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Pancreatic Neoplasms: HELP
Articles by Oliver Strobel
Based on 110 articles published since 2010
(Why 110 articles?)
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Between 2010 and 2020, O. Strobel wrote the following 110 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5
1 Guideline [Borderline resectable pancreatic cancer: ISGPS consensus statement]. 2014

Strobel, O / Büchler, M W / Anonymous4340811. ·Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universität Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Deutschland, Oliver.Strobel@med.uni-heidelberg.de. ·Chirurg · Pubmed #25385138.

ABSTRACT: -- No abstract --

2 Review Conversion Surgery for Advanced Pancreatic Cancer. 2019

Hank, Thomas / Strobel, Oliver. ·Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany. ·J Clin Med · Pubmed #31718103.

ABSTRACT: While primarily unresectable locally advanced pancreatic cancer (LAPC) used to be an indication for palliative therapy, a strategy of neoadjuvant therapy (NAT) and conversion surgery is being increasingly used after more effective chemotherapy regimens have become available for pancreatic ductal adenocarcinoma. While high-level evidence from prospective studies is still sparse, several large retrospective studies have recently reported their experience with NAT and conversion surgery for LAPC. This review aims to provide a current overview about different NAT regimens, conversion rates, survival outcomes and determinants of post-resection outcomes, as well as surgical strategies in the context of conversion surgery after NAT. FOLFIRINOX is the predominant regimen used and associated with the highest reported conversion rates. Conversion rates considerably vary between less than 5% and more than half of the study population with heterogeneous long-term outcomes, owing to a lack of intention-to-treat analyses in most studies and a high heterogeneity in resectability criteria, treatment strategies, and reporting among studies. Since radiological criteria of local resectability are no longer applicable after NAT, patients without progressive disease should undergo surgical exploration. Surgery after NAT has to be aimed at local radicality around the peripancreatic vessels and should be performed in expert centers. Future studies in this rapidly evolving field need to be prospective, analyze intention-to-treat populations, report stringent and objective inclusion criteria and criteria for resection. Innovative regimens for NAT in combination with a radical surgical approach hold high promise for patients with LAPC in the future.

3 Review Local radicality and survival outcome of pancreatic cancer surgery. 2019

Niesen, Willem / Hank, Thomas / Büchler, Markus / Strobel, Oliver. ·Department of General, Visceral and Transplantation Surgery Heidelberg University Hospital Heidelberg Germany. ·Ann Gastroenterol Surg · Pubmed #31549006.

ABSTRACT: Pancreatic cancer remains a therapeutic challenge. Surgical resection in combination with systemic chemotherapy is the only option promising long-term survival and potential cure. However, only about 20% of patients are diagnosed with tumors that are still in a resectable stage. Even after potentially curative resection and modern regimens for adjuvant chemotherapy, the majority of patients develop local and systemic recurrence resulting in median overall survival times of 28-54 months. The predominance of systemic recurrence and its impact on survival may lead to the assumption that surgical radicality and local control play only minor roles in the treatment of pancreatic cancer. This review provides an overview of the recent literature on surgical radicality and survival outcome in pancreatic cancer. The current evidence on the extent of lymphadenectomy, the prognostic impact of the extent of lymph node involvement, and the impact of the resection margin status on postresection survival are reviewed. Data from recent studies performed in the context of modern surgery and adjuvant therapy provide good evidence of a considerable impact of local radicality on survival after pancreatic cancer surgery. Surgical techniques that have been developed to refine oncological resections and to increase local control as well as resectability are highlighted. These techniques include artery-first approaches, level-3 dissection with removal of the periarterial nerve plexus, the triangle operation, and extended resections. Local radicality and quality of surgical resection remain among the most important parameters that determine the chances for survival in patients with non-metastatic pancreatic cancer.

4 Review Chemotherapy for pancreatic cancer. 2019

Springfeld, Christoph / Jäger, Dirk / Büchler, Markus W / Strobel, Oliver / Hackert, Thilo / Palmer, Daniel H / Neoptolemos, John P. ·Heidelberg University Hospital, National Center for Tumor Diseases, Department of Medical Oncology, Heidelberg, Germany. Electronic address: christoph.springfeld@med.uni-heidelberg.de. · Heidelberg University Hospital, National Center for Tumor Diseases, Department of Medical Oncology, Heidelberg, Germany. · Heidelberg University Hospital, Department of Surgery, Heidelberg, Germany. · University of Liverpool, Department of Molecular and Clinical Cancer Medicine, Liverpool, UK. ·Presse Med · Pubmed #30879894.

ABSTRACT: Chemotherapy is an important part of multimodality pancreatic cancer treatment. After curative resection, adjuvant chemotherapy can significantly improve disease free survival and overall survival. The current standard of care is six months adjuvant chemotherapy with modified folinic acid, 5-fluorouracil, irinotecan and oxaliplatin (mFOLFIRINOX) in patients fit enough for this protocol, otherwise six months of gemcitabine and capecitabine based on the European Study Group for Pancreatic Cancer (ESPAC)-4 study. In patients with metastatic disease, combination chemotherapy according to the FOLFIRINOX protocol or with gemcitabine plus nab-paclitaxel is an important improvement to gemcitabine monotherapy that was the standard for many years. Patients not fit for combination chemotherapy however may still benefit from gemcitabine. Patients with good performance status may benefit from second-line chemotherapy. Chemoradiation has long been used in locally advanced pancreatic cancer but is now tempered following the LAP07 study. This trial showed no difference in overall survival in those patients with stable disease after four months of gemcitabine (with or without erlotinib) randomized to either continuation of gemcitabine therapy or chemoradiation (54Gy with capecitabine). As an alternative to radiation, other forms local therapies including radiofrequency ablation, irreversible electroporation, high-intensity focused ultrasound, microwave ablation and local anti-KRAS therapy (using siG12D-LODER) are currently under investigation. Given the systemic nature of pancreas cancer from an early stage, the success of any local approach other than complete surgical resection (with adjuvant systemic therapy) is likely to be very limited. In patients with locally advanced, irresectable cancer, chemotherapy may offer the chance for secondary resection with a survival similar to patients with primary resectable disease. Downstaging regimens need to be evaluated in prospective randomized trials in order to make firm recommendations. Selection of patient groups for specific therapy including cytotoxics is becoming a reality using assays based on drug cellular transport and metabolism, and molecular signatures. Going forward, high throughput screening of different chemotherapy agents using molecular signatures based on patients' derived organoids holds considerable promise.

5 Review Optimizing the outcomes of pancreatic cancer surgery. 2019

Strobel, Oliver / Neoptolemos, John / Jäger, Dirk / Büchler, Markus W. ·Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany. · Department of Medical Oncology and Internal Medicine VI, National Center for Tumor Diseases, Heidelberg University Hospital, Heidelberg, Germany. · Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany. markus.buechler@med.uni-heidelberg.de. ·Nat Rev Clin Oncol · Pubmed #30341417.

ABSTRACT: Pancreatic cancer is likely to become the second most frequent cause of cancer-associated mortality within the next decade. Surgical resection with adjuvant systemic chemotherapy currently provides the only chance of long-term survival. However, only 10-20% of patients with pancreatic cancer are diagnosed with localized, surgically resectable disease. The majority of patients present with metastatic disease and are not candidates for surgery, while surgery remains underused even in those with resectable disease owing to historical concerns regarding safety and efficacy. However, advances made over the past decade in the safety and efficacy of surgery have resulted in perioperative mortality of around 3% and 5-year survival approaching 30% after resection and adjuvant chemotherapy. Furthermore, owing to advances in both surgical techniques and systemic chemotherapy, the indications for resection have been extended to include locally advanced tumours. Many aspects of pancreatic cancer surgery, such as the management of postoperative morbidities, sequencing of resection and systemic therapy, and use of neoadjuvant therapy followed by resection for tumours previously considered unresectable, are rapidly evolving. In this Review, we summarize the current status of and new developments in pancreatic cancer surgery, while highlighting the most important research questions for attempts to further optimize outcomes.

6 Review Neoadjuvant and adjuvant chemotherapy in pancreatic cancer. 2018

Klaiber, Ulla / Leonhardt, Carl-Stephan / Strobel, Oliver / Tjaden, Christine / Hackert, Thilo / Neoptolemos, John P. ·Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany. · Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany. john.neoptolemos@med.uni-heidelberg.de. ·Langenbecks Arch Surg · Pubmed #30397779.

ABSTRACT: BACKGROUND: Only 15-20% of patients with pancreatic ductal adenocarcinoma (PDAC) have a resectable tumor at the time of diagnosis. Effective multimodal treatment concepts including neoadjuvant chemotherapy are therefore needed. Following upfront resection, adjuvant chemotherapy has become mandatory to prevent early tumor recurrence. PURPOSE: The aim of this article was to summarize existing evidence on neoadjuvant and adjuvant chemotherapy in PDAC with a focus on high-level evidence based on randomized controlled phase III clinical trials. RESULTS AND CONCLUSIONS: Neoadjuvant chemotherapy represents an emerging concept for borderline resectable and locally advanced PDAC. To date, randomized trials have failed to provide proof-of-concept outcomes, mostly because of failure to achieve recruitment targets. Nevertheless, this approach needs to be further evaluated scientifically as recent data from a large single-arm cohort study showed that neoadjuvant multimodal therapy could achieve a resection rate in the order of 60% of patients with locally advanced PDAC. For patients with a primarily resectable tumor, however, study results remain unconvincing, and therefore, neoadjuvant therapy should not be used routinely outside of a clinical trial. Adjuvant chemotherapy with gemcitabine and capecitabine in unselected patients can double 5-year overall survival to around 30% compared to mono-chemotherapy with either 5-fluorouracil with folinic acid or gemcitabine. In selected patients, adjuvant modified FOLFIRINOX can produce a 5-year survival rate of around 50%. Further potential gains are to be made in the selection of patients for particular therapies based on the transcriptomic and genetic signature of individual tumors.

7 Review Definition and classification of chyle leak after pancreatic operation: A consensus statement by the International Study Group on Pancreatic Surgery. 2017

Besselink, Marc G / van Rijssen, L Bengt / Bassi, Claudio / Dervenis, Christos / Montorsi, Marco / Adham, Mustapha / Asbun, Horacio J / Bockhorn, Maximillian / Strobel, Oliver / Büchler, Markus W / Busch, Olivier R / Charnley, Richard M / Conlon, Kevin C / Fernández-Cruz, Laureano / Fingerhut, Abe / Friess, Helmut / Izbicki, Jakob R / Lillemoe, Keith D / Neoptolemos, John P / Sarr, Michael G / Shrikhande, Shailesh V / Sitarz, Robert / Vollmer, Charles M / Yeo, Charles J / Hartwig, Werner / Wolfgang, Christopher L / Gouma, Dirk J / Anonymous1010883. ·Department of Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. Electronic address: m.g.besselink@amc.nl. · Department of Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. · Department of Surgery and Oncology, Pancreas Institute, University of Verona, Verona, Italy. · Department of First Surgery, Agia Olga Hospital, Athens, Greece. · Department of Surgery, Humanitas Research Hospital and University, Milan, Italy. · Department of HPB Surgery, Hopital Edouard Herriot, HCL, UCBL1, Lyon, France. · Department of Surgery, Mayo Clinic, Jacksonville, FL. · Department of General-, Visceral-, and Thoracic-Surgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany. · Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany. · Department of HPB & Transplant Surgery, Freeman Hospital, Newcastle upon Tyne, UK. · Professorial Surgical Unit, University of Dublin, Trinity College, Dublin, Ireland. · Department of Surgery, Clinic Hospital of Barcelona, University of Barcelona, Barcelona, Spain. · First Department of Digestive Surgery, Hippokrateon Hospital, University of Athens, Athens, Greece; Section for Surgical Research, Department of Surgery, Medical University of Graz, Graz, Austria. · Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. · Department of Surgery, Massachusetts General Hospital and the Harvard Medical School, Boston, MA. · Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK. · Division of Subspecialty General Surgery, Mayo Clinic, Rochester, MN. · Department of GI and HPB Surgical Oncology, Tata Memorial Hospital, Mumbai, India. · Department of Surgical Oncology, Medical University in Lublin, Poland. · Department of Surgery, Penn Medicine, The University of Pennsylvania, Philadelphia, PA. · Department of Surgery, Jefferson Pancreas, Biliary and Related Cancer Center, Thomas Jefferson University, Philadelphia, PA. · Division of Pancreatic Surgery, Department of General, Visceral, and Transplantation Surgery, Ludwig Maximilians University, University of Munich, Germany. · Department of Surgery, Johns Hopkins Medicine, Baltimore, MD. ·Surgery · Pubmed #27692778.

ABSTRACT: BACKGROUND: Recent literature suggests that chyle leak may complicate up to 10% of pancreatic resections. Treatment depends on its severity, which may include chylous ascites. No international consensus definition or grading system of chyle leak currently is available. METHODS: The International Study Group on Pancreatic Surgery, an international panel of pancreatic surgeons working in well-known, high-volume centers, reviewed the literature and worked together to establish a consensus on the definition and classification of chyle leak after pancreatic operation. RESULTS: Chyle leak was defined as output of milky-colored fluid from a drain, drain site, or wound on or after postoperative day 3, with a triglyceride content ≥110 mg/dL (≥1.2 mmol/L). Three different grades of severity were defined according to the management needed: grade A, no specific intervention other than oral dietary restrictions; grade B, prolongation of hospital stay, nasoenteral nutrition with dietary restriction, total parenteral nutrition, octreotide, maintenance of surgical drains, or placement of new percutaneous drains; and grade C, need for other more invasive in-hospital treatment, intensive care unit admission, or mortality. CONCLUSION: This classification and grading system for chyle leak after pancreatic resection allows for comparison of outcomes between series. As with the other the International Study Group on Pancreatic Surgery consensus statements, this classification should facilitate communication and evaluation of different approaches to the prevention and treatment of this complication.

8 Review [Therapy of locally advanced pancreatic cancer with FOLFIRINOX]. 2016

Strobel, O / Büchler, M W. ·Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universität Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Deutschland. Oliver.Strobel@med.uni-heidelberg.de. · Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universität Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Deutschland. ·Chirurg · Pubmed #27418266.

ABSTRACT: -- No abstract --

9 Review Sonic Hedgehog in pancreatic cancer: from bench to bedside, then back to the bench. 2012

Rosow, David E / Liss, Andrew S / Strobel, Oliver / Fritz, Stefan / Bausch, Dirk / Valsangkar, Nakul P / Alsina, Janivette / Kulemann, Birte / Park, Joo Kyung / Yamaguchi, Junpei / LaFemina, Jennifer / Thayer, Sarah P. ·Pancreatic Biology Laboratory, Department of Surgery, Massachusetts General Hospital, Boston, MA, USA. ·Surgery · Pubmed #22770959.

ABSTRACT: -- No abstract --

10 Clinical Trial Sphincter of Oddi botulinum toxin injection to prevent pancreatic fistula after distal pancreatectomy. 2017

Hackert, Thilo / Klaiber, Ulla / Hinz, Ulf / Kehayova, Tzveta / Probst, Pascal / Knebel, Phillip / Diener, Markus K / Schneider, Lutz / Strobel, Oliver / Michalski, Christoph W / Ulrich, Alexis / Sauer, Peter / Büchler, Markus W. ·Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany. · Interdisciplinary Center of Endoscopy, University of Heidelberg, Heidelberg, Germany. · Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany. Electronic address: markus.buechler@med.uni-heidelberg.de. ·Surgery · Pubmed #27865590.

ABSTRACT: BACKGROUND: Postoperative pancreatic fistula represents the most important complication after distal pancreatectomy. The aim of this study was to evaluate the use of a preoperative endoscopic injection of botulinum toxin into the sphincter of Oddi to prevent postoperative pancreatic fistula (German Clinical Trials Register number: DRKS00007885). METHODS: This was an investigator-initiated, prospective clinical phase I/II trial with an exploratory study design. We included patients who underwent preoperative endoscopic sphincter botulinum toxin injection (100 units of Botox). End points were the feasibility, safety, and postoperative outcomes, including postoperative pancreatic fistula within 30 days after distal pancreatectomy. Botulinum toxin patients were compared with a control collective of patients undergoing distal pancreatectomy without botulinum toxin injection by case-control matching in a 1:1 ratio. RESULTS: Between February 2015 and February 2016, 29 patients were included. All patients underwent successful sphincter of Oddi botulinum toxin injection within a median of 6 (range 0-10) days before operation. One patient had an asymptomatic, self-limiting (48 hours) increase in serum amylase and lipase after injection. Distal pancreatectomy was performed in 24/29 patients; 5 patients were not resectable. Of the patients receiving botulinum toxin, 7 (29%) had increased amylase levels in drainage fluid on postoperative day 3 (the International Study Group of Pancreatic Surgery definition of postoperative pancreatic fistula grade A) without symptoms or need for reintervention. Importantly, no clinically relevant fistulas (International Study Group of Pancreatic Surgery grades B/C) were observed in botulinum toxin patients compared to 33% postoperative pancreatic fistula grade B/C in case-control patients (P < .004). CONCLUSION: Preoperative sphincter of Oddi botulinum toxin injection is a novel and safe approach to decrease the incidence of clinically relevant postoperative pancreatic fistula after distal pancreatectomy. The results of the present trial suggest its efficacy in the prevention of clinically relevant postoperative pancreatic fistula and are validated currently in the German Federal Government-sponsored, multicenter, randomized controlled PREBOT trial.

11 Article Pancreatic resection for cancer-the Heidelberg technique. 2019

Schneider, Martin / Strobel, Oliver / Hackert, Thilo / Büchler, Markus W. ·Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld 110, D-69120, Heidelberg, Germany. · Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld 110, D-69120, Heidelberg, Germany. markus.buechler@med.uni-heidelberg.de. ·Langenbecks Arch Surg · Pubmed #31728630.

ABSTRACT: BACKGROUND: Pancreatic cancer is associated with high recurrence rates, and any surgery should aim to prevent local recurrence. However, systematic resection of putatively tumor-infiltrated soft tissue adjacent to the celiac branches and superior mesenteric artery has not regularly been applied in pancreatic head resection. OBJECTIVE: We describe a technique of vessel-oriented pancreatic head resection, allowing for extended removal of lymphatic and neural tissue that is situated in the TRIANGLE in between the celiac trunk, the superior mesenteric artery, and the portal vein. CONCLUSIONS: Vessel-oriented dissection or vascular resection facilitates complete removal of putatively tumor-infiltrated soft tissue, thus potentially reducing the risk of isolated local recurrence in pancreatic cancer.

12 Article Immunohistochemical profiling of liver metastases and matched-pair analysis in patients with metastatic pancreatic ductal adenocarcinoma. 2019

Held, Thomas / Verbeke, Caroline S / Strobel, Oliver / Rutkowski, Wiktor / Villard, Christina / Moro, Carlos Fernández / Del Chiaro, Marco / Büchler, Markus / Heuchel, Rainer / Löhr, Matthias. ·Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany; Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany; National Center for Tumor Diseases (NCT), Heidelberg, Germany; Pancreas Cancer Research Lab, Department of Clinical Intervention and Technology (CLINTEC), Karolinska Institute, Stockholm, Sweden. Electronic address: thomas.held@med.uni-heidelberg.de. · Department of Pathology, Karolinska University Hospital, Stockholm, Sweden; Institute of Clinical Medicine, University of Oslo, Oslo, Norway. Electronic address: c.s.verbeke@medisin.uio.no. · Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany. Electronic address: oliver.strobel@med.uni-heidelberg.de. · Pancreas Cancer Research Lab, Department of Clinical Intervention and Technology (CLINTEC), Karolinska Institute, Stockholm, Sweden. Electronic address: wiktor.rutkowski@stud.ki.se. · Department of Cancer, Karolinska University Hospital, Stockholm, Sweden. Electronic address: christina.villard@sll.se. · Department of Pathology, Karolinska University Hospital, Stockholm, Sweden. Electronic address: carlos.fernandez.moro@ki.se. · Department of Cancer, Karolinska University Hospital, Stockholm, Sweden. Electronic address: marco.del.chiaro@ki.se. · Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany. Electronic address: markus.buechler@med.uni-heidelberg.de. · Pancreas Cancer Research Lab, Department of Clinical Intervention and Technology (CLINTEC), Karolinska Institute, Stockholm, Sweden. Electronic address: rainer.heuchel@ki.se. · Pancreas Cancer Research Lab, Department of Clinical Intervention and Technology (CLINTEC), Karolinska Institute, Stockholm, Sweden; Department of Cancer, Karolinska University Hospital, Stockholm, Sweden. Electronic address: matthias.lohr@ki.se. ·Pancreatology · Pubmed #31542399.

ABSTRACT: BACKGROUND: The purpose of the current study was to investigate the immunohistochemical (IHC) profile of liver metastases (LM) in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: Expression of 15 IHC markers in liver biopsies from 77 patients with PDAC, who were diagnosed between 2010 and 2014, were evaluated. In a separate subgroup analysis (n = 12), paired samples (LM and primary tumor) from the same patient were investigated for IHC profile differences. RESULTS: LM samples were classified as pancreatobiliary-type (PB-type) in 72 patients (93.5%), intestinal-type (INT-type) in four patients (5.2%), and squamous in one patient (1.3%). There was no significant difference in overall survival (OS) between LM of the PB-type or INT-type (p = 0.097). In a multivariate analysis, age <70 years (p = 0.047), absence of SMAD4 mutation (p = 0.026), absence of CDX2 expression (p = 0.003), and well to moderate differentiation were significant prognostic factors for better OS in patients with LM (p = 0.031). Analysis of paired tissue samples from LM and the primary tumor revealed a difference in CDX2 (50% increase, p = 0.125) and SMAD4 (33% loss of SMAD4, p = 0.375). CONCLUSIONS: CDX2 expression and SMAD4 mutation indicate a poor outcome in patients with LM of PDAC. Matched-pair analysis revealed differences in distinct IHC marker expression.

13 Article [Progress in neoadjuvant therapy for locally advanced pancreatic cancer]. 2019

Strobel, O / Büchler, M W. ·Klinik für Allgemein‑, Viszeral- und Transplantationschirurgie, Universität Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Deutschland. Oliver.Strobel@med.uni-heidelberg.de. · Klinik für Allgemein‑, Viszeral- und Transplantationschirurgie, Universität Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Deutschland. ·Chirurg · Pubmed #31286168.

ABSTRACT: -- No abstract --

14 Article [Laparoscopic pancreatoduodenectomy: risk without benefits?] 2019

Strobel, O / Büchler, M W. ·Klinik für Allgemein‑, Viszeral- und Transplantationschirurgie, Universität Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Deutschland. Oliver.Strobel@med.uni-heidelberg.de. · Klinik für Allgemein‑, Viszeral- und Transplantationschirurgie, Universität Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Deutschland. ·Chirurg · Pubmed #31065768.

ABSTRACT: -- No abstract --

15 Article Systematic Generation of Patient-Derived Tumor Models in Pancreatic Cancer. 2019

Ehrenberg, Karl Roland / Gao, Jianpeng / Oppel, Felix / Frank, Stephanie / Kang, Na / Dieter, Sebastian M / Herbst, Friederike / Möhrmann, Lino / Dubash, Taronish D / Schulz, Erik R / Strakerjahn, Hendrik / Giessler, Klara M / Weber, Sarah / Oberlack, Ava / Rief, Eva-Maria / Strobel, Oliver / Bergmann, Frank / Lasitschka, Felix / Weitz, Jürgen / Glimm, Hanno / Ball, Claudia R. ·Translational Functional Cancer Genomics, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. roland.ehrenberg@nct-heidelberg.de. · Department of Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg, 69120 Heidelberg, Germany. roland.ehrenberg@nct-heidelberg.de. · Translational Functional Cancer Genomics, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. gjp01891@rjh.com.cn. · Translational Functional Cancer Genomics, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. felix.oppel@klinikumbielefeld.de. · Translational Functional Cancer Genomics, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. stephanie.frank@nct-heidelberg.de. · Translational Functional Cancer Genomics, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. na.kang@nct-heidelberg.de. · Translational Functional Cancer Genomics, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. sebastian.dieter@nct-heidelberg.de. · German Consortium for Translational Cancer Research (DKTK) Heidelberg, 69120 Heidelberg, Germany. sebastian.dieter@nct-heidelberg.de. · Translational Functional Cancer Genomics, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. friederike.herbst@nct-heidelberg.de. · Department of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Dresden and German Cancer Research Center (DKFZ), 01309 Dresden, Germany. lino.moehrmann@nct-dresden.de. · Center for Personalized Oncology, University Hospital Carl Gustav Carus Dresden at TU Dresden, 01307 Dresden, Germany. lino.moehrmann@nct-dresden.de. · Translational Functional Cancer Genomics, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. tdubash@mgh.harvard.edu. · Translational Functional Cancer Genomics, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. erik.schulz@med.uni-heidelberg.de. · Translational Functional Cancer Genomics, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. strakerjahn@stud.uni-heidelberg.de. · Translational Functional Cancer Genomics, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. klara.giessler@gmx.de. · Translational Functional Cancer Genomics, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. weber.sarah@mail.de. · Translational Functional Cancer Genomics, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. ava.oberlack@googlemail.com. · Department of General Surgery, Heidelberg University Hospital, 69120 Heidelberg, Germany. oliver.strobel@med.uni-heidelberg.de. · Institute of Pathology, Heidelberg University Hospital, 69120 Heidelberg, Germany. frank.bergmann@med.uni-heidelberg.de. · Institute of Pathology, Heidelberg University Hospital, 69120 Heidelberg, Germany. felix.lasitschka@med.uni-heidelberg.de. · Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus Dresden at TU Dresden, 01307 Dresden, Germany. juergen.weitz@uniklinikum-dresden.de. · Translational Functional Cancer Genomics, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. hanno.glimm@nct-dresden.de. · Department of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Dresden and German Cancer Research Center (DKFZ), 01309 Dresden, Germany. hanno.glimm@nct-dresden.de. · Center for Personalized Oncology, University Hospital Carl Gustav Carus Dresden at TU Dresden, 01307 Dresden, Germany. hanno.glimm@nct-dresden.de. · German Consortium for Translational Cancer Research (DKTK) Dresden, 01307 Dresden, Germany. hanno.glimm@nct-dresden.de. · Department of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Dresden and German Cancer Research Center (DKFZ), 01309 Dresden, Germany. claudia.ball@nct-dresden.de. ·Cells · Pubmed #30744205.

ABSTRACT: In highly aggressive malignancies like pancreatic cancer (PC), patient-derived tumor models can serve as disease-relevant models to understand disease-related biology as well as to guide clinical decision-making. In this study, we describe a two-step protocol allowing systematic establishment of patient-derived primary cultures from PC patient tumors. Initial xenotransplantation of surgically resected patient tumors (n = 134) into immunodeficient mice allows for efficient in vivo expansion of vital tumor cells and successful tumor expansion in 38% of patient tumors (51/134). Expansion xenografts closely recapitulate the histoarchitecture of their matching patients' primary tumors. Digestion of xenograft tumors and subsequent in vitro cultivation resulted in the successful generation of semi-adherent PC cultures of pure epithelial cell origin in 43.1% of the cases. The established primary cultures include diverse pathological types of PC: Pancreatic ductal adenocarcinoma (86.3%, 19/22), adenosquamous carcinoma (9.1%, 2/22) and ductal adenocarcinoma with oncocytic IPMN (4.5%, 1/22). We here provide a protocol to establish quality-controlled PC patient-derived primary cell cultures from heterogeneous PC patient tumors. In vitro preclinical models provide the basis for the identification and preclinical assessment of novel therapeutic opportunities targeting pancreatic cancer.

16 Article Germline BRCA2 K3326X and CHEK2 I157T mutations increase risk for sporadic pancreatic ductal adenocarcinoma. 2019

Obazee, O / Archibugi, L / Andriulli, A / Soucek, P / Małecka-Panas, E / Ivanauskas, A / Johnson, T / Gazouli, M / Pausch, T / Lawlor, R T / Cavestro, G M / Milanetto, A C / Di Leo, M / Pasquali, C / Hegyi, P / Szentesi, A / Radu, C E / Gheorghe, C / Theodoropoulos, G E / Bergmann, F / Brenner, H / Vodickova, L / Katzke, V / Campa, D / Strobel, O / Kaiser, J / Pezzilli, R / Federici, F / Mohelnikova-Duchonova, B / Boggi, U / Lemstrova, R / Johansen, J S / Bojesen, S E / Chen, I / Jensen, B V / Capurso, G / Pazienza, V / Dervenis, C / Sperti, C / Mambrini, A / Hackert, T / Kaaks, R / Basso, D / Talar-Wojnarowska, R / Maiello, E / Izbicki, J R / Cuk, K / Saum, K U / Cantore, M / Kupcinskas, J / Palmieri, O / Delle Fave, G / Landi, S / Salvia, R / Fogar, P / Vashist, Y K / Scarpa, A / Vodicka, P / Tjaden, C / Iskierka-Jazdzewska, E / Canzian, F. ·Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Digestive and Liver Disease Unit, Pancreatic Disorders Clinic, S. Andrea Hospital, University of Sapienza, Rome, Italy. · Pancreatico/Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy. · Division of Gastroenterology and Research Laboratory, Department of Oncology, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy. · Laboratory of Pharmacogenomics, Biomedical Centre, Faculty of Medicine in Plzen, Charles University in Prague, Plzen, Czech Republic. · Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland. · Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania. · Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Department of Basic Medical Sciences, Laboratory of Biology, Medical School National and Kapodistrian University of Athens, Athens, Greece. · Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Heidelberg, Germany. · ARC-Net, Applied Research on Cancer Centre, University of Verona, Verona, Italy. · Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy. · Department of Surgery, Oncology and Gastroenterology -DiSCOG, University of Padova, Padova, Italy. · Institute for Translational Medicine and 1st Department of Medicine, University of Pécs, Pécs, Hungary. · Fundeni Clinical Institute, Bucharest, Romania. · First Propaedeutic Surgical Department, "Hippocratio" General Hospital Athens Medical School, National and Kapodistrian University of Athens, Athens, Greece. · Pathologisches Institut der Universität Heidelberg, Heidelberg, Germany. · Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany. · German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. · Institute of Biology and Medical Genetics, 1st Medical Faculty, Charles University, Prague and Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Prague, Czech Republic. · Dipartimento di Biologia, Università di Pisa, Pisa, Italy. · Pancreas Unit, Department of Digestive System, Sant'Orsola-Malpighi Hospital, Bologna, Italy. · Department of Massa Carrara Oncological, Azienda USL Toscana Nord Ovest, Carrara, Italy. · Department of Oncology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic. · Division of General and Transplant Surgery, Pisa University Hospital, Pisa, Italy. · Department of Oncology, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark. · Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark. · Department of Surgery, Konstantopouleion General Hospital of Athens, Athens, Greece. · Department of Laboratory Medicine, University-Hospital of Padova, Padova, Italy. · Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. · Department of Surgery, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy. · Section for Visceral Surgery, Department of Surgery, Kantonsspital Aarau AG, Aarau, Switzerland. · Institute of Experimental Medicine, Czech Academy of Science, Prague and Institute of Biology and Medical Genetics, 1st Medical Faculty, Charles University, Prague, Czech Republic. · Department of Hematology, Medical University of Lodz, Lodz, Poland. ·Int J Cancer · Pubmed #30672594.

ABSTRACT: Rare truncating BRCA2 K3326X (rs11571833) and pathogenic CHEK2 I157T (rs17879961) variants have previously been implicated in familial pancreatic ductal adenocarcinoma (PDAC), but not in sporadic cases. The effect of both mutations in important DNA repair genes on sporadic PDAC risk may shed light on the genetic architecture of this disease. Both mutations were genotyped in germline DNA from 2,935 sporadic PDAC cases and 5,626 control subjects within the PANcreatic Disease ReseArch (PANDoRA) consortium. Risk estimates were evaluated using multivariate unconditional logistic regression with adjustment for possible confounders such as sex, age and country of origin. Statistical analyses were two-sided with p values <0.05 considered significant. K3326X and I157T were associated with increased risk of developing sporadic PDAC (odds ratio (OR

17 Article Dexamethasone-induced inhibition of miR-132 via methylation promotes TGF-β-driven progression of pancreatic cancer. 2019

Abukiwan, Alia / Nwaeburu, Clifford C / Bauer, Nathalie / Zhao, Zhefu / Liu, Li / Gladkich, Jury / Gross, Wolfgang / Benner, Axel / Strobel, Oliver / Fellenberg, Jörg / Herr, Ingrid. ·Molecular Oncosurgery, Section of Surgical Research, University of Heidelberg, 69120 Heidelberg, Germany. · Department of Biostatistics, German Cancer Research Center (DKFZ), University of Heidelberg, 69120 Heidelberg, Germany. · Department of General, Visceral and Transplant Surgery, University of Heidelberg, 69120 Heidelberg, Germany. · Orthopedics and Trauma Surgery, Experimental Orthopedics, University of Heidelberg, 69120 Heidelberg, Germany. ·Int J Oncol · Pubmed #30387838.

ABSTRACT: Glucocorticoids (GCs) such as dexamethasone (DEX) are administered as cancer co‑treatment for palliative purposes due to their pro‑apoptotic effects in lymphoid cancer and limited side effects associated with cancer growth and chemotherapy. However, there is emerging evidence that GCs induce therapy resistance in most epithelial tumors. Our recent data reveal that DEX promotes the progression of pancreatic ductal adenocarcinoma (PDA). In the present study, we examined 1 primary and 2 established PDA cell lines, and 35 PDA tissues from patients who had received (n=14) or not received (n=21) GCs prior to surgery. Through microRNA microarray analysis, in silico, and RT‑qPCR analyses, we identified 268 microRNAs differentially expressed between DEX‑treated and untreated cells. With a focus on cancer progression, we selected miR‑132 and its target gene, transforming growth factor-β2 (TGF‑β2), as top candidates. miR‑132 mimics directly bound to the 3' untranslated region (3'UTR) of a TGF‑β2 luciferase construct and enhanced expression, as shown by increased luciferase activity. By contrast, DEX inhibited miR‑132 expression via promoter methylation. miR‑132 mimics also reduced DEX‑induced clonogenicity, migration and expression of vimentin and E‑cadherin in vitro and in tumor xenografts. In patients, GC intake prior to surgery enhanced global hypermethylation and expression of TGF‑β2 in tissues; expression of miR‑132 was detected but could not be quantified. Our results demonstrate that DEX‑mediated inhibition of miR‑132 is a key mediator in the progression of pancreatic cancer, and the findings provide a foundation for miRNA‑based therapies.

18 Article Genetic determinants of telomere length and risk of pancreatic cancer: A PANDoRA study. 2019

Campa, Daniele / Matarazzi, Martina / Greenhalf, William / Bijlsma, Maarten / Saum, Kai-Uwe / Pasquali, Claudio / van Laarhoven, Hanneke / Szentesi, Andrea / Federici, Francesca / Vodicka, Pavel / Funel, Niccola / Pezzilli, Raffaele / Bueno-de-Mesquita, H Bas / Vodickova, Ludmila / Basso, Daniela / Obazee, Ofure / Hackert, Thilo / Soucek, Pavel / Cuk, Katarina / Kaiser, Jörg / Sperti, Cosimo / Lovecek, Martin / Capurso, Gabriele / Mohelnikova-Duchonova, Beatrice / Khaw, Kay-Tee / König, Anna-Katharina / Kupcinskas, Juozas / Kaaks, Rudolf / Bambi, Franco / Archibugi, Livia / Mambrini, Andrea / Cavestro, Giulia Martina / Landi, Stefano / Hegyi, Péter / Izbicki, Jakob R / Gioffreda, Domenica / Zambon, Carlo Federico / Tavano, Francesca / Talar-Wojnarowska, Renata / Jamroziak, Krzysztof / Key, Timothy J / Fave, Gianfranco Delle / Strobel, Oliver / Jonaitis, Laimas / Andriulli, Angelo / Lawlor, Rita T / Pirozzi, Felice / Katzke, Verena / Valsuani, Chiara / Vashist, Yogesh K / Brenner, Hermann / Canzian, Federico. ·Department of Biology, University of Pisa, Pisa, Italy. · Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Institute for Health Research Liverpool Pancreas Biomedical Research Unit, University of Liverpool, Liverpool, United Kingdom. · Medical Oncology, Academic Medical Centre, Amsterdam, The Netherlands. · Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Pancreatic and Digestive Endocrine Surgery - Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padova, Padova, Italy. · Institute for Translational Medicine, University of Pécs, Pécs, Hungary. · First Department of Medicine, University of Szeged, Szeged, Hungary. · Oncological Department, Azienda USL Toscana Nord Ovest, Oncological Unit of Massa Carrara, Carrara, Italy. · Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Science of Czech Republic, Prague, Czech Republic. · Institute of Biology and Medical Genetics, 1st Medical Faculty, Charles University, Prague, Czech Republic. · Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic. · Department of Surgery, Unit of Experimental Surgical Pathology, University of Pisa, Pisa, Italy. · Pancreas Unit, Department of Digestive System, Sant'Orsola-Malpighi Hospital, Bologna, Italy. · Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. · Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands. · Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, United Kingdom. · Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. · Department of Laboratory Medicine, University-Hospital of Padova, Padua, Italy. · Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany. · Third Surgical Clinic - Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padova, Padova, Italy. · Department of Surgery I, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic. · Digestive and Liver Disease Unit, S. Andrea Hospital, 'Sapienza' University, Rome, Italy. · PancreatoBiliary Endoscopy and EUS Division, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Vita Salute San Raffaele University, Milan, Italy. · Department of Oncology, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic. · University of Cambridge School of Clinical Medicine Clinical Gerontology Unit, Addenbrooke's Hospital, Cambridge, United Kingdom. · Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania. · Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Blood Transfusion Service, Azienda Ospedaliero-Universitaria Meyer, Florence, Italy. · Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan, Italy. · MTA-SZTE Momentum Translational Gastroenterology Research Group, Szeged, Hungary. · Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. · Division of Gastroenterology and Molecular Biology Lab, IRCCS Ospedale Casa Sollievo Sofferenza, San Giovanni Rotondo, Italy. · Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland. · Institute of Hematology and Transfusion Medicine, Warsaw, Poland. · Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. · ARC-NET, University and Hospital Trust of Verona, Verona, Italy. · Division of Abdominal Surgery, IRCCS Ospedale Casa Sollievo Sofferenza, San Giovanni Rotondo, Italy. · Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany. · German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. ·Int J Cancer · Pubmed #30325019.

ABSTRACT: Telomere deregulation is a hallmark of cancer. Telomere length measured in lymphocytes (LTL) has been shown to be a risk marker for several cancers. For pancreatic ductal adenocarcinoma (PDAC) consensus is lacking whether risk is associated with long or short telomeres. Mendelian randomization approaches have shown that a score built from SNPs associated with LTL could be used as a robust risk marker. We explored this approach in a large scale study within the PANcreatic Disease ReseArch (PANDoRA) consortium. We analyzed 10 SNPs (ZNF676-rs409627, TERT-rs2736100, CTC1-rs3027234, DHX35-rs6028466, PXK-rs6772228, NAF1-rs7675998, ZNF208-rs8105767, OBFC1-rs9420907, ACYP2-rs11125529 and TERC-rs10936599) alone and combined in a LTL genetic score ("teloscore", which explains 2.2% of the telomere variability) in relation to PDAC risk in 2,374 cases and 4,326 controls. We identified several associations with PDAC risk, among which the strongest were with the TERT-rs2736100 SNP (OR = 1.54; 95%CI 1.35-1.76; p = 1.54 × 10

19 Article The Impact of Positive Resection Margins on Survival and Recurrence Following Resection and Adjuvant Chemotherapy for Pancreatic Ductal Adenocarcinoma. 2019

Ghaneh, Paula / Kleeff, Jorg / Halloran, Christopher M / Raraty, Michael / Jackson, Richard / Melling, James / Jones, Owain / Palmer, Daniel H / Cox, Trevor F / Smith, Chloe J / O'Reilly, Derek A / Izbicki, Jakob R / Scarfe, Andrew G / Valle, Juan W / McDonald, Alexander C / Carter, Ross / Tebbutt, Niall C / Goldstein, David / Padbury, Robert / Shannon, Jennifer / Dervenis, Christos / Glimelius, Bengt / Deakin, Mark / Anthoney, Alan / Lerch, Markus M / Mayerle, Julia / Oláh, Attila / Rawcliffe, Charlotte L / Campbell, Fiona / Strobel, Oliver / Büchler, Markus W / Neoptolemos, John P / Anonymous291017. ·Liverpool Cancer Research U.K. Cancer Trials Unit, University of Liverpool, Liverpool, United Kingdom University of Liverpool, Liverpool, UK. · The Department of Surgery, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK. · Department of Surgery, Manchester Royal Infirmary, Manchester, UK. · Department of Surgery, University of Hamburg Medical institutions UKE, Hamburg, Germany. · Department of Oncology Division of Medical Oncology 2228 Cross Cancer Institute and University of Alberta, Canada. · Department of Medical Oncology , The Christie, Manchester, UK. · Department of Medical Oncology, The Beatson West of Scotland Cancer Centre, Glasgow, Scotland, UK. · Department of Surgery, Glasgow Royal Infirmary, Glasgow, Scotland, UK. · Department of Medical Oncology, Austin Health, Melbourne, Australia. · Department of Medical Oncology, Prince of Wales hospital and Clinical School University of New South Wales, Australia. · Department of Surgery, Flinders Medical Centre, Adelaide, South Australia. · Department of Medical Oncology, Nepean Cancer Centre and University of Sydney, Australia. · Department of Surgery, The Agia Olga Hospital, Athens, Greece. · Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology, Uppsala Clinical Research Center, Uppsala, Sweden. · Department of Surgery, University Hospital, North Staffordshire, UK. · Division of Oncology at the University of Leeds, St James's University Hospital, Leeds, UK. · Department of Medicine A, University Medicine Greifswald, Greifswald, Germany. · Department of Surgery, The Petz Aladar Hospital, Gyor, Hungary. · Department of Pathology, The Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK. · The Department of Surgery, University of Heidelberg, Heidelberg, Germany. ·Ann Surg · Pubmed #29068800.

ABSTRACT: OBJECTIVE AND BACKGROUND: Local and distant disease recurrence are frequently observed following pancreatic cancer resection, but an improved understanding of resection margin assessment is required to aid tailored therapies. METHODS: Analyses were carried out to assess the association between clinical characteristics and margin involvement as well as the effects of individual margin involvement on site of recurrence and overall and recurrence-free survival using individual patient data from the European Study Group for Pancreatic Cancer (ESPAC)-3 randomized controlled trial. RESULTS: There were 1151 patients, of whom 505 (43.9%) had an R1 resection. The median and 95% confidence interval (CI) overall survival was 24.9 (22.9-27.2) months for 646 (56.1%) patients with resection margin negative (R0 >1 mm) tumors, 25.4 (21.6-30.4) months for 146 (12.7%) patients with R1<1 mm positive resection margins, and 18.7 (17.2-21.1) months for 359 (31.2%) patients with R1-direct positive margins (P < 0.001). In multivariable analysis, overall R1-direct tumor margins, poor tumor differentiation, positive lymph node status, WHO performance status ≥1, maximum tumor size, and R1-direct posterior resection margin were all independently significantly associated with reduced overall and recurrence-free survival. Competing risks analysis showed that overall R1-direct positive resection margin status, positive lymph node status, WHO performance status 1, and R1-direct positive superior mesenteric/medial margin resection status were all significantly associated with local recurrence. CONCLUSIONS: R1-direct resections were associated with significantly reduced overall and recurrence-free survival following pancreatic cancer resection. Resection margin involvement was also associated with an increased risk for local recurrence.

20 Article [mFOLFIRINOX for adjuvant therapy of pancreatic cancer]. 2018

Strobel, O / Büchler, M W. ·Klinik für Allgemein‑, Viszeral- und Transplantationschirurgie, Universität Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Deutschland. Oliver.Strobel@med.uni-heidelberg.de. · Klinik für Allgemein‑, Viszeral- und Transplantationschirurgie, Universität Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Deutschland. ·Chirurg · Pubmed #30357431.

ABSTRACT:

21 Article None 2018

Heining, Christoph / Horak, Peter / Uhrig, Sebastian / Codo, Paula L / Klink, Barbara / Hutter, Barbara / Fröhlich, Martina / Bonekamp, David / Richter, Daniela / Steiger, Katja / Penzel, Roland / Endris, Volker / Ehrenberg, Karl Roland / Frank, Stephanie / Kleinheinz, Kortine / Toprak, Umut H / Schlesner, Matthias / Mandal, Ranadip / Schulz, Lothar / Lambertz, Helmut / Fetscher, Sebastian / Bitzer, Michael / Malek, Nisar P / Horger, Marius / Giese, Nathalia A / Strobel, Oliver / Hackert, Thilo / Springfeld, Christoph / Feuerbach, Lars / Bergmann, Frank / Schröck, Evelin / von Kalle, Christof / Weichert, Wilko / Scholl, Claudia / Ball, Claudia R / Stenzinger, Albrecht / Brors, Benedikt / Fröhling, Stefan / Glimm, Hanno. ·Department of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Dresden, Dresden, Germany. · University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany. · German Cancer Research Center (DKFZ), Heidelberg, Germany. · German Cancer Consortium (DKTK), Dresden, Germany. · Department of Translational Oncology, National Center for Tumor Diseases (NCT) Heidelberg and DKFZ, Heidelberg, Germany. · Section for Personalized Oncology, Heidelberg University Hospital, Heidelberg, Germany. · DKTK, Heidelberg, Germany. · Division of Applied Bioinformatics, DKFZ and NCT Heidelberg, Heidelberg, Germany. · Faculty of Biosciences, Heidelberg University, Heidelberg, Germany. · Translational Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg, Germany. · Institute for Clinical Genetics, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany. · National Center for Tumor Diseases (NCT) Dresden, Dresden, Germany. · Division of Radiology, DKFZ, Heidelberg, Germany. · Institute of Pathology, Technical University Munich, Munich, Germany. · DKTK, Munich, Germany. · Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany. · Department of Medical Oncology, NCT, Heidelberg, Germany. · Division of Theoretical Bioinformatics, DKFZ, Heidelberg, Germany. · Department for Bioinformatics and Functional Genomics, Institute for Pharmacy and Molecular Biotechnology and BioQuant, Heidelberg University, Heidelberg, Germany. · Bioinformatics and Omics Data Analytics, DKFZ, Heidelberg, Germany. · Division of Applied Functional Genomics, DKFZ, Heidelberg, Germany. · Department of Oncology, Klinikum Garmisch-Partenkirchen, Garmisch-Partenkirchen, Germany. · Department of Oncology, Sana Kliniken Lübeck, Lübeck, Germany. · Department of Gastroenterology, Hepatology and Infectious Diseases, Tübingen University Hospital, Tübingen, Germany. · DKTK, Tübingen, Germany. · Department of Radiology, Tübingen University Hospital, Tübingen, Germany. · Department of Surgery, Heidelberg University Hospital, Heidelberg, Germany. · DKFZ-Heidelberg Center for Personalized Oncology (HIPO), Heidelberg, Germany. · Department of Translational Oncology, National Center for Tumor Diseases (NCT) Heidelberg and DKFZ, Heidelberg, Germany. hanno.glimm@nct-dresden.de stefan.froehling@nct-heidelberg.de. · Department of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Dresden, Dresden, Germany. hanno.glimm@nct-dresden.de stefan.froehling@nct-heidelberg.de. ·Cancer Discov · Pubmed #29802158.

ABSTRACT: We used whole-genome and transcriptome sequencing to identify clinically actionable genomic alterations in young adults with pancreatic ductal adenocarcinoma (PDAC). Molecular characterization of 17 patients with PDAC enrolled in a precision oncology program revealed gene fusions amenable to pharmacologic inhibition by small-molecule tyrosine kinase inhibitors in all patients with

22 Article [Artery-first approach for partial pancreatoduodenectomy]. 2018

Strobel, O / Büchler, M W. ·Klinik für Allgemein‑, Viszeral- und Transplantationschirurgie, Universität Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Deutschland. Oliver.Strobel@med.uni-heidelberg.de. · Klinik für Allgemein‑, Viszeral- und Transplantationschirurgie, Universität Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Deutschland. ·Chirurg · Pubmed #29766212.

ABSTRACT: -- No abstract --

23 Article Validation of at least 1 mm as cut-off for resection margins for pancreatic adenocarcinoma of the body and tail. 2018

Hank, T / Hinz, U / Tarantino, I / Kaiser, J / Niesen, W / Bergmann, F / Hackert, T / Büchler, M W / Strobel, O. ·Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany. · Institute of Pathology, University of Heidelberg, Heidelberg, Germany. ·Br J Surg · Pubmed #29738626.

ABSTRACT: BACKGROUND: The definition of resection margin (R) status in pancreatic cancer is under debate. Although a margin of at least 1 mm is an independent predictor of survival after resection for pancreatic head cancer, its relevance to pancreatic body and tail cancers remains unclear. This study aimed to validate R status based on a 1-mm tumour-free margin as a prognostic factor for resected adenocarcinoma involving the pancreatic body and tail. METHODS: Patients who underwent distal or total pancreatectomy for adenocarcinomas of the pancreatic body and tail between January 2006 and December 2014 were identified from a prospective database. Resection margins were evaluated using a predefined cut-off of 1 mm. Rates of R0, R1 with invasion within 1 mm of the margin (R1 less than 1 mm), and R1 with direct invasion of the resection margin (R1 direct) were determined, and overall survival in each group assessed by Kaplan-Meier analysis. Univariable and multivariable Cox regression analyses were performed to identify predictors of survival. RESULTS: R0 resection was achieved in 107 (23·5 per cent) and R1 in 348 (76·5 per cent) of 455 patients. Among R1 resections, invasion within 1 mm of the margin was found in 104 (22·9 per cent) and direct invasion in 244 (53·6 per cent). The R0 rate was 28·9 per cent after distal and 18·6 per cent after total pancreatectomy. In the total cohort, median survival times for patients with R0, R1 (less than 1 mm) and R1 (direct) status were 62·4, 24·6 and 17·2 months respectively, with 5-year survival rates of 52·6, 16·8 and 13·0 per cent (P < 0·001). In patients who received adjuvant chemotherapy, respective median survival times were 68·6, 32·8 and 21·4 months, with 5-year survival rates of 56, 22 and 16·0 per cent (P < 0·001). In multivariable analysis, R status was independently associated with survival. CONCLUSION: A cut-off of at least 1 mm for evaluation of resection margins is an independent determinant of survival after resection of adenocarcinomas of the pancreatic body and tail.

24 Article Simvastatin inhibits sonic hedgehog signaling and stemness features of pancreatic cancer. 2018

Yin, Yefeng / Liu, Li / Zhao, Zhefu / Yin, Libo / Bauer, Nathalie / Nwaeburu, Clifford C / Gladkich, Jury / Gross, Wolfgang / Hackert, Thilo / Sticht, Carsten / Gretz, Norbert / Strobel, Oliver / Herr, Ingrid. ·Molecular OncoSurgery, Germany; Section Surgical Research, Germany; Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany. Electronic address: yefeng541009@gmail.com. · Molecular OncoSurgery, Germany; Section Surgical Research, Germany; Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany. Electronic address: li.liu@dkfz-heidelberg.de. · Molecular OncoSurgery, Germany; Section Surgical Research, Germany; Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany. Electronic address: zhaozhefumd@gmail.com. · Molecular OncoSurgery, Germany; Section Surgical Research, Germany; Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany. Electronic address: Yin@uni-heidelberg.de. · Molecular OncoSurgery, Germany; Section Surgical Research, Germany; Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany. Electronic address: nathaliebauer1989@web.de. · Molecular OncoSurgery, Germany; Section Surgical Research, Germany; Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany. Electronic address: klif4ord@yahoo.com. · Molecular OncoSurgery, Germany; Section Surgical Research, Germany; Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany. Electronic address: gladkich@uni-heidelberg.de. · Molecular OncoSurgery, Germany; Section Surgical Research, Germany; Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany. Electronic address: WGross@uni-hd.de. · Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany. · Medical Research Center, Medical Faculty Mannheim, University of Heidelberg, Germany. Electronic address: carsten.sticht@medma.uni-heidelberg.de. · Medical Research Center, Medical Faculty Mannheim, University of Heidelberg, Germany. Electronic address: norbert.gretz@medma.uni-heidelberg.de. · Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany. Electronic address: Oliver.Strobel@med.uni-heidelberg.de. · Molecular OncoSurgery, Germany; Section Surgical Research, Germany; Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany. Electronic address: i.herr@uni-heidelberg.de. ·Cancer Lett · Pubmed #29627496.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDA) has poor therapeutic options. Recent patient studies indicate that cholesterol-lowering statins have anti-tumor capacities. We examined several established and primary PDA and normal cell lines as well as PDA patient tissues (n = 68). We found that simvastatin inhibited viability, stemness, tumor growth and metastasis and that it enhanced the efficacy of gemcitabine. These changes were associated with modulation of Shh-related gene expression. Overexpression of Shh prevented the anti-cancer effect of simvastatin, and inhibition of Shh mimicked the simvastatin effect. In PDA tissues, expression levels of Shh, downstream mediators of Shh and progression markers, namely, cMet, CxCR4 and Vimentin, were lower when patients were prescribed statin medication prior to surgery. These results suggested that statins are cost effective and well-tolerated drugs for prevention and co-treatment of PDA.

25 Article Overcoming chemoresistance in pancreatic cancer cells: role of the bitter taste receptor T2R10. 2018

Stern, Louisa / Giese, Nathalia / Hackert, Thilo / Strobel, Oliver / Schirmacher, Peter / Felix, Klaus / Gaida, Matthias M. ·Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany. · Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany. ·J Cancer · Pubmed #29556329.

ABSTRACT: Bitter taste receptors (T2Rs) are G-protein coupled transmembrane proteins initially identified in the gustatory system as sensors for the taste of bitter. Recent evidence on expression of these receptors outside gustatory tissues suggested alternative functions, and there is growing interest of their potential role in cancer biology. In this study, we report for the first time, expression and functionality of the bitter receptor family member T2R10 in both human pancreatic ductal adenocarcinoma (PDAC) tissue and PDAC derived cell lines. Caffeine, a known ligand for T2R10, rendered the tumor cells more susceptible to two standard chemotherapeutics, Gemcitabine and 5-Fluoruracil. Knocking down T2R10 in the cell line BxPC-3 reduced the caffeine-induced effect. As possible underlying mechanism, we found that caffeine via triggering T2R10 inhibited Akt phosphorylation and subsequently downregulated expression of ABCG2, the so-called multi-drug resistance protein that participates in rendering cells resistant to a variety of chemotherapeutics. In conclusion, T2R10 is expressed in pancreatic cancer and it downmodulates the chemoresistance of the tumor cells.

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