRACT: Circulating agents cause intestinal secretion or changes in motility with decreased intestinal transit time, resulting in secretory-type diarrhea. Secretory diarrhea as opposed to osmotic diarrhea is characterized by large-volume, watery stools, often more than 1 L per day; by persistence of diarrhea when patients fast; and by the fact that on analysis of stool-water, measured osmolarity is identical to that calculated from the electrolytes present. Although sodium plays the main role in water and electrolyte absorption, chloride is the major ion involved in secretion.

22 Review Unilateral face swelling as first manifestation of metastatic pancreatic cancer: case report and review of the literature. 2008

Vormittag, Laurenz / Erovic, Boban / Schopper, Christian / Zielinski, Christoph C / Kornek, Gabriela / Thurnher, Dietmar. ·Department of Internal Medicine I and Cancer Center, Medical University of Vienna, Vienna, Austria. ·Wien Klin Wochenschr · Pubmed #19116711.

ABSTRACT: OBJECTIVE: Metastasis to the jaw is a rare finding in pancreatic cancer; only five cases of tumor spread to the oral region have been described. CASE REPORT: We report on a previously healthy 54-year-old man who attended the hospital in 2006 because of a mandibular mass. Histology was positive for adenocarcinoma and computed tomography led to the diagnosis of pancreatic cancer. Chemoradiotherapy was started but had to be stopped early because of intraoral bleeding from the metastasis. The patient subsequently received palliative chemotherapy. The primary cancer was stabilized but the mandibular mass progressed despite cytostatic therapy. Despite best supportive measures the patient died nine months after presentation. CONCLUSION: In making the decision on whether metastasectomy should be performed in an uncommon site of metastatic spread such as the mandibula, both the possibility of cure and also the potentially decreased response to conservative therapy and the patient's decreased quality of life have to be considered.

23 Review Chemotherapy-induced thrombosis: a role for microparticles and tissue factor? 2008

Lechner, Daniel / Weltermann, Ansgar. ·Department of Medicine I, Medical University of Vienna, Vienna, Austria. ·Semin Thromb Hemost · Pubmed #18645926.

ABSTRACT: Chemotherapy is an independent risk factor of thromboembolic events in cancer patients. Various pathogenetic mechanisms have been hypothesized in the past, but until now their individual contribution to the risk of thrombosis has been hardly investigated in clinical trials. In recent years, studies increasingly suggested an association between the prothrombotic state in cancer patients and circulating tissue factor-exposing microparticles. In this review, we discuss the roles of tissue factor and microparticles with regard to chemotherapy-induced hypercoagulability.

24 Review [Benign neuroendocrine and other rare benign tumors of the pancreas]. 2008

Happel, B / Niederle, B / Puespoek, A / Ba-Ssalamah, A / Schima, W. ·Universitätsklinik für Radiodiagnostik, Medizinische Universität Wien, Währinger Gürtel 18-20, A-1090, Wien, Osterreich. brigitte.happel@meduniwien.ac.at ·Radiologe · Pubmed #18633589.

ABSTRACT: Neuroendocrine tumors (NET) of the pancreas are rare neoplasms, which arise from cells of the islets of Langerhans. The most common NET are the insulinoma, gastrinoma and hormone inactive NET. Very rare entities are the schwannoma, leiomyoma, teratoma, intrapancreatic lipoma, hemangioma and the intrapancreatic accessory spleen. Essential for therapy, which in most cases is difficult, are an exact localization and various modalities of imaging diagnostics.

25 Clinical Trial A Phase II Study of BEZ235 in Patients with Everolimus-resistant, Advanced Pancreatic Neuroendocrine Tumours. 2016

Fazio, Nicola / Buzzoni, Roberto / Baudin, Eric / Antonuzzo, Lorenzo / Hubner, Richard A / Lahner, Harald / DE Herder, Wouter W / Raderer, Markus / Teulé, Alexandre / Capdevila, Jaume / Libutti, Steven K / Kulke, Matthew H / Shah, Manisha / Dey, Debarshi / Turri, Sabine / Aimone, Paola / Massacesi, Cristian / Verslype, Chris. ·European Institute of Oncology, Milan, Italy nicola.fazio@ieo.it. · IRCCS National Tumor Institute, Milan, Italy. · Institut Gustave Roussy, Villejuif, France. · Careggi University Hospital, Florence, Italy. · The Christie NHS Foundation Trust, Manchester, U.K. · University of Duisburg-Essen, Essen, Germany. · Erasmus MC, Rotterdam, the Netherlands. · University Hospital of Vienna, Vienna, Austria. · Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona, Spain. · Montefiore Medical Center and Albert Einstein College of Medicine, New York, NY, U.S.A. · Dana-Farber Cancer Institute, Boston, MA, U.S.A. · The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH, U.S.A. · Novartis Healthcare Private Limited, Hyderabad, India. · Novartis Pharma AG, Basel, Switzerland. · Novartis Oncology, Paris, France. · University Hospitals Leuven, Leuven, Belgium. ·Anticancer Res · Pubmed #26851029.

ABSTRACT: BACKGROUND: This was a two-stage, phase II trial of the dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor BEZ235 in patients with everolimus-resistant pancreatic neuroendocrine tumours (pNETs) (NCT01658436). PATIENTS AND METHODS: In stage 1, 11 patients received 400 mg BEZ235 orally twice daily (bid). Due to tolerability concerns, a further 20 patients received BEZ235 300 mg bid. Stage 2 would be triggered by a 16-week progression-free survival (PFS) rate of ≥60% in stage 1. RESULTS: As of 30 June, 2014, 29/31 patients had discontinued treatment. Treatment-related grade 3/4 adverse events were reported in eight (72.7%) patients at 400 mg and eight (40.0%) patients at 300 mg, including hyperglycaemia, diarrhoea, nausea, and vomiting. The estimated 16-week PFS rate was 51.6% (90% confidence interval=35.7-67.3%). CONCLUSION: BEZ235 was poorly tolerated by patients with everolimus-resistant pNETs at 400 and 300 mg bid doses. Although evidence of disease stability was observed, the study did not proceed to stage 2.

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