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Pancreatic Neoplasms: HELP
Articles by Patrick Wenzel
Based on 8 articles published since 2010
(Why 8 articles?)
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Between 2010 and 2020, P. Wenzel wrote the following 8 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 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.

2 Article The hepatic microenvironment essentially determines tumor cell dormancy and metastatic outgrowth of pancreatic ductal adenocarcinoma. 2017

Lenk, Lennart / Pein, Maren / Will, Olga / Gomez, Beatriz / Viol, Fabrice / Hauser, Charlotte / Egberts, Jan-Hendrik / Gundlach, Jan-Paul / Helm, Ole / Tiwari, Sanjay / Weiskirchen, Ralf / Rose-John, Stefan / Röcken, Christoph / Mikulits, Wolfgang / Wenzel, Patrick / Schneider, Günter / Saur, Dieter / Schäfer, Heiner / Sebens, Susanne. ·Institute for Experimental Cancer Research, Christian-Albrechts-University Kiel (CAU) and University Medical Center Schleswig-Holstein (UKSH) Campus Kiel, Kiel, Germany. · Cell Biology and Tumor Biology Program, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany. · Molecular Imaging North Competence Center, Clinic of Radiology and Neuroradiology, CAU and UKSH Campus Kiel, Kiel, Germany. · Department of Medicine I, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. · Department of General, Visceral-, Thoracic-, Transplantation- and Pediatric Surgery, UKSH Campus Kiel, Kiel, Germany. · Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry, RWTH Aachen University, Aachen, Germany. · Department of Biochemistry, CAU, Kiel, Germany. · Institute of Pathology, UKSH Campus Kiel, Kiel, Germany. · Department of Medicine I, Division: Institute of Cancer Research, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. · II. Medizinische Klinik und Poliklinik, Klinikum Rechts der Isar, Technical University Munich, Munich, Germany. ·Oncoimmunology · Pubmed #29296518.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed when liver metastases already emerged. This study elucidated the impact of hepatic stromal cells on growth behavior of premalignant and malignant pancreatic ductal epithelial cells (PDECs). Liver sections of tumor-bearing KPC mice comprised micrometastases displaying low proliferation located in an unobtrusive hepatic microenvironment whereas macrometastases containing more proliferating cells were surrounded by hepatic myofibroblasts (HMFs). In an age-related syngeneic PDAC mouse model livers with signs of age-related inflammation exhibited significantly more proliferating disseminated tumor cells (DTCs) and micrometastases despite comparable primary tumor growth and DTC numbers. Hepatic stellate cells (HSC), representing a physiologic liver stroma, promoted an IL-8 mediated quiescence-associated phenotype (QAP) of PDECs in coculture. QAP included flattened cell morphology, Ki67-negativity and reduced proliferation, elevated senescence-associated β galactosidase activity and diminished p-Erk/p-p38-ratio. In contrast, proliferation of PDECs was enhanced by VEGF in the presence of HMF. Switching the micromilieu from HSC to HMF or blocking VEGF reversed QAP in PDECs. This study demonstrates how HSCs induce and maintain a reversible QAP in disseminated PDAC cells, while inflammatory HMFs foster QAP reversal and metastatic outgrowth. Overall, the importance of the hepatic microenvironment in induction and reversal of dormancy during PDAC metastasis is emphasized.

3 Article Apparent Diffusion Coefficient (ADC) predicts therapy response in pancreatic ductal adenocarcinoma. 2017

Trajkovic-Arsic, M / Heid, I / Steiger, K / Gupta, A / Fingerle, A / Wörner, C / Teichmann, N / Sengkwawoh-Lueong, S / Wenzel, P / Beer, A J / Esposito, I / Braren, R / Siveke, J T. ·Division of Solid Tumor Translational Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany. · German Cancer Consortium (DKTK, partner site Essen) and German Cancer Research Center (DKFZ), Heidelberg, Germany. · Institute of Radiology, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany. · Institute of Pathology, TUM School of Medicine, Technical University of Munich, Munich, Germany. · 2. Medizinische Klinik, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany. · Department of Nuclear Medicine, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany. · Department of Nuclear Medicine, University Hospital of Ulm, Ulm, Germany. · Institute of Pathology, University Clinic Duesseldorf, Heinrich-Heine University, Duesseldorf, Germany. · Institute of Radiology, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany. rbraren@tum.de. · Division of Solid Tumor Translational Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany. j.siveke@dkfz.de. · German Cancer Consortium (DKTK, partner site Essen) and German Cancer Research Center (DKFZ), Heidelberg, Germany. j.siveke@dkfz.de. · 2. Medizinische Klinik, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany. j.siveke@dkfz.de. ·Sci Rep · Pubmed #29213099.

ABSTRACT: Recent advances in molecular subtyping of Pancreatic Ductal Adenocarcinoma (PDAC) support individualization of therapeutic strategies in this most aggressive disease. With the emergence of various novel therapeutic strategies and neoadjuvant approaches in this quickly deteriorating disease, robust approaches for fast evaluation of therapy response are urgently needed. To this aim, we designed a preclinical imaging-guided therapy trial where genetically engineered mice harboring endogenous aggressive PDAC were treated with the MEK targeting drug refametinib, which induces rapid and profound tumor regression in this model system. Multi-parametric non-invasive imaging was used for therapy response monitoring. A significant increase in the Diffusion-Weighted Magnetic Resonance Imaging derived Apparent Diffusion Coefficient (ADC) was noted already 24 hours after treatment onset. Histopathological analyses showed increased apoptosis and matrix remodeling at this time point. Our findings suggest the ADC parameter as an early predictor of therapy response in PDAC.

4 Article Extended RAS analysis and correlation with overall survival in advanced pancreatic cancer. 2017

Haas, Michael / Ormanns, Steffen / Baechmann, Sibylle / Remold, Anna / Kruger, Stephan / Westphalen, Christoph B / Siveke, Jens T / Wenzel, Patrick / Schlitter, Anna Melissa / Esposito, Irene / Quietzsch, Detlef / Clemens, Michael R / Kettner, Erika / Laubender, Ruediger P / Jung, Andreas / Kirchner, Thomas / Boeck, Stefan / Heinemann, Volker. ·Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Marchioninistr. 15, Munich 81377, Germany. · Institute of Pathology, Ludwig-Maximilians-University of Munich, Germany and German Cancer Consortium (DKTK), Partner Site Munich, Thalkirchner Str. 36, Munich 80377, Germany. · 2nd Medical Department, Klinikum Rechts der Isar, Technical University of Munich, Ismaninger Str. 22, Munich 81675, Germany. · German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany. · Division of Solid Tumour Translational Oncology, German Cancer Consortium (DKTK), Partner Site Essen, University Hospital Essen, Hufelandstr. 55, Essen 45147, Germany. · Institute of Pathology, Technical University of Munich, Trogerstr. 18, Munich 81675, Germany. · Institute of Pathology, Heinrich Heine University of Duesseldorf, Moorenstr. 5, Duesseldorf 40225, Germany. · Department of Internal Medicine II, Klinikum Chemnitz gGmbH, Flemmingstr. 2, Chemnitz 09116, Germany. · Department of Hematology and Oncology, Mutterhaus der Boromaeerinnen, Feldstr. 16, Trier 54290, Germany. · Department of Hematology and Oncology, Klinikum Magdeburg, Birkenallee 34, Magdeburg 39130, Germany. · Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-University of Munich, Marchioninistr. 15, Munich 81377, Germany. ·Br J Cancer · Pubmed #28449008.

ABSTRACT: BACKGROUND: Mutations in the KRAS gene can be detected in about 70-90% of pancreatic cancer (PC) cases. Whether these mutations have a prognostic or predictive value remains elusive. Furthermore, the clinical relevance of the extended RAS (KRAS+NRAS) mutational status is unclear in PC. METHODS: We prospectively defined a PC patient population who received erlotinib-free chemotherapy regimens. A statistically significant difference between KRAS wild-type and KRAS mutated tumours in at least 160 patients in this population would support the assumption of a rather prognostic role of KRAS. RESULTS: One hundred and seventy-eight tumour samples were collected from prospective clinical studies and successfully analysed for the extended RAS status: 37 tumours were KRAS wild-type (21%), whereas 141 (79%) carried a KRAS mutation; 132 of these mutations were found in KRAS exon 2 (74%), whereas only 9 mutations (5%) were detected in KRAS exon 3. Within KRAS exon 4 and NRAS exons 2-4, no mutations were apparent. There was no significant difference in overall survival for KRAS wild-type vs mutant patients (9.9 vs 8.3 months, P=0.70). CONCLUSIONS: Together with the results of the AIO-PK-0104-trial, the present analysis supports the notion that KRAS mutation status is rather predictive than prognostic in advanced PC.

5 Article HDAC1 and HDAC2 integrate the expression of p53 mutants in pancreatic cancer. 2017

Stojanovic, N / Hassan, Z / Wirth, M / Wenzel, P / Beyer, M / Schäfer, C / Brand, P / Kroemer, A / Stauber, R H / Schmid, R M / Arlt, A / Sellmer, A / Mahboobi, S / Rad, R / Reichert, M / Saur, D / Krämer, O H / Schneider, G. ·II. Medizinische Klinik, Technische Universität München, München, Germany. · Department of Toxicology, University of Mainz Medical Center, Mainz, Germany. · Institute of Biochemistry and Biophysics/Center for Molecular Biomedicine (CMB), Friedrich-Schiller-University Jena, Jena, Germany. · Molecular and Cellular Oncology/ENT, University Medical Center Mainz, Mainz, Germany. · Laboratory of Molecular Gastroenterology and Hepatology, 1st Department of Internal Medicine I, University Hospital Schleswig-Holstein, Kiel, Germany. · Institute of Pharmacy, Department of Pharmaceutical Chemistry I, Faculty of Chemistry and Pharmacy, University of Regensburg, Regensburg, Germany. · German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany. · Division of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. ·Oncogene · Pubmed #27721407.

ABSTRACT: Mutation of p53 is a frequent genetic lesion in pancreatic cancer being an unmet clinical challenge. Mutants of p53 have lost the tumour-suppressive functions of wild type p53. In addition, p53 mutants exert tumour-promoting functions, qualifying them as important therapeutic targets. Here, we show that the class I histone deacetylases HDAC1 and HDAC2 contribute to maintain the expression of p53 mutants in human and genetically defined murine pancreatic cancer cells. Our data reveal that the inhibition of these HDACs with small molecule HDAC inhibitors (HDACi), as well as the specific genetic elimination of HDAC1 and HDAC2, reduce the expression of mutant p53 mRNA and protein levels. We further show that HDAC1, HDAC2 and MYC directly bind to the TP53 gene and that MYC recruitment drops upon HDAC inhibitor treatment. Therefore, our results illustrate a previously unrecognized class I HDAC-dependent control of the TP53 gene and provide evidence for a contribution of MYC. A combined approach targeting HDAC1/HDAC2 and MYC may present a novel and molecularly defined strategy to target mutant p53 in pancreatic cancer.

6 Article Resectability After First-Line FOLFIRINOX in Initially Unresectable Locally Advanced Pancreatic Cancer: A Single-Center Experience. 2015

Nitsche, Ulrich / Wenzel, Patrick / Siveke, Jens T / Braren, Rickmer / Holzapfel, Konstantin / Schlitter, Anna M / Stöß, Christian / Kong, Bo / Esposito, Irene / Erkan, Mert / Michalski, Christoph W / Friess, Helmut / Kleeff, Jörg. ·Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. · Department of Internal Medicine II, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. · Department of Diagnostic and Interventional Radiology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. · Institute of Pathology, Technische Universität München, Munich, Germany. · Institute of Pathology, Heinrich Heine University, Düsseldorf, Germany. · Department of Surgery, Koc University School of Medicine, Istanbul, Turkey. · Department of Surgery, University of Heidelberg, Heidelberg, Germany. · Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. kleeff@tum.de. ·Ann Surg Oncol · Pubmed #26350368.

ABSTRACT: BACKGROUND: FOLFIRINOX is an active but relatively toxic chemotherapeutic regimen for patients with metastatic pancreatic ductal adenocarcinoma (PDAC). The increased frequency of responding tumors shift interest to neoadjuvant approaches. We report our institutional experience with FOLFIRINOX for therapy-naïve patients with locally advanced and initially unresectable PDAC. METHODS: All patients with unresectable locally advanced PDAC who underwent treatment with FOLFIRINOX at a single center between 2011 and 2014 were identified and evaluated retrospectively regarding chemotherapy response, toxicity, conversion to resectability, and survival. Resectability, response to chemotherapy, and postoperative complications were reported according to NCCN-guidelines, RECIST-criteria, and Clavien-Dindo-classification, respectively. RESULTS: Overall, 14 patients received FOLFIRINOX as first-line therapy for locally advanced and unresectable PDAC. Fifty-seven percent of the patients had severe tumor-related comorbidities at the time of diagnosis, and in 86 %, dose reduction due to toxicity was necessary during a median of seven cycles. Nevertheless, only one patient had progressive disease during FOLFIRINOX, whereas the others experienced stable disease (n = 6) or partial remission (n = 6; no restaging in one patient). Oncological tumor resection was possible in 4 patients (29 % of all patients) with no postoperative mortality and only one grade 2 surgical complication. After a median follow-up of 10 months, 4 of the 14 patients were still in remission, 5 were alive with stable disease under ongoing systemic chemotherapy, and 5 died tumor-related. CONCLUSIONS: FOLFIRINOX is a powerful first-line regimen that leads to resectability in a substantial portion of patients with initially unresectable pancreatic cancer.

7 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.

8 Article Efemp1 and p27(Kip1) modulate responsiveness of pancreatic cancer cells towards a dual PI3K/mTOR inhibitor in preclinical models. 2013

Diersch, Sandra / Wenzel, Patrick / Szameitat, Melanie / Eser, Philipp / Paul, Mariel C / Seidler, Barbara / Eser, Stefan / Messer, Marlena / Reichert, Maximilian / Pagel, Philipp / Esposito, Irene / Schmid, Roland M / Saur, Dieter / Schneider, Günter. ·II. Medizinische Klinik, Technische Universität München, München, Germany. ·Oncotarget · Pubmed #23470560.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) remains a dismal disease with a poor prognosis and targeted therapies have failed in the clinic so far. Several evidences point to the phosphatidylinositol 3-kinase (PI3K)-mTOR pathway as a promising signaling node for targeted therapeutic intervention. Markers, which predict responsiveness of PDAC cells towards PI3K inhibitors are unknown. However, such markers are needed and critical to better stratify patients in clinical trials. We used a large murine Kras(G12D)- and PI3K (p110α(H1047R))-driven PDAC cell line platform to unbiased define modulators of responsiveness towards the dual PI3K-mTOR inhibitor Bez235. In contrast to other tumor models, we show that Kras(G12D)- and PI3K (p110α(H1047R))-driven PDAC cell lines are equally sensitive towards Bez235. In an unbiased approach we found that the extracellular matrix protein Efemp1 controls sensitivity of murine PDAC cells towards Bez235. We show that Efemp1 expression is connected to the cyclin-dependent kinase inhibitor p27(Kip1). In a murine Kras(G12D)-driven PDAC model, p27(Kip1) haploinsufficiency accelerates cancer development in vivo. Furthermore, p27(Kip1) controls Bez235 sensitivity in a gene dose-dependent fashion in murine PDAC cells and lowering of p27(Kip1) decreases Bez235 responsiveness in murine PDAC models. Together, we define the Efemp1-p27(Kip1) axis as a potential marker module of PDAC cell sensitivity towards dual PI3K-mTOR inhibitors, which might help to better stratify patients in clinical trials.