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Pancreatic Neoplasms: HELP
Articles by Ronald R. de Krijger
Based on 8 articles published since 2010
(Why 8 articles?)

Between 2010 and 2020, R. de Krijger wrote the following 8 articles about Pancreatic Neoplasms.
+ Citations + Abstracts
1 Article False-positive findings on 6-[18F]fluor-l-3,4-dihydroxyphenylalanine PET ( 2018

Berends, Annika M A / Kerstens, Michiel N / Bolt, Janne W / Links, Thera P / Korpershoek, Esther / de Krijger, Ronald R / Walenkamp, Annemiek M E / Noordzij, Walter / van Etten, Boudewijn / Kats-Ugurlu, Gursah / Brouwers, Adrienne H / van der Horst-Schrivers, Anouk N A. ·Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. · Department of Pathology, Erasmus University Medical Center, Rotterdam and Reinier de Graaf Hospital, Delft, The Netherlands. · Departments of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. · Departments of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. · Departments of Surgical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. · Departments of Pathology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. ·Eur J Endocrinol · Pubmed #29875288.

ABSTRACT: BACKGROUND/AIM: PET with 6-[18F]fluor-l-3,4-dihydroxyphenylalanine ( PATIENTS AND METHODS: Retrospective single-center study among adult patients in whom RESULTS: 1070 CONCLUSIONS: Pathological uptake of

2 Article Effects of Somatostatin Analogs and Dopamine Agonists on Insulin-Like Growth Factor 2-Induced Insulin Receptor Isoform A Activation by Gastroenteropancreatic Neuroendocrine Tumor Cells. 2016

van Adrichem, Roxanne C S / de Herder, Wouter W / Kamp, Kimberly / Brugts, Michael P / de Krijger, Ronald R / Sprij-Mooij, Diana M / Lamberts, Steven W J / van Koetsveld, Peter M / Janssen, Joseph A M J L / Hofland, Leo J. ·Division of Endocrinology, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands. ·Neuroendocrinology · Pubmed #26836610.

ABSTRACT: BACKGROUND: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) express insulin-like growth factor (IGF)-related factors [IGF1, IGF2; insulin receptor (IR)-A, IR-B; IGF-binding protein (IGFBP) 1-3] as well as somatostatin (SSTRs) and dopamine D2 receptors (D2Rs). OBJECTIVES: To (1) compare mRNA expression of IGF-related factors in human pancreatic NET (panNET) cell lines with that in human GEP-NETs to evaluate the usefulness of these cells as a model for studying the IGF system in GEP-NETs, (2) determine whether panNET cells produce growth factors that activate IR-A, and (3) investigate whether somatostatin analogs (SSAs) and/or dopamine agonists (DAs) influence the production of these growth factors. METHODS: In panNET cells (BON-1 and QGP-1) and GEP-NETs, mRNA expression of IGF-related factors was measured by quantitative real-time PCR. Effects of the SSAs octreotide and pasireotide (PAS), the DA cabergoline (CAB), and the dopastatin BIM-23A760 (all 100 nM) were evaluated at the IGF2 mRNA and protein level (by ELISA) and regarding IR-A bioactivity (by kinase receptor activation assay) in panNET cells. RESULTS: panNET cells and GEP-NETs had comparable expression profiles of IGF-related factors. Especially in BON-1 cells, IGF2 and IR-A were most highly expressed. PAS + CAB inhibited IGF2 (-29.5 ± 4.9%, p < 0.01) and IGFBP3 (-20.0 ± 4.0%, p < 0.01) mRNA expression in BON-1 cells. In BON-1 cells, IGF2 protein secretion was significantly inhibited with BIM-23A760 (-23.7 ± 3.8%). BON-1- but not QGP-1- conditioned medium stimulated IR-A bioactivity. In BON-1 cells, IR-A bioactivity was inhibited by BIM-23A760 and PAS + CAB (-37.8 ± 2.1% and -30.9 ± 4.1%, respectively, p < 0.0001). CONCLUSIONS: (1) The BON-1 cell line is a representative model for studying the IGF system in GEP-NETs, (2) BON-1 cells produce growth factors (IGF2) activating IR-A, and (3) combined SSTR and D2R targeting with PAS + CAB and BIM-23A760 suppresses IGF2-induced IR-A activation.

3 Article Neoadjuvant Treatment of Nonfunctioning Pancreatic Neuroendocrine Tumors with [177Lu-DOTA0,Tyr3]Octreotate. 2015

van Vliet, Esther I / van Eijck, Casper H / de Krijger, Ronald R / Nieveen van Dijkum, Elisabeth J / Teunissen, Jaap J / Kam, Boen L / de Herder, Wouter W / Feelders, Richard A / Bonsing, Bert A / Brabander, Tessa / Krenning, Eric P / Kwekkeboom, Dik J. ·Department of Nuclear Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands esthervanvliet@yahoo.com. · Department of Surgery, Erasmus Michoacande Ocampo, University Medical Center, Rotterdam, The Netherlands. · Department of Pathology, Erasmus Michoacande Ocampo, University Medical Center, Rotterdam, The Netherlands. · Department of Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. · Department of Nuclear Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. · Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands; and. · Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands. ·J Nucl Med · Pubmed #26272813.

ABSTRACT: METHODS: We studied 29 Dutch patients with a pathology-proven nonfunctioning pancreatic NET treated with (177)Lu-octreotate. All patients had a borderline or unresectable pancreatic tumor (group 1) or oligometastatic disease (defined as ≤3 liver metastases) (group 2). Progression-free survival (PFS) was analyzed using the Kaplan-Meier method and Cox proportional hazards modeling. RESULTS: After the treatment with (177)Lu-octreotate, successful surgery was performed in 9 of 29 patients (31%). Six patients had a Whipple procedure, 2 patients had a pylorus-preserving pancreaticoduodenectomy, and 1 patient had a distal pancreatectomy and splenectomy. The median PFS was 69 mo for patients with successful surgery and 49 mo for the other patients. For comparison, the median PFS in 90 other patients with a nonfunctioning pancreatic NET with more than 3 liver metastases or other metastases was 25 mo. CONCLUSION: Neoadjuvant treatment with (177)Lu-octreotate is a valuable option for patients with initially unresectable pancreatic NETs.

4 Article Succinate Dehydrogenase (SDH)-Deficient Pancreatic Neuroendocrine Tumor Expands the SDH-Related Tumor Spectrum. 2015

Niemeijer, Nicolasine D / Papathomas, Thomas G / Korpershoek, Esther / de Krijger, Ronald R / Oudijk, Lindsey / Morreau, Hans / Bayley, Jean-Pierre / Hes, Frederik J / Jansen, Jeroen C / Dinjens, Winand N M / Corssmit, Eleonora P M. ·Department of Endocrinology and Metabolic Diseases (N.D.N., E.P.M.C.), Leiden University Medical Center, 2300 RC Leiden, The Netherlands · Department of Pathology (T.G.P., E.K., L.O., W.N.M.D., R.R.d.K.) Erasmus Medical Center, 3015 CE Rotterdam, The Netherlands · Department of Pathology (R.R.d.K.), Reinier de Graaf Hospital, 2625 AD Delft, The Netherlands · and Departments of Pathology (H.M.), Human Genetics (J.P.B.), Clinical Genetics (F.J.H.), and Otorhinolaryngology (J.C.J.), Leiden University Medical Center, 2300 RC Leiden, The Netherlands. ·J Clin Endocrinol Metab · Pubmed #26259135.

ABSTRACT: CONTEXT: Mutations in genes encoding the subunits of succinate dehydrogenase (SDH) can lead to pheochromocytoma/paraganglioma formation. However, SDH mutations have also been linked to nonparaganglionic tumors. OBJECTIVE: The objective was to investigate which nonparaganglionic tumors belong to the SDH-associated tumor spectrum. DESIGN: This was a retrospective cohort study. SETTING: The setting was a tertiary referral center. PATIENTS: Patients included all consecutive SDHA/SDHB/SDHC and SDHD mutation carriers followed at the Department of Endocrinology of the Leiden University Medical Center who were affected by non-pheochromocytoma/paraganglioma solid tumors. MAIN OUTCOME MEASURES: Main outcome measures were SDHA/SDHB immunohistochemistry, mutation analysis, and loss of heterozygosity analysis of the involved SDH-encoding genes. RESULTS: Twenty-five of 35 tumors (from 26 patients) showed positive staining on SDHB and SDHA immunohistochemistry. Eight tumors showed negative staining for SDHB and positive staining for SDHA: a pancreatic neuroendocrine tumor, a macroprolactinoma, two gastric gastrointestinal stromal tumors, an abdominal ganglioneuroma, and three renal cell carcinomas. With the exception of the abdominal ganglioneuroma, loss of heterozygosity was detected in all tumors. A prolactinoma in a patient with a germline SDHA mutation was the only tumor immunonegative for both SDHA and SDHB. Sanger sequencing of this tumor revealed a somatic mutation (p.D38V) as a likely second hit leading to biallelic inactivation of SDHA. One tumor (breast cancer) showed heterogeneous SDHB staining, positive SDHA staining, and retention of heterozygosity. CONCLUSIONS: This study strengthens the etiological association of SDH genes with pituitary neoplasia, renal tumorigenesis, and gastric gastrointestinal stromal tumors. Furthermore, our results indicate that pancreatic neuroendocrine tumor also falls within the SDH-related tumor spectrum.

5 Article [Appendectomy followed by a pancreaticoduodenectomy: a solid pseudopapillary neoplasm of the pancreas]. 2015

Fest, Jesse / van den Boom, Anne Loes / de Krijger, Ronald R / Roos, Daphne. ·Reinier de Graaf Gasthuis, Delft. ·Ned Tijdschr Geneeskd · Pubmed #26173659.

ABSTRACT: BACKGROUND: Increasing usage and improved quality of imaging has increased the probability of incidentalomas which raises the question of how to deal with them. The following case illustrates the incidental finding of a tumour on a CT-scan. CASE DESCRIPTION: A 23-year-old woman presented at our emergency department with acute abdominal pain. During the workup we found that in addition to an acute appendicitis, she had a tumour in the pancreas. Cytology initially indicated pancreatic carcinoma, however, further analysis showed a solid pseudopapillary neoplasm of the pancreas. The patient underwent a pylorus-preserving pancreaticoduodenectomy. CONCLUSION: A solid pseudopapillary neoplasm is a relatively rare disorder of the pancreas which is mostly seen in young females. It is a benign disorder carrying a small risk of malignant transformation. A pylorus-preserving pancreaticoduodenectomy is the treatment of choice for this benign tumour of the head of pancreas.

6 Article Tumor response assessment to treatment with [177Lu-DOTA0,Tyr3]octreotate in patients with gastroenteropancreatic and bronchial neuroendocrine tumors: differential response of bone versus soft-tissue lesions. 2012

van Vliet, Esther I / Hermans, John J / de Ridder, Maria A / Teunissen, Jaap J / Kam, Boen L / de Krijger, Ronald R / Krenning, Eric P / Kwekkeboom, Dik J. ·Department of Nuclear Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. e.i.vanvliet@erasmusmc.nl ·J Nucl Med · Pubmed #22782312.

ABSTRACT: METHODS: Forty-two patients with well-differentiated NETs who had bone metastases that were positive on [(111)In-DTPA(0)]octreotide somatostatin receptor scintigraphy (SRS) before treatment, and who had soft-tissue lesions, were studied. All patients had had a minimum of 1 follow-up CT scan. Lesions were scored on CT and bone lesions also on SRS before and after treatment. Tumor markers (chromogranin A and 5-hydroxyindoleacetic acid) before and after treatment were compared. RESULTS: Because bone lesions were not visible on CT before treatment in 11 of 42 patients (26%), bone and soft-tissue lesions were evaluated in 31 patients. Whereas bone lesions increased in size, soft-tissue lesions decreased in size. The percentage change in bone and soft-tissue lesions was significantly different at all time points up to 12 mo of follow-up (P < 0.001). The intensity or number of bone lesions on SRS decreased after treatment in 19 of 23 patients (83%) in whom SRS after treatment was available. The tumor markers also decreased significantly after treatment. In 1 patient, bone lesions became visible on CT after treatment, mimicking progressive disease with "new" bone lesions, although there was an overall treatment response. CONCLUSION: In patients with NETs, the apparent increase in size of bone lesions or the appearance of new bone lesions on CT after treatment with (177)Lu-octreotate should be interpreted cautiously, as this finding may be therapy-related rather than indicative of tumor progression.

7 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.

8 Article Immunohistochemical localization and quantitative expression of somatostatin receptors in normal human spleen and thymus: Implications for the in vivo visualization during somatostatin receptor scintigraphy. 2012

Ferone, D / Pivonello, R / Kwekkeboom, D J / Gatto, F / Ameri, P / Colao, A / de Krijger, R R / Minuto, F / Lamberts, S W J / van Hagen, P M / Hofland, L J. ·Department of Endocrinological and Medical Sciences and Center of Excellence for Biomedical Research, University of Genoa, Viale Benedetto XV, 6-16132-Genoa, Italy. ferone@unige.it ·J Endocrinol Invest · Pubmed #21765239.

ABSTRACT: BACKGROUND: [111In-DTPA-D-Phe1]-octreotide scintigraphy allows the visualization of SRIF receptor (SSR)-expressing tumors, including thymic tumors, and normal tissues. While the spleen is clearly visualized, the thymus is not depicted, although both contain SSR. AIM: We evaluated whether the heterogeneity, the type, and the amount of SSR might explain this contrasting finding. MATERIALS, METHODS, AND RESULTS: By ligand-binding the number of [125I-Tyr11]-SRIF- 14 binding sites resulted comparable between the two tissues, whereas the number of [125I-Tyr3]-octreotide sites was significantly higher in the spleen (p<0.001). Quantitative RTPCR showed a significantly higher expression of sst2A mRNA in the spleen, whereas a significantly higher expression of SRIF and sst3 in the thymus. The highest density of sst2A in the spleen is in line with the in vivo uptake of [111In-DTPA-D-Phe1]- octreotide, which is considered a sst2-preferring ligand. The specificity is confirmed by the evidence that in vivo [111In-DTPA- D-Phe1]-octreotide uptake can be abolished during chronic administration of "cold" octreotide. Immunohistochemistry confirmed a preferential expression of sst2A on microenvironmental cells and of sst3 on lymphoid cells. CONCLUSIONS: The heterogeneity of SSR expression and the higher SRIF content explain the lack of thymus visualization during scintigraphy, whereas thymic tumors, which do not express SRIF, are visualized. Apart from the affinity of the radioligand, also the efficacy of the internalization is crucial for the in vivo uptake, and both heterogeneity and SRIF content affect this process. These observations might have an important impact when interpretating in vivo visualization of SSR-positive lesions, and when treatment with novel SRIF analogs is considered.