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Pancreatic Neoplasms: HELP
Articles by Christine Tjaden
Based on 14 articles published since 2010
(Why 14 articles?)
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Between 2010 and 2020, C. Tjaden wrote the following 14 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 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.

2 Review [Developments in pancreatic surgery during the past ten years]. 2014

Hackert, T / Tjaden, C / Büchler, M W. ·Klinik für Allgemeine, Viszerale und Transplantationschirurgie, Universität Heidelberg, Deutschland. ·Zentralbl Chir · Pubmed #23824618.

ABSTRACT: Pancreatic surgery has undergone significant progress during recent years. Specialised centres with interdisciplinary expertise have led to improved patient care with decreased morbidity and mortality. Regarding evidence-based medicine, consensus definitions on morbidity as well as high-quality studies, systematic reviews and meta-analyses on different topics of pancreatic surgery have been published. In acute pancreatitis paradigms have shifted towards conservative management, in chronic pancreatitis parenchyma-sparing resection techniques have widely become accepted. Management of cystic lesions - especially intraductal papillary mucinous neoplasms (IPMN) - has attracted great interest in surgical practice. In pancreatic cancer treatment not only surgical resection techniques have improved but also the central impact of adjuvant treatment has been demonstrated in large multicentre trials.

3 Clinical Trial Randomized controlled phase I/II study to investigate immune stimulatory effects by low dose radiotherapy in primarily operable pancreatic cancer. 2011

Timke, Carmen / Winnenthal, Hubertus Schmitz / Klug, Felix / Roeder, Falk F F / Bonertz, Andreas / Reissfelder, Christoph / Rochet, Nathalie / Koch, Moritz / Tjaden, Christine / Buechler, Markus W / Debus, Juergen / Werner, Jens / Beckhove, Philipp / Weitz, Jürgen / Huber, Peter E. ·Department of Radiation Oncology, German Cancer Research Center and University Hospital Center, Heidelberg, Germany. ·BMC Cancer · Pubmed #21489291.

ABSTRACT: BACKGROUND: The efficiencies of T cell based immunotherapies are affected by insufficient migration and activation of tumor specific effector T cells in the tumor. Accumulating evidence exists on the ability of ionizing radiation to modify the tumor microenvironment and generate inflammation. The aim of this phase I/II clinical trial is to evaluate whether low dose single fraction radiotherapy can improve T cell associated antitumor immune response in patients with pancreatic cancer. METHODS/DESIGN: This trial has been designed as an investigator initiated; prospective randomised, 4-armed, controlled Phase I/II trial. Patients who are candidates for resection of pancreatic cancer will be randomized into 4 arms. A total of 40 patients will be enrolled. The patients receive 0 Gy, 0.5 Gy, 2 Gy or 5 Gy radiation precisely targeted to their pancreatic carcinoma. Radiation will be delivered by external beam radiotherapy using a 6 MV Linac with IMRT technique 48 h prior to the surgical resection. The primary objective is the determination of an active local external beam radiation dose, leading to tumor infiltrating T cells as a surrogate parameter for antitumor activity. Secondary objectives include local tumor control and recurrence patterns, survival, radiogenic treatment toxicity and postoperative morbidity and mortality, as well as quality of life. Further, frequencies of tumor reactive T cells in blood and bone marrow as well as whole blood cell transcriptomics and plasma-proteomics will be correlated with clinical outcome. An interim analysis will be performed after the enrollment of 20 patients for safety reasons. The evaluation of the primary endpoint will start four weeks after the last patient's enrollment. DISCUSSION: This trial will answer the question whether a low dose radiotherapy localized to the pancreatic tumor only can increase the number of tumor infiltrating T cells and thus potentially enhance the antitumor immune response. The study will also investigate the prognostic and predictive value of radiation-induced T cell activity along with transcriptomic and proteomic data with respect to clinical outcome.

4 Article Outcome and prognosis after pancreatectomy in patients with solid pseudopapillary neoplasms. 2019

Tjaden, Christine / Hassenpflug, Matthias / Hinz, Ulf / Klaiber, Ulla / Klauss, Miriam / Büchler, Markus W / Hackert, Thilo. ·Department of Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany. · Department of Radiology, University of Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany. · Department of Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany. Electronic address: thilo.hackert@med.uni-heidelberg.de. ·Pancreatology · Pubmed #31227367.

ABSTRACT: BACKGROUND: Solid pseudopapillary neoplasms (SPN) are rare and represent approximately 4% of all cystic pancreatic tumors. The prognosis is excellent, although 10-15% of SPN patients show metastasis at the time of surgery or tumor recurrence during follow-up after pancreatectomy. Aim of the study was to analyze surgical management, risk factors for malignancy as well as long-term outcome and prognosis of this distinct tumor entity. METHOD: All patients with pancreatic resection for SPN between 10/2001 and 07/2018 in the authors' institution were identified from a prospective database. Clinicopathologic details, perioperative data and long-term follow-up results were retrospectively analyzed. RESULTS: Fifty-two patients were identified, 44 (85%) of them were female and the median age was 29 years (IQR 9-71). Seven (13%) patients showed a malignant behaviour of SPN with N1 (n = 2) or M1 (n = 1) disease at resection; 5 patients developed tumor recurrence, after a median of 21 months. During follow-up time (median 54 months) all patients were alive, the 5- and 10-year rates for disease-free survival were 89.0% and 81.6%, respectively. Significant risk factors for recurrence were age <18 years (p = 0.0087) and parenchyma-preserving surgical approaches (p = 0.0006). The postoperative long-term outcome showed ECOG = 0-1 in all patients, with resection related exocrine insufficiency in 20 (41%) and diabetes mellitus in 2 (4%) patients. CONCLUSIONS: Age < 18 years is a significant risk factor for malignancy in SPN, and parenchyma preserving resections harbor a significant risk for tumor recurrence. As recurrence may occur late, a systematic life-long follow-up should be performed.

5 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

6 Article Progressive Resistance Training to Impact Physical Fitness and Body Weight in Pancreatic Cancer Patients: A Randomized Controlled Trial. 2019

Wiskemann, Joachim / Clauss, Dorothea / Tjaden, Christine / Hackert, Thilo / Schneider, Lutz / Ulrich, Cornelia M / Steindorf, Karen. ·Division of Physical Activity, Prevention and Cancer, National Center for Tumor Diseases and German Cancer Research Center. · Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany. · Department of Population Health Sciences, Huntsman Cancer Institute and University of Utah, Salt Lake City, UT. ·Pancreas · Pubmed #30589829.

ABSTRACT: OBJECTIVES: Maintaining or improving muscle mass and muscle strength is an important treatment goal in pancreatic cancer (PC) patients because of high risk of cachexia. Therefore, we assessed feasibility and effectivity of a 6-month progressive resistance training (RT) in PC patients within a randomized controlled trial. METHODS: Sixty-five PC patients were randomly assigned to either supervised progressive RT (RT1), home-based RT (RT2), or usual care control group (CON). Both exercise groups performed training 2 times per week for 6 months. Muscle strength for knee, elbow, and hip extensors and flexors and cardiorespiratory fitness and body weight were assessed before and after the intervention period. RESULTS: Of 65 patients, 43 patients were analyzed. Adherence rates were 64.1% (RT1) and 78.4% (RT2) of the prescribed training sessions. RT1 showed significant improvements in elbow flexor/extensor muscle strength and in maximal work load versus CON and RT2 (P < 0.05). Further, knee extensors were significantly improved for RT1 versus CON (P < 0.05). Body weight revealed no significant group differences over time. CONCLUSIONS: Progressive RT was feasible in PC patients and improved muscle strength with significant results for some muscle groups. Supervised RT seemed to be more effective than home-based RT.

7 Article Cardiorespiratory fitness and muscle strength in pancreatic cancer patients. 2017

Clauss, Dorothea / Tjaden, Christine / Hackert, Thilo / Schneider, Lutz / Ulrich, Cornelia M / Wiskemann, Joachim / Steindorf, Karen. ·Division of Physical Activity, Prevention and Cancer, National Center for Tumor Diseases and German Cancer Research Center, Im Neuenheimer Feld 460, 69120, Heidelberg, Germany. · Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany. · Division of Preventive Oncology, National Center for Tumor Diseases and German Cancer Research Center, Im Neuenheimer Feld 460, 69120, Heidelberg, Germany. · Department of Population Health Sciences, Huntsman Cancer Institute and University of Utah, 2000 Circle of Hope, Salt Lake City, UT, 84112, USA. · Division of Medical Oncology, National Center for Tumor Diseases and Heidelberg University Hospital, Im Neuenheimer Feld 460, 69120, Heidelberg, Germany. · Division of Physical Activity, Prevention and Cancer, National Center for Tumor Diseases and German Cancer Research Center, Im Neuenheimer Feld 460, 69120, Heidelberg, Germany. k.steindorf@dkfz.de. ·Support Care Cancer · Pubmed #28417202.

ABSTRACT: PURPOSE: Cancer patients frequently experience reduced physical fitness due to the disease itself as well as treatment-related side effects. However, studies on physical fitness in pancreatic cancer patients are missing. Therefore, we assessed cardiorespiratory fitness and muscle strength of pancreatic cancer patients. METHODS: We included 65 pancreatic cancer patients, mostly after surgical resection. Cardiorespiratory fitness was assessed using cardiopulmonary exercise testing (CPET) and 6-min walk test (6MWT). Hand-held dynamometry was used to evaluate isometric muscle strength. Physical fitness values were compared to reference values of a healthy population. Associations between sociodemographic and clinical variables with patients' physical fitness were analyzed using multiple regression models. RESULTS: Cardiorespiratory fitness (VO CONCLUSIONS: Pancreatic cancer patients had significantly impaired physical fitness with regard to both cardiorespiratory function and isometric muscle strength, already in the early treatment phase (median 95 days after surgical resection). Our findings underline the need to investigate exercise training in pancreatic cancer patients to counteract the loss of physical fitness.

8 Article Radical surgery of oligometastatic pancreatic cancer. 2017

Hackert, T / Niesen, W / Hinz, U / Tjaden, C / Strobel, O / Ulrich, A / Michalski, C W / Büchler, M W. ·Department of Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany. · Department of Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany. Electronic address: markus_buechler@med.uni-heidelberg.de. ·Eur J Surg Oncol · Pubmed #27856064.

ABSTRACT: BACKGROUND: In metastatic disease (M1), chemotherapy (expected survival: 6-10 months) is considered the only treatment option. The aim of this study was to evaluate the outcome of curative M1 PDAC resections. METHODS: Prospective data of all patients undergoing primary tumour and metastasis resection for stage IV PDAC during a 12-year period was analysed regarding localisation (liver or distant interaortocaval lymph nodes; ILN), morbidity and survival. Patients were stratified with regard to syn- or metachronous metastases resection. RESULTS: Patients (n = 128) undergoing PDAC and metastases resection (intention-to-treat, oligometastatic stage; liver n = 85; ILN n = 43) were included. Surgical morbidity and 30-day mortality after synchronous resection of M1 tumours were 45% and 2.9%, respectively. Overall median survival after M1 resection was 12.3 months in both groups. Long-term outcome showed a 5-year survival of 8.1% after surgery for both liver metastases and 10.1% following ILN resection. CONCLUSIONS: The present collective is the largest series of resected metastatic PDAC and shows that resection of liver or ILN metastases can be done safely and should be considered as it may be superior to palliative treatment, and it is associated with long-term survival of 10% in selected patients. Further studies to stratify patients for these procedures are warranted.

9 Article Association of genetic polymorphisms with survival of pancreatic ductal adenocarcinoma patients. 2016

Rizzato, Cosmeri / Campa, Daniele / Talar-Wojnarowska, Renata / Halloran, Christopher / Kupcinskas, Juozas / Butturini, Giovanni / Mohelníková-Duchoňová, Beatrice / Sperti, Cosimo / Tjaden, Christine / Ghaneh, Paula / Hackert, Thilo / Funel, Niccola / Giese, Nathalia / Tavano, Francesca / Pezzilli, Raffaele / Pedata, Mariangela / Pasquali, Claudio / Gazouli, Maria / Mambrini, Andrea / Souček, Pavel / di Sebastiano, Pierluigi / Capurso, Gabriele / Cantore, Maurizio / Oliverius, Martin / Offringa, Rienk / Małecka-Panas, Ewa / Strobel, Oliver / Scarpa, Aldo / Canzian, Federico. ·Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany, Department of Translational Research and New Technologies in Medicine and Surgery and. · Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany, Department of Biology, University of Pisa, Pisa, Italy. · Department of Digestive Tract Diseases, Medical University of Łódź, Łódź, Poland. · Department of Molecular and Clinical Cancer Medicine, NIHR Liverpool Pancreas Biomedical Research Unit, University of Liverpool, Liverpool, UK. · Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania. · Unit of Surgery B, The Pancreas Institute, Department of Surgery and Oncology, G.B. Rossi Hospital, University of Verona Hospital Trust, Verona, Italy. · Department of Oncology, Palacky University Medical School and Teaching Hospital, Olomouc, Czech Republic. · Department of Surgery, Gastroenterology and Oncology, University of Padua, Padua, Italy. · Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany. · Department of Translational Research and New Technologies in Medicine and Surgery and. · Division of Gastroenterology and Research Laboratory, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza", S. Giovanni Rotondo (FG), Italy. · Pancreas Unit, Department of Digestive Disease, Sant'Orsola-Malpighi Hospital, Bologna, Italy. · Oncological Department, ASL 1 Massa Carrara, Massa Carrara, Italy. · Department of Basic Medical Science, Laboratory of Biology, School of Medicine, University of Athens, Athens, Greece. · Department of Surgery, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza", San Giovanni Rotondo (FG), Italy. · Digestive and Liver Disease Unit, 'Sapienza' University of Rome, Rome, Italy. · Transplant Surgery Department, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. · Division of Molecular Oncology of Gastrointestinal Tumors, German Cancer Research Center (DKFZ), Heidelberg, Germany and. · ARC-NET, Centre for Applied Research on Cancer, University and Hospital Trust of Verona, Verona, Italy. · Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany, f.canzian@dkfz.de. ·Carcinogenesis · Pubmed #27497070.

ABSTRACT: Germline genetic variability might contribute, at least partially, to the survival of pancreatic ductal adenocarcinoma (PDAC) patients. Two recently performed genome-wide association studies (GWAS) on PDAC overall survival (OS) suggested (P < 10(-5)) the association between 30 genomic regions and PDAC OS. With the aim to highlight the true associations within these regions, we analyzed 44 single-nucleotide polymorphisms (SNPs) in the 30 candidate regions in 1722 PDAC patients within the PANcreatic Disease ReseArch (PANDoRA) consortium. We observed statistically significant associations for five of the selected regions. One association in the CTNNA2 gene on chromosome 2p12 [rs1567532, hazard ratio (HR) = 1.75, 95% confidence interval (CI) 1.19-2.58, P = 0.005 for homozygotes for the minor allele] and one in the last intron of the RUNX2 gene on chromosome 6p21 (rs12209785, HR = 0.88, 95% CI 0.80-0.98, P = 0.014 for heterozygotes) are of particular relevance. These loci do not coincide with those that showed the strongest associations in the previous GWAS. In silico analysis strongly suggested a possible mechanistic link between these two SNPs and pancreatic cancer survival. Functional studies are warranted to confirm the link between these genes (or other genes mapping in those regions) and PDAC prognosis in order to understand whether these variants may have the potential to impact treatment decisions and design of clinical trials.

10 Article Clinical Impact of Structured Follow-up After Pancreatic Surgery. 2016

Tjaden, Christine / Michalski, Christoph W / Strobel, Oliver / Giese, Nathalia / Hennche, Anne-Kathrin / Büchler, Markus W / Hackert, Thilo. ·From the *Department of Surgery, University of Heidelberg, Heidelberg; †Department of Orthopedics, Neckar-Odenwald-Kliniken, Mosbach, Germany. ·Pancreas · Pubmed #26646267.

ABSTRACT: OBJECTIVES: Structured follow-up after surgery for pancreatic ductal adenocarcinoma (PDAC) remains controversial and is currently not recommended due to a supposed lack of therapeutic consequences. Furthermore, it is not clear whether noncancer patients after pancreas resection need to be seen in the clinic on a regular basis. The present study analyzed how follow-up after pancreatic surgery affected postoperative treatment and long-term outcomes. METHODS: Data of all postoperative visits in a specialized outpatient clinic for pancreatic diseases were analyzed for a 1-year period with regard to symptoms, diagnostic procedures, and therapeutic consequences. RESULTS: Six hundred eighteen patients underwent 940 postoperative follow-ups. Nearly half of them needed a change of medication due to altered pancreatic function. In 74 (40%) of 184 resected PDAC patients, recurrence (local or systemic) was detected during follow-up, although only 19 of these had shown associated symptoms (26%). In all patients with recurrence, a cancer-directed treatment was induced. Eleven (69%) of 16 patients with isolated local recurrence were referred for reresection. CONCLUSIONS: Follow-up examinations are a substantial part of the clinical management after pancreas resections. Follow-up is particularly important for PDAC because recurrence is often asymptomatic, but its detection allows for therapeutic interventions and potentially improved prognosis. This should be implemented in future guidelines.

11 Article IVIM DW-MRI of autoimmune pancreatitis: therapy monitoring and differentiation from pancreatic cancer. 2016

Klauß, Miriam / Maier-Hein, Klaus / Tjaden, Christine / Hackert, Thilo / Grenacher, Lars / Stieltjes, Bram. ·Department of Diagnostic and Interventional Radiology, University of Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany. miriam.klauss@med.uni-heidelberg.de. · Department of Medical and Biological Informatics, DKFZ, Heidelberg, Germany. · Department of Surgery, University of Heidelberg, Heidelberg, Germany. · Department of Diagnostic and Interventional Radiology, University of Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany. · Department of Radiology, University Hospital Basel, Basel, Switzerland. ·Eur Radiol · Pubmed #26449558.

ABSTRACT: OBJECTIVES: To evaluate IVIM DW-MRI for changes in IVIM-derived parameters during steroid treatment of autoimmune pancreatitis (AIP) and for the differentiation from pancreatic cancer (PC). METHODS: Fifteen AIP-patients, 11 healthy patients and 20 PC-patients were examined with DWI-MRI using eight b-values (50, 100, 150, 200, 300, 400, 600, 800). 12 AIP-patients underwent follow-up examinations during treatment. IVIM-parameters and ADC800-values were tested for significant differences and an ROC analysis was performed. RESULTS: The perfusion fraction f was significantly lower in patients with AIP at the time of diagnosis (10.5 ± 4.3 %) than in patients without AIP (20.7 ± 4.3 %). In AIP follow-up, f increased significantly to 17.1 ± 7.0 % in the first and 21.0 ± 4.1 % in the second follow up. In PC, the f-values were lower (8.2 ± 4.0 %, n.s.) compared to initial AIP and were significantly lower compared to first and second follow-up examination. In the ROC-analysis AUC-values for f were 0.63, 0.88 and 0.98 for differentiation of PC from initial, first and second follow up AIP-examination. CONCLUSIONS: The found differences in f between AIP, AIP during steroid treatment and pancreatic cancer suggest that IVIM-diffusion MRI could serve as imaging biomarker during treatment in AIP-patients and as a helpful tool for differentiation between PC and AIP. KEY POINTS: • MRI is used for follow-up examinations during therapy in AIP-patients • IVIM-DWI-MRI offers parameters which reflect perfusion and true diffusion • IVIM-parameters are helpful for differentiation between AIP and pancreatic cancer • IVIM-parameters could serve as an imaging biomarker during steroid treatment.

12 Article Chondroitin sulfate proteoglycan CSPG4 as a novel hypoxia-sensitive marker in pancreatic tumors. 2014

Keleg, Shereen / Titov, Alexandr / Heller, Anette / Giese, Thomas / Tjaden, Christine / Ahmad, Sufian S / Gaida, Matthias M / Bauer, Andrea S / Werner, Jens / Giese, Nathalia A. ·European Pancreas Centre, Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany. · Institute of Immunology, University Hospital Heidelberg, Heidelberg, Germany. · Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany. · Department of Functional Genomics, German Cancer Research Centre, Heidelberg, Germany. ·PLoS One · Pubmed #24932730.

ABSTRACT: CSPG4 marks pericytes, undifferentiated precursors and tumor cells. We assessed whether the shed ectodomain of CSPG4 (sCSPG4) might circulate and reflect potential changes in CSPG4 tissue expression (pCSPG4) due to desmoplastic and malignant aberrations occurring in pancreatic tumors. Serum sCSPG4 was measured using ELISA in test (n = 83) and validation (n = 221) cohorts comprising donors (n = 11+26) and patients with chronic pancreatitis (n = 11+20) or neoplasms: benign (serous cystadenoma SCA, n = 13+20), premalignant (intraductal dysplastic IPMNs, n = 9+55), and malignant (IPMN-associated invasive carcinomas, n = 4+14; ductal adenocarcinomas, n = 35+86). Pancreatic pCSPG4 expression was evaluated using qRT-PCR (n = 139), western blot analysis and immunohistochemistry. sCSPG4 was found in circulation, but its level was significantly lower in pancreatic patients than in donors. Selective maintenance was observed in advanced IPMNs and PDACs and showed a nodal association while lacking prognostic relevance. Pancreatic pCSPG4 expression was preserved or elevated, whereby neoplastic cells lacked pCSPG4 or tended to overexpress without shedding. Extreme pancreatic overexpression, membranous exposure and tissue(high)/sera(low)-discordance highlighted stroma-poor benign cystic neoplasm. SCA is known to display hypoxic markers and coincide with von-Hippel-Lindau and Peutz-Jeghers syndromes, in which pVHL and LBK1 mutations affect hypoxic signaling pathways. In vitro testing confined pCSPG4 overexpression to normal mesenchymal but not epithelial cells, and a third of tested carcinoma cell lines; however, only the latter showed pCSPG4-responsiveness to chronic hypoxia. siRNA-based knockdowns failed to reduce the malignant potential of either normoxic or hypoxic cells. Thus, overexpression of the newly established conditional hypoxic indicator, CSPG4, is apparently non-pathogenic in pancreatic malignancies but might mark distinct epithelial lineage and contribute to cell polarity disorders. Surficial retention on tumor cells renders CSPG4 an attractive therapeutic target. Systemic 'drop and restoration' alterations accompanying IPMN and PDAC progression indicate that the interference of pancreatic diseases with local and remote shedding/release of sCSPG4 into circulation deserves broad diagnostic exploration.

13 Article Extrapancreatic malignancies in patients with pancreatic cancer: epidemiology and clinical consequences. 2012

Hackert, Thilo / Tjaden, Christin / Müller, Sascha / Hinz, Ulf / Hartwig, Werner / Strobel, Oliver / Fritz, Stefan / Schmied, Bruno / Büchler, Markus W / Werner, Jens. ·Department of Surgery, University of Heidelberg, Heidelberg, Germany. Thilo_Hackert@med.uni-heidelberg.de ·Pancreas · Pubmed #21934549.

ABSTRACT: OBJECTIVES: To investigate the incidence, characteristics, and prognostic impact of prior extrapancreatic malignancies on patients with pancreatic cancer (PDAC). METHODS: Records from 1733 patients who underwent surgery for PDAC were analyzed for the occurrence of prior extrapancreatic malignancies. Patients' records showing extrapancreatic malignancies were then analyzed for tumor type, epidemiological data, risk factors, PDAC tumor stage, and long-term survival. RESULTS: A total of 239 patients with PDAC (13.8%) had a history of 271 extrapancreatic tumors; 26 patients had a history of two pancreatic cancers, and 3 patients had 3 extrapancreatic cancers. The most common extrapancreatic tumors were breast cancer (56 patients) and prostate cancer (41 patients), followed by colorectal, reno/urothelial, and gynecologic tumors (39, 32, and 23 patients, respectively). No significant difference in overall survival was found between patients with PDAC with or without extrapancreatic malignancies. CONCLUSIONS: Pancreatic cancer is associated with extrapancreatic malignancies in a remarkable number of patients. A history of extrapancreatic malignancies does not influence prognosis and should not be an obstacle to a curative therapeutic approach. Surveillance of patients with extrapancreatic malignancies, especially breast, prostate, and colorectal cancer, could allow for earlier PDAC diagnosis and therefore improve prognosis of these patients.

14 Article Reactive hypertrophy of an accessory spleen mimicking tumour recurrence of metastatic renal cell carcinoma. 2011

Tjaden, Christin / Werner, Jens / Buechler, Markus W / Hackert, Thilo. ·Department of Surgery, University of Heidelberg, Germany. ·Asian J Surg · Pubmed #21515214.

ABSTRACT: De novo occurrence of an accessory spleen after splenectomy is worth noting for two reasons. First, it is known that splenectomy can cause reactive hypertrophy of initially inactive and macroscopically invisible splenic tissue. Second, it can mimic tumour recurrence in situations in which splenectomy has been performed for oncological reasons. This might cause difficulties in differential diagnosis and the clinical decision for reoperation. We report the case of a patient with suspected recurrence of renal cell carcinoma after total pancreatectomy and splenectomy for metastatic renal cell carcinoma, which finally revealed an accessory spleen as the morphological correlate of the newly diagnosed mass in the left retroperitoneum.