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Pancreatic Neoplasms: HELP
Articles by Richard A. Feelders
Based on 17 articles published since 2010
(Why 17 articles?)
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Between 2010 and 2020, R. A. Feelders wrote the following 17 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Review New therapeutic options for metastatic malignant insulinomas. 2011

de Herder, Wouter W / van Schaik, Ellen / Kwekkeboom, Dik / Feelders, Richard A. ·Department of Internal Medicine, Sector of Endocrinology, Erasmus MC, Rotterdam, the Netherlands. w.w.deherder@erasmusmc.nl ·Clin Endocrinol (Oxf) · Pubmed #21649688.

ABSTRACT: Insulinomas are the most common, functioning, pancreatic neuroendocrine tumours. The great majority (>90%) of insulinomas are nonmetastatic at presentation and can be surgically cured. The <10% patients with distant (liver-bone) metastases have a median survival of < 2 years. Everolimus and sunitinib have been recently introduced as targeted therapies for metastatic pancreatic neuroendocrine tumours. An additional advantage of everolimus in the treatment of patients with metastatic insulinomas is its capability to increase blood glucose levels. Peptide receptor radiotherapy using radiolabelled somatostatin analogues has also been shown to be successful in controlling tumour growth of metastatic pancreatic neuroendocrine tumours. In patients with metastatic insulinomas, this therapeutic modality was also effective in controlling hypoglycaemia, even in the presence of tumour regrowth. With the introduction of these new therapeutic modalities, the therapeutic arsenal for the 'tailor-made' approach of patients with metastatic insulinomas is further expanded.

2 Article Effects of Ketoconazole on ACTH-Producing and Non-ACTH-Producing Neuroendocrine Tumor Cells. 2019

Herrera-Martínez, Aura D / Feelders, Richard A / de Herder, Wouter W / Castaño, Justo P / Gálvez Moreno, María Ángeles / Dogan, Fadime / van Dungen, Rosanna / van Koetsveld, Peter / Hofland, Leo J. ·Department of Internal Medicine, Division of Endocrinology, Erasmus MC, Wytemaweg 80, 3015, CN, Rotterdam, The Netherlands. · Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), Córdoba, Spain. · Department of Internal Medicine, Division of Endocrinology, Erasmus MC, Wytemaweg 80, 3015, CN, Rotterdam, The Netherlands. l.hofland@erasmusmc.nl. ·Horm Cancer · Pubmed #31102172.

ABSTRACT: Prolonged remission of hypercortisolism with steroidogenesis inhibitors has been described in patients with ectopic adrenocorticotropic hormone (ACTH) syndrome. The anti-proliferative and pro-apoptotic effect of ketoconazole in human cancer cells was previously suggested. The aim of this study was to explore the effects of ketoconazole on ACTH-producing and non-ACTH-producing neuroendocrine tumor (NET) cell lines. The effects of ketoconazole alone, and in combination with somatostatin analogs, were evaluated in two human cell lines: DMS-79 (ectopic ACTH-producing small cell lung carcinoma) and BON-1 (human pancreatic NET). Total DNA measurement, apoptosis, cell cycle, chromogranin A (CgA)/proopiomelanocortin (POMC) expression by qRT-PCR, serotonin, CgA, and ACTH secretion assays were performed. In both cell lines, ketoconazole significantly suppressed cell growth and colony formation in a dose and time-dependent manner. The effect in DMS-79 was primarily cytotoxic, while it was more apoptotic in BON-1 cells. Ketoconazole also induced increase in G0/G1 phase in both cell lines and arrest in phase G2/M of BON-1 cells. Ketoconazole did not affect the secretion of serotonin, CgA, ACTH, or the mRNA expression of CgA and POMC. Decreased serotonin secretion was observed after the combination treatment with pasireotide. These results suggest a direct effect of ketoconazole on cell proliferation, apoptosis, and cell cycle in both ACTH- and non-ACTH-producing NET cells.

3 Article Hyponatraemia and hyperpigmentation in primary adrenal insufficiency. 2019

Benner, Bernadette Johanna Maria / Alsma, Jelmer / Feelders, Richard A. ·Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands. ·BMJ Case Rep · Pubmed #30850564.

ABSTRACT: Hyponatraemia is a common electrolyte disturbance with multiple causes. We present a case of a 49-year-old Caucasian female with cholangiocarcinoma, who had a hyponatraemia which was initially assumed to be based on a syndrome of inappropriate antidiuretic hormone secretion as paraneoplastic phenomenon. At physical examination, hyperpigmentation was seen and multiple episodes with syncope were reported. Subsequent endocrine assessment with a synthetic adrenocorticotropin hormone (ACTH) stimulation test and measurement of ACTH levels revealed primary adrenal insufficiency also known as Morbus Addison. We started hydrocortisone and fludrocortisone replacement therapy, resulting in resolving of symptoms, hyponatraemia and hyperpigmentation.

4 Article Symptomatic and Radiological Response to 177Lu-DOTATATE for the Treatment of Functioning Pancreatic Neuroendocrine Tumors. 2019

Zandee, Wouter T / Brabander, Tessa / Blažević, Anela / Kam, Boen L R / Teunissen, Jaap J M / Feelders, Richard A / Hofland, Johannes / de Herder, Wouter W. ·Department of Internal Medicine, Sector of Endocrinology, Erasmus Medical Center and Erasmus MC Cancer Institute, Rotterdam, Netherlands. · Department of Radiology & Nuclear Medicine, Erasmus Medical Center and Erasmus MC Cancer Institute, Rotterdam, Netherlands. ·J Clin Endocrinol Metab · Pubmed #30566620.

ABSTRACT: PURPOSE: Peptide receptor radionuclide therapy (PRRT) with the radiolabeled somatostatin analogue [Lutetium-177-DOTA0-Tyr3]octreotate (177Lu-DOTATATE) is widely applied for inoperable metastatic small intestinal and nonfunctioning pancreatic neuroendocrine tumors (pNETs). The aim of this study is to describe the safety and efficacy of the treatment of functioning pNETs. METHODS: Patients were treated with up to four cycles of 177Lu-DOTATATE with an intended dose of 7.4 Gbq per cycle. Radiological (Response Evaluation Criteria in Solid Tumors 1.1), symptomatic, and biochemical response were analyzed retrospectively for all patients with a functioning pNET (insulinoma, gastrinoma, VIPoma, and glucagonoma) treated with 177Lu-DOTATATE. Quality of life (QOL) was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core Module questionnaire. RESULTS: Thirty-four patients with a metastatic functioning pNET (European Neuroendocrine Tumor Society grade 1 or 2) were included: 14 insulinomas, 5 VIPomas, 7 gastrinomas, and 8 glucagonomas. Subacute hematological toxicity, grade 3 or 4 occurred in 4 patients (12%) and a hormonal crisis in 3 patients (9%). PRRT resulted in partial or complete response in 59% of patients and the disease control rate was 78% in patients with baseline progression. 71% of patients with uncontrolled symptoms had a reduction of symptoms and a more than 80% decrease of circulating hormone levels was measured during follow-up. After PRRT, median progression-free survival was 18.1 months (interquartile range: 3.3 to 35.7) with a concurrent increase in QOL. CONCLUSION: Treatment with 177Lu-DOTATATE is a safe and effective therapy resulting in radiological, symptomatic and biochemical response in a high percentage of patients with metastatic functioning pNETs. Hormonal crises occur relatively frequent and preventive therapy should be considered before and/or during PRRT.

5 Article Salvage peptide receptor radionuclide therapy with [ 2019

van der Zwan, W A / Brabander, T / Kam, B L R / Teunissen, J J M / Feelders, R A / Hofland, J / Krenning, E P / de Herder, W W. ·Department of Radiology & Nuclear Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands. w.vanderzwan@erasmusmc.nl. · Department of Radiology & Nuclear Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands. · Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands. · Cyclotron Rotterdam BV, Erasmus Medical Centre, Rotterdam, The Netherlands. ·Eur J Nucl Med Mol Imaging · Pubmed #30267116.

ABSTRACT: PURPOSE: Therapy with [ METHODS: Patients with progressive bronchial NET or GEP-NET were selected for re-(re)treatment if they had benefited from initial peptide receptor radionuclide therapy (I-PRRT) with a minimal progression-free survival (PFS) of 18 months. Patients received an additional cumulative dose of 14.8 GBq of [ RESULTS: The safety and efficacy analyses included 181 patients and 168 patients, respectively, with bronchial NET or GEP-NET. Overall median follow-up was 88.6 months (95% CI 79.0-98.2). Median cumulative doses were 44.7 GBq (range 26.3-46.4 GBq) during R-PRRT (168 patients) and 59.7 GBq (range 55.2-≤60.5 GBq) during RR-PRRT (13 patients). Objective response and stable disease, as best response, were observed in 26 patients (15.5%) and 100 patients (59.5%) following R-PRRT, and in 5 patients (38.5%) and 7 patients (53.8%) following RR-PRRT, respectively. Median PFS was 14.6 months (95% CI 12.4-16.9) following R-PRRT and 14.2 months (95% CI 9.8-18.5) following RR-PRRT. Combined overall survival (OS) after I-PRRT plus R-PRRT and RR-PRRT was 80.8 months (95% CI 66.0-95.6). Grade III/IV bone marrow toxicity occurred in 6.6% and 7.7% of patients after R-PRRT and RR-PRRT, respectively. Salvage therapy resulted in a significantly longer OS in patients with bronchial NET, GEP-NET and midgut NET than in a nonrandomized control group. The total incidence of acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) was 2.2%. No PRRT-related grade III/IV nephrotoxicity was observed. CONCLUSION: A cumulative dose of up to 60.5 GBq salvage PRRT with [

6 Article Incidence and prognostic value of serotonin secretion in pancreatic neuroendocrine tumours. 2017

Zandee, Wouter T / van Adrichem, Roxanne C / Kamp, Kimberly / Feelders, Richard A / van Velthuysen, Marie-Louise F / de Herder, Wouter W. ·Department of Internal Medicine, Sector Endocrinology, ENETS Centre of Excellence, Erasmus MC Cancer Institute, Erasmus MC, Rotterdam, The Netherlands. · Department of Pathology, Erasmus MC, Rotterdam, The Netherlands. ·Clin Endocrinol (Oxf) · Pubmed #28464233.

ABSTRACT: BACKGROUND: Serotonin secretion occurs in approximately 1%-4% of patients with a pancreatic neuroendocrine tumour (PNET), but the incidence is not well defined. The aim of this study was to determine the incidence of serotonin secretion with and without carcinoid syndrome and the prognostic value for overall survival (OS). METHODS: Data were collected from 255 patients with a PNET if 24-hours urinary 5-hydroxyindoleacetic acid excretion (5-HIAA) was assessed. Patients were diagnosed with serotonin secretion if 24-hours urinary 5-HIAA excretion was more than 3× the upper limit of normal (ULN) of 50 μmol/24 hours during follow-up. The effect of serotonin secretion on OS was estimated with uni- and multivariate analyses using a Cox regression. RESULTS: Two (0.8%) patients were diagnosed with carcinoid syndrome, and another 20 (7.8%) had a serotonin-secreting PNET without symptoms. These patients mostly had ENETS stage IV disease with high chromogranin A (CgA). Serotonin secretion was a negative prognostic factor in univariate analysis (HR 2.2, 95% CI: 1.27-3.81), but in multivariate analysis, only CgA>10× ULN (HR: 1.81, 95% CI: 1.10-2.98) and neuron-specific enolase (NSE) >ULN (HR: 3.51, 95% CI: 2.26-5.46) were predictors for OS. Immunohistochemical staining for serotonin was positive in 28.6% of serotonin-secreting PNETs (one with carcinoid syndrome) and negative in all controls. CONCLUSION: Carcinoid syndrome is rare in patients with a PNET, but serotonin secretion occurs often. This is a negative prognostic factor for OS, but after correction for CgA and NSE, it is no longer a predictor and probably only a "not-so innocent bystander" in patients with high tumour burden.

7 Article Long-Term Efficacy, Survival, and Safety of [ 2017

Brabander, Tessa / van der Zwan, Wouter A / Teunissen, Jaap J M / Kam, Boen L R / Feelders, Richard A / de Herder, Wouter W / van Eijck, Casper H J / Franssen, Gaston J H / Krenning, Eric P / Kwekkeboom, Dik J. ·Department of Radiology & Nuclear Medicine, Erasmus Medical Center, Rotterdam, the Netherlands. t.brabander@erasmusmc.nl. · Department of Radiology & Nuclear Medicine, Erasmus Medical Center, Rotterdam, the Netherlands. · Department of Internal Medicine, Erasmus Medical Center, ENETS Center of Excellence, Rotterdam, the Netherlands. · Department of Surgery, Erasmus Medical Center, Rotterdam, the Netherlands. ·Clin Cancer Res · Pubmed #28428192.

ABSTRACT:

8 Article Prevalence and clinical features of the ectopic ACTH syndrome in patients with gastroenteropancreatic and thoracic neuroendocrine tumors. 2016

Kamp, K / Alwani, R A / Korpershoek, E / Franssen, G J H / de Herder, W W / Feelders, R A. ·Sector of EndocrinologyDepartment of Internal MedicineDepartment of PathologyDepartment of Surgery, ENETS Center of Excellence, Erasmus Medical Center's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands k.kamp@erasmusmc.nl. · Sector of EndocrinologyDepartment of Internal MedicineDepartment of PathologyDepartment of Surgery, ENETS Center of Excellence, Erasmus Medical Center's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands. ·Eur J Endocrinol · Pubmed #26643855.

ABSTRACT: OBJECTIVE: Several series report on the relative contribution of ectopic ACTH syndrome (EAS) in the spectrum of Cushing's syndrome. However, prevalence of EAS in patients with thoracic or gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is currently unknown. DESIGN: We assessed, in a tertiary referral center, the prevalence of EAS in a large cohort of thoracic and GEP-NET patients including clinical, biochemical, and radiological features; management; and treatment outcome. METHODS: In total, 918 patients with thoracic or GEP-NETs were studied (1993-2012). Multiple endocrine neoplasia type 1 and small cell lung carcinoma patients were excluded. Differentiation between synchronous, metachronous, and cyclic occurrence of EAS was made. RESULTS: Out of the 918 patients with thoracic and GEP-NETs (469 males and 449 females; median age 58.7 years (range: 17.3-87.3)), 29 patients (3.2%) had EAS (ten males and 19 females; median age 48.1 years (range: 24.7-77.9)). EAS occurred synchronously in 23 patients (79%), metachronously in four patients (14%), and cyclical in two patients (7%) respectively. NETs causing EAS included lung/bronchus (n=9), pancreatic (n=9), and thymic (n=4). In four patients, the cause of EAS was unknown (n=4). Median overall survival (OS) of non-EAS thoracic and GEP-NET patients was 61.2 months (range: 0.6-249.4). Median OS of EAS patients was 41.4 months (range: 2.2-250.9). After comparison, only the first 5-year survival was significantly shorter (P=0.013) in EAS patients. CONCLUSION: Prevalence of EAS in this large cohort of patients with thoracic and GEP-NETs was 3.2%. EAS was mostly caused by thoracic and pancreatic NETs. First 5-year survival of EAS patients was shorter compared with non-EAS patients.

9 Article Is There an Additional Value of Using Somatostatin Receptor Subtype 2a Immunohistochemistry Compared to Somatostatin Receptor Scintigraphy Uptake in Predicting Gastroenteropancreatic Neuroendocrine Tumor Response? 2016

van Adrichem, Roxanne C S / Kamp, Kimberly / van Deurzen, Carolien H M / Biermann, Katharina / Feelders, Richard A / Franssen, Gaston J H / Kwekkeboom, Dik J / Hofland, Leo J / de Herder, Wouter W. · ·Neuroendocrinology · Pubmed #26536001.

ABSTRACT: BACKGROUND AND AIMS: It is unknown whether tumoral somatostatin receptor subtype 2a (sst2a) immunohistochemistry (IHC) has additional value compared to somatostatin receptor scintigraphy (SRS) uptake using OctreoScan® in predicting response to peptide receptor radiotherapy using 177Lu-octreotate (PRRT) in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs). The aims of this study were: (1) to establish the percentage of sst2a immunopositivity in GEP-NET samples of PRRT-treated patients, (2) to determine the relationship between best GEP-NET response using RECIST 1.0 criteria 1 year after PRRT and tumoral sst2a IHC, and (3) to compare characteristics of patients with sst2a IHC-negative and -positive tumors. METHODS: All 73 consecutive patients were selected for PRRT based on a positive SRS. Radiological response was scored according to RECIST 1.0 criteria. sst2a status was detected on tumor samples by IHC. RESULTS: In total, 93% of GEP-NET samples showed sst2a IHC positivity. No statistically significant relationship was observed between in vitro sst2a expression and in vivo best GEP-NET response 1 year after PRRT (p = 0.47). Sex, primary tumor site, disease stage, ENETS TNM classification, Ki-67 index, highest serum chromogranin-A level, and highest neuron-specific enolase level were not significantly different between patients with negative and positive sst2a tumoral IHC with the exception of age at diagnosis (p = 0.007). CONCLUSIONS: sst2a IHC of tumor samples has no additional value compared to SRS uptake using OctreoScan® in predicting tumor response after PRRT.

10 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.

11 Article EUS is superior for detection of pancreatic lesions compared with standard imaging in patients with multiple endocrine neoplasia type 1. 2015

van Asselt, Sophie J / Brouwers, Adrienne H / van Dullemen, Hendrik M / van der Jagt, Eric J / Bongaerts, Alfons H H / Kema, Ido P / Koopmans, Klaas P / Valk, Gerlof D / Timmers, Henri J / de Herder, Wouter W / Feelders, Richard A / Fockens, Paul / Sluiter, Wim J / de Vries, Elisabeth G E / Links, Thera P. ·Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. · Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. · Department of Gastroenterology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. · Department of Radiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. · Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. · Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. · Department of Nuclear Medicine and Molecular Imaging, Martini Hospital Groningen, Groningen, The Netherlands. · Department of Endocrinology, University Medical Center Utrecht, Utrecht, The Netherlands. · Department of Medicine, Division of Endocrinology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. · Department of Endocrinology, University Erasmus Medical Center, Rotterdam, The Netherlands. · Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. · Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. · Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. ·Gastrointest Endosc · Pubmed #25527055.

ABSTRACT: BACKGROUND: In multiple endocrine neoplasia type 1 (MEN1), pancreatic neuroendocrine tumors (pNETs) are the leading MEN1-related cause of death. OBJECTIVE: To evaluate EUS and (11)C-5-hydroxytryptophan positron emission tomography ((11)C-5-HTP PET), compared with the recommended screening techniques in MEN1 patients for early detection of pNETs. DESIGN: Cross-sectional study. SETTING: Tertiary-care university medical center. PATIENTS: This study involved 41 patients with a proven MEN1 mutation or with one MEN1 manifestation and a mutation carrier as a first-degree family member, with recent screening by abdominal CT or magnetic resonance imaging (MRI) and somatostatin receptor scintigraphy (SRS). INTERVENTIONS: EUS by using a linear Pentax echoendoscope and Hitachi EUB-525 and (11)C-5-HTP PET. MAIN OUTCOME MEASUREMENTS: Patient-based and lesion-based positivity for pNET was calculated for all imaging techniques. The McNemar test was used to compare the yield of the 4 imaging techniques. RESULTS: In 35 of 41 patients, 107 pancreatic lesions were detected in total. EUS detected 101 pancreatic lesions in 34 patients, (11)C-5-HTP PET detected 35 lesions in 19 patients, and CT/MRI + SRS detected 32 lesions in 18 patients (P < .001). (11)C-5-HTP PET performed similarly to CT/MRI + SRS and better compared with SRS only (13 lesions in 12 patients), both at a patient-based and lesion-based level (P < .05). LIMITATIONS: Single-center study. CONCLUSION: EUS is superior to CT/MRI + SRS for pancreatic lesion detection in patients with MEN1. In this setting, (11)C-5-HTP PET is not useful. We recommend EUS as the first-choice pancreas imaging technique in patients with MEN1. ( CLINICAL TRIAL REGISTRATION NUMBER: NTR1668.).

12 Article Parathyroid hormone-related peptide (PTHrP) secretion by gastroenteropancreatic neuroendocrine tumors (GEP-NETs): clinical features, diagnosis, management, and follow-up. 2014

Kamp, Kimberly / Feelders, Richard A / van Adrichem, Roxanne C S / de Rijke, Yolanda B / van Nederveen, Francien H / Kwekkeboom, Dik J / de Herder, Wouter W. ·Department of Internal Medicine, Sector of Endocrinology (K.K., R.A.F., R.C.S.v.A., W.W.d.H.), Department of Clinical Chemistry (Y.B.d.R.), Department of Pathology (F.H.v.N.), and Department of Nuclear Medicine (D.J.K.), ENETS Centre of Excellence, Erasmus Medical Center, 3015 CE Rotterdam, The Netherlands. ·J Clin Endocrinol Metab · Pubmed #24905065.

ABSTRACT: CONTEXT: Only a small number of case reports has been published on patients with PTHrP-hypersecreting metastatic gastroenteropancreatic (GEP) neuroendocrine tumors (NETs). OBJECTIVE: The objective of this study was to evaluate the clinical, biochemical, and radiological features, management, and treatment outcome of patients with PTHrP-hypersecreting GEP-NETs. DESIGN: Retrospective case series. SETTING: Tertiary referral hospital. MAIN OUTCOME MEASURES: Clinical, biochemical, and radiological features were measured, as well as response to therapy and survival. PATIENTS: Ten patients with PTHrP-secreting GEP-NETs (nine pancreatic and one unknown primary) with a median age of 50.4 years (range, 38.3-61.1) were studied. Multiple endocrine neoplasia type 1 patients were excluded. RESULTS: The median follow-up was 57.2 months (range, 11.6-204.5 mo). Median overall survival was 86.0 months. In total, 51 different treatment interventions and combinations were applied. In seven of the 10 patients, somatostatin analog (SSA) treatment resulted in a temporary normalization of serum calcium levels with a long-term response observed in two patients (up to 35.2 mo). Peptide receptor radiotherapy (PRRT) with radiolabeled SSAs induced long-term responses ranging from 9.0-49.0 months in four of six patients treated with PRRT. CONCLUSIONS: Hypersecretion of PTHrP by metastatic GEP-NETs is very rare and seems to be exclusively associated with metastatic pancreatic NETs. PTHrP production has major clinical impact because poorly controllable hypercalcemia is associated with increased morbidity and mortality. The most successful treatment options for PTHrP-producing GEP-NETs are SSAs and PRRT using radiolabeled SSAs. Isotonic saline and bisphosphonates can be considered as supportive therapies.

13 Article Safety and efficacy of everolimus in gastrointestinal and pancreatic neuroendocrine tumors after (177)Lu-octreotate. 2013

Kamp, Kimberly / Gumz, Brenda / Feelders, Richard A / Kwekkeboom, Dik J / Kaltsas, Gregory / Costa, Frederico P / de Herder, Wouter W. ·Sector of Endocrinology, Department of Internal Medicine Department of Nuclear Medicine, Erasmus Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands Centro de Oncologia, Hospital Sírio Libanês, São Paulo, Brazil Department of Pathophysiology, National University of Athens, Athens, Greece. ·Endocr Relat Cancer · Pubmed #24036133.

ABSTRACT: Although (177)Lu-octreotate is an effective treatment for patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs), some patients will fail or develop disease progression necessitating further treatment. We examined whether the safety and efficacy of everolimus after prior treatment with (177)Lu-octreotate is different from the published safety profile of everolimus in GEP-NETs. In this multicenter study, 24 GEP-NET patients were included. Adverse events were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Tumor response was measured according to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.0. Major clinical adverse events (grade 3 or 4) during treatment with everolimus were hyperglycemia (20.8%), fatigue (8.3%), thrombocytopenia (8.3%), and elevated alanine transaminase levels (8.3%). By radiological review, there were four partial responses (16.7%), five patients (62.5%) with stable disease, and three patients (12.5%) with progressive disease. For two patients (8.3%), no data on tumor response were available. Median progression-free survival (PFS) was 13.1 months (95% CI, 11.5-21.2). Median PFS of the current study was longer when compared with the RADIANT-3 trial (13.1 vs 11.4 months) and shorter when compared with the RADIANT-1 trial (13.1 vs 16.7 months). In conclusion, the safety profile of everolimus is not influenced by previous treatment with peptide receptor radiotherapy.

14 Article The prevalence and relevance of adrenal masses in patients with sporadic gastroenteropancreatic neuroendocrine tumours (GEP-NET). 2013

Kanakis, George / Kamp, Kimberly / Tsiveriotis, Konstantinos / Feelders, Richard A / Zormpala, Alexandra / de Herder, Wouter W / Kaltsas, Gregory. ·Department of Pathophysiology, Endocrine Unit, University of Athens Medical School, Athens, Greece. geokan@endo.gr ·Clin Endocrinol (Oxf) · Pubmed #22970733.

ABSTRACT: OBJECTIVE: The widespread application of abdominal computerized tomography (CT) imaging has revealed that 0.98-4.0% of individuals harbour adrenal lesions (incidentalomas). There is, however, paucity of information regarding the prevalence of adrenal lesions in patients with gastroenteropancreatic neuroendocrine tumours (GEP-NETS). Purpose of this study was to estimate the prevalence of adrenal lesions in patients with GEP-NETS and identify their radiological features and clinical significance. DESIGN: The prevalence of adrenal lesions was estimated retrospectively in 438 patients with GEP-NETS who underwent abdominal imaging. Secretory status and changes in size were documented during subsequent follow-up. MEN-1 patients and ectopic ACTH-secreting tumours were excluded. RESULTS: Adrenal lesions were detected in 32 (8.4%) of 383 patients included. The majority (22 patients - 69%) were located at the left adrenal gland and the mean size was 23.6 mm. In two patients, one with a well and another with a poorly differentiated tumour, clinicopathological features suggested adrenal metastases. During a mean follow-up period of 69.5 months, no subsequent growth of any adrenal lesion was observed. Endocrine evaluation documented subclinical glucocorticoid hypersecretion in 4 cases (14%). The presence of adrenal lesions did not correlate to distant metastases, however, they were observed more frequently in patients with G3 tumours. CONCLUSION: The prevalence of adrenal lesions in patients with GEP-NETs was found to be higher than the general population and mostly represent benign adrenal adenomas (except patients with G3 tumours). Nevertheless, individualized assessment of imaging characteristics should be still considered.

15 Article Occurrence of second primary malignancies in patients with neuroendocrine tumors of the digestive tract and pancreas. 2012

Kamp, Kimberly / Damhuis, Ronald A M / Feelders, Richard A / de Herder, Wouter W. ·Department of Internal Medicine, Sector of Endocrinology, Erasmus MC, S-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands. ·Endocr Relat Cancer · Pubmed #22194442.

ABSTRACT: An increased association between neuroendocrine tumors of the gastrointestinal tract and pancreas (GEP-NET) and other second primary malignancies has been suggested. We determined whether there is indeed an increased risk for second primary malignancies in GEP-NET patients compared with an age- and sex-matched control group of patients with identical malignancies. The series comprised 243 men and 216 women, diagnosed with a GEP-NET between 2000 and 2009 in a tertiary referral center. The timeline, before-at-after diagnosis, and the type of other malignancies were studied using person-year methodology. Poisson distributions were used for testing statistical significance. All data were cross-checked with the Dutch National Cancer Registry. Out of 459 patients with GEP-NET, 67 (13.7%) had a second primary cancer diagnosis: 25 previous cancers (5.4%), 13 synchronous cancers (2.8%), and 29 metachronous cancers (6.3%). The most common types of second primary cancer were breast cancer (n=10), colorectal cancer (n=8), melanoma (n=6), and prostate cancer (n=5). The number of patients with a cancer history was lower than expected, although not significant (n=25 vs n=34.5). The diagnosis of synchronous cancers, mainly colorectal tumors, was higher than expected (n=13 vs n=6.1, P<0.05). Metachronous tumors occurred as frequent as expected (n=29 vs n=25.2, NS). In conclusion, our results are in contrast to previous studies and demonstrate that only the occurrence of synchronous second primary malignancies, mainly colorectal cancers, is increased in GEP-NET patients compared with the general population.

16 Article Improved control of severe hypoglycemia in patients with malignant insulinomas by peptide receptor radionuclide therapy. 2011

van Schaik, E / van Vliet, E I / Feelders, R A / Krenning, E P / Khan, S / Kamp, K / Valkema, R / van Nederveen, F H / Teunissen, J J M / Kwekkeboom, D J / de Herder, W W. ·Department of Internal Medicine, Section of Endocrinology, Erasmus Medical Center, 's Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands. ·J Clin Endocrinol Metab · Pubmed #21917872.

ABSTRACT: CONTEXT: Insulinomas are relatively rare neuroendocrine tumors of the pancreas. Only 10% are considered malignant. Control of insulin hypersecretion and hypoglycemia in patients with malignant insulinomas may be extremely difficult. Different medications and chemotherapy schedules have been used. PATIENTS: Five patients with metastatic insulinomas and severe, poorly controllable, hypoglycemia are described. These patients required continuous glucose infusion to control severe hypoglycemia, which were induced by the high levels of insulin secretion. Conventional medications, such as diazoxide, or streptozotocin-based chemotherapies had been used to control hypoglycemia but were ineffective and/or produced adverse effects. All patients were treated with sc octreotide. INTERVENTION: Peptide receptor radionuclide therapy with radiolabeled-somatostatin analogs was used. RESULTS: After the start of radiolabeled somatostatin analog therapy, the five patients with metastatic insulinomas had stable disease for a mean period of 27 months. During these months, the patients were without any hypoglycemic episodes. Finally, three of five patients died because of progressive disease. CONCLUSIONS: Radiolabeled somatostatin analog therapy can stabilize tumor growth and can be very successful in further controlling severe hypoglycemia in malignant insulinomas. In our series, this eventually resulted in improved survival outside the hospital setting.

17 Minor Serum neuron-specific enolase level is an independent predictor of overall survival in patients with gastroenteropancreatic neuroendocrine tumors. 2016

van Adrichem, R C S / Kamp, K / Vandamme, T / Peeters, M / Feelders, R A / de Herder, W W. ·Department of Internal Medicine, Sector of Endocrinology, ENETS Centre of Excellence for Neuroendocrine Tumors, Erasmus MC, Rotterdam, The Netherlands. · Department of Oncology, University of Antwerp, Antwerp, Belgium. · Department of Internal Medicine, Sector of Endocrinology, ENETS Centre of Excellence for Neuroendocrine Tumors, Erasmus MC, Rotterdam, The Netherlands w.w.deherder@erasmusmc.nl. ·Ann Oncol · Pubmed #26712902.

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