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Pancreatic Neoplasms: HELP
Articles by Andrea Tannapfel
Based on 32 articles published since 2010
(Why 32 articles?)

Between 2010 and 2020, A. Tannapfel wrote the following 32 articles about Pancreatic Neoplasms.
+ Citations + Abstracts
Pages: 1 · 2
1 Guideline [Update of the S3 guidelines for pancreatic cancer. What is new for pathologists?]. 2014

Munding, J / Lüttges, J / Esposito, I / Tannapfel, A. ·Institut für Pathologie, Deutsches Mesotheliomregister, Ruhr-Universität Bochum, BG-Universitätsklinikum Bergmannsheil, Bürkle-de-la-Camp Platz 1, 44789, Bochum, Deutschland. ·Pathologe · Pubmed #24981895.

ABSTRACT: The S3 guidelines for pancreatic cancer were revised in 2013. Besides the oncological and palliative therapy modalities and surgical therapy, the guidelines for pathologists in topic 3 were updated. The modifications essentially concern the histopathological assessment of surgical specimens and in particular the circumferential resection margin and the R classification. In addition, the current recommendations were amended by recommendations concerning the pathohistological records, which should include the lymph node ratio in the future.

2 Guideline Ductal pancreatic adenocarcinoma. 2014

Seufferlein, Thomas / Porzner, Marc / Heinemann, Volker / Tannapfel, Andrea / Stuschke, Martin / Uhl, Waldemar. ·Ulm University Hospital Medical Center, Department of Internal Medicine I, Medical Clinic III, Department of Hematology & Oncology, Großhadern Hospital, Ludwig-Maximilian-¬Universität, Munich, Institute of Pathology, Ruhr-University Bochum, Radiation and Tumor Clinic, University Hospital of Duisburg-Essen, Surgical Clinic at the St. Josef-Hospital, Ruhr-University Bochum. ·Dtsch Arztebl Int · Pubmed #24980565.

ABSTRACT: BACKGROUND: Ductal adenocarcinoma of the pancreas is the fourth most common cause of death from cancer in men and women in Germany: about 15 000 persons die of this disease each year. METHOD: The S3 guideline on exocrine pancreatic carcinoma was updated with the aid of systematic literature reviews on the surgical, neoadjuvant, and adjuvant treatment of ductal pancreatic carcinoma, and on treatment in the metastatic stage. These reviews covered the periods 2002 to February 2012 (for radiotherapy) and 2006 to August 2011 (for all other topics). RESULTS: The criteria for borderline resectable pancreatic tumors are the same as those of the guidelines of the National Comprehensive Cancer Network. Preoperative biliary drainage with a stent is recommended only if cholangitis is present or if a planned operation cannot be performed soon after the diagnosis is made. When a pancreatic carcinoma is resected, at least 10 regional lymph nodes should be excised, and the ratio of affected to excised nodes should be documented in the pathology report. Gemcitabine and 5-fluorouracil are recommended for adjuvant therapy. Neither of these drugs is preferred over the other; if the one initially given is poorly tolerated, the other one should be given instead. When gemcitabine and erlotinib are given for palliative treatment, erlotinib should be given for no longer than 8 weeks if no skin rash develops. In selected patients, the folfirinox protocol yields markedly better results than gemcitabin. Moreover, the new combination of nab-paclitaxel and gemcitabine can be used as first-line treatment. In the event of disease progression under first-line treatment, second-line treatment should be initiated. CONCLUSION: In recent years, new chemotherapeutic protocols have brought about marked improvement in palliative care. Further trials are needed to determine whether the perioperative or adjuvant use of these protocols might also improve the outcome of surgical treatment with curative intent.

3 Guideline [S3-guideline exocrine pancreatic cancer]. 2013

Seufferlein, T / Porzner, M / Becker, T / Budach, V / Ceyhan, G / Esposito, I / Fietkau, R / Follmann, M / Friess, H / Galle, P / Geissler, M / Glanemann, M / Gress, T / Heinemann, V / Hohenberger, W / Hopt, U / Izbicki, J / Klar, E / Kleeff, J / Kopp, I / Kullmann, F / Langer, T / Langrehr, J / Lerch, M / Löhr, M / Lüttges, J / Lutz, M / Mayerle, J / Michl, P / Möller, P / Molls, M / Münter, M / Nothacker, M / Oettle, H / Post, S / Reinacher-Schick, A / Röcken, C / Roeb, E / Saeger, H / Schmid, R / Schmiegel, W / Schoenberg, M / Siveke, J / Stuschke, M / Tannapfel, A / Uhl, W / Unverzagt, S / van Oorschot, B / Vashist, Y / Werner, J / Yekebas, E / Anonymous260779 / Anonymous270779 / Anonymous280779. ·Klinik für Innere Medizin I, Universitätsklinikum Ulm. · Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Kiel. · Klinik für Radioonkologie und Strahlentherapie, Charité Universitätsmedizin Berlin. · Chirurgische Klinik und Poliklinik, Klinikum rechts der Isar, TU München. · Institut für Allgemeine Pathologie, Klinikum rechts der Isar, TU München. · Strahlenklinik, Universitätsklinikum Erlangen. · Leitlinienprogramm Onkologie, Deutsche Krebsgesellschaft e. V., Berlin. · I. Medizinische Klinik und Poliklinik, Universitätsmedizin Mainz. · Klinik für Allgemeine Innere Medizin, Onkologie/Hämatologie, Gastroenterologie und Infektiologie, Klinikum Esslingen. · Klinik für Allgemeine Chirurgie, Viszeral-, Gefäß- und Kinderchirurgie, Universitätsklinikum des Saarlandes Homburg/Saar. · Klinik für Gastroenterologie, Endokrinologie und Stoffwechsel, Universitätsklinikum Gießen und Marburg. · Medizinischen Klinik und Poliklinik III, Klinikum der Universität München LMU. · Chirurgische Klinik, Universitätsklinikum Erlangen. · Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Freiburg. · Klinik für Allgemein-, Viszeral- und Thoraxchirurgie, Universitätsklinikum Hamburg-Eppendorf. · Klinik für Allgemeine Chirurgie, Thorax-, Gefäß- und Transplantationschirurgie, Universitätsmedizin Rostock. · AWMF-Institut für Medizinisches Wissensmanagement, Marburg. · Medizinische Klinik I, Klinikum Weiden. · Klinik für Allgemein-, Gefäß- und Viszeralchirurgie, Martin-Luther-Krankenhaus Berlin. · Klinik und Poliklinik für Innere Medizin A, Universitätsmedizin Greifswald. · Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm. · Institut für Pathologie, Marienkrankenhaus Hamburg. · Medizinische Klinik - Schwerpunkt Gastroenterologie, Endokrinologie, Infektiologie, Caritasklinikum Saarbrücken. · Institut für Pathologie, Universitätsklinikum Ulm. · Klinik und Poliklinik für Strahlentherapie und Radiologische Onkologie, Klinikum rechts der Isar, TU München. · Klinik für Strahlentherapie und Radioonkologie, Klinikum Stuttgart. · AWMF-Institut für Medizinisches Wissensmanagement, Berlin. · Medizinische Klinik mit Schwerpunkt Hämatologie und Onkologie, Charité Universitätsmedizin Berlin. · Chirurgische Klinik, Universitätsmedizin Mannheim. · Abt. für Hämatologie und Onkologie, St. Josef-Hospital, Klinikum der Ruhr-Universität Bochum. · Institut für Pathologie, Universitätsklinikum Kiel. · Medizinische Klinik II, SP Gastroenterologie, Universitätsklinikum Gießen und Marburg. · Klinik für Viszeral-, Thorax- und Gefäßchirurgie, Universitätsklinikum Dresden. · II. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, TU München. · Medizinische Klinik, Klinikum der Ruhr-Universität Bochum. · Klinik für Chirurgie, Rotkreuzklinikum München. · Klinik für Strahlentherapie, Universitätsklinikum Essen. · Institut für Pathologie, Ruhr-Universität Bochum. · Chirurgische Klinik, St. Josef-Hospital, Klinikum der Ruhr-Universität Bochum. · Institut für Medizinische Epidemiologie, Biometrie und Informatik, Martin-Luther-Universität Halle-Wittenberg. · Klinik und Poliklinik für Strahlentherapie, Universitätsklinikum Würzburg. · Klinik für Allgemeine, Viszerale und Transplantationschirurgie, Universitätsklinikum Heidelberg. · Klinik für Allgemein-, Thorax- und Viszeralchirurgie, Klinikum Darmstadt. ·Z Gastroenterol · Pubmed #24338757.

ABSTRACT: -- No abstract --

4 Guideline [New S3 guidelines on exocrine pancreatic cancer]. 2012

Tannapfel, A / Anonymous6230737. ·Institut für Pathologie der Ruhr-Universität Bochum am BG-Universitätsklinikum Bergmannsheil, Deutsches Mesotheliomregister, Bürkle-de-la-Camp-Platz 1, 44789 Bochum. Andrea.Tannapfel@rub.de ·Pathologe · Pubmed #23011018.

ABSTRACT: In order to guarantee a unified application of the R classification, the S3 guidelines were amended. With the introduction of the so-called CRM concept the special situation of ductal adenocarcinoma of the pancreas head can be taken into account. In contrast to the R classification, in the CRM concept lymph node metastases, lymph vessel and perineural sheath infiltration are taken into consideration. The distance of the tumor from the resection margins is particularly documented. Because of the prognostic significance of tumor-free lymph nodes, in future the lymph node ratio should be given. This is defined as the relationship of lymph node metastases to the total number of lymph nodes removed/examined.

5 Review Chloroma of pancreas-initial manifestation of a secondary leukemia after stem cell transplantation case report and review of the literature. 2013

Tabriz, Navid / Tannapfel, Andrea / Griesinger, Frank / Weyhe, Dirk. ·Department of Visceral Surgery, Pius-Hospital Oldenburg, Georgstrasse 12, 26121, Oldenburg, Germany. ntabriz@gmx.de ·J Gastrointest Surg · Pubmed #23417741.

ABSTRACT: INTRODUCTION: Chloroma is an extramedullary solid tumor consisting of immature myeloid cells. CASE PRESENTATION: We report a patient with painless jaundice 6 years after allogeneic peripheral stem cell transplantation because of an acute myeloid leukemia leading us to the diagnosis of a chloroma of the pancreas as the first manifestation of a secondary host leukemia. DISCUSSION: A histological examination of unclear pancreatic tumors should be mandatory in patients with a history of leukemia. If surgical therapy is unavoidable because of stenosis symptoms or for histological proof, a resection should be avoided. CONCLUSION: Bypass surgery can ease the symptoms and it allows timely curative chemotherapy or stem cell transplantation.

6 Review [New data on pancreatic cancer]. 2010

Fietkau, Rainer / Heinemann, Volker / Oettle, Helmut / Knoefel, Wolfram Trudo / Tannapfel, Andrea. ·Klinik für Strahlentherapie, Universitätsklinik Erlangen, Deutschland. rainer.fietkau@uk-erlangen.de ·Onkologie · Pubmed #20431311.

ABSTRACT: In pancreatic cancer there is a marked discrepancy between the recorded R0 resection rates and the long-term clinical outcome. Therefore, it seems to be necessary to find additional parameters that will be of more prognostic value here. Differences in how the R classification is applied within the studies are conspicuous. It would seem important to examine standards in histopathological preparation and to return to the 'classical' R classification and, if appropriate, in line with experiences in rectum cancer, to introduce a 'circumferential resection margin'. To obtain optimum long-term survival, a distance of >1.0 mm or even >1.5 mm between tumor and resection margin is required. In too few patients with vascular invasion is the tumor properly removed surgically, even though infiltration of the portal vein or the superior mesenteric vein is not an exclusion criterion according to the S3 guideline. An improvement in the quality of treatment might be achieved by establishing 'high-volume' pancreas centers. The value of perioperative radiochemotherapy (RCT) is currently being examined in several large studies. Adjuvant chemotherapy is standard and is well established in routine clinical practice.

7 Article A Blood-Based Multi Marker Assay Supports the Differential Diagnosis of Early-Stage Pancreatic Cancer. 2019

Berger, Andreas W / Schwerdel, Daniel / Reinacher-Schick, Anke / Uhl, Waldemar / Algül, Hana / Friess, Helmut / Janssen, Klaus-Peter / König, Alexander / Ghadimi, Michael / Gallmeier, Eike / Bartsch, Detlef K / Geissler, Michael / Staib, Ludger / Tannapfel, Andrea / Kleger, Alexander / Beutel, Alica / Schulte, Lucas-Alexander / Kornmann, Marko / Ettrich, Thomas J / Seufferlein, Thomas. ·Ulm University, Department of Internal Medicine I, Albert-Einstein-Allee 23, 89081 Ulm, Germany. · Ruhr-University Bochum, Division of Hematology, Oncology and Palliative Care, Gudrunstr. 56, 44791 Bochum, Germany. · Ruhr-University Bochum, Department of Surgery, Gudrunstr. 56, 44791 Bochum, Germany. · Technical University Munich, Department of Internal Medicine I, Ismaninger Str. 22, 81675 Munich, Germany. · Technical University Munich, Department of Surgery, Ismaninger Str. 22, 81675 Munich, Germany. · University Medical Center Goettingen, Department of Gastroenterology and Gastrointestinal Oncology, Robert-Koch-Str. 40, 37075 Goettingen, Germany. · University Medical Centre Goettingen, Department of General, Visceral and Paediatric Surgery, Robert-Koch-Str. 40, 37075 Goettingen, Germany. · Philipps University Marburg, Department of Gastroenterology and Endocrinology, Baldingerstraße, 35043 Marburg, Germany. · Philipps University Marburg, Department of Visceral, Thoracic and Vascular Surgery, Baldingerstrasse, 35041, Marburg, Germany. · Esslingen Hospital, Department of Internal Medicine, Oncology/Hematology, Gastroenterology, Hirschlandstr. 97, 73730 Esslingen, Germany. · Esslingen Hospital, Department of General and Visceral Surgery, Hirschlandstr. 97, 73730 Esslingen, Germany. · Ruhr-University Bochum, Department of Pathology, Buerkle-de-la-Camp-Platz 1, 44789 Bochum, Germany. · Ulm University, Department of General and Visceral Surgery, Albert-Einstein-Allee 23, 89081 Ulm, Germany. ·Theranostics · Pubmed #30867830.

ABSTRACT: The most frequent malignancy of the pancreas is the pancreatic ductal adenocarcinoma (PDAC). Despite many efforts PDAC has still a dismal prognosis. Biomarkers for early disease stage diagnosis as a prerequisite for a potentially curative treatment are still missing. Novel blood-based markers may help to overcome this limitation. Methods: Prior to surgery plasma levels of thrombospondin-2 (THBS2), which was recently published as a novel biomarker, and CA19-9 from 52 patients with histologically proven PDAC were determined, circulating cell-free (cfDNA) was quantified. 15 patients with side-branch IPMNs without worrisome features and 32 patients with chronic pancreatitis served for comparison. Logit (logistic regression) models were used to test the performance of single biomarkers and biomarker combinations. Results: CA19-9 and THBS2 alone showed comparable c-statistics of 0.80 and 0.73, respectively, improving to 0.87 when combining these two markers. The c-statistic was further increased to 0.94 when combining CA19-9 and THBS2 with cfDNA quantification. This marker combination performed best for all PDAC stages but also for PDACs grouped by stage. The greatest improvement over CA19-9 was seen in the group of stage I PDAC, from 0.69 to 0.90 for the three marker combination.

8 Article Preclinical Efficacy of Covalent-Allosteric AKT Inhibitor Borussertib in Combination with Trametinib in 2019

Weisner, Jörn / Landel, Ina / Reintjes, Christoph / Uhlenbrock, Niklas / Trajkovic-Arsic, Marija / Dienstbier, Niklas / Hardick, Julia / Ladigan, Swetlana / Lindemann, Marius / Smith, Steven / Quambusch, Lena / Scheinpflug, Rebekka / Depta, Laura / Gontla, Rajesh / Unger, Anke / Müller, Heiko / Baumann, Matthias / Schultz-Fademrecht, Carsten / Günther, Georgia / Maghnouj, Abdelouahid / Müller, Matthias P / Pohl, Michael / Teschendorf, Christian / Wolters, Heiner / Viebahn, Richard / Tannapfel, Andrea / Uhl, Waldemar / Hengstler, Jan G / Hahn, Stephan A / Siveke, Jens T / Rauh, Daniel. ·Faculty of Chemistry and Chemical Biology, TU Dortmund University, Dortmund, Germany. · Drug Discovery Hub Dortmund (DDHD) am Zentrum für Integrierte Wirkstoffforschung (ZIW), Dortmund, Germany. · Department of Molecular Gastrointestinal Oncology, Ruhr-University Bochum, Bochum, Germany. · German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany. · Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK), partner site Essen, West German Cancer Center, University Hospital Essen, Essen, Germany. · Lead Discovery Center GmbH, Dortmund, Germany. · Leibniz Research Centre for Working Environment and Human Factors (IfADo), TU Dortmund University, Dortmund, Germany. · Department of Internal Medicine, Ruhr-University Bochum, Knappschaftskrankenhaus, Bochum, Germany. · Department of Internal Medicine, St. Josefs-Hospital, Dortmund, Germany. · Department of Visceral and General Surgery, St. Josefs-Hospital, Dortmund, Germany. · Department of Surgery, Ruhr-University Bochum, Knappschaftskrankenhaus, Bochum, Germany. · Institute of Pathology, Ruhr-University of Bochum, Bochum, Germany. · Department of Visceral and General Surgery, St. Josef Hospital, Ruhr-University Bochum, Germany. · Department of Molecular Gastrointestinal Oncology, Ruhr-University Bochum, Bochum, Germany. daniel.rauh@tu-dortmund.de stephan.hahn@rub.de jens.siveke@uk-essen.de. · German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany. daniel.rauh@tu-dortmund.de stephan.hahn@rub.de jens.siveke@uk-essen.de. · Faculty of Chemistry and Chemical Biology, TU Dortmund University, Dortmund, Germany. daniel.rauh@tu-dortmund.de stephan.hahn@rub.de jens.siveke@uk-essen.de. ·Cancer Res · Pubmed #30858154.

ABSTRACT: Aberrations within the PI3K/AKT signaling axis are frequently observed in numerous cancer types, highlighting the relevance of these pathways in cancer physiology and pathology. However, therapeutic interventions employing AKT inhibitors often suffer from limitations associated with target selectivity, efficacy, or dose-limiting effects. Here we present the first crystal structure of autoinhibited AKT1 in complex with the covalent-allosteric inhibitor borussertib, providing critical insights into the structural basis of AKT1 inhibition by this unique class of compounds. Comprehensive biological and preclinical evaluation of borussertib in cancer-related model systems demonstrated a strong antiproliferative activity in cancer cell lines harboring genetic alterations within the PTEN, PI3K, and RAS signaling pathways. Furthermore, borussertib displayed antitumor activity in combination with the MEK inhibitor trametinib in patient-derived xenograft models of mutant

9 Article Neoadjuvant plus adjuvant or only adjuvant nab-paclitaxel plus gemcitabine for resectable pancreatic cancer - the NEONAX trial (AIO-PAK-0313), a prospective, randomized, controlled, phase II study of the AIO pancreatic cancer group. 2018

Ettrich, Thomas J / Berger, Andreas W / Perkhofer, Lukas / Daum, Severin / König, Alexander / Dickhut, Andreas / Wittel, Uwe / Wille, Kai / Geissler, Michael / Algül, Hana / Gallmeier, Eike / Atzpodien, Jens / Kornmann, Marko / Muche, Rainer / Prasnikar, Nicole / Tannapfel, Andrea / Reinacher-Schick, Anke / Uhl, Waldemar / Seufferlein, Thomas. ·Department of Internal Medicine I, University of Ulm, Albert-Einstein-Allee 23, 89081, Ulm, Germany. · Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité University Medicine Berlin, Hindenburgdamm 30, 12200, Berlin, Germany. · Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center Goettingen, Robert-Koch-Str. 40, 37075, Göttingen, Germany. · Department of Oncology/Hematology, Fulda Hospital, Pacelliallee 4, 36043, Fulda, Germany. · Department of General and Visceral Surgery, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany. · Department of Hematology and medical oncology, Johannes-Wesling-Klinikum Minden, Hans-Nolte-Straße 1, 32429, Minden, Germany. · Department of Internal Medicine, Oncology/Hematology, Gastroenterology, Esslingen Hospital, Hirschlandstr. 97, 73730 Esslingen, Esslingen, Germany. · Department of Internal Medicine II, Technical University Munich, Ismaninger Str. 22, 81675, Munich, Germany. · Department of Gastroenterology and Endocrinology, University of Marburg, Baldingerstraße, 35043, Marburg, Germany. · Department of Medical Oncology and Hematology, Niels-Stensen-Kliniken, Alte Rothenfelder Str. 23, 49124, Georgsmarienhütte, Germany. · Department of General and Visceral Surgery, University of Ulm, Albert-Einstein-Allee 23, 89081, Ulm, Germany. · Institute of Epidemiology and Medical Biometry, University of Ulm, Schwabstrasse 13, 89081, Ulm, Germany. · Department of Oncologie, Asklepios Klinik Barmbek, Rübenkamp 220, 22291, Hamburg, Germany. · Department of Pathology, Ruhr-University Bochum, Bürkle-de-la-Camp-Platz 1, 44789, Bochum, Germany. · Department of Internal Medicine, Ruhr-University Bochum, Gudrunstr. 56, 44791, Bochum, Germany. · Department of Surgery, Ruhr-University Bochum, Gudrunstr. 56, 44791, Bochum, Germany. · Department of Internal Medicine I, University of Ulm, Albert-Einstein-Allee 23, 89081, Ulm, Germany. thomas.seufferlein@uniklinik-ulm.de. ·BMC Cancer · Pubmed #30594153.

ABSTRACT: BACKGROUND: Even clearly resectable pancreatic cancer still has an unfavorable prognosis. Neoadjuvant or perioperative therapies might improve the prognosis of these patients. Thus, evaluation of perioperative chemotherapy in resectable pancreatic cancer in a prospective, randomized trial is warranted. A substantial improvement in overall survival of patients with metastatic pancreatic cancer with FOLFIRINOX and nab-paclitaxel/gemcitabine vs standard gemcitabine has been demonstrated in phase III-trials. Indeed nab-paclitaxel/gemcitabine has a more favorable toxicity profile compared to the FOLFIRINOX protocol and appears applicable in a perioperative setting. METHODS: NEONAX is an interventional, prospective, randomized, controlled, open label, two sided phase II study with an unconnected analysis of the results in both experimental arms against a fixed survival probability (38% at 18 months with adjuvant gemcitabine), NCT02047513. NEONAX will enroll 166 patients with resectable pancreatic ductal adenocarcinoma (≤ cT3, N0 or N1, cM0) in two arms: Arm A (perioperative arm): 2 cycles nab-paclitaxel (125 mg/m2)/gemcitabine (1000 mg/m2, d1, 8 and 15 of an 28 day-cycle) followed by tumor surgery followed by 4 cycles nab-paclitaxel/gemcitabine, Arm B (adjuvant arm): tumor surgery followed by 6 cycles nab-paclitaxel/gemcitabine. The randomization (1:1) is eminent to avoid allocation bias between the groups. Randomization is stratified for tumor stage (ct1/2 vs. cT3) and lymph node status (cN0 vs. cN1). Primary objective is disease free survival (DFS) at 18 months after randomization. Key secondary objectives are 3-year overall survival (OS) rate and DFS rate, progression during neoadjuvant therapy, R0 and R1 resection rate, quality of life and correlation of DFS, OS and tumor regression with pharmacogenomic markers, tumor biomarkers and molecular analyses (ctDNA, transcriptome, miRNA-arrays). In addition, circulating tumor-DNA will be analyzed in patients with the best and the worst responses to the neoadjuvant treatment. The study was initiated in March 2015 in 26 centers for pancreatic surgery in Germany. DISCUSSION: The NEONAX trial is an innovative study on resectable pancreatic cancer and currently one of the largest trials in this field of research. It addresses the question of the role of intensified perioperative treatment with nab-paclitaxel plus gemcitabine in resectable pancreatic cancers to improve disease-free survival and offers a unique potential for translational research. TRIAL REGISTRATION: ClinicalTrials.gov : NCT02047513, 08/13/2014.

10 Article Criteria for Determining Malignancy in Pancreatic Intraductal Papillary Mucinous Neoplasm Based on Computed Tomography. 2016

Mönnings, Peter / Belyaev, Orlin / Uhl, Waldemar / Giese, Arnd / Tannapfel, Andrea / Köster, Odo / Meier, Juris J. ·Department of Diagnostic and Interventional Radiology, St. Josef-Hospital, Bochum, Germany. ·Digestion · Pubmed #28030856.

ABSTRACT: INTRODUCTION: Determining the dignity of intraductal papillary mucinous neoplasms (IPMNs) by imaging procedures is challenging. Various CT-based criteria were evaluated. PATIENTS AND METHODS: Preoperative CT scans from 47 patients with IPMN were analyzed. Predefined criteria of malignancy were compared between patients with benign (bIPMN; n = 28) and malignant (mIPMN; n = 19) tumors, and a summation score was determined. RESULTS: Preoperative carbohydrate-antigen 19-9 levels were higher in patients with mIPMN (p = 0.013). The diameter of the main pancreatic duct was greater in patients with mIPMN (p < 0.0001). More patients with mIPMN showed bile duct obstruction (p = 0.0076), solid tumor components (p = 0.0076), contrast enhancement in cystic walls (p = 0.0086), peripancreatic lymph nodes (p = 0.0076), and abrupt diameter changes of the main pancreatic duct (p = 0.0008). The CT density of the cysts was higher in mIPMN (p = 0.0063). The diagnostic accuracy of the summation score (sensitivity: 0.84, specificity: 0.96) was greater when compared to each individual CT parameter. CONCLUSIONS: The prevalence and extent of various CT-based abnormalities are greater in patients with mIPMN, but the wide overlap limits the diagnostic value of each individual parameter. A simple summation score largely enhances the diagnostic accuracy.

11 Article Histological changes in endocrine and exocrine pancreatic tissue from patients exposed to incretin-based therapies. 2016

Ueberberg, Sandra / Jütte, Hendrik / Uhl, Waldemar / Schmidt, Wolfgang / Nauck, Michael / Montanya, Eduard / Tannapfel, Andrea / Meier, Juris. ·Diabetes Division, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany. · Department of Pathology, Ruhr-University Bochum, Bochum, Germany. · Department of Surgery, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany. · Bellvitge Hospital, Department of Endocrinology, Feixa Llarga s/n, Hospitalet de Llobregat, 08907, Barcelona, Spain. ·Diabetes Obes Metab · Pubmed #27545110.

ABSTRACT: AIMS: Incretin-based therapies have been associated with an increased risk of pancreatitis. Recently, various histological abnormalities have been reported in human pancreatic tissue from brain-dead organ donors who had been exposed to incretin-based drugs. In the present study we examined pancreatic tissue collected at surgery. METHODS: Human pancreatic tissue from 7 type 2-diabetic patients treated with incretin-based drugs (type 2-I), 6 diabetic patients without incretin treatment (type 2-NI), 11 patients without diabetes (no diabetes group) and 9 brain-dead organ donors (BDOD group) was examined. RESULTS: Fractional beta-cell area was reduced in the type 2-NI group compared to the group without diabetes (P < .05), but there was no difference compared to the type 2-I patients. Alpha-cell area (P = .30), beta-cell replication (P = .17) and alpha-cell replication (P = .91) were not different. There were also no differences in acinar cell (P = .13) and duct cell replication (P = .099). Insulin-positive duct cells were more frequent in the type 2-I and the BDOD groups (P = .034). No co-expression of insulin and glucagon was detected. Pancreatic intraepithelial neoplasia (PanIN) lesions were very rare, all low-grade (PanIN 1a and 1b) and tended to occur more frequently in the type 2-I group (P = .084). CONCLUSIONS: The present results did not reveal marked histological abnormalities in the pancreas of incretin-treated patients with type 2 diabetes. Low numbers of specimens available and a large inter-individual variability of the findings warrant caution regarding the interpretation of histological data concerning drug effects on the human pancreas.

12 Article Differential expression of cell-cycle regulators in human beta-cells derived from insulinoma tissue. 2016

Ueberberg, Sandra / Tannapfel, Andrea / Schenker, Peter / Viebahn, Richard / Uhl, Waldemar / Schneider, Stephan / Meier, Juris J. ·Diabetes Division, St. Josef-Hospital, Ruhr-University Bochum, Gudrunstrasse 56, Bochum 44791, Germany. · Department of Pathology, Ruhr-University Bochum, Bürkle de la Camp-Platz 1, Bochum 44789, Germany. · Department of Surgery, Knappschaftskrankenhaus Bochum, Ruhr-University Bochum, In der Schornau 23-25, Bochum 44892, Germany. · Department of Surgery, St. Josef-Hospital, Ruhr-University Bochum, Gudrunstrasse 56, Bochum 44791, Germany. · Department of Medicine II, St. Vinzenz Hospital, Merheimer Str. 221-223, Cologne 50733, Germany. · Diabetes Division, St. Josef-Hospital, Ruhr-University Bochum, Gudrunstrasse 56, Bochum 44791, Germany. Electronic address: Juris.meier@rub.de. ·Metabolism · Pubmed #27085780.

ABSTRACT: INTRODUCTION: The low frequency of beta-cell replication in the adult human pancreas limits beta-cell regeneration. A better understanding of the regulation of human beta-cell proliferation is crucial to develop therapeutic strategies aiming to enhance beta-cell mass. METHODS: To identify factors that control beta-cell proliferation, cell-cycle regulation was examined in human insulinomas as a model of increased beta-cell proliferation (n=11) and healthy pancreatic tissue from patients with benign pancreatic tumors (n=9). Tissue sections were co-stained for insulin and cell-cycle proteins. Transcript levels of selected cell-cycle factors in beta-cells were determined by qRT-PCR after performing laser-capture microdissection. RESULTS: The frequency of beta-cell replication was 3.74±0.92% in the insulinomas and 0.11±0.04% in controls (p=0.0016). p21 expression was higher in insulinomas (p=0.0058), and Rb expression was higher by trend (p=0.085), whereas p16 (p<0.0001), Cyclin C (p<0.0001), and p57 (p=0.018) expression levels were lower. The abundance of Cyclin D3 (p=0.62) and p27 (p=0.68) was not different between the groups. The reduced expression of p16 (p<0.0001) and p57 (p=0.012) in insulinomas and the unchanged expression of Cyclin D3 (p=0.77) and p27 (p=0.55) were confirmed using qRT-PCR. CONCLUSIONS: The expression of certain cell-cycle factors in beta-cells derived from insulinomas and healthy adults differs markedly. Targeting such differentially regulated cell-cycle proteins may evolve as a future strategy to enhance beta-cell regeneration.

13 Article [Recurrent hypoglycemia due to an occult insulinoma]. 2016

Breuer, T G K / Breuer, H L / Menge, B A / Giese, A / Uhl, W / Schmidt, W E / Tannapfel, A / Wild, D / Nauck, M A / Meier, J J. ·Abteilung für Diabetologie, Medizinische Klinik I, St. Josef-Hospital, Ruhr-Universität Bochum, Gudrunstr. 56, 44791, Bochum, Deutschland. · Klinik für Allgemein- und Viszeralchirurgie, St. Josef-Hospital, Ruhr-Universität Bochum, Bochum, Deutschland. · Institut für Pathologie, Ruhr-Universität Bochum, Bochum, Deutschland. · Klinik für Radiologie und Nuklearmedizin, Universitätsspital Basel, Basel, Schweiz. · Abteilung für Diabetologie, Medizinische Klinik I, St. Josef-Hospital, Ruhr-Universität Bochum, Gudrunstr. 56, 44791, Bochum, Deutschland. juris.meier@rub.de. ·Internist (Berl) · Pubmed #26873007.

ABSTRACT: A 64-year-old woman presented with a history of recurrent hypoglycemia. A prolonged fasting test revealed an increased "amended" insulin-glucose ratio. Transabdominal ultrasound (US), computed tomography (CT) scan, and magnetic resonance imaging (MRI) did not show abnormal results. An insulinoma was suspected based on a contrast-enhanced endoscopic US examination as well as a (68)gallium-DOTA-exendin-4 positron-emission tomography (PET)/CT. The diagnosis of an insulinoma was confirmed histologically after surgical removal of the tumor. Hypoglycemia did not occur during the postoperative period. The prolonged fasting test is the gold standard for the diagnosis of an insulinoma. Novel imaging procedures, such as contrast-enhanced endoscopic US or (68)gallium-DOTA-exendin-4 PET/CT are valuable additions to the diagnostic workup.

14 Article A subset of metastatic pancreatic ductal adenocarcinomas depends quantitatively on oncogenic Kras/Mek/Erk-induced hyperactive mTOR signalling. 2016

Kong, Bo / Wu, Weiwei / Cheng, Tao / Schlitter, Anna Melissa / Qian, Chengjia / Bruns, Philipp / Jian, Ziying / Jäger, Carsten / Regel, Ivonne / Raulefs, Susanne / Behler, Nora / Irmler, Martin / Beckers, Johannes / Friess, Helmut / Erkan, Mert / Siveke, Jens T / Tannapfel, Andrea / Hahn, Stephan A / Theis, Fabian J / Esposito, Irene / Kleeff, Jörg / Michalski, Christoph W. ·Department of Surgery, Technische Universität München (TUM), Munich, Germany. · Institute of Pathology, TUM, Munich, Germany. · Department of Surgery, Technische Universität München (TUM), Munich, Germany Institute of Computational Biology, Helmholtz-Zentrum München, Munich, Germany. · Institute of Experimental Genetics (IEG), Helmholtz-Zentrum München, Munich, Germany. · Institute of Experimental Genetics (IEG), Helmholtz-Zentrum München, Munich, Germany Technische Universität München, Chair of Experimental Genetics, Freising, Germany Deutsches Zentrum für Diabetesforschung (DZD), Neuherberg, Germany. · Department of Surgery, Koc University School of Medicine, Istanbul, Turkey. · Department of Gastroenterology, TUM, Munich, Germany. · Institute of Pathology, Ruhr-University Bochum, Bochum, Germany. · Department of Molecular Gastrointestinal Oncology, Ruhr-University Bochum, Bochum, Germany. · Institute of Computational Biology, Helmholtz-Zentrum München, Munich, Germany. · Department of Surgery, University of Heidelberg, Heidelberg, Germany. ·Gut · Pubmed #25601637.

ABSTRACT: OBJECTIVE: Oncogenic Kras-activated robust Mek/Erk signals phosphorylate to the tuberous sclerosis complex (Tsc) and deactivates mammalian target of rapamycin (mTOR) suppression in pancreatic ductal adenocarcinoma (PDAC); however, Mek and mTOR inhibitors alone have demonstrated minimal clinical antitumor activity. DESIGN: We generated transgenic mouse models in which mTOR was hyperactivated either through the Kras/Mek/Erk cascade, by loss of Pten or through Tsc1 haploinsufficiency. Primary cancer cells were isolated from mouse tumours. Oncogenic signalling was assessed in vitro and in vivo, with and without single or multiple targeted molecule inhibition. Transcriptional profiling was used to identify biomarkers predictive of the underlying pathway alterations and of therapeutic response. Results from the preclinical models were confirmed on human material. RESULTS: Reduction of Tsc1 function facilitated activation of Kras/Mek/Erk-mediated mTOR signalling, which promoted the development of metastatic PDACs. Single inhibition of mTOR or Mek elicited strong feedback activation of Erk or Akt, respectively. Only dual inhibition of Mek and PI3K reduced mTOR activity and effectively induced cancer cell apoptosis. Analysis of downstream targets demonstrated that oncogenic activity of the Mek/Erk/Tsc/mTOR axis relied on Aldh1a3 function. Moreover, in clinical PDAC samples, ALDH1A3 specifically labelled an aggressive subtype. CONCLUSIONS: These results advance our understanding of Mek/Erk-driven mTOR activation and its downstream targets in PDAC, and provide a mechanistic rationale for effective therapeutic matching for Aldh1a3-positive PDACs.

15 Article False-Positive PET/CT After Cyanoacrylate Sealing of a Pancreaticojejunostomy. 2015

Belyaev, Orlin / Munding, Johanna / Tannapfel, Andrea / Uhl, Waldemar. ·Department of Surgery, St. Josef Hospital, Ruhr University of Bochum, Gudrunstr. 56, 44791, Bochum, Germany, o.belyaev@klinikum-bochum.de. ·J Gastrointest Surg · Pubmed #25731826.

ABSTRACT: In 2013, a 68-year-old male had a pancreaticoduodenectomy for pancreatic cancer. The pancreaticojejunostomy was sealed with cyanoacrylate (Dermabond) to prevent postoperative pancreatic fistula. Local recurrence of malignancy at the anastomosis was suspected 18 months later in PET/CT. Surgical revision was performed and anastomosis resected. However, histology showed no tumor recurrence, but strong inflammation and foreign-body reaction towards Dermabond. The sealant caused false-positive PET/CT findings, so its use in oncologic surgery should be abandoned.

16 Article A microRNA-based test improves endoscopic ultrasound-guided cytologic diagnosis of pancreatic cancer. 2014

Brand, Randall E / Adai, Alex T / Centeno, Barbara A / Lee, Linda S / Rateb, George / Vignesh, Shivakumar / Menard, Charles / Wiechowska-Kozłowska, Anna / Bołdys, Hubert / Hartleb, Marek / Sanders, Michael K / Munding, Johanna B / Tannapfel, Andrea / Hahn, Stephan A / Stefańczyk, Ludomir / Tsongalis, Gregory J / Whitcomb, David C / Conwell, Darwin L / Morisset, Jean A / Gardner, Timothy B / Gordon, Stuart R / Suriawinata, Arief A / Lloyd, Maura B / Wylie, Dennis / Labourier, Emmanuel / Andruss, Bernard F / Szafranska-Schwarzbach, Anna E. ·Department of Medicine, Division of Gastroenterology, Hepatology & Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. · Asuragen, Inc, Austin, Texas. · Department of Pathology and Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida. · Center for Pancreatic Disease, Brigham and Women's Hospital, Boston, Massachusetts. · Department of Medicine, Division of Gastroenterology, University of Sherbrooke, Fleurimont, Quebec, Canada. · Department of Endoscopy, Hospital of the Ministry of Internal Affairs and Administration, Szczecin, Poland. · Department of Gastroenterology and Hepatology, Medical University of Silesia, Katowice, Poland. · Institute of Pathology, Ruhr-University of Bochum, Bochum, Germany. · Molecular GI-Oncology and Department of Pathology, Ruhr-University of Bochum, Bochum, Germany. · Department of Medicine, Division of Radiology, Medical University of Łódź, Łódz, Poland. · Department of Pathology and Department of Gasteroenterology and Hepatology, Dartmouth Hitchcock Medical Center and The Audrey and Theodor Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire. · Asuragen, Inc, Austin, Texas. Electronic address: aschwarzbach@asuragen.com. ·Clin Gastroenterol Hepatol · Pubmed #24662333.

ABSTRACT: BACKGROUND & AIMS: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in combination with cytopathology is the optimal method for diagnosis and staging of pancreatic ductal adenocarcinoma (PDAC) and other pancreatic lesions. Its clinical utility, however, can be limited by high rates of indeterminate or false-negative results. We aimed to develop and validate a microRNA (miRNA)-based test to improve preoperative detection of PDAC. METHODS: Levels of miRNAs were analyzed in a centralized clinical laboratory by relative quantitative polymerase chain reaction in 95 formalin-fixed paraffin-embedded specimens and 228 samples collected by EUS-FNA during routine evaluations of patients with solid pancreatic masses at 4 institutions in the United States, 1 in Canada, and 1 in Poland. RESULTS: We developed a 5-miRNA expression classifier, consisting of MIR24, MIR130B, MIR135B, MIR148A, and MIR196, that could identify PDAC in well-characterized, formalin-fixed, paraffin-embedded specimens. Detection of PDAC in EUS-FNA samples increased from 78.8% by cytology analysis alone (95% confidence interval, 72.2%-84.5%) to 90.8% when combined with miRNA analysis (95% confidence interval, 85.6%-94.5%). The miRNA classifier correctly identified 22 additional true PDAC cases among 39 samples initially classified as benign, indeterminate, or nondiagnostic by cytology. Cytology and miRNA test results each were associated significantly with PDAC (P < .001), with positive predictive values greater than 99% (95% confidence interval, 96%-100%). CONCLUSIONS: We developed and validated a 5-miRNA classifier that can accurately predict which preoperative pancreatic EUS-FNA specimens contain PDAC. This test might aid in the diagnosis of pancreatic cancer by reducing the number of FNAs without a definitive adenocarcinoma diagnosis, thereby reducing the number of repeat EUS-FNA procedures.

17 Article Influence of MRE11, RAD50 and NIBRIN protein expression on survival in pancreatic carcinoma after curative resection. 2013

Horst, Klemens / Ganzera, Silke / Kaisers, Wolfgang / Munding, Johanna / Flott-Rahmel, Berenike / Tannapfel, Andrea / Zirngibl, Hubert. ·Department of Orthopedic Trauma Surgery, RWTH Aachen, Aachen, Germany. Electronic address: khorst@ukaachen.de. ·Pathol Res Pract · Pubmed #23954013.

ABSTRACT: The MRE11/RAD50/NIBRIN complex, a protein complex that repairs DNA double-strand breaks, could serve as an early marker for new lesions in pancreatic cancer. We determined the expression of MRE11, RAD50 and NIBRIN, and their possible prognostic value regarding survival. Forty-one patients with ductal adenocarcinoma of the pancreas were included. All underwent curative surgery. Immunohistochemistry was performed for MRE11, RAD50 and NIBRIN. Subsequent analyses were based on a modified immunoreactive score. Statistical analysis was conducted using the statistics program "R". The mean follow-up period was 509 days. The mean age of the patients was 67±8 years, male=56%, female=44%. Eighty-seven percent underwent a Kausch-Whipple procedure, whereas a left side resection was performed in 22% of patients. Positive lymph nodes were found in 80% of cases, and patients were staged UICC IIa (12%), IIb (56%) and IV (29%). Overall significant results were found for MRE11 (p=0.02) and NIBRIN (p=0.01) expression and postoperative survival. We found a significant relation between the expression of MRE11, NIBRIN and the postoperative survival of patients with ductal adenocarcinoma. The link between the expression of the MRN complex, ATM and pancreatic cancer can be used to develop new treatment options for pancreatic carcinoma.

18 Article Circulating U2 small nuclear RNA fragments as a novel diagnostic biomarker for pancreatic and colorectal adenocarcinoma. 2013

Baraniskin, Alexander / Nöpel-Dünnebacke, Stefanie / Ahrens, Maike / Jensen, Steffen Grann / Zöllner, Hannah / Maghnouj, Abdelouahid / Wos, Alexandra / Mayerle, Julia / Munding, Johanna / Kost, Dennis / Reinacher-Schick, Anke / Liffers, Sven / Schroers, Roland / Chromik, Ansgar M / Meyer, Helmut E / Uhl, Waldemar / Klein-Scory, Susanne / Weiss, Frank U / Stephan, Christian / Schwarte-Waldhoff, Irmgard / Lerch, Markus M / Tannapfel, Andrea / Schmiegel, Wolff / Andersen, Claus Lindbjerg / Hahn, Stephan A. ·Department of Molecular Gastrointestinal Oncology, Ruhr-University Bochum, Bochum, Germany. ·Int J Cancer · Pubmed #22907602.

ABSTRACT: Improved non-invasive strategies for early cancer detection are urgently needed to reduce morbidity and mortality. Non-coding RNAs, such as microRNAs and small nucleolar RNAs, have been proposed as biomarkers for non-invasive cancer diagnosis. Analyzing serum derived from nude mice implanted with primary human pancreatic ductal adenocarcinoma (PDAC), we identified 15 diagnostic microRNA candidates. Of those miR-1246 was selected based on its high abundance in serum of tumor carrying mice. Subsequently, we noted a cross reactivity of the established miR-1246 assays with RNA fragments derived from U2 small nuclear RNA (RNU2-1). Importantly, we found that the assay signal discriminating tumor from controls was derived from U2 small nuclear RNA (snRNA) fragments (RNU2-1f) and not from miR-1246. In addition, we observed a remarkable stability of RNU2-1f in serum and provide experimental evidence that hsa-miR-1246 is likely a pseudo microRNA. In a next step, RNU2-1f was measured by qRT-PCR and normalized to cel-54 in 191 serum/plasma samples from PDAC and colorectal carcinoma (CRC) patients. In comparison to 129 controls, we were able to classify samples as cancerous with a sensitivity and specificity of 97.7% [95% CI = (87.7, 99.9)] and 90.6% [95% CI = (80.7, 96.5)], respectively [area under the ROC curve 0.972]. Of note, patients with CRC were detected with our assay as early as UICC Stage II with a sensitivity of 81%. In conclusion, this is the first report showing that fragments of U2 snRNA are highly stable in serum and plasma and may serve as novel diagnostic biomarker for PDAC and CRC for future prospective screening studies.

19 Article Site- and grade-specific diversity of LINE1 methylation pattern in gastroenteropancreatic neuroendocrine tumours. 2012

Stricker, Ingo / Tzivras, Dimitri / Nambiar, Sandeep / Wulf, Juergen / Liffers, Sven-Thorsten / Vogt, Markus / Verdoodt, Berlinda / Tannapfel, Andrea / Mirmohammadsadegh, Alireza. ·Institute of Pathology, Ruhr University Bochum, Bochum, Germany. ingo.stricker@ruhr-unibochum.de ·Anticancer Res · Pubmed #22993308.

ABSTRACT: BACKGROUND: Recent data indicate that gastroenteropancreatic neuroendocrine tumours (GEP-NETs) have a hypomethylated long interspersed element (LINE1) promoter. To answer the question, of whether LINE1 may be of value in assessing the malignant potential of GEP-NETs, we analysed LINE1 methylation in different organs. MATERIALS AND METHODS: A total of 58 GEP-NETs of gastric (n=14), pancreatic (n=15), small intestine (n=17), appendix (n=8), colorectal (n=4) and non-neoplastic tissues were analysed using DNA isolation, bisulphite-treatment and pyrosequencing. RESULTS: LINE1 hypomethylation was detected in 50% of gastric, 100% pancreatic, 82% small intestine, 87.5% appendix and 100% colorectal NETs. G1 (p<0.001) and G2 (p<0.05) colorectal, and G1 (p<0.001) and G2 (p<0.001) pancreatic NETs exhibited significant LINE1 hypomethylation compared with non-neoplastic tissues. Higher rates of LINE1 hypomethylation in G2 pancreatic NETs than in G1 NETs (p<0.05) were observed. NETs exhibited a significantly lower frequency of hypomethylation in cases with lymph node metastases (p<0.05). CONCLUSION: LINE1 hypomethylation may serve as a marker of tumour grade and lymph node metastasis.

20 Article Can the new RCP R0/R1 classification predict the clinical outcome in ductal adenocarcinoma of the pancreatic head? 2012

Janot, M S / Kersting, S / Belyaev, O / Matuschek, A / Chromik, A M / Suelberg, D / Uhl, W / Tannapfel, A / Bergmann, U. ·Department of General and Visceral Surgery, St. Josef-Hospital, Ruhr University Bochum, Gudrunstrasse 56, Bochum, Germany. ·Langenbecks Arch Surg · Pubmed #22695970.

ABSTRACT: PURPOSE: According to the International Union Against Cancer (UICC), R1 is defined as the microscopic presence of tumor cells at the surface of the resection margin (RM). In contrast, the Royal College of Pathologists (RCP) suggested to declare R1 already when tumor cells are found within 1 mm of the RM. The aim of this study was to determine the significance of the RM concerning the prognosis of pancreatic ductal adenocarcinoma (PDAC). METHODS: From 2007 to 2009, 62 patients underwent a curative operation for PDAC of the pancreatic head. The relevance of R status on cumulative overall survival (OS) was assessed on univariate and multivariate analysis for both the classic R classification (UICC) and the suggestion of the RCP. RESULTS: Following the UICC criteria, a positive RM was detected in 8 %. Along with grading and lymph node ratio, R status revealed a significant impact on OS on univariate and multivariate analysis. Applying the suggestion of the RCP, R1 rate rose to 26 % resulting in no significant impact on OS in univariate analysis. CONCLUSIONS: Our study has shown that the RCP suggestion for R status has no impact on the prognosis of PDAC. In contrast, our data confirmed the UICC R classification of RM as well as N category, grading, and lymph node ratio as significant prognostic factors.

21 Article Rare solid tumors of the pancreas as differential diagnosis of pancreatic adenocarcinoma. 2012

Kersting, Sabine / Janot, Monika S / Munding, Johanna / Suelberg, Dominique / Tannapfel, Andrea / Chromik, Ansgar M / Uhl, Waldemar / Bergmann, Uwe. ·Department of General and Visceral Surgery, St. Josef-Hospital, Ruhr-University Bochum. Bochum, Germany. ·JOP · Pubmed #22572130.

ABSTRACT: CONTEXT: Rare solid tumors of the pancreas can be misinterpreted as primary pancreatic cancer. OBJECTIVE: The aim of this study was to report our experience in the treatment of patients with rare tumor lesions of the pancreas and to discuss clinical and pathological characteristics in the context of the role of surgery. DESIGN: Data from patients of our prospective data-base with rare benign and malignant tumors of the pancreas, treated in our division from January 2004 to August 2010, were analyzed retrospectively. RESULTS: One-thousand and ninety-eight patients with solid tumors of the pancreas underwent pancreatic surgery. In 19 patients (10 women, 9 men) with a mean age of 57 years (range: 20-74 years) rare pancreatic tumors (metastasis, solid pseudopapillary tumor, teratoma, hemangioma, accessory spleen, lymphoepithelial cyst, hamartoma, sarcoidosis, yolk sac tumor) were the reason for surgical intervention. CONCLUSION: If rare benign and malignant pancreatic tumors, intrapancreatic metastasis, as well as pancreatic malformations or other abnormalities, present themselves as solid masses of the pancreas, they constitute an important differential diagnosis to primary pancreatic neoplasia, e.g. pancreatic ductal adenocarcinoma. Clinical imaging techniques cannot always rule out malignancy, thus operative exploration often remains the treatment of choice to provide the correct diagnosis and initiate adequate surgical therapy.

22 Article Global microRNA expression profiling of microdissected tissues identifies miR-135b as a novel biomarker for pancreatic ductal adenocarcinoma. 2012

Munding, Johanna B / Adai, Alex T / Maghnouj, Abdelouahid / Urbanik, Aleksandra / Zöllner, Hannah / Liffers, Sven T / Chromik, Ansgar M / Uhl, Waldemar / Szafranska-Schwarzbach, Anna E / Tannapfel, Andrea / Hahn, Stephan A. ·Institute of Pathology, Ruhr-University Bochum, Bochum, Germany. ·Int J Cancer · Pubmed #21953293.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is known for its poor prognosis resulting from being diagnosed at an advanced stage. Accurate early diagnosis and new therapeutic modalities are therefore urgently needed. MicroRNAs (miRNAs), considered a new class of biomarkers and therapeutic targets, may be able to fulfill those needs. Combining tissue microdissection with global miRNA array analyses, cell type-specific miRNA expression profiles were generated for normal pancreatic ductal cells, acinar cells, PDAC cells derived from xenografts and also from macrodissected chronic pancreatitis (CP) tissues. We identified 78 miRNAs differentially expressed between ND and PDAC cells providing new insights into the miRNA-driven pathophysiological mechanisms involved in PDAC development. Having filtered miRNAs which are upregulated in the three pairwise comparisons of PDAC vs. ND, PDAC vs. AZ and PDAC vs. CP, we identified 15 miRNA biomarker candidates including miR-135b. Using relative qRT-PCR to measure miR-135b normalized to miR-24 in 75 FFPE specimens (42 PDAC and 33 CP) covering a broad range of tumor content, we discriminated CP from PDAC with a sensitivity and specificity of 92.9% [95% CI=(80.5, 98.5)] and 93.4% [95% CI=(79.8, 99.3)], respectively. Furthermore, the area under the curve (AUC) value reached of 0.97 was accompanied by positive and negative predictive values of 95% and 91%, respectively. In conclusion, we report pancreatic cell-specific global miRNA profiles, which offer new candidate miRNAs to be exploited for functional studies in PDAC. Furthermore, we provide evidence that miRNAs are well-suited analytes for development of sensitive and specific aid-in-diagnosis tests for PDAC.

23 Article Diagnostic value of quantitative EUS elastography for malignant pancreatic tumors: relationship with pancreatic fibrosis. 2012

Schrader, H / Wiese, M / Ellrichmann, M / Belyaev, O / Uhl, W / Tannapfel, A / Schmidt, W / Meier, J. ·Medizinische Klinik I, St.-Josef-Hospital. ·Ultraschall Med · Pubmed #21630184.

ABSTRACT: PURPOSE: EUS elastography has been used to facilitate the diagnosis of pancreatic cancer, but as yet the interpretation of this procedure has been largely subjective. The present study has been designed to validate a quantitative approach for the analysis of EUS elastography, and to assess its relationship with pancreatic fibrosis. MATERIALS AND METHODS: 86 patients with malignant pancreatic masses and 28 control subjects without any evidence of pancreatic diseases were examined by EUS elastography. EUS video sequences were subjected to a quantitative analysis based on mean hue histogram analysis. Pancreatic fibrosis was determined by quantitative morphometry in tissue specimens from 36 patients. RESULTS: The mean RGB (red, green, blue) value was significantly higher in the cancer patients compared to the controls (14.0 ± 0.4 vs. 11.5 ± 0.9; p = 0.0085), albeit with significant overlap between the groups. In contrast, a much sharper separation between the groups was obtained based on the individual color values for blue, green and red (p < 0.0001, respectively). By these means, 100 % sensitivity and specificity for the distinction between tumor and normal tissue was obtained for the blue color value, while the red and green color values were less discriminative. The fractional fiber content of the tumors was unrelated to the respective hue histogram color values. CONCLUSION: Quantitative EUS elastography allows for clear differentiation between malignant pancreatic tumors and normal tissue. Using this approach, we demonstrated that the stiffness of pancreatic tumors is largely independent of their fiber content.

24 Article [R classification and pancreatic ductal adenocarcinoma--R 0 is R 0]. 2011

Munding, J / Uhl, W / Tannapfel, A. ·Institut für Pathologie, Ruhr-Universität Bochum. johanna.munding@rub.de ·Z Gastroenterol · Pubmed #21964897.

ABSTRACT: The ductal adenocarcinoma of the pancreas is characterised by a very poor prognosis due to an early inoperability of the tumours. Even if operated under curative aspects, local recurrence of the disease is quite frequent with corresponding poorer prognosis. For a better assessment, standardised protocols for the pathohistological processing of resection specimens of the pancreas are needed urgently as well as a strict adherence to the R classification. In order to establish a reliable marker for the risk of recurrence, the smallest distance to the circumferential resection margin should be indicated in comparison to the circumferential resection margin (CRM) concept in colorectal carcinoma.

25 Article Solid pseudopapillary tumors of the pancreas: a case series, comparison of histopathological and clinical data. 2011

Munding, J / Sunitsch, S / Belyaev, O / Liffers, S-T / Uhl, W / Tannapfel, A. ·Institut für Pathologie der Ruhr-Universität Bochum, Bochum, Germany. ·Z Gastroenterol · Pubmed #21964896.

ABSTRACT: Solid pseudopapillary neoplasms (SPNs) are rare pancreatic tumors. They occur most frequently in young females and are often diagnosed accidentally. SPNs are characterized by an excellent clinical outcome. In our case series the clinical course, pathohistological data and clinical outcome of eight patients (7 female patients, 1 male patient) with SPN are described. Histological examination as well as immunohistochemical analysis shows similar results in all eight cases. Although in the literature a few cases of SPNs with bad prognosis have been reported, up to now none of our patients shows any signs of recurrence or metastasis. Moreover, we give in this case series a summary of SPNs in the literature, important clinical and pathological differential diagnosis, and additionally discuss relevant differential diagnosis occurring in daily routine work.