Browsing by Author "Jaeger, Carsten"
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Item Diabetes and Weight Loss Are Associated With Malignancies in Patients With Intraductal Papillary Mucinous Neoplasms(ELSEVIER SCIENCE INC, 2021-01-01) Pergolini, Ilaria; Jaeger, Carsten; Safak, Okan; Goess, Ruediger; Novotny, Alexander; Ceyhan, Guralp O.; Friess, Helmut; Demir, Ihsan EkinBACKGROUND \& AIMS: The role of diabetes in intraductal papillary mucinous neoplasms (IPMNs) is not known. We investigated the prevalence of diabetes among patients with resected IPMNs and the association between diabetes, clinical and morphological features, and high-grade dysplasia or invasive cancer. METHODS: We collected clinical, pathology, laboratory, and demographic data from 134 patients who underwent pancreatic resection for IPMN from a referral center in Germany. We identified 50 patients with diabetes (37\%). RESULTS: Higher proportions of patients with diabetes were male and older, but did not have increased body mass index, compared to patients without diabetes. Diabetes was significantly associated with main-duct involvement (odds ratio {[}OR], 2.827Item Indirect cholinergic activation slows down pancreatic cancer growth and tumor-associated inflammation(BMC, 2020-01-01) Pfitzinger, Paulo L.; Fangmann, Laura; Wang, Kun; Demir, Elke; Guerlevik, Engin; Fleischmann-Mundt, Bettina; Brooks, Jennifer; D'Haese, Jan G.; Teller, Steffen; Hecker, Andreas; Jesinghaus, Moritz; Jaeger, Carsten; Ren, Lei; Istvanffy, Rouzanna; Kuehnel, Florian; Friess, Helmut; Ceyhan, Guralp Onur; Demir, Ihsan EkinBackground Nerve-cancer interactions are increasingly recognized to be of paramount importance for the emergence and progression of pancreatic cancer (PCa). Here, we investigated the role of indirect cholinergic activation on PCa progression through inhibition of acetylcholinesterase (AChE) via clinically available AChE-inhibitors, i.e. physostigmine and pyridostigmine. Methods We applied immunohistochemistry, immunoblotting, MTT-viability, invasion, flow-cytometric-cell-cycle-assays, phospho-kinase arrays, multiplex ELISA and xenografted mice to assess the impact of AChE inhibition on PCa cell growth and invasiveness, and tumor-associated inflammation. Survival analyses were performed in a novel genetically-induced, surgically-resectable mouse model of PCa under adjuvant treatment with gemcitabine+/-physostigmine/pyridostigmine (n = 30 mice). Human PCa specimens (n = 39) were analyzed for the impact of cancer AChE expression on tumor stage and survival. Results We discovered a strong expression of AChE in cancer cells of human PCa specimens. Inhibition of this cancer-cell-intrinsic AChE via pyridostigmine and physostigmine, or administration of acetylcholine (ACh), diminished PCa cell viability and invasion in vitro and in vivo via suppression of pERK signaling, and reduced tumor-associated macrophage (TAM) infiltration and serum pro-inflammatory cytokine levels. In the novel genetically-induced, surgically-resectable PCa mouse model, adjuvant co-therapy with AChE blockers had no impact on survival. Accordingly, survival of resected PCa patients did not differ based on tumor AChE expression levels. Patients with higher-stage PCa also exhibited loss of the ACh-synthesizing enzyme, choline-acetyltransferase (ChAT), in their nerves. Conclusion For future clinical trials of PCa, direct cholinergic stimulation of the muscarinic signaling, rather than indirect activation via AChE blockade, may be a more effective strategy.Item Venous resection during pancreatectomy for pancreatic cancer: a systematic review(AME PUBLISHING COMPANY, 2019-01-01) Wang, Xiaobo; Demir, Ihsan Ekin; Schorn, Stephan; Jaeger, Carsten; Scheufele, Florian; Friess, Helmut; Ceyhan, Guralp O.Pancreatic cancer is one of the most aggressive and lethal malignancies with a dismal prognosis and survival. The curative effects of venous resection (VR) in pancreatic cancer remain controversial. A systematic literature search was performed in PubMed, Embase and the Cochrane Library. The overall postoperative complications, perioperative mortality, histopathology, and long-term survival were compared between patients undergoing pancreatectomy combined with (VR+ group) or without (VR- group) VR. Forty-one studies were included in the systematic review. Pancreatectomy combined with VR required longer operation time and led to increased perioperative blood loss, whereas postoperative complications were similar. Patients in the VR+ group showed larger tumors and reduced R0 rates. Regarding long-term survival, patients with VR+ seemed to have impaired 1-, 3-, and 5-year survival. Based on our results, VR in pancreatic cancer is a safe and feasible procedure. Given the fact that patients have miserable outcomes and survival in the palliative setting alone, extended resection including VR is required for the purpose of achieving radical resection.