Wouter Herder
Erasmus University Rotterdam, Internal Medicine, Faculty Member
Research Interests:
The aim of this study was to explore the possible mechanisms involved in an observed decline in serum calcium levels in patients with a neuroendocrine tumour (NET) treated with [(177)Lu-DOTA(0),Tyr(3)]octreotate ((177)Lu-octreotate). In... more
The aim of this study was to explore the possible mechanisms involved in an observed decline in serum calcium levels in patients with a neuroendocrine tumour (NET) treated with [(177)Lu-DOTA(0),Tyr(3)]octreotate ((177)Lu-octreotate). In 47 patients with NET who were normocalcaemic at baseline, serum calcium, albumin, creatinine, alkaline phosphatase, gamma glutamyl transpeptidase, magnesium, phosphate and 25-hydroxyvitamin D were prospectively analysed at baseline and up to 6 months after treatment. Parathyroid hormone (PTH), 1,25-dihydroxyvitamin D3, type 1 aminoterminal propeptide of procollagen, bone-specific alkaline phosphatase, carboxyterminal crosslinking telopeptide of bone collagen, collagen type I crosslinked N-telopeptide, and creatinine and calcium in 24-h urine samples, were evaluated at baseline and at 3 and 6 months. Another 153 patients with NET were included in a retrospective study to estimate the occurrence of hypocalcaemia in a larger patient group. In the prospectively included patients, the mean serum calcium level decreased significantly after treatment (2.31 ± 0.01 to 2.26 ± 0.02 mmol/l, p = 0.02). Eight patients (17%) showed a marked decrease in serum calcium levels with a nadir of ≤ 2.10 mmol/l. In five patients (11%), calcium substitution therapy was prescribed. PTH increased significantly (5.9 ± 0.6 to 6.7 ± 0.8 pmol/l, p = 0.02), presumably in response to the decreasing serum calcium levels. 25-Hydroxyvitamin D remained stable after treatment. Creatinine levels increased significantly (73 ± 3 to 77 ± 3 μmol/l, p = 0.01), but not enough to explain the hypocalcaemia. Phosphate levels remained unaffected. In the retrospectively analysed patients, the mean serum calcium level decreased significantly from 2.33 ± 0.01 at baseline to a nadir of 2.24 ± 0.01 mmol/l at 18 months after treatment (p < 0.001). Of the 153 patients, 33 (22%) showed a serum calcium nadir of ≤ 2.10 mmol/l, and 11 (7%) received calcium substitution therapy. The mean serum calcium level decreased significantly after treatment with (177)Lu-octreotate, resulting in mild hypocalcaemia in about 20% of patients. We excluded several potential causes of this hypocalcaemia, so the cause remains unknown. Serum calcium levels should be monitored after peptide receptor radionuclide therapy, and calcium substitution therapy should be initiated if appropriate.
Research Interests:
Regular therapy with the radiolabeled somatostatin analog (177)Lu-octreotate (22.2-29.6 GBq) in patients with gastroenteropancreatic or bronchial neuroendocrine tumors results in tumor remission in 46% of patients, including minor... more
Regular therapy with the radiolabeled somatostatin analog (177)Lu-octreotate (22.2-29.6 GBq) in patients with gastroenteropancreatic or bronchial neuroendocrine tumors results in tumor remission in 46% of patients, including minor response. We present the effects of additional therapy with (177)Lu-octreotate in patients in whom progressive disease developed after an initial benefit from regular therapy. Thirty-three patients with progressive disease after an initial radiologic or clinical response were treated with additional cycles of (177)Lu-octreotate. The intended cumulative dose of additional therapy was 14.8 GBq in 2 cycles. Responses were evaluated using Southwest Oncology Group criteria, including minor response (tumor size reduction of >or=25% and <50%). Median time to progression (TTP) after regular therapy was 27 mo. In 4 patients, the intended cumulative dose was not achieved (2 had progressive disease, 2 had long-lasting thrombocytopenia). Hematologic toxicity grade 3 was observed in 4 patients, and grade 4, in 1. The median follow-up time was 16 mo (range, 1-40 mo). No kidney failure or myelodysplastic syndrome was observed. Renewed tumor regression was observed in 8 patients (2 partial remission, 6 minor response), and 8 patients had stable disease. Median TTP was 17 mo. Treatment outcome was less favorable in patients with a short TTP after regular cycles. Treatment effects in patients with pancreatic neuroendocrine tumors were similar to those in patients with other gastroenteropancreatic neuroendocrine tumors. Most patients tolerated additional cycles with (177)Lu-octreotate well. None developed serious delayed adverse events. Additional cycles with (177)Lu-octreotate can have antitumor effects, but effects were less than for the regular cycles. This may be because of a worse clinical condition, more extensive tumor burden, or changed tumor characteristics. We conclude that this salvage therapy can be effective and is safe.
Research Interests: Nuclear medicine, Treatment Outcome, Nuclear, Humans, Myelodysplastic Syndrome, and 13 moreClinical Sciences, Aged, Middle Aged, Adult, Adverse Event, Disease Progression, Neuroendocrine Tumor, Organometallic Compounds, Chronic Kidney Failure, Neuroendocrine Tumors, Treatment Effect, Cumulant, and Chromogranin A
Research Interests: Magnetic Resonance Imaging, Neuroendocrinology, Echocardiography, Humans, Fasting, and 13 moreHypoglycemia, Cancer Diagnosis, Insulinoma, Clinical Sciences, Biological markers, Diagnostic Accuracy, Neuroendocrine Tumor, X ray Computed Tomography, Standard of Care, Antineoplastic Agents, Neuroendocrine Tumors, Neurosciences, and Chromogranin A
It is unknown whether tumoral somatostatin receptor subtype 2a (sst2a) immunohistochemistry (IHC) has additional value over somatostatin receptor scintigraphy (SRS) uptake using OctreoScan® in predicting response to peptide receptor... more
It is unknown whether tumoral somatostatin receptor subtype 2a (sst2a) immunohistochemistry (IHC) has additional value over 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). Aims of the study were to: (1) establish the percentage of sst2a immunopositivity in GEP-NET samples of PRRT-treated patients, (2) determine the relationship between best GEP-NET response using RECIST 1.0 at one year to PRRT and tumoral sst2a IHC, and (3) compare characteristics of patients with sst2a IHC-negative and -positive tumors. All 73 consecutive patients were selected for PRRT based on a positive SRS. Radiological response was scored according to RECIST 1.0. Sst2a status was detected on tumor samples by IHC. GEP-NET samples showed in 93% sst2a IHC-positivity. No statistically significant relationship was observed between in vitro ...
Research Interests:
Research Interests:
Management of neuroendocrine neoplasia represents a clinical challenge because of its late presentation, lack of treatment options, and limitations in present imaging modalities and biomarkers to guide management. Monoanalyte biomarkers... more
Management of neuroendocrine neoplasia represents a clinical challenge because of its late presentation, lack of treatment options, and limitations in present imaging modalities and biomarkers to guide management. Monoanalyte biomarkers have poor sensitivity, specificity, and predictive ability. A National Cancer Institute summit, held in 2007, on neuroendocrine tumours noted biomarker limitations to be a crucial unmet need in the management of neuroendocrine tumours. A multinational consensus meeting of multidisciplinary experts in neuroendocrine tumours assessed the use of current biomarkers and defined the perquisites for novel biomarkers via the Delphi method. Consensus (at >75%) was achieved for 88 (82%) of 107 assessment questions. The panel concluded that circulating multianalyte biomarkers provide the highest sensitivity and specificity necessary for minimum disease detection and that this type of biomarker had sufficient information to predict treatment effectiveness and...
Research Interests:
Research Interests:
Research Interests:
The skeletons of 2 famous acromegalic giants: Charles Byrne (1761-1783) and Henri Cot = Joseph Dusorc (1883-1912) and the embalmed body of the famous acromegalic giant Édouard Beaupré (1881-1904) all ended up in the medical collections of... more
The skeletons of 2 famous acromegalic giants: Charles Byrne (1761-1783) and Henri Cot = Joseph Dusorc (1883-1912) and the embalmed body of the famous acromegalic giant Édouard Beaupré (1881-1904) all ended up in the medical collections of museums despite the fact that these patients had never donated or even refused to donate their corpses, nor had their relatives given permission. The corpse of the acromegalic giant John Aasen (1890-1938) was voluntarily donated to a physician annex collector of trivia from acromegalic giants. The autopsy on the acromegalic giant John Turner (1874-1911) was performed during his funeral ceremony without the relatives being informed. Only recently, the acromegalic giant Alexander Sizonenko (1959-2012) was made a financial offer during his life in exchange for his body after his death. The case-histories of these 6 patients and also the circumstances that led to the (in-) voluntary donation of their bodies are reviewed.
Research Interests:
Peptide receptor radionuclide therapy (PRRT) is a promising new treatment modality for inoperable or metastasized gastroenteropancreatic neuroendocrine tumors (GEPNETs) patients. Most studies report objective response rates in 15-35% of... more
Peptide receptor radionuclide therapy (PRRT) is a promising new treatment modality for inoperable or metastasized gastroenteropancreatic neuroendocrine tumors (GEPNETs) patients. Most studies report objective response rates in 15-35% of patients. Also, outcome in terms of progression free survival (PFS) and overall survival compares very favorably with that for somatostatin analogs, chemotherapy, or new, 'targeted' therapies. They also compare favorably to PFS data for liver-directed therapies. Two decades after the introduction of PRRT, there is a growing need for randomized controlled trials comparing PRRT to 'standard' treatment, that is treatment with agents that have proven benefit when tested in randomized trials. Combining PRRT with liver-directed therapies or with targeted therapies could improve treatment results. The question to be answered, however, is whether a combination of therapies performed within a limited time-span from one another results in a bet...
Research Interests:
Glucuronidation of iodothyronines in rat liver is catalyzed by at least three UDP-glucuronyltransferases (UGTs): bilirubin UGT, phenol UGT, and androsterone UGT. Bilirubin and phenol UGT activities are regulated by thyroid hormone, but... more
Glucuronidation of iodothyronines in rat liver is catalyzed by at least three UDP-glucuronyltransferases (UGTs): bilirubin UGT, phenol UGT, and androsterone UGT. Bilirubin and phenol UGT activities are regulated by thyroid hormone, but the effect of thyroid status on hepatic glucuronidation of iodothyronines is unknown. We examined the effects of hypothyroidism induced by treatment of rats with propylthiouracil (PTU) or methimazole (MMI) or by thyroidectomy as well as the effects of T4-induced hyperthyroidism on the hepatic UGT activities for T4, T3, bilirubin,p-nitrophenol (PNP), and androsterone. Bilirubin UGT activity was increased in MMI- or PTU-induced hypothyroid and thyroidectomized rats, and decreased in hyperthyroid animals. T4 and, to a lesser extent, T3 UGT activities were increased in MMI- or PTU-induced hypothyroid rats, and T4 but not T3 glucuronidation also showed a significant increase in thyroidectomized rats. T4 but not T3 UGT activity was slightly decreased in hyp...
Research Interests:
In 1886 Pierre Marie used the term "acromegaly" for the first time and gave a full description of the characteristic clinical picture. However several others had already given clear clinical descriptions before him and sometimes... more
In 1886 Pierre Marie used the term "acromegaly" for the first time and gave a full description of the characteristic clinical picture. However several others had already given clear clinical descriptions before him and sometimes had given the disease other names. After 1886, it gradually became clear that pituitary enlargement (caused by a pituitary adenoma) was the cause and not the consequence of acromegaly, as initially thought. Pituitary adenomas could be found in the great majority of cases. It also became clear that acromegaly and gigantism were the same disease but occurring at different stages of life and not different diseases as initially thought. At the end of the 19th and beginning of the 20th century most information was derived from case descriptions and post-mortem examinations of patients with acromegaly or (famous) patients with gigantism. The stage was set for further research into the pathogenesis, diagnosis and therapy of acromegaly and gigantism.
Research Interests:
Tumors and metastases that express the somatostatin receptor subtypes sst2 sst3 or sst5 can be visualized in vivo after injection of radiolabeled octapeptide somatostatin analogs, like (111)In-pentetreotide. (111)In-pentetreotide... more
Tumors and metastases that express the somatostatin receptor subtypes sst2 sst3 or sst5 can be visualized in vivo after injection of radiolabeled octapeptide somatostatin analogs, like (111)In-pentetreotide. (111)In-pentetreotide scintigraphy also allows for more accurate staging of the disease by demonstrating tumor sites, which were not shown by conventional imaging. (111)In-pentetreotide scintigraphy may also detect resectable tumors that would have remained unrecognized using conventional radiological imaging techniques; it may prevent surgery with curative intent in those patients whose tumors have metastasized to a greater extend than could be detected with conventional radiological imaging and it may be used to select patients for treatment with the currently available octapeptide somatostatin analogs or with tumor targeted radioactive treatment with radiolabelled somatostatin analogs. (111)In-pentetreotide scintigraphy has also been used to select patients with pituitary tum...
Research Interests:
Long-acting octapeptide somatostatin analogs can effectively control symptoms resulting from excessive hormone release in patients with endocrine tumors of the gastrointestinal tract, provided that these tumors and metastases show a high... more
Long-acting octapeptide somatostatin analogs can effectively control symptoms resulting from excessive hormone release in patients with endocrine tumors of the gastrointestinal tract, provided that these tumors and metastases show a high expression of the somatostatin receptor subtype 2. The presence of this receptor subtype on these tumors can be demonstrated by in vitro studies, but also in vivo using 111In-pentetreotide scintigraphy. In a few studies, significant antiproliferative effects of these drugs on these tumors have also been demonstrated. The effectiveness of octapeptide somatostatin analogs in the management of chemotherapy- related and AIDS-related diarrhea and in reducing postoperative complications of pancreatic surgery have also been demonstrated. These drugs have been used to decrease the output of enterocutaneous pancreatic fistulas and are prophylactically used to prevent the development of these fistulas. Octapeptide somatostatin analog therapy is widely accepte...
Research Interests:
Research Interests:
X-linked acro-gigantism (X-LAG) is a new syndrome of pituitary gigantism, caused by microduplications on chromosome Xq26.3, encompassing the gene GPR101, which is highly upregulated in pituitary tumors. We conducted this study to explore... more
X-linked acro-gigantism (X-LAG) is a new syndrome of pituitary gigantism, caused by microduplications on chromosome Xq26.3, encompassing the gene GPR101, which is highly upregulated in pituitary tumors. We conducted this study to explore the clinical, radiological and hormonal phenotype and responses to therapy in patients with X-LAG syndrome. The study included 18 patients (13 sporadic) with X-LAG and a microduplication in chromosome Xq26.3. All sporadic cases had unique duplications and the inheritance pattern in 2 families was dominant with all Xq26.3 duplication carriers being affected. Patients began to grow rapidly as early as 2-3 months of age (median 12 months). At diagnosis (median delay 27 months), patients had a median height and weight SDS score of >+3.9 SDS. Apart from the increased overall body size, the children had acromegalic symptoms including acral enlargement and facial coarsening. More than a third of cases had increased appetite. Patients had marked hypersec...
Research Interests:
Leukocyte activation has been associated with vascular complications in type 2 diabetes mellitus (T2DM). Hyperglycemia may be involved in this leukocyte activation. Our aim was to investigate the role of elevated glucose concentrations on... more
Leukocyte activation has been associated with vascular complications in type 2 diabetes mellitus (T2DM). Hyperglycemia may be involved in this leukocyte activation. Our aim was to investigate the role of elevated glucose concentrations on leukocyte activation in patients with a wide range of insulin sensitivity. Leukocyte activation was determined after ingestion of 75 gram glucose in subjects with T2DM, familial combined hyperlipidemia (FCH) and healthy controls. Leukocyte activation markers were measured by flow cytometry. Postprandial changes were calculated as the area under the curve (AUC), and the incremental area under the curve corrected for baseline values (dAUC). 51 Subjects (20 T2DM, 17 FCH and 14 controls) were included. Fasting neutrophil CD66b expression and CD66b-AUC were respectively 36% and 39% higher in T2DM patients than in controls (p=0.004 and p=0.003). Fasting neutrophil CD66b expression correlated positively with glucose-AUC (Spearman's rho 0.481, p<0.001) and HbA1c (rho 0.433, p=0.002). Although fasting monocyte CD11b expression was not significantly different between subjects, monocyte CD11b-AUC was 26% higher in T2DM than in controls (p=0.006). Similar trends were observed for FCH patients. Monocyte CD11b-dAUC correlated positively with glucose-AUC (rho 0.322, p=0.022) and HbA1c (rho 0.319, p=0.023). These data suggest that both acute and chronic hyperglycemia, associated with insulin resistance as seen in T2DM and FCH, are involved in the increased fasting and postprandial leukocyte activation observed in these conditions.
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Orbital lymphocytic infiltration in thyroid eye disease (TED), as well as identification of somatostatin (SMS) receptors on activated lymphocytes, has provided a rationale for receptor imaging with the radiolabeled SMS analog... more
Orbital lymphocytic infiltration in thyroid eye disease (TED), as well as identification of somatostatin (SMS) receptors on activated lymphocytes, has provided a rationale for receptor imaging with the radiolabeled SMS analog Pentetreotide. In 80 patients with TED, single-photon emission computed tomography (SPECT) images of the orbit were performed 4 and 24 hours after injection of Pentetreotide. Semiquantitative evaluation was performed using the SPECT slices with irregular regions of interests placed over the orbits and both hemispheres. In contrast to controls (median 5 counts per voxel per millibecquerel (cts/vox/MBq) injected activity), TED patients showed threefold increased orbital accumulation of Pentetreotide (15 cts/vox/MBq, p = 0.003). When considering patients with active TED only, even higher uptake was registered (23 cts/vox/MBq, p = 0.0006 vs. controls, sensitivity for active TED 61/68, 90%; specificity 12/12, 100%). In 40 patients with active TED, the radionuclide accumulation decreased sharply after completion of immunosuppressive therapy. A high pretreatment Pentetreotide orbit-to-brain ratio correlated with a response to therapy (positive and negative predictive values 28/32, 88%, and 8/8, 100%, respectively). In conclusion, SMS receptor scintigraphy may be regarded as a semiobjective tool in the evaluation of TED, both at initial stages as well as during treatment.
Research Interests:
Research Interests:
Laparoscopic ultrasonography as a diagnostic tool for the localization of islet cell tumors has been described before, but few reports on laparoscopic resection of insulinomas exist. We retrospectively reviewed the results of our... more
Laparoscopic ultrasonography as a diagnostic tool for the localization of islet cell tumors has been described before, but few reports on laparoscopic resection of insulinomas exist. We retrospectively reviewed the results of our experience with laparoscopic detection and the resection of insulinomas to determine its feasibility. Between February 1996 and February 1999, 10 patients underwent operation for organic hyperinsulinism at our institution. Patient and clinical characteristics were studied retrospectively. Laparoscopic ultrasonography was performed to localize the insulinoma and then laparoscopic resection was performed. Eight women and 2 men underwent operation for hyperinsulinism. In 6 patients the insulinoma could be resected laparoscopically, either by enucleation (5 patients) or by resection of the pancreatic tail (1 patient). Four procedures were converted to laparotomy for the proximate location of the insulinoma to the portal vein or pancreatic duct (3 procedures) and failure to identify the insulinoma (1 procedure). The overall success rate of preoperative localization of an insulinoma with the use of various imaging techniques was 60% (6/10 patients). Laparoscopic ultrasonography could identify an insulinoma in 90% of the patients (9/10 patients). The median hospital stay was 7 days. Laparoscopic ultrasonography followed by laparoscopic removal of the insulinoma in patients with clinically manifested hyperinsulinism is a feasible and safe technique with low morbidity and fast postoperative recovery. Preoperative localization studies appear of limited value.
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests: Treatment, Treatment Outcome, Risk assessment, Humans, Toxicity, and 22 moreFemale, Clinical, Male, Clinical oncology, Analog, Aged, Middle Aged, Adult, Neuropeptide Y, Time Factors, Risk Assessment, Neuroendocrine Tumor, Radiopharmaceuticals, Hematologic Diseases, Organometallic Compounds, Drug Induced Liver Injury, Overall Survival, Neuroendocrine Tumors, Radionuclide Therapy, Proportional Hazards Models, Logistic Models, and Severity of Illness Index
The assessment of tumor markers for diagnosing pancreatic neuroendocrine tumors (pNET) in multiple endocrine neoplasia type 1 (MEN1) patients is advised in the current guidelines but has never been validated for this purpose. The... more
The assessment of tumor markers for diagnosing pancreatic neuroendocrine tumors (pNET) in multiple endocrine neoplasia type 1 (MEN1) patients is advised in the current guidelines but has never been validated for this purpose. The objective of the study was to assess the diagnostic accuracy of chromogranin A (CgA), pancreatic polypeptide (PP), and glucagon for pNET in MEN1. This was a diagnostic study. The study was conducted at Dutch university medical centers from 2008 to 2011, representing 90% of the total Dutch MEN1 population. Patients for whom data on tumor markers in combination with the reference standard (ie, radiological imaging) were available between 2008 and 2011 were included. The reference standard for the presence of pNET was pathology or detection on magnetic resonance imaging, computed tomography, or endoscopic ultrasound confirmed on subsequent imaging, irrespective of modality at follow-up. The area under the receiver-operating characteristic curve (AUC), positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, sensitivity, and specificity were calculated for each marker. For the analysis of PP, CgA, and glucagon, 73, 81, and 94 patients were available, respectively. The AUC for CgA was 0.48 [95% confidence interval (CI) 0.35-0.61] with a sensitivity 0.33 and a specificity 0.73; the AUC for glucagon was 0.58 (95% CI 0.46-0.70) with a sensitivity 0.43 and a specificity 0.73; and the AUC for PP was 0.64 (95% CI 0.50-0.77) with a sensitivity 0.36 and a specificity 0.74. Age, imaging modality, tumor size, and number did not influence the outcomes. The diagnostic accuracy of the tumor markers CgA, PP, and glucagon for pNET in MEN1 is low.
Research Interests: Adolescent, Humans, Glucagon, Female, Male, and 6 moreClinical Sciences, Aged, Middle Aged, Adult, Neuroendocrine Tumors, and Chromogranin A
Research Interests:
ABSTRACT Abstract Not Available.