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Pancreatic Neoplasms: HELP
Articles by Ulrich Frank Pape
Based on 14 articles published since 2010
(Why 14 articles?)
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Between 2010 and 2020, U. Pape wrote the following 14 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Guideline ENETS Consensus Guidelines Update for the Management of Distant Metastatic Disease of Intestinal, Pancreatic, Bronchial Neuroendocrine Neoplasms (NEN) and NEN of Unknown Primary Site. 2016

Pavel, M / O'Toole, D / Costa, F / Capdevila, J / Gross, D / Kianmanesh, R / Krenning, E / Knigge, U / Salazar, R / Pape, U-F / Öberg, K / Anonymous6200853. ·Charite Virchow Klinikum, Berlin, Germany. ·Neuroendocrinology · Pubmed #26731013.

ABSTRACT: -- No abstract --

2 Review Gastroenteropancreatic neuroendocrine tumors (GEP-NETs): a closer look at the characteristics of these diverse tumors. 2014

Pape, Ulrich-Frank. ·Charité University Hospital, Berlin, Germany. ·Clin Adv Hematol Oncol · Pubmed #25768103.

ABSTRACT: -- No abstract --

3 Article Competitive Testing of the WHO 2010 versus the WHO 2017 Grading of Pancreatic Neuroendocrine Neoplasms: Data from a Large International Cohort Study. 2018

Rindi, Guido / Klersy, Catherine / Albarello, Luca / Baudin, Eric / Bianchi, Antonio / Buchler, Markus W / Caplin, Martyn / Couvelard, Anne / Cros, Jérôme / de Herder, Wouter W / Delle Fave, Gianfranco / Doglioni, Claudio / Federspiel, Birgitte / Fischer, Lars / Fusai, Giuseppe / Gavazzi, Francesca / Hansen, Carsten P / Inzani, Frediano / Jann, Henning / Komminoth, Paul / Knigge, Ulrich P / Landoni, Luca / La Rosa, Stefano / Lawlor, Rita T / Luong, Tu V / Marinoni, Ilaria / Panzuto, F / Pape, Ulrich-Frank / Partelli, Stefano / Perren, Aurel / Rinzivillo, Maria / Rubini, Corrado / Ruszniewski, Philippe / Scarpa, Aldo / Schmitt, Anja / Schinzari, Giovanni / Scoazec, Jean-Yves / Sessa, Fausto / Solcia, Enrico / Spaggiari, Paola / Toumpanakis, Christos / Vanoli, Alessandro / Wiedenmann, Bertram / Zamboni, Giuseppe / Zandee, Wouter T / Zerbi, Alessandro / Falconi, Massimo. ·Institute of Pathology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma-Università Cattolica del Sacro Cuore, Roma ENETS Center of Excellence, Rome, Italyguido.rindi@unicatt.it. · Service of Biometry and Clinical Epidemiology, Research Department, and IRCCS Fondazione Policlinico San Matteo, Pavia, Italy. · Pathology Unit, San Raffaele Scientific Institute, Milan, Italy. · Department of Oncology, Cancer Campus, Villejuif, France. · Department of Endocrinology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma-Università Cattolica del Sacro Cuore, Roma ENETS Center of Excellence, Rome, Italy. · Department of Surgery, University Hospital Heidelberg, Neu Heidelberg, Germany. · Neuroendocrine Tumour Unit, Centre for Gastroenterology, London, United Kingdom. · Department of Pathology, Hopital Beaujon, Paris ENETS Center of Excellence, Clichy, France. · Section Endocrinology, Department of Internal Medicine, Erasmus University Medical Center and and Erasmus MC Cancer Institute Rotterdam, Rotterdam ENETS Center of Excellence, Rotterdam, The Netherlands. · Digestive and Liver Disease Unit, Sant'Andrea University Hospital, Roma ENETS Center of Excellence, Rome, Italy. · Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Copenhagen ENETS Center of Excellence, Copenhagen, Denmark. · Department of Surgery, University College, Royal Free Hospital, London ENETS Center of Excellence, London, United Kingdom. · Pancreatic Surgery, Humanitas Clinical and Research Center, Humanitas Milan ENETS Center of Excellence, Milan, Italy. · Department of Surgery, Rigshospitalet, Copenhagen University Hospital, Copenhagen ENETS Center of Excellence, Copenhagen, Denmark. · Institute of Pathology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma-Università Cattolica del Sacro Cuore, Roma ENETS Center of Excellence, Rome, Italy. · Department of Hepatology and Gastroenterology, Charité, Campus Virchow Klinikum and Charite Mitte, University Medicine Berlin, Berlin ENETS Center of Excellence, Berlin, Germany. · Institute of Pathology, Stadtspital Triemli, Zurich, Switzerland. · Department of Surgery and Oncology, General and Pancreatic Surgery, The Pancreas Institute, Verona ENETS Center of Excellence, Verona, Italy. · Department of Pathology, Ospedale di Circolo, Università dell'Insubria, Varese, Italy. · Section of Pathology and ARC-Net Research Centre, Department of Diagnostics and Public Health, University and Hospital Trust of Verona, Verona ENETS Center of Excellence, Verona, Italy. · Department of Pathology, University College, Royal Free Hospital, London ENETS Center of Excellence, London, United Kingdom. · Institute of Pathology, University of Bern, Bern, Switzerland. · Pancreatic Surgery Unit, San Raffaele Scientific Institute, Milan, Italy. · Department of Pathology, Marche Polytechnic University, Ancona, Italy. · Department of Gastroenterology and Pancreatology, Hopital Beaujon, Paris ENETS Center of Excellence, Clichy, France. · Department of Medical Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma-Università Cattolica del Sacro Cuore, Roma ENETS Center of Excellence, Rome, Italy. · Department of Medical Biology and Pathology, Cancer Campus, Villejuif, France. · Department of Molecular Medicine, University of Pavia, Pavia, Italy. · Pathology Department, Humanitas Clinical and Research Center, Humanitas Milan ENETS Center of Excellence, Milan, Italy. · Department of Pathology, Sacro Cuore-Don Calabria Hospital, Negrar, Italy. ·Neuroendocrinology · Pubmed #30300897.

ABSTRACT: BACKGROUND: The World Health Organization (WHO) and the American Joint Cancer Committee (AJCC) modified the grading of pancreatic neuroendocrine neoplasms from a three-tier (WHO-AJCC 2010) to a four-tier system by introducing the novel category of NET G3 (WHO-AJCC 2017). OBJECTIVES: This study aims at validating the WHO-AJCC 2017 and identifying the most effective grading system. METHOD: A total of 2,102 patients were enrolled; entry criteria were: (i) patient underwent surgery; (ii) at least 2 years of follow-up; (iii) observation time up to 2015. Data from 34 variables were collected; grading was assessed and compared for efficacy by statistical means including Kaplan-Meier method, Cox regression analysis, Harrell's C statistics, and Royston's explained variation in univariable and multivariable analyses. RESULTS: In descriptive analysis, the two grading systems demonstrated statistically significant differences for the major category sex but not for age groups. In Cox regression analysis, both grading systems showed statistically significant differences between grades for OS and EFS; however, no statistically significant difference was observed between the two G3 classes of WHO-AJCC 2017. In multivariable analysis for the two models fitted to compare efficacy, the two grading systems performed equally well with substantially similar optimal discrimination and well-explained variation for both OS and EFS. The WHO-AJCC 2017 grading system retained statistically significant difference between the two G3 classes for OS but not for EFS. CONCLUSIONS: The WHO-AJCC 2017 grading system is at least equally performing as the WHO-AJCC 2010 but allows the successful identification of the most aggressive PanNET subgroup. Grading is confirmed as probably the most powerful tool for predicting patient survival.

4 Article A score derived from routine biochemical parameters increases the diagnostic accuracy of chromogranin A in detecting patients with neuroendocrine neoplasms. 2018

Kruljac, Ivan / Vurnek, Ivan / Maasberg, Sebastian / Kust, Davor / Blaslov, Kristina / Ladika Davidović, Blaženka / Štefanović, Mario / Demirović, Alma / Bišćanin, Alen / Filipović-Čugura, Jakša / Marić Brozić, Jasmina / Pape, Ulrich-Frank / Vrkljan, Milan. ·Department of Endocrinology, Diabetes and Metabolic Diseases "Mladen Sekso", University Hospital Center "Sestre Milosrdnice", University of Zagreb School of Medicine, Zagreb, Croatia. ivkruljac@gmail.com. · University of Zagreb School of Medicine, Zagreb, Croatia. · Department of Hepatology and Gastroenterology, ENETS Center of Excellence for Neuroendocrine Tumors, Charité Campus Mitte and Virchow Clinic, Charité University Medicine, Berlin, Germany. · Department of Oncology and Nuclear Medicine, University Hospital Center "Sestre Milosrdnice", Zagreb, Croatia. · Department of Endocrinology, Diabetes and Metabolic Diseases "Mladen Sekso", University Hospital Center "Sestre Milosrdnice", University of Zagreb School of Medicine, Zagreb, Croatia. · Clinical Institute of Chemistry, University Hospital Center "Sestre Milosrdnice", University of Zagreb Faculty of Pharmacy and Biochemistry, Zagreb, Croatia. · Department of Pathology, University Hospital Center "Sestre Milosrdnice", University of Zagreb School of Medicine, Zagreb, Croatia. · Department of Gastroenterology and Hepatology, University Hospital Center "Sestre Milosrdnice", Zagreb, Croatia. · Department of Surgery, University Hospital Center "Sestre Milosrdnice", Zagreb, Croatia. ·Endocrine · Pubmed #29633144.

ABSTRACT: BACKGROUND: Chromogranin A (CgA) is a valuable biomarker for detection and follow-up of patients with neuroendocrine neoplasms (NENs). However, various comorbidities may influence serum CgA, which decreases its diagnostic accuracy. We aimed to investigate which laboratory parameters are independently associated with increased CgA in real-life setting and to develop a scoring system, which could improve the diagnostic accuracy of CgA in detecting patients with NENs. METHODS: This retrospective study included 55 treatment naïve patients with NENs and160 patients with various comorbidities but without NEN (nonNENs). Scoring system (CgA-score) was developed based on z-scores obtained from receiver operating curve analysis for each parameter that was associated with elevated serum CgA in nonNENs. RESULTS: CgA correlated positively with serum BUN, creatinine, α2-globulin, red-cell distribution width, erythrocyte sedimentation rate, plasma glucose and correlated inversely with hemoglobin, thrombocytes and serum albumin. Serum CgA was also associated with the presence of chronic renal failure, arterial hypertension and diabetes and the use of PPI. In the entire study population, CgA showed an area under the curve of 0.656. Aforementioned parameters were used to develop a CgA-score. In a cohort of patients with CgA-score <12.0 (N = 87), serum CgA >156.5 ng/ml had 77.8% sensitivity and 91.5% specificity for detecting NENs (AUC 0.841, 95% CI 0.713-0.969, P < 0.001). Serum CgA had no diagnostic value in detecting NENs in patients with CgA-score >12.0 (AUC 0.554, 95% CI 0.405-0.702, P = 0.430). CONCLUSIONS: CgA-score encompasses a wide range of comorbidities and represents a promising tool that could improve diagnostic performance of CgA in everyday clinical practice.

5 Article Stage IV Gastro-Entero-Pancreatic Neuroendocrine Neoplasms: A Risk Score to Predict Clinical Outcome. 2017

Panzuto, Francesco / Merola, Elettra / Pavel, Marianne Ellen / Rinke, Anja / Kump, Patrizia / Partelli, Stefano / Rinzivillo, Maria / Rodriguez-Laval, Victor / Pape, Ulrich Frank / Lipp, Rainer / Gress, Thomas / Wiedenmann, Bertram / Falconi, Massimo / Delle Fave, Gianfranco. ·Department of Digestive and Liver Disease, Sapienza University of Rome - Sant'Andrea Hospital, Rome, Italy. · Department of Hepatology and Gastroenterology, Charité Campus Mitte and Virchow Clinic, Charité University Medicine, Berlin, Germany. · Department of Gastroenterology, Philipps-University of Marburg, Germany. · Clinical Division of Gastroenterology, Medical University Graz, Austria. · Division of Pancreatic Surgery, Vita-Salute University, San Raffaele Scientific Institute, Milan, Italy. · Department of Radiology Charité University, Campus Virchow Klinikum, Berlin, Germany. · Clinical Division of Oncology, Medical University Graz, Austria. · Department of Digestive and Liver Disease, Sapienza University of Rome - Sant'Andrea Hospital, Rome, Italy gianfranco.dellefave@uniroma1.it. ·Oncologist · Pubmed #28232598.

ABSTRACT: BACKGROUND: Several risk factors predict clinical outcome in gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs); however, the impact of their combination has not been investigated so far. PATIENTS AND METHODS: A retrospective analysis of stage IV GEP-NENs was performed. Multivariate analysis for progression of disease (PD) was performed by Cox proportional hazards method to obtain a risk score. Area under the curve obtained by receiver operating characteristic analysis was used to assess the score performance. Progression-free survival analysis was performed by Kaplan-Meier method. RESULTS: Two hundred eighty-three stage IV GEP-NENs were evaluated, including 93 grade 1 neuroendocrine tumors (32.9%), 153 grade 2 neuroendocrine tumors (54%), and 37 grade 3 neuroendocrine carcinomas (13.1%). Independent risk factors for PD were Ki67, proportion of metastatic liver involvement, and presence of extra-abdominal metastases. The risk score was calculated as follows: (0.025 × Ki67) + [(0 if no liver metastases or liver involvement <25%) OR (0.405 if liver involvement 25%-50%) OR (0.462 if liver involvement >50%)] + [(0 if no extra-abdominal metastases) OR (0.528 if extra-abdominal metastases present)]. The risk score accuracy to predict PD was superior compared with the G grading system (area under the curve: 0.705 and 0.622, respectively). Three subgroups of patients with low, intermediate, and high risk of PD according to risk score were identified, median progression-free survival being 26 months, 19 months, and 12 months, respectively. CONCLUSION: In stage IV GEP-NENs, a risk score able to predict PD was obtained by combining Ki67, proportion of metastatic liver involvement, and presence of extra-abdominal metastases. The score may help to discriminate patients with different progression risk level to plan tailored therapeutic approaches and follow-up programs.

6 Article Streptozocin/5-fluorouracil chemotherapy is associated with durable response in patients with advanced pancreatic neuroendocrine tumours. 2015

Dilz, Lisa-Marie / Denecke, Timm / Steffen, Ingo G / Prasad, Vikas / von Weikersthal, Ludwig Fischer / Pape, Ulrich-Frank / Wiedenmann, Bertram / Pavel, Marianne. ·Dept. of Hepatology and Gastroenterology, Campus Virchow Klinikum, Charité Universitätsmedizin Berlin, Germany. · Dept. of Radiology, Campus Virchow Klinikum, Charité Universitätsmedizin Berlin, Germany. · Dept. of Nuclear Medicine, Campus Virchow Klinikum, Charité Universitätsmedizin Berlin, Germany. · Klinikum St. Marien, Dept. of Internal Medicine, Amberg, Germany. · Dept. of Hepatology and Gastroenterology, Campus Virchow Klinikum, Charité Universitätsmedizin Berlin, Germany. Electronic address: marianne.pavel@charite.de. ·Eur J Cancer · Pubmed #25935542.

ABSTRACT: BACKGROUND: The role of systemic chemotherapy for pancreatic neuroendocrine tumours (pNET) is controversially discussed. Objective response rates (RR) reported for streptozocin (STZ)-based chemotherapy are variable and novel targeted drugs have recently been approved. However, the sequence of treatment remains unclear. We aimed to evaluate the efficacy of STZ plus 5-fluorouracil (STZ/5-FU) in a large pNET cohort. METHODS: Data from 96 pNET patients treated with STZ/5-FU were analysed retrospectively. Endpoints of the study were RR, time to tumour progression (TTP) and overall survival (OS). RESULTS: Mean age of patients at the start of chemotherapy was 57.6years (range, 32.1-80.4). STZ/5-FU was the 1st line treatment in 56.3%. 11.5% had G1, 79.2% G2 and 6.3% G3 neoplasms. Baseline progression was evident in 74%. Objective response rate was 42.7%. 40.6% of patients showed stable disease as best response while 16.7% showed progressive disease. Treatment was discontinued due to toxicity in 16 patients. Median TTP and OS were 19.4 (95% confidence interval (CI), 13.6-25.2) and 54.8months (95% CI, 34.7-74.9), respectively. In Cox regression analysis, Ki67>15% was the only negative prognostic factor for TTP (hazard ratio (HR), 3.3; P<0.001), confirmed by multivariate analysis (HR, 6.7; P=0.001). CONCLUSIONS: STZ/5-FU was associated with considerable RR. Treatment was associated with durable TTP especially in patients with Ki67-index of ⩽15%. These findings along with good tolerability strengthen the value of this two-drug chemotherapy for the management of unresectable pNET.

7 Article Continued advances in targeting gastroenteropancreatic neuroendocrine tumors: general discussion. 2014

Capdevila, Jaume / Weber, Matthias / Pape, Ulrich-Frank. ·Vall d'Hebron University Hospital, Barcelona, Spain. · Johannes Gutenberg University Mainz, Mainz, Germany. · Charité University Hospital, Berlin, Germany. ·Clin Adv Hematol Oncol · Pubmed #25768107.

ABSTRACT: -- No abstract --

8 Article Long-term hematotoxicity after peptide receptor radionuclide therapy with 177Lu-octreotate. 2013

Sabet, Amir / Ezziddin, Khaled / Pape, Ulrich-Frank / Ahmadzadehfar, Hojjat / Mayer, Karin / Pöppel, Thorsten / Guhlke, Stefan / Biersack, Hans-Jürgen / Ezziddin, Samer. ·Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany. ·J Nucl Med · Pubmed #24009272.

ABSTRACT: METHODS: A total of 632 PRRT courses were performed in 203 patients with metastatic neuroendocrine tumors. A mean activity of 7.9 GBq of (177)Lu-octreotate was administered per treatment cycle, with a goal of 4 courses at standard intervals of 3 mo. Hematologic parameters were determined before each treatment course, at 2- to 4-wk intervals between the courses, 8-12 wk after the last course of PRRT, and at 3-month intervals for further follow-up. Toxicity was recorded with Common Terminology Criteria for Adverse Events (version 3.0). RESULTS: Myelodysplastic syndrome as a delayed adverse event was documented in 3 patients (1.4%). Relevant but reversible hematotoxicity (grade 3 or 4) occurred in 23 patients (11.3%) and 29 administrations (4.6%), with leukopenia in 2.7% and thrombocytopenia in 1.7%. The mean time to blood count recovery was 12 mo after the termination of PRRT (range, 3-22 mo). The only preexisting factor that contributed to hematotoxicity was initial cytopenia (P < 0.001). A high level of cumulative administered activity (>29.6 GBq) was associated with relevant leukopenia (P < 0.001). None of the patients with a history of splenectomy developed grade 3 or 4 hematotoxicity, and splenectomy was inversely associated with the incidence and degree of leukopenia (P = 0.02) and thrombocytopenia (P = 0.03). CONCLUSION: PRRT-induced myelosuppression is almost invariably reversible and rarely requires clinical measures. Administered activity and initial cytopenia are the only factors contributing to myelosuppression, whereas splenectomy may exert a protective effect.

9 Article Impact of octreotide long-acting release on tumour growth control as a first-line treatment in neuroendocrine tumours of pancreatic origin. 2013

Jann, H / Denecke, T / Koch, M / Pape, U F / Wiedenmann, B / Pavel, M. ·Department of Hepatology and Gastroenterology, Charité, Berlin, Germany. ·Neuroendocrinology · Pubmed #23797176.

ABSTRACT: BACKGROUND: Somatostatin analogues (SSA) are widely used in the treatment of patients with functioning and non-functioning neuroendocrine tumours (NET). The aim of our investigation was to evaluate the antiproliferative effect of SSA in patients with pancreatic NET. METHODS: We retrospectively analysed records of 43 patients with pancreatic NET treated at our clinic with octreotide long-lasting release as a first-line therapy. The aim of our study was to investigate the overall best response according to the RECIST criteria, overall best response defined as disease control rate (SD+PR), response and disease control rate at 12 months, and time to tumour progression (TTP). RESULTS: The mean age (± SD) of the patients (16 female/27 male) at initial diagnosis was 54.7 ± 11.86 years. At the start of therapy, 39 of 43 patients were classified as stage IV according to ENETS-TNM. Tumours were graded, based on MiB-1/Ki67 staining, as G1 (n = 8), G2 (n = 30) or unknown (n = 5). The octreoscan was positive in 37 patients, negative in 2 and unknown in 4 cases. Nineteen patients had functioning tumours, 24 patients had non-functioning tumours. Median overall survival was 98 months, and median TTP was 13 months. Analysis of grading showed a statistically significant influence on TTP when comparing the median TTP for Ki67 >10% with Ki67 <5% (p = 0.009) and Ki67 5-10% (p = 0.036). CONCLUSION: SSA may be considered as a first-line treatment for antiproliferative purposes in metastatic NET of the pancreas. Patients with a proliferation index <10% displayed a more durable response compared to those with a higher proliferation index.

10 Article Placental growth factor supports neuroendocrine tumor growth and predicts disease prognosis in patients. 2013

Hilfenhaus, Georg / Göhrig, Andreas / Pape, Ulrich-Frank / Neumann, Tabea / Jann, Henning / Zdunek, Dietmar / Hess, Georg / Stassen, Jean Marie / Wiedenmann, Bertram / Detjen, Katharina / Pavel, Marianne / Fischer, Christian. ·Charité Medical Faculty and the Max-Delbrück Center for Molecular Medicine, Lindenberger Weg 80, 13125 Berlin, Germany. ·Endocr Relat Cancer · Pubmed #23463017.

ABSTRACT: Placental growth factor (PlGF), a VEGF-homolog implicated in tumor angiogenesis and adaptation to antiangiogenic therapy, is emerging as candidate target in malignancies. Here, we addressed the expression, function, and prognostic value of PlGF in neuroendocrine tumors (NETs). PlGF was determined in NET patients' sera collected retrospectively (n=88) and prospectively (n=87) using Roche-Elecsys and correlated with clinicopathological data. Tumoral PlGF was evaluated by immunohistochemistry, effects of PlGF on proliferation and migration in vitro were assessed using different NET cell lines and effects on tumor growth in vivo in orthotopic xenografts. Circulating and tumoral PlGF was elevated in patients with pancreatic NETs (pNETs) compared with control sera and respective healthy tissue. De novo PlGF expression occurred primarily in the tumor stroma, suggesting paracrine stimulatory circuits. Indeed, PlGF enhanced NET proliferation and migration in vitro and, conversely, neutralizing antibodies to PlGF reduced tumor growth in vivo. Elevated circulating PlGF levels in NET patients correlated with advanced tumor grading and were associated with reduced tumor-related survival in pNETs. Subsequent determinations confirmed and extended our observation of elevated PlGF levels in a prospective cohort of grade 1 and grade 2 pNETs (n=30) and intestinal NETs (n=57). In low-grade pNETs, normal circulating PlGF levels were associated with better survival. In intestinal NETs, circulating PlGF above median emerged as an independent prognostic factor for shorter time-to-progression in multivariate analyses. These data assign to PlGF a novel function in the pathobiology of NETs and propose PlGF as a prognostic parameter and therapeutic target.

11 Article Assessment and clinical implications of RANK/RANKL/OPG pathway as markers of bone tumor progression in patients with NET harboring bone metastases. 2013

Milone, F / Pivonello, C / Cariati, F / Sarnataro, M / Ramundo, V / Marotta, V / Jann, H / Pape, U-F / Wiedenmann, B / Colao, A / Pavel, M / Faggiano, A. ·Department of Molecular and Clinical Endocrinology and Oncology, Federico II University, Naples, Italy. ·Biomarkers · Pubmed #23336103.

ABSTRACT: INTRODUCTION: The impact on the survival of bone metastases (BM) in patients with neuroendocrine tumor (NET) is a matter of debate. BM have a key role in causing symptoms and in decreasing patients' quality of life. Although the mechanisms of the development of BM are not completely clear, it is now well understood that the Receptor Activator of Nuclear factor Kappa-B-/Ligand (RANK/RANKL)/osteoprotegerin (OPG) pathway plays a relevant role. AIM: To characterize the RANK/RANKL/OPG pathway in patients affected with NET. PATIENTS AND METHODS: Two cohorts of 15 patients each were enrolled in the study; one cohort was affected with NET without BM and the second cohort was affected with NET with BM. The serum RANK/RANKL/OPG pathway was assessed in both the groups. RESULTS: Serum OPG levels and RANKL/OPG ratio were lower and higher, respectively, in NET patients harboring BM than in those without BM. During the ROC analysis, a cut-off value of 1071 pg/ml for OPG and 0.62 for RANKL/OPG ratio were able to significantly distinguish between the two groups. CONCLUSIONS: This study indicates that RANK/RANKL/OPG pathway is imbalanced in patients with NET harboring BM. Specific alterations of this pathway could predict an early development of BM.

12 Article [Gastroenteropancreatic neuro-endocrine neoplasms]. 2012

Sigal, M / Pape, U / Wiedenmann, B. ·Medizinische Klinik mit Schwerpunkt Gastroenterologie, Hepatologie, interdisziplinäres Stoffwechselzentrum, Campus Virchow Klinikum, Charité Universitätsmedizin Berlin. ·Ther Umsch · Pubmed #23026885.

ABSTRACT: Neuroendocrine neoplasms (NEN) occur in the entire gastrointestinal tract. The updated classification of the WHO (2010) and current TNM-classification provide a basis for the therapeutic decision and assess the prognosis. Endoscopy and different imaging techniques are important for the localization of the primary tumor as well as local and distant metastases. The most important diagnostic imaging technique is somatostatin receptor scintigraphy. Therapeutic strategy should be discussed within the scope of a multidisciplinary tumor board. Surgery of NEN is the sole curative option. The treatment options for liver metastases include surgical resection as well as radiofrequency ablation and hepatic artery embolization. In advanced stage, systemic therapy should be used. Recent studies demonstrated a significantly prolonged progression-free survival using octreotide in well differentiated NEN. Besides the well established steptozotocine based chemotherapy regimens for pancreatic NEN, novel agents such as the mTOR-inhibitor everolimus and multityrosine kinase inhibitor sunitinib have recently also shown a prolonged progression-free survival. Moreover, temozolomide-based chemotherapy appears to be effective in pancreatic NEN. Finally, somatostatin receptor targeted radionuclide therapy can be effective in progressing gastroenteropancreatic NEN.

13 Article TNM staging of neoplasms of the endocrine pancreas: results from a large international cohort study. 2012

Rindi, G / Falconi, M / Klersy, C / Albarello, L / Boninsegna, L / Buchler, M W / Capella, C / Caplin, M / Couvelard, A / Doglioni, C / Delle Fave, G / Fischer, L / Fusai, G / de Herder, W W / Jann, H / Komminoth, P / de Krijger, R R / La Rosa, S / Luong, T V / Pape, U / Perren, A / Ruszniewski, P / Scarpa, A / Schmitt, A / Solcia, E / Wiedenmann, B. ·Institute of Anatomic Pathology, Università Cattolica del Sacro Cuore, Histopathology and Cytodiagnosis Unit, Policlinico Gemelli, Largo A. Gemelli, 8, Roma I-00168, Italy. guido.rindi@rm.unicatt.it ·J Natl Cancer Inst · Pubmed #22525418.

ABSTRACT: BACKGROUND: Both the European Neuroendocrine Tumor Society (ENETS) and the International Union for Cancer Control/American Joint Cancer Committee/World Health Organization (UICC/AJCC/WHO) have proposed TNM staging systems for pancreatic neuroendocrine neoplasms. This study aims to identify the most accurate and useful TNM system for pancreatic neuroendocrine neoplasms. METHODS: The study included 1072 patients who had undergone previous surgery for their cancer and for which at least 2 years of follow-up from 1990 to 2007 was available. Data on 28 variables were collected, and the performance of the two TNM staging systems was compared by Cox regression analysis and multivariable analyses. All statistical tests were two-sided. RESULTS: Differences in distribution of sex and age were observed for the ENETS TNM staging system. At Cox regression analysis, only the ENETS TNM staging system perfectly allocated patients into four statistically significantly different and equally populated risk groups (with stage I as the reference; stage II hazard ratio [HR] of death = 16.23, 95% confidence interval [CI] = 2.14 to 123, P = .007; stage III HR of death = 51.81, 95% CI = 7.11 to 377, P < .001; and stage IV HR of death = 160, 95% CI = 22.30 to 1143, P < .001). However, the UICC/AJCC/WHO 2010 TNM staging system compressed the disease into three differently populated classes, with most patients in stage I, and with the patients being equally distributed into stages II-III (statistically similar) and IV (with stage I as the reference; stage II HR of death = 9.57, 95% CI = 4.62 to 19.88, P < .001; stage III HR of death = 9.32, 95% CI = 3.69 to 23.53, P = .94; and stage IV HR of death = 30.84, 95% CI = 15.62 to 60.87, P < .001). Multivariable modeling indicated curative surgery, TNM staging, and grading were effective predictors of death, and grading was the second most effective independent predictor of survival in the absence of staging information. Though both TNM staging systems were independent predictors of survival, the UICC/AJCC/WHO 2010 TNM stages showed very large 95% confidence intervals for each stage, indicating an inaccurate predictive ability. CONCLUSION: Our data suggest the ENETS TNM staging system is superior to the UICC/AJCC/WHO 2010 TNM staging system and supports its use in clinical practice.

14 Article Cost comparison of 111In-DTPA-octreotide scintigraphy and 68Ga-DOTATOC PET/CT for staging enteropancreatic neuroendocrine tumours. 2012

Schreiter, Nils F / Brenner, Winfried / Nogami, Munenobu / Buchert, Ralph / Huppertz, Alexander / Pape, Ulrich-Frank / Prasad, Vikas / Hamm, Bernd / Maurer, Martin H. ·Department of Nuclear Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany. nils.schreiter@charite.de ·Eur J Nucl Med Mol Imaging · Pubmed #21927931.

ABSTRACT: PURPOSE: Although somatostatin receptor positron emission tomography (PET)/CT is gaining increasing popularity and has shown its diagnostic superiority in several studies, (111)In-diethylenetriaminepentaacetic acid (DTPA)-octreotide is still the current standard for diagnosis of neuroendocrine tumours (NET). The aim of this study was to compare the costs for the two diagnostic tests and the respective consequential costs. METHODS: From January 2009 to July 2009, 51 consecutive patients with enteropancreatic NET who underwent contrast-enhanced (68)Ga-DOTATOC PET/CT (n = 29) or (111)In-DTPA-octreotide (mean 3 whole-body scans plus 1.6 low-dose single photon emission computed tomography/CT; n = 22) were included. For cost analysis, direct costs (equipment) and variable costs (material, labour) per examination were calculated. Additionally required CT and/or MRI examinations within the staging process were assessed as consequential costs. An additional deterministic sensitivity analysis was performed. RESULTS: A (68)Ga-DOTATOC PET/CT examination yielded total costs (equipment, personnel and material costs) of 548 euro. On the other hand, an (111)In-DTPA-octreotide examination resulted in 827 euro total costs. Costs for equipment and material had a share of 460 euro/720 euro for (68)Ga-DOTATOC/(111)In-DTPA-octreotide and labour costs of 89 euro/106 euro. With (68)Ga-DOTATOC additional MRI had to be performed in 7% of the patients resulting in a mean of 20 euro for supplementary imaging per patient; 82% of patients with (111)In-DTPA-octreotide needed additional MRI and/or CT resulting in mean additional costs of 161 euro per patient. CONCLUSION: (68)Ga-DOTATOC PET/CT was considerably cheaper than (111)In-DTPA-octreotide with respect to both material and personnel costs. Furthermore, by using (68)Ga-DOTATOC PET/CT considerably fewer additional examinations were needed reducing the consequential costs significantly.