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Permanent URI for this collectionhttps://hdl.handle.net/11443/932

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Author: search.filters.author.Friess, HelmutSubject: search.filters.subject.pancreatic cancer

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    Patterns and Relevance of Langerhans Islet Invasion in Pancreatic Cancer
    (MDPI, 2021-01-01) Goess, Ruediger; Mutgan, Ayse Ceren; Calisan, Umut; Erdogan, Yusuf Ceyhun; Ren, Lei; Jager, Carsten; Safak, Okan; Stupakov, Pavel; Istvanffy, Rouzanna; Friess, Helmut; Ceyhan, Guralp O.; Demir, Ihsan Ekin
    Simple Summary The pathogenesis of pancreatic cancer-associated diabetes mellitus is poorly understood. We analyzed tumor infiltration into Langerhans islets and characterized it systematically for the first time, identifying four different main patterns of islet invasion. In a cohort of 68 pancreatic ductal adenocarcinoma (PDAC) patients, these islet invasion patterns were not related to occurrence of diabetes mellitus. However, severe islet invasion was associated with worsened overall survival. Background: Pancreatic cancer-associated diabetes mellitus (PC-DM) is present in most patients with pancreatic cancer, but its pathogenesis remains poorly understood. Therefore, we aimed to characterize tumor infiltration in Langerhans islets in pancreatic cancer and determine its clinical relevance. Methods: Langerhans islet invasion was systematically analyzed in 68 patients with pancreatic ductal adenocarcinoma (PDAC) using histopathological examination and 3D in vitro migration assays were performed to assess chemoattraction of pancreatic cancer cells to islet cells. Results: Langerhans islet invasion was present in all patients. We found four different patterns of islet invasion: (Type I) peri-insular invasion with tumor cells directly touching the boundary, but not penetrating the islet
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    Regulatory T Cells in Pancreatic Cancer: Of Mice and Men
    (MDPI, 2022-01-01) Reyes, Carmen Mota; Demir, Elke; Cifcibasi, Kaan; Istvanffy, Rouzanna; Friess, Helmut; Demir, Ihsan Ekin
    Simple Summary Regulatory T cells (Treg) are a major immunosuppressive cell subset in the pancreatic tumor microenvironment. Tregs influence tumor growth by acting either directly on cancer cells or via the inhibition of effector immune cells. Treg cells form a partially redundant network with other immunosuppressive cells such as myeloid-derived suppressor cells (MDSC) that confer robustness to tumor immunosuppression and resistance to immunotherapy. The results obtained in preclinical studies, whereupon Treg depletion, MDSCs concomitantly decreased in early tumors whereas an inverse association was seen in advanced PCa, urge a comprehensive analysis of the immunosuppressive profile of PCa throughout tumorigenesis. One relevant context to analyse these compensatory mechanisms may be patients with locally advanced PCa undergoing neoadjuvant therapy (neoTx). In order to understand these dynamics and to uncover stage-specific actional strategies involving Tregs, pre-clinical models that allow the administration of neoTx to different stages of PCa may be a very useful platform. Regulatory T cells (Treg) are one of the major immunosuppressive cell subsets in the pancreatic tumor microenvironment. Tregs influence tumor growth by acting either directly on cancer cells or via the inhibition of effector immune cells. Treg cells mechanisms form a partially redundant network with other immunosuppressive cells such as myeloid-derived suppressor cells (MDSC) that confer robustness to tumor immunosuppression and resistance to immunotherapy. The results obtained in preclinical studies where after Treg depletion, MDSCs concomitantly decreased in early tumors whereas an inverse association was seen in advanced PCa, urge a comprehensive analysis of the immunosuppressive profile of PCa throughout tumorigenesis. One relevant context to analyse these complex compensatory mechanisms may be the tumors of patients who underwent neoTx. Here, we observed a parallel decrease in the numbers of both intratumoral Tregs and MDSC after neoTx even in locally advanced PCa. NeoTx also led to decreased amounts of alpha SMA(+) myofibroblastic cancer-associated fibroblasts (myCAF) and increased proportions of CD8(+) cytotoxic T lymphocytes in the tumor. In order to understand these dynamics and to uncover stage-specific actional strategies involving Tregs, pre-clinical models that allow the administration of neoTx to different stages of PCa may be a very useful platform.
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    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.