Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Pancreatic Neoplasms: HELP
Articles by Jan G. D'Haese
Based on 16 articles published since 2009
(Why 16 articles?)
||||

Between 2009 and 2019, J. G. D'Haese wrote the following 16 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Review Surgery of Cystic Tumors of the Pancreas - Why, When, and How? 2018

D'Haese, Jan G / Werner, Jens. ·Department of General, Visceral, and Transplantation Surgery, Ludwig Maximilians-University, Munich, Germany. ·Visc Med · Pubmed #30182025.

ABSTRACT: The management of cystic pancreatic neoplasms has increasingly gained clinical attention due to their frequent incidental detection by cross-sectional imaging and their potential for progression to pancreatic cancer. Surgical resection is warranted for all mucinous cystic neoplasms, solid pseudopapillary neoplasms, and main-duct intraductal papillary mucinous neoplasms since these lesions harbor a major risk for malignant transformation. For branch-duct IPMN (BD-IPMN), the risk for malignancy is considerably lower so that some lesions may be safely followed while others require surgical resection. The clinical challenge lies in making the correct preoperative diagnosis and estimation of the risk of malignancy in BD-IPMN. Therefore, the existing evidence and current guidelines on the management of cystic lesions of the pancreas are summarized and controversially discussed from a surgical point of view.

2 Review [Resectability of pancreatic cancer: New criteria]. 2016

D'Haese, J G / Werner, J. ·Klinik für Allgemeine, Viszeral-, Transplantations-, Gefäß- und Thoraxchirurgie, Klinikum der Universität München, Standort Großhadern, Marchioninistr. 15, 81377, München, Deutschland. · Klinik für Allgemeine, Viszeral-, Transplantations-, Gefäß- und Thoraxchirurgie, Klinikum der Universität München, Standort Großhadern, Marchioninistr. 15, 81377, München, Deutschland. Jens.Werner@med.uni-muenchen.de. ·Radiologe · Pubmed #26993121.

ABSTRACT: BACKGROUND: Pancreatic cancer is notoriously one of the most aggressive cancers and still has a poor prognosis. Surgical resection is the only chance for a curative therapy approach, with which at least a 5‑year survival can be achieved for 25% of patients. Recent advances in surgical techniques have led to a change in the criteria for resectability. OBJECTIVE: This review summarizes the currently available evidence on the criteria for resectability of pancreatic cancer and discusses the treatment options. MATERIAL AND METHODS: The study was based on a selective literature search and a summary of the latest data on criteria for resectability is given. RESULTS: Patients with pancreatic cancer must be differentiated into those with primarily resectable disease, borderline resectable disease, locally advanced (primarily unresectable) and metastatic disease. While infiltration into the major surrounding venous vessels (e.g. superior mesenteric vein, portal vein and confluence of splenic vein) used to be a criterion for unresectable disease, these tumors can nowadays be safely resected in specialized centers. Tumor infiltration into adjacent arteries (e.g. hepatic artery, superior mesenteric artery and celiac artery) remains a clinical problem and surgical resection is often technically possible but associated with an increased morbidity and mortality and therefore not generally recommended. Borderline resectable tumors represent a special group for which neoadjuvant treatment concepts are increasingly being implemented. Radiological therapy response evaluation is challenging after neoadjuvant therapy as it is not usually associated with a radiologically detectable reduction in tumor volume. CONCLUSION: Pancreatic resections can nowadays be more radically performed due to advances in surgical techniques. This has led to a change in the criteria for resectability, especially concerning venous tumor infiltration.

3 Review [Cystic tumors of the pancreas: diagnosis and therapy]. 2015

D'Haese, Jan G / Hartwig, Werner / Angele, Martin / Werner, Jens. ·Klinik für Allgemeine, Viszeral-, Transplantations-, Gefäß- und Thoraxchirurgie am Klinikum, Universität München, Standort Großhadern Marchioninistr. 15, D-81377, München, Deutschland, Jens.Werner@med.uni-muenchen.de. ·MMW Fortschr Med · Pubmed #26015016.

ABSTRACT: -- No abstract --

4 Review Increased incidence of extrapancreatic neoplasms in patients with IPMN: Fact or fiction? A critical systematic review. 2015

Pugliese, Luigi / Keskin, Muharrem / Maisonneuve, Patrick / D'Haese, Jan G / Marchegiani, Giovanni / Wenzel, Patrick / Del Chiaro, Marco / Ceyhan, Güralp O. ·Unit of General Surgery 2, Department of Surgery, IRCCS Policlinico San Matteo, Pavia, Italy. · Division of Gastroenterology, Department of Internal Medicine, Ege University, Izmir, Turkey. · Division of Epidemiology and Statistics, European Institute of Oncology, Milan, Italy. · Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. · Department of Surgery, Pancreas Institute, Verona University Hospital, Verona, Italy. · Department of Gastroenterology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. · Division of Surgery, CLINTEC, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden. · Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. Electronic address: gueralp.ceyhan@tum.de. ·Pancreatology · Pubmed #25841270.

ABSTRACT: BACKGROUND: To identify potential associations between intraductal papillary mucinous neoplasm of the pancreas (IPMN) and extrapancreatic neoplasms (EPN), a systematic review of the literature has been performed. METHODS: A systematic search of Medline/Pubmed was performed according to the PRISMA guidelines for reporting systematic reviews and meta-analysis for the following search terms: "extrapancreatic", "non pancreatic", "additional pancreatic", "additional primary" and alternatively matched with "neoplasms/tumours/cancers/malignancies/lesions". The results obtained specifically for IPMN were examined one by one by two independent investigators for further data selection and extraction. RESULTS: Fifteen studies were identified to be suitable and included for systematic review. Fourteen reported an elevated risk for extrapancreatic malignancy, particularly gastric and colon cancer, while the largest and only prospective study did not find any association. Most studies were retrospective with a weak level of evidence that was not substantially enhanced even by a recent multicentre case series. CONCLUSIONS: The available data on this clinically relevant question remain inconclusive. Due to lacking evidence on extrapancreatic neoplasms in IPMN patients, only a standard surveillance can be advised.

5 Review Update on surgical treatment of pancreatic neuroendocrine neoplasms. 2014

D'Haese, Jan G / Tosolini, Chiara / Ceyhan, Güralp O / Kong, Bo / Esposito, Irene / Michalski, Christoph W / Kleeff, Jörg. ·Jan G D'Haese, Chiara Tosolini, Güralp O Ceyhan, Bo Kong, Christoph W Michalski, Jörg Kleeff, Department of Surgery, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany. ·World J Gastroenterol · Pubmed #25320524.

ABSTRACT: Pancreatic neuroendocrine neoplasms (PNENs) are rare and account for only 2%-4% of all pancreatic neoplasms. All PNENs are potential (neurendocrine tumors PNETs) or overt (neuroendocrine carcinomas PNECs) malignant, but a subset of PNETs is low-risk. Even in case of low-risk PNETs surgical resection is frequently required to treat hormone-related symptoms and to obtain an appropriate pathological diagnosis. Low-risk PNETs in the body and the tail are ideal for minimally-invasive approaches which should be tailored to the individual patient. Generally, surgeons must aim for parenchyma sparing in these cases. In high-risk and malignant PNENs, indications for tumor resection are much wider than for pancreatic adenocarcinoma, in many cases due to the relatively benign tumor biology. Thus, patients with locally advanced and metastatic PNETs may benefit from extensive resection. In experienced hands, even multi-organ resections are accomplished with acceptable perioperative morbidity and mortality rates and are associated with excellent long term survival. However, poorly differentiated neoplasms with high proliferation rates are associated with a dismal prognosis and may frequently only be treated with chemotherapy. The evidence on surgical treatment of PNENs stems from reviews of mostly single-center series and some analyses of nation-wide tumor registries. No randomized trial has been performed to compare surgical and non-surgical therapies in potentially resectable PNEN. Though such a trial would principally be desirable, ethical considerations and the heterogeneity of PNENs preclude realization of such a study. In the current review, we summarize recent advances in the surgical treatment of PNENs.

6 Review Fractalkine/CX3CR1: why a single chemokine-receptor duo bears a major and unique therapeutic potential. 2010

D'Haese, Jan G / Demir, Ihsan Ekin / Friess, Helmut / Ceyhan, Güralp O. ·Department of Surgery, Klinikum Rechts der Isar, Technische Universität München, Ismaninger Str. 22, D-81675 Munich, Germany. ·Expert Opin Ther Targets · Pubmed #20055718.

ABSTRACT: IMPORTANCE OF THE FIELD: Fractalkine, also known as CX3CL1, is the unique member of the fourth class of chemokines and mediates both chemotaxis and adhesion of inflammatory cells via its highly selective receptor CX3CR1. Fractalkine mediates inflammatory responses and pain sensation and is involved in the pathogenesis and progression of numerous inflammatory disorders and malignancies. AREAS COVERED IN THIS REVIEW: We performed a Medline/PubMed search to detect all published studies that explored the role of fractalkine and CX3CR1 and the possibilities of therapeutic intervention in the fractalkine/CX3CR1 axis in a wide range of clinical disorders, using CX3CR1 blocking antibodies, different fractalkine antagonists, CX3CR1 depletion or transfection of fractalkine expression vectors. WHAT THE READER WILL GAIN: This review summarizes the role of fractalkine and its receptor CX3CR1 in various diseases, focusing on their high potential as novel therapeutic targets, with special emphasis on pancreatic diseases. TAKE HOME MESSAGE: The reviewed studies provide promising results demonstrating fractalkine and CX3CR1 as potential target molecules for future therapeutics that may attenuate pain, inflammation and furthermore serve as an anti-cancer therapy. However, to date, no therapeutics targeting fractalkine or CX3CR1 are in clinical use.

7 Article Immune Cell and Stromal Signature Associated With Progression-Free Survival of Patients With Resected Pancreatic Ductal Adenocarcinoma. 2018

Mahajan, Ujjwal Mukund / Langhoff, Eno / Goni, Elisabetta / Costello, Eithne / Greenhalf, William / Halloran, Christopher / Ormanns, Steffen / Kruger, Stephan / Boeck, Stefan / Ribback, Silvia / Beyer, Georg / Dombroswki, Frank / Weiss, Frank-Ulrich / Neoptolemos, John P / Werner, Jens / D'Haese, Jan G / Bazhin, Alexandr / Peterhansl, Julian / Pichlmeier, Svenja / Büchler, Markus W / Kleeff, Jörg / Ganeh, Paula / Sendler, Matthias / Palmer, Daniel H / Kohlmann, Thomas / Rad, Roland / Regel, Ivonne / Lerch, Markus M / Mayerle, Julia. ·Department of Medicine II, University Hospital, LMU Munich, Germany; Department of Medicine A, University Medicine Greifswald, Greifswald, Germany. · Department of Medicine A, University Medicine Greifswald, Greifswald, Germany. · Department of Medicine II, University Hospital, LMU Munich, Germany. · Institute of Translational Medicine, University of Liverpool, Liverpool, UK. · Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany. · Department of Medicine III, University Hospital, LMU Munich, Germany. · Department of Pathology, University Medicine Greifswald, Greifswald, Germany. · Institute of Translational Medicine, University of Liverpool, Liverpool, UK; Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany. · Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, Munich, Germany. · Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany. · Department of Visceral, Vascular and Endocrine Surgery, Martin-Luther University Halle-Wittenberg, Halle, Germany. · Institute of Translational Medicine, University of Liverpool, Liverpool, UK; Clatterbridge Cancer Centre NHS Foundation Trust, Wirral, UK. · Department of Community Medicine, University Medicine Greifswald, Greifswald, Germany. · Center for Translational Cancer Research (TranslaTUM), Technische Universität München, Munich, Germany. · Department of Medicine II, University Hospital, LMU Munich, Germany; Department of Medicine A, University Medicine Greifswald, Greifswald, Germany. Electronic address: julia.mayerle@med.uni-muenchen.de. ·Gastroenterology · Pubmed #30092175.

ABSTRACT: BACKGROUND & AIMS: Changes to the microenvironment of pancreatic ductal adenocarcinomas (PDACs) have been associated with poor outcomes of patients. We studied the associations between composition of the pancreatic stroma (fibrogenic, inert, dormant, or fibrolytic stroma) and infiltration by inflammatory cells and times of progression-free survival (PFS) of patients with PDACs after resection. METHODS: We obtained 1824 tissue microarray specimens from 385 patients included in the European Study Group for Pancreatic Cancer trial 1 and 3 and performed immunohistochemistry to detect alpha smooth muscle actin, type 1 collagen, CD3, CD4, CD8, CD68, CD206, and neutrophils. Tumors that expressed high and low levels of these markers were compared with patient outcomes using Kaplan-Meier curves and multivariable recursive partitioning for discrete-time survival tree analysis. Prognostic index was delineated by a multivariable Cox proportional hazards model of immune cell and stromal markers and PFS. Findings were validated using 279 tissue microarray specimens from 93 patients in a separate cohort. RESULTS: Levels of CD3, CD4, CD8, CD68, and CD206 were independently associated with tumor recurrence. Recursive partitioning for discrete-time survival tree analysis identified a high level of CD3 as the strongest independent predictor for longer PFS. Tumors with levels of CD3 and high levels of CD206 associated with a median PFS time of 16.6 months and a median prognostic index of -0.32 (95% confidence interval [CI] -0.35 to -0.31), whereas tumors with low level of CD3 cell and low level of CD8 and high level of CD68 associated with a median PFS time of 7.9 months and a prognostic index of 0.32 (95% CI 0.050-0.32); we called these patterns histologic signatures. Stroma composition, when unassociated with inflammatory cell markers, did not associate significantly with PFS. In the validation cohort, the histologic signature resulted in an error matrix accuracy of predicted response of 0.75 (95% CI 0.64-0.83; accuracy P < .001). CONCLUSIONS: In an analysis of PDAC tissue microarray specimens, we identified and validated a histologic signature, based on leukocyte and stromal factors, that associates with PFS times of patients with resected PDACs. Immune cells might affect the composition of the pancreatic stroma to affect progression of PDAC. These findings provide new insights into the immune response to PDAC.

8 Article Therapies Targeting the Tumor Stroma and the VEGF/VEGFR Axis in Pancreatic Ductal Adenocarcinoma: a Systematic Review and Meta-Analysis. 2018

Lu, Zipeng / Weniger, Maximilian / Jiang, Kuirong / Boeck, Stefan / Zhang, Kai / Bazhin, Alexander / Miao, Yi / Werner, Jens / D'Haese, Jan G. ·Pancreas Center & Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China. · Department of General, Visceral, and Transplantation Surgery, Ludwig Maximilians-University, Marchioninistraße 15, 81377, Munich, Germany. · Department of Internal Medicine III and Comprehensive Cancer Center, Ludwig Maximilians-University, Marchioninistr. 15, 81377, Munich, Germany. · Pancreas Center & Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China. miaoyi@njmu.edu.cn. ·Target Oncol · Pubmed #30062609.

ABSTRACT: Abundant tumor stroma is a hallmark of pancreatic ductal adenocarcinoma (PDAC), and is suggested to play a role in the resistance of this deadly disease to systemic treatment. Despite promising results from preclinical studies, clinical trials with therapies targeting the tumor stroma and the vascular endothelial growth factor (VEGF) and its receptor VEGFR yielded conflicting results. With this systematic review and meta-analysis, we aim to summarize the existing evidence in this important field with a special focus on anti-VEGF/VEGFR therapy. A total of 24 clinical studies were included in the qualitative synthesis, and six randomized controlled trials (RCTs) investigating anti-VEGF/VEGFR agents were further included in the quantitative synthesis. The qualitative synthesis revealed a treatment advantage of combined therapy with nab-paclitaxel, while the meta-analysis on anti-VEGF/VEGFR drugs demonstrated marginal improvement of objective response rates and progression-free survival, but not overall survival. Stroma targeting is a promising and rapidly-developing treatment strategy in PDAC. However, novel drugs balancing stroma depletion and modulation are needed.

9 Article [Chronic Pancreatitis and Pancreatic Cancer - Tumor Risk and Screening]. 2018

Beyer, Georg / D'Haese, Jan G / Ormanns, Steffen / Mayerle, Julia. · ·Dtsch Med Wochenschr · Pubmed #29898491.

ABSTRACT: Chronic pancreatitis is a fibroinflammatory syndrome of the exocrine pancreas, which is characterized by an increasing incidence, high morbidity and lethality. Common etiologies besides alcohol and nicotine consumption include genetic causes and risk factors. The life time risk for the development of pancreatic cancer is elevated 13- to 45-fold depending on the underlying etiology. In patients with chronic pancreatitis clinical, laboratory and imaging surveillance for early detection of complications, including pancreatic cancer, is recommended, although the available methods lack the desired sensitivity and specificity. In this article we review the epidemiology, etiologies and risk factors for chronic pancreatitis and pancreatic cancer and discuss current recommendations for screening and management of patients at risk for tumor development.

10 Article [Not Available]. 2016

D'Haese, Jan G / Hartwig, Werner / Werner, Jens. · ·Zentralbl Chir · Pubmed #27088269.

ABSTRACT: -- No abstract --

11 Article The novel mitochondria-targeted antioxidant SkQ1 modulates angiogenesis and inflammatory micromilieu in a murine orthotopic model of pancreatic cancer. 2016

Bazhin, Alexandr V / Yang, Yuhui / D'Haese, Jan G / Werner, Jens / Philippov, Pavel P / Karakhanova, Svetlana. ·Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Hospital of the University of Munich, LMU Munich, Germany. · Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. · Department of Cell Signalling, Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow, Russia. · Department of General Surgery, University Hospital Heidelberg, Germany. ·Int J Cancer · Pubmed #26914404.

ABSTRACT: Our understanding in the last few years about reactive oxygen species (ROS) has changed from being harmful substances to crucial intra- and extracellular messengers as well as important regulators controlling a wide spectrum of signaling pathways, including those in cancer immunology. Therefore, these multiple essential roles of ROS and especially of mitochondria-derived ROS in malignant transformation and cancer progression make them a promising target for anticancer therapy. Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers in the world. A link between ROS, antioxidants and the PDAC development and progression has been recently established. Therefore, usage of specific highly efficient antioxidants could bring an option for treatment and/or prevention of PDAC. 10-(6'-plastoquinonyl) decyltriphenylphosphonium (SkQ1) is a new antioxidant with the highest mitochondrion membrane penetrating ability and potent antioxidant capability. In this work, we investigated an impact of SkQ1 on tumor angiogenesis, immune micromilieu, and oncological parameters in the orthotopic Panc02 murine model of PDAC. We showed that in this model SkQ1 treatment leads to the elevation of pro-angiogenic factors and to building of mainly an anti-inflammatory cytokine milieu. On the cellular level we showed an increase in a percentage of memory T cells and a decrease in frequency on natural killer T (NKT) cells. At the same time, SkQ1 was ineffective in the improvement of oncological parameters of PDAC-bearing mice. New studies are needed to clarify the absence of therapeutic and/or prophylactic benefits of the antioxidant.

12 Article Anti-tumor properties of the cGMP/protein kinase G inhibitor DT3 in pancreatic adenocarcinoma. 2015

Soltek, Sabine / Karakhanova, Svetlana / Golovastova, Marina / D'Haese, Jan G / Serba, Susanne / Nachtigall, Ines / Philippov, Pavel P / Werner, Jens / Bazhin, Alexandr V. ·Department of General Surgery, University Hospital Heidelberg, Heidelberg,, Germany. · Department of Cell Signalling, Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia. · Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University, Munich,, Germany. · Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University, Munich,, Germany. alexandr.bazhin@med.uni-muenchen.de. ·Naunyn Schmiedebergs Arch Pharmacol · Pubmed #26105003.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers in the world. Therefore, new therapeutic options are urgently needed to improve the survival of PDAC patients. Protein kinase G (PKG) conducts the interlude of cGMP signaling which is important for healthy as well as for cancer cells. DT3 is a specific inhibitor of PKG, and it has been shown to possess an anti-tumor cytotoxic activity in vitro. The main aim of this work was to investigate anti-tumor effects of DT3 upon PDAC in vivo.Expression of PKG was assessed with real-time PCR analysis in the normal and tumor pancreatic cells. In vitro cell viability, proliferation, apoptosis, necrosis, migration, and invasion of the murine PDAC cell line Panc02 were assessed after DT3 treatment. In vivo anti-tumor effects of DT3 were investigated in the murine Panc02 orthotopic model of PDAC. Western blot analysis was used to determine the phosphorylation state of the proteins of interest.Functional PKGI is preferentially expressed in PDAC cells. DT3 was capable to reduce viability, proliferation, and migration of murine PDAC cells in vitro. At the same time, DT3 treatment did not change the viability of normal epithelial cells of murine liver. In vivo, DT3 treatment reduced the tumor volume and metastases in PDAC-bearing mice, but it was ineffective to prolong the survival of the tumor-bearing animals. In addition, DT3 treatment decreased phosphorylation of GSK-3, P38, and CREB in murine PDAC.Inhibition of PKG could be a potential therapeutic strategy for PDAC treatment which should be carefully validated in future pre-clinical studies.

13 Article Association between pancreatic intraductal papillary mucinous neoplasms and extrapancreatic malignancies. 2015

Marchegiani, Giovanni / Malleo, Giuseppe / D'Haese, Jan G / Wenzel, Patrick / Keskin, Muharrem / Pugliese, Luigi / Borin, Alex / Benning, Valentina / Nilsson, Linda / Oruc, Nevin / Segersvard, Ralf / Friess, Helmut / Schmid, Roland / Löhr, Matthias / Maisonneuve, Patrick / Bassi, Claudio / Ceyhan, Güralp O / Salvia, Roberto / Del Chiaro, Marco. ·Unit of Surgery B, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy. Electronic address: giovanni.marchegiani@ospedaleuniverona.it. · Unit of Surgery B, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy. · Department of Surgery, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany. · Department of Gastroenterology, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany. · Division of Gastroenterology, Department of Internal Medicine, Ege University, Izmir, Turkey. · Unit of General Surgery 2, Department of Surgery, IRCCS Policlinico San Matteo, Pavia, Italy. · Division of Surgery, CLINTEC, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden. · Division of Gastroenterology, CLINTEC, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden. · Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy. ·Clin Gastroenterol Hepatol · Pubmed #25478920.

ABSTRACT: BACKGROUND & AIMS: The association between pancreatic intraductal papillary mucinous neoplasms (IPMNs) and extrapancreatic neoplasms (EPNs) is controversial. We performed a multicenter observational study to assess the incidence of EPNs after an IPMN diagnosis. METHODS: 1340 patients with IPMNs were evaluated from 2000 through 2013 at 4 academic institutions in Europe for development of EPN. To estimate the actual incidence of EPN, we excluded patients with an EPN previous or synchronous to the IPMN, and patients who had been followed for less than 12 months, resulting in a study population of 816 patients. The incidence of EPN was compared with sex-specific, age-adjusted European cancer statistics; the standardized incidence ratio (SIR), and the 5- and 10-year cumulative incidence rates were calculated. RESULTS: A total of 290/1340 patients had a history of EPN (prevalence of 21.6%). In this subgroup of patients, the IPMN was discovered incidentally in 241. Among the 816 patients included in the incidence analysis, 50 developed an EPN after a median time of 46 months from study enrollment. The incidence of any EPN was not greater in patients with than without IPMN with a SIR of 1.48 (95% confidence interval, 0.94-2.22) in males and of 1.39 (95% CI 0.90-2.05) in females. The 5- and 10-year cumulative incidence rates for development of EPN in patients with IPMN were 7.9% and 16.6% in men, and 3.4% and 23.1% in women. CONCLUSIONS: Patients with IPMN do not have a significantly higher incidence of EPNs than the general European population. It might not be necessary to screen patients with IPMN for EPN.

14 Article Pain sensation in pancreatic diseases is not uniform: the different facets of pancreatic pain. 2014

D'Haese, Jan G / Hartel, Mark / Demir, Ihsan Ekin / Hinz, Ulf / Bergmann, Frank / Büchler, Markus W / Friess, Helmut / Ceyhan, Güralp O. ·Jan G D'Haese, Mark Hartel, Ihsan Ekin Demir, Helmut Friess, Güralp O Ceyhan, Department of Surgery, Klinikum Rechts der Isar, Technische Universität München, D-81675 Munich, Germany. ·World J Gastroenterol · Pubmed #25083089.

ABSTRACT: AIM: To systematically characterize specific pain patterns in the most frequent pancreatic diseases. METHODS: Pain in patients with chronic pancreatitis (n = 314), pancreatic cancer (n = 469), and other pancreatic tumors (n = 249) including mucinous (n = 20) and serous cystadenoma (n = 31), invasive (n = 37) and non-invasive intraductal papillary mucinous neoplasia (IPMN; n = 48), low stage (n = 18) and high stage neuroendocrine neoplasia (n = 44), and ampullary cancer (n = 51) was registered and correlated with clinicopathological data. Survival times were estimated by the Kaplan-Meier method. Patients alive at the follow-up time were censored. Survival curves were compared statistically using the log-rank test. RESULTS: Forty-nine point one percent of pancreatic cancer patients revealed no pain, whereas in chronic pancreatitis only 18.3% were pain free. In contrary, moderate/severe pain was registered in 15.1% in pancreatic cancer patients that was increased in chronic pancreatitis with up to 34.2%. Serous cystadenoma was asymptomatic in most cases (58.1%), whereas 78.9% of all mucinous cystadenoma patients suffered pain. In neuroendocrine neoplasia pain was not a key clinical symptom since 64% of low stage neuroendocrine neoplasia and 59% of high stage neuroendocrine neoplasia patients were pain free. Cancer localization in the pancreatic body and patients with malignant pancreatic neoplasms were associated with more severe pain. Tumor grading and stage did not show any impact on pain. Only in pancreatic cancer, pain was directly associated with impaired survival. CONCLUSION: Pancreatic pain depicts different patterns of abdominal pain sensation according to the respective pancreatic disorder and does not allow a unification of the term pancreatic pain.

15 Article The neurotrophic factor neurturin contributes toward an aggressive cancer cell phenotype, neuropathic pain and neuronal plasticity in pancreatic cancer. 2014

Wang, Kun / Demir, Ihsan Ekin / D'Haese, Jan G / Tieftrunk, Elke / Kujundzic, Kristina / Schorn, Stephan / Xing, Baocai / Kehl, Timo / Friess, Helmut / Ceyhan, Güralp O. ·Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, Munich D-81675, Germany and. ·Carcinogenesis · Pubmed #24067900.

ABSTRACT: SUMMARY: PCa is characterized by intrapancreatic neuroplasticity and NI. Here, we show that PCC produce the neurotrophic factor NRTN, which reinforces their biological properties, triggers neuroplastic alterations, NI and influences pain sensation via the GFRα-2 receptor.

16 Article Combined targeted treatment to eliminate tumorigenic cancer stem cells in human pancreatic cancer. 2009

Mueller, Maria-Theresa / Hermann, Patrick C / Witthauer, Juliane / Rubio-Viqueira, Belen / Leicht, Simon F / Huber, Stephan / Ellwart, Joachim W / Mustafa, Mona / Bartenstein, Peter / D'Haese, Jan G / Schoenberg, Michael H / Berger, Frank / Jauch, Karl-Walter / Hidalgo, Manuel / Heeschen, Christopher. ·Clinical Research Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. ·Gastroenterology · Pubmed #19501590.

ABSTRACT: BACKGROUND & AIMS: Pancreatic cancers contain exclusively tumorigenic cancer stem cells (CSCs), which are highly resistant to chemotherapy, resulting in a relative increase in CSC numbers during gemcitabine treatment. Signaling through sonic hedgehog and mammalian target of rapamycin (mTOR), respectively, may be essential for CSC self-renewal and could represent putative targets for novel treatment modalities. METHODS: We used in vitro and in vivo models of pancreatic cancer to examine the effects of sonic hedgehog inhibition (cyclopamine/CUR199691) and mTOR blockade (rapamycin) on the tumorigenic CSC population. RESULTS: Surprisingly, neither cyclopamine nor rapamycin alone or as supplements to chemotherapy were capable of effectively diminishing the CSC pool. Only the combined inhibition of both pathways together with chemotherapy reduced the number of CSCs to virtually undetectable levels in vitro and in vivo. Most importantly, in vivo administration of this triple combination in mice with established patient-derived pancreatic tumors was reasonably tolerated and translated into significantly prolonged long-term survival. CONCLUSIONS: The combined blockade of sonic hedgehog and mTOR signaling together with standard chemotherapy is capable of eliminating pancreatic CSCs. Further preclinical investigation of this promising approach may lead to the development of a novel therapeutic strategy to improve the devastating prognosis of patients with pancreatic cancer.