Inne H M Borel Rinkes

University Medical Center Utrecht, Utrecht, Utrecht, Netherlands

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Publications (296)990.49 Total impact

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    ABSTRACT: Since the 1950s, preoperative medical preparation has been widely applied in patients with pheochromocytoma to improve intraoperative hemodynamic instability and postoperative complications. However, advancements in preoperative imaging, laparoscopic surgical techniques, and anesthesia have considerably improved management in patients with pheochromocytoma. In consequence, there is no validated consensus on current predictive factors for postoperative morbidity. The aim of this study was to determine perioperative factors which are predictive for postoperative morbidity in patients undergoing laparoscopic adrenalectomy for pheochromocytoma. It is a retrospective analysis of prospectively maintained databases in five medical centers from 2002 to 2013. Inclusion criteria were consecutive patients who underwent non-converted laparoscopic unilateral total adrenalectomy for pheochromocytoma. Two-hundred and twenty-five patients were included. All-cause and cardiovascular postoperative morbidity rates were 16 % (n = 36) and 4.8 % (n = 11), respectively. Preinduction blood pressure normalization after preoperative medical preparation had no impact on postoperative morbidity. However, past medical history of coronary artery disease (OR [CI95 %] = 3.39; [1.317-8.727]) and incidence of intraoperative hemodynamic instability episodes (both SBP ≥ 160 mmHg and MAP < 60 mmHg) (OR [CI95 %] = 3.092; [1.451-6.587]) remained independent predictors for postoperative all-cause morbidity. Similarly, past medical history of coronary artery disease (OR [CI95 %] = 14.41; [3.119-66.57]), female sex (OR [CI95 %] = 12.05; [1.807-80.31]), and incidence of intraoperative hemodynamic instability episodes (both SBP ≥ 200 mmHg and MAP < 60 mmHg) (OR [CI95 %] = 4.13; [1.009-16.90]) remained independent predictors for postoperative cardiovascular morbidity. This study identifies risk factors for cardiovascular and all-cause postoperative morbidity after laparoscopic adrenalectomy in current clinical setting. These data can help physicians to guide intra-operative blood pressure management and have to be taken into account in further studies.
    Surgical Endoscopy 06/2015; DOI:10.1007/s00464-015-4294-7 · 3.31 Impact Factor
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    ABSTRACT: Primary hyperparathyroidism is a common endocrine disorder for which the primary treatment is surgery. For minimal invasive parathyroidectomy adequate pre-operative imaging is essential. Conventional imaging is often inconclusive. There are reports that (18)F-fluorocholine PET-CT might be a superior imaging modality, however evidence is still very scarce. This is the first report of a case with negative ultrasound and sestamibi SPECT-CT imaging that underwent successful minimal invasive surgery because of (18)F-fluorocholine PET-CT. A 57 year-old man presented to us with complaints of fatigue. Laboratory results showed a biochemical primary hyperparathyroidism and an additional DEXA-scan revealed osteopenia of the lumbar spine. Conventional imaging consisting of neck ultrasound and Tc-99m-sestamibi SPECT-CT was however unable to localize the pathological gland. Subsequent (18)F-fluorocholine PET-CT did clearly localize an adenoma dorsally of the left thyroid lobe which was removed at that exact location using minimal invasive parathyroidectomy. Histological examination confirmed the diagnosis adenoma and calcium levels remained normal at follow-up. There is clinical need for a superior imaging modality to detect pathological parathyroid glands to enable minimal invasive surgery. (18)F-Fluorocholine is widely available. (18)F-Fluorocholine PET-CT is a promising new imaging modality for localizing parathyroid adenomas and enabling minimal invasive parathyroidectomy when conventional imaging fails to do. Clinicians should consider its use as a second line modality for optimal patient care. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
    06/2015; 79. DOI:10.1016/j.ijscr.2015.06.012
  • Endocrine 06/2015; DOI:10.1007/s12020-015-0654-2 · 3.53 Impact Factor
  • Pancreatology 06/2015; 15(3):S103-S104. DOI:10.1016/j.pan.2015.05.373 · 2.50 Impact Factor
  • Pancreatology 06/2015; 15(3):S85-S86. DOI:10.1016/j.pan.2015.05.315 · 2.50 Impact Factor
  • Pancreatology 06/2015; 15(3):S19. DOI:10.1016/j.pan.2015.05.101 · 2.50 Impact Factor
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    ABSTRACT: Open transthoracic esophagectomy is the worldwide gold standard in the treatment of resectable esophageal cancer. Robot-assisted minimally invasive thoraco-laparoscopic esophagectomy (RAMIE) for esophageal cancer may be associated with reduced blood loss, shorter intensive care unit (ICU) stay, and less cardiopulmonary morbidity; however, long-term oncologic results have not been reported to date. Between June 2007 and September 2011, a total of 108 patients with potentially resectable esophageal cancer underwent RAMIE at the University Medical Centre Utrecht, with curative intent. All data were recorded prospectively. Median duration of the surgical procedure was 381 min (range 264-636). Pulmonary complications were most common and were observed in 36 patients (33 %). Median ICU stay was 1 day, and median overall postoperative hospital stay was 16 days. In-hospital mortality was 5 %. The majority of patients (78 %) presented with T3 and T4 disease, and 68 % of patients had nodal-positive disease (cN1-3). In 65 % of patients, neoadjuvant treatment (chemotherapy 57 %, chemoradiotherapy 7 %, radiotherapy 1 %) was administered, and in 103 (95 %) patients, a radical resection (R0) was achieved. The median number of lymph nodes was 26, median follow-up was 58 months, 5-year overall survival was 42 %, median disease-free survival was 21 months, and median overall survival was 29 months. Tumor recurrence occurred in 51 patients and was locoregional only in 6 (6 %) patients, systemic only in 31 (30 %) patients, and combined in 14 (14 %) patients. RAMIE was shown to be oncologically effective, with a high percentage of R0 radical resections and adequate lymphadenectomy. RAMIE provided good local control with a low percentage of local recurrence at long-term follow up.
    Annals of Surgical Oncology 05/2015; DOI:10.1245/s10434-015-4544-x · 3.94 Impact Factor
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    ABSTRACT: Assessment of the diagnostic value of ultrasound (US), single photon-emission computed tomography-computed tomography (SPECT-CT) and (18)F-fluorocholine (FCH) PET-CT for preoperative localization of hyper-functioning parathyroid(s) in order to create a more efficient diagnostic pathway and enable minimal invasive parathyroidectomy (MIP) in patients with biochemical proven non-familial primary hyperparathyroidism (pHPT). A single-institution retrospective study of 63 consecutive patients with a biochemical diagnosis of non-familial pHPT who received a Tc-99m-sestamibi SPECT-CT and neck ultrasound. Surgical findings were used in calculating the sensitivity and the positive predictive value (PPV) of both imaging modalities. Furthermore we present 5 cases who received additional FCH PET-CT. A total of 42 (66.7%) patients underwent MIP. The PPV and sensitivity of SPECT-CT, 93.0% and 80.3%, were significantly higher than those of US with 78.3% and 63.2%, respectively. Adding US to SPECT-CT for initial pre-operative localization did not significantly increase sensitivity but did significantly decrease PPV. Performance of US was significantly better when performed after SPECT-CT. (18)F-fluorocholine PET-CT localized the hyper-functioning parathyroid gland in 4/5 cases with discordant conventional imaging, enabling MIP. SPECT-CT is the imaging modality of choice for initial pre-operative localization of hyper-functioning parathyroid gland(s) in patients with biochemical pHPT. Ultrasound should be performed after SPECT-CT for confirmation of positive SPECT-CT findings and for pre-operative marking allowing MIP. In cases with negative or discordant imaging additional FCH PET-CT should be considered since this might enable the surgeon to perform MIP. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    European journal of radiology 05/2015; DOI:10.1016/j.ejrad.2015.05.024 · 2.16 Impact Factor
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    ABSTRACT: Colon tumors contain a fraction of undifferentiated stem cell-like cancer cells with high tumorigenic potential. Little is known about the signals that maintain these stem-like cells. We investigated whether differentiated tumor cells provide support. We established undifferentiated colonosphere cultures from human colon tumors and used them to generate stably differentiated cell lines. Antibody arrays were used to identify secreted factors. Expression of genes involved in stemness, differentiation, and the epithelial to mesenchymal (EMT) transition was measured using reverse transcription quantitative PCR. Expression of KIT in human tumors was analyzed with gene expression arrays and by immunohistochemistry. Colonospheres were injected into the livers of CBy.Cg-Foxn1nu/J mice. After liver tumors had formed hypoxia was induced by vascular clamping. Differentiated cells from various tumors, or medium conditioned by them, increased the clonogenic capacity of colonospheres. Stem cell factor (SCF) was secreted by differentiated tumor cells and supported the clonogenic capacity of KIT(+) colonosphere cells. Differentiated tumor cells induced the EMT in colonosperes; this was prevented by inhibition of KIT or SCF. SCF prevented loss of clonogenic potential under differentiation-inducing conditions. Suppression of SCF or KIT signaling greatly reduced the expression of genes that regulate stemness and the EMT and inhibited clonogenicity and tumor initiation. Bioinformatic and immunohistochemical analyses revealed a correlation between expression of KIT- and hypoxia-related genes in colon tumors, which was highest in relapse-prone mesenchymal-type tumors. Hypoxia induced expression of KIT in cultured cells and in human colon tumor xenografts and this contributed to the clonogenic capacity of the tumor cells. Paracrine signaling from SCF to KIT, between differentiated tumor cells and undifferentiated stem-like tumor cells, helps maintain the stem-like features of tumor cells, predominantly under conditions of hypoxia. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.
    Gastroenterology 05/2015; DOI:10.1053/j.gastro.2015.05.003 · 13.93 Impact Factor
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    ABSTRACT: Cardiac and pulmonary complications account for a large part of postoperative mortality, especially in the growing number of elderly patients. This review studies the effect of laparoscopic surgery for colorectal cancer on short term non-surgical morbidity. A literature search was conducted to identify randomised trials on laparoscopic compared to open surgery for colorectal cancer with reported cardiac or pulmonary complications. The search retrieved 3302 articles; 18 studies were included with a total of 6153 patients. Reported median or mean age varied from 56 years to 72 years. The percentage of included patients with ASA-scores ≥3 ranged from 7% to 38%. Morbidity was poorly defined. Overall reported incidence of postoperative cardiac complications was low for both laparoscopic and open colorectal resection (median 2%). There was a trend towards fewer cardiac complications following laparoscopic surgery (OR 0.66, 95% CI 0.41-1.06, p = 0.08), and this effect was most marked for laparoscopic colectomy (OR 0.28, 95% CI 0.11-0.71, p = 0.007). Incidence of pulmonary complications ranged from 0 to 11% and no benefit was found for laparoscopic surgery, although a possible trend was seen in favour of laparoscopic colectomy (OR 0.78, 95% CI 0.53-1.13, p = 0.19). Overall morbidity rates varied from 11% to 69% with a median of 33%. Although morbidity was poorly defined, for laparoscopic colectomies, significantly less cardiac complications occurred compared with open surgery and a trend towards less pulmonary complications was observed. Subgroup analysis from two RCTs suggests that elderly patients benefit most from a laparoscopic approach based on overall morbidity rates. Copyright © 2015 Elsevier Ltd. All rights reserved.
    European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 05/2015; DOI:10.1016/j.ejso.2015.04.007 · 2.89 Impact Factor
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    ABSTRACT: Previous studies have shown that 5-14% of patients undergoing pancreatoduodenectomy for suspected malignancy ultimately are diagnosed with benign disease. A "pancreatic mass" on computed tomography (CT) is considered to be the strongest predictor of malignancy, but studies describing its diagnostic value are lacking. The aim of this study was to determine the diagnostic value of a pancreatic mass on CT in patients with presumed pancreatic cancer, as well as the interobserver agreement among radiologists and the additional value of reassessment by expert-radiologists. Reassessment of preoperative CT scans was performed within a previously described multicenter retrospective cohort study in 344 patients undergoing pancreatoduodenectomy for suspected malignancy (2003-2010). Preoperative CT scans were reassessed by 2 experienced abdominal radiologists separately and subsequently in a consensus meeting, after defining a pancreatic mass as "a measurable space occupying soft tissue density, except for an enlarged papilla or focal steatosis". CT scans of 86 patients with benign and 258 patients with (pre)malignant disease were reassessed. In 66% of patients a pancreatic mass was reported in the original CT report, versus 48% and 50% on reassessment by the 2 expert radiologists separately and 44% in consensus (P < .001 vs original report). Interobserver agreement between the original CT report and expert consensus was fair (kappa = 0.32, 95% confidence interval 0.23-0.42). Among both expert-radiologists agreement was moderate (kappa = 0.47, 95% confidence interval 0.38-0.56), with disagreement on the presence of a pancreatic mass in 29% of cases. The specificity for malignancy of pancreatic masses identified in expert consensus was twice as high compared with the original CT report (87% vs 42%, respectively). Positive predictive value increased to 98% after expert consensus, but negative predictive value was low (12%). Clinicians need to be aware of potential considerable disagreement among radiologists about the presence of a pancreatic mass. The specificity for malignancy doubled by expert radiologist reassessment when a uniform definition of "pancreatic mass" was used. Copyright © 2015 Elsevier Inc. All rights reserved.
    Surgery 04/2015; 158(1). DOI:10.1016/j.surg.2015.03.008 · 3.11 Impact Factor
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    ABSTRACT: Chemotherapy treatment of metastatic colon cancer ultimately fails due to development of drug resistance. Identification of chemotherapy-induced changes in tumor biology may provide insight into drug resistance mechanisms. We studied gene expression differences between groups of liver metastases that were exposed to pre-operative chemotherapy or not. Multiple patient-derived colonosphere cultures were used to assess how chemotherapy alters energy metabolism by measuring mitochondrial biomass, oxygen consumption and lactate production. Genetically manipulated colonosphere-initiated tumors were used to assess how altered energy metabolism affects chemotherapy efficacy. Gene ontology and pathway enrichment analysis revealed significant upregulation of genes involved in oxidative phosphorylation (OXPHOS) and mitochondrial biogenesis in metastases that were exposed to chemotherapy. This suggested chemotherapy induces a shift in tumor metabolism from glycolysis towards OXPHOS. Indeed, chemo-treatment of patient-derived colonosphere cultures resulted in an increase of mitochondrial biomass, increased expression of respiratory chain enzymes and higher rates of oxygen consumption. This was mediated by the histone deacetylase sirtuin-1 (SIRT1) and its substrate, the transcriptional co-activator PGC1α. Knockdown of SIRT1 or PGC1α prevented chemotherapy-induced OXPHOS and significantly sensitized patient-derived colonospheres, as well as tumor xenografts to chemotherapy. Chemotherapy of colorectal tumors induces a SIRT1/PGC1α-dependent increase in OXPHOS that promotes tumor survival during treatment. This phenomenon is also observed in chemotherapy-exposed resected liver metastases, strongly suggesting that chemotherapy induces long-lasting changes in tumor metabolism that potentially interfere with drug efficacy. In conclusion, we propose a novel mechanism of chemotherapy resistance that may be clinically relevant and therapeutically exploitable. Copyright © 2015, American Association for Cancer Research.
    Clinical Cancer Research 03/2015; 21(12). DOI:10.1158/1078-0432.CCR-14-2290 · 8.19 Impact Factor
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    ABSTRACT: Novel spheroid-type tumor cell cultures directly isolated from patients’ tumors preserve tumor characteristics better than traditionally grown cell lines. However, such cultures are not generally used for high-throughput toxicity drug screens. In addition, the assays that are commonly used to assess drug-induced toxicity in such screens usually measure a proxy for cell viability such as mitochondrial activity or ATP-content per culture well, rather than actual cell death. This generates considerable assay-dependent differences in the measured toxicity values. To address this problem we developed a robust method that documents drug-induced toxicity on a per-cell, rather than on a per-well basis. The method involves automated drug dispensing followed by paired image- and FACS-based analysis of cell death and cell cycle changes. We show that the two methods generate toxicity data in 96-well format which are highly concordant. By contrast, the concordance of these methods with frequently used well-based assays was generally poor. The reported method can be implemented on standard automated microscopes and provides a low-cost approach for accurate and reproducible high-throughput toxicity screens in spheroid type cell cultures. Furthermore, the high versatility of both the imaging and FACS platforms allows straightforward adaptation of the high-throughput experimental setup to include fluorescence-based measurement of additional cell biological parameters.
    FEBS Open Bio 01/2015; 445. DOI:10.1016/j.fob.2015.01.003 · 1.52 Impact Factor
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    ABSTRACT: Only a minority of thyroid nodules is malignant; nevertheless, many invasive diagnostic procedures are performed to distinguish between benign and malignant nodules. Qualitative ultrasound elastography is a non-invasive technique to evaluate thyroid nodules.
    European Journal of Radiology 01/2015; 84(4). DOI:10.1016/j.ejrad.2015.01.003 · 2.16 Impact Factor
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    ABSTRACT: Background Perioperative epirubicin, cisplatin, and capecitabine (ECC) chemotherapy was evaluated in patients who underwent esophageal resection for adenocarcinoma of the esophagus or gastroesophageal junction (GEJ). Methods A cohort of 93 consecutive patients was analyzed. The median follow-up period was 60 months. Source data verification of adverse events was performed by two independent observers. Results All three planned preoperative chemotherapy cycles were administered to 65 patients (69.9 %). Only 27 % of the patients completed both pre- and postoperative chemotherapy. The reasons for not receiving postoperative adjuvant chemotherapy could be separated in two main problems: toxicity of the preoperative chemotherapy and postoperative problems involving difficulty in recovery and postoperative complications. Finally, 25 patients (27 %), completed three preoperative and three postoperative cycles. Grades 3 and 4 nonhematologic adverse events of preoperative chemotherapy mainly consisted of thromboembolic events (16.2 %) and cardiac complications (7.5 %). A history of cardiac and vascular disease was independently associated with discontinuation of preoperative chemotherapy and the occurrence of grade 3 or higher adverse events. Surgery was performed for 94 % of all the patients who started with ECC chemotherapy. A radical resection (R0) was achieved in 93 % of the patients. A complete pathologic response was observed in 8 % of the patients. During a median follow-up period of 60 months, the median disease-free survival time was 28 months, and the median overall survival time was 36 months. The 3-year overall survival rate was 50 %, and the 5-year overall survival rate was 42 %. Conclusion For patients with adenocarcinoma of the esophagus or GEJ, six cycles of ECC-based perioperative chemotherapy is associated with a relatively high number of adverse events. Although this toxicity did not affect the esophageal resectability rate, this regimen should be used with caution in this patient population.
    Annals of Surgical Oncology 01/2015; 22(5). DOI:10.1245/s10434-014-4120-9 · 3.94 Impact Factor
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    ABSTRACT: Pancreatic cancer is one of the most lethal malignancies due to its late diagnosis and limited response to treatment. Tractable methods to identify and interrogate pathways involved in pancreatic tumorigenesis are urgently needed. We established organoid models from normal and neoplastic murine and human pancreas tissues. Pancreatic organoids can be rapidly generated from resected tumors and biopsies, survive cryopreservation, and exhibit ductal- and disease-stage-specific characteristics. Orthotopically transplanted neoplastic organoids recapitulate the full spectrum of tumor development by forming early-grade neoplasms that progress to locally invasive and metastatic carcinomas. Due to their ability to be genetically manipulated, organoids are a platform to probe genetic cooperation. Comprehensive transcriptional and proteomic analyses organoids revealed genes and pathways altered during disease progression. The confirmation of many of these protein changes in human tissues demonstrates that organoids are a facile model of murine pancreatic system to discover characteristics of this deadly malignancy.
    Cell 12/2014; DOI:10.1016/j.cell.2014.12.021 · 33.12 Impact Factor
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    ABSTRACT: Computed tomography (CT) is the most widely used method to assess resectability of pancreatic and peri-ampullary cancer. One of the contra-indications for curative resection is the presence of extra-regional lymph node metastases. This meta-analysis investigates the accuracy of CT in assessing extra-regional lymph node metastases in pancreatic and peri-ampullary cancer. We systematically reviewed the literature according to the PRISMA guidelines. Studies reporting on CT assessment of extra-regional lymph nodes in patients undergoing pancreatoduodenectomy were included. Data on baseline characteristics, CT-investigations and histopathological outcomes were extracted. Diagnostic accuracy, positive predictive value (PPV), negative predictive value (NPV), sensitivity and specificity were calculated for individual studies and pooled data. After screening, 4 cohort studies reporting on CT-findings and histopathological outcome in 157 patients with pancreatic or peri-ampullary cancer were included. Overall, diagnostic accuracy, specificity and NPV varied from 63 to 81, 80-100% and 67-90% respectively. However, PPV and sensitivity ranged from 0 to 100% and 0-38%. Pooled sensitivity, specificity, PPV and NPV were 25%, 86%, 28% and 84% respectively. CT has a low diagnostic accuracy in assessing extra-regional lymph node metastases in pancreatic and peri-ampullary cancer. Therefore, suspicion of extra-regional lymph node metastases on CT alone should not be considered a contra-indication for exploration. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Surgical Oncology 10/2014; 23(4):229-235. DOI:10.1016/j.suronc.2014.10.005 · 2.37 Impact Factor
  • A.H.W. Schiphorst, A. Pronk, I.H.M. Borel Rinkes, M.E. Hamaker
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    ABSTRACT: AimMost colorectal cancer patients are elderly, but there are few data on the optimal surgical treatment for this age group and most studies are observational. We have reviewed the characteristics of randomised trials reporting laparoscopic surgery for colorectal cancer to determine the degree to which the elderly are represented.MethodA search was conducted of the NIH clinical trial registry and the ISRCTN register for randomized trials on laparoscopic surgery for colorectal cancer. Trial characteristics and end points were extracted from the registry website and supplemented by published results where available.ResultsOf 52 trial protocols the majority did not state any restrictions regarding cardiac (40 [77%]) or pulmonary function (41 [79%]). More than half (30 [58%]) had no restrictions regarding ASA-score. Twenty three (44%) trials excluded the elderly either simply on age or by comorbidity or organ function. When an upper age limit was set, half of the studies had no restriction regarding organ function, indicating that chronologic age rather than physical condition was taken as the reason for exclusion. In 45 (86%) of the trials the average age of participants was less than 70years, and no details of concurrent disease were given.Conclusion Participation of the elderly in trials of laparoscopic surgery for colorectal cancer is very limited. This should be remedied in future trials if adequate information on the majority of patients with colorectal cancer is to be obtained.This article is protected by copyright. All rights reserved.
    Colorectal Disease 10/2014; DOI:10.1111/codi.12806 · 2.02 Impact Factor
  • Cancer Research 10/2014; 74(19 Supplement):3351-3351. DOI:10.1158/1538-7445.AM2014-3351 · 9.28 Impact Factor
  • Cancer Research 10/2014; 74(19 Supplement):5388-5388. DOI:10.1158/1538-7445.AM2014-5388 · 9.28 Impact Factor

Publication Stats

4k Citations
990.49 Total Impact Points

Institutions

  • 1997–2015
    • University Medical Center Utrecht
      • • Department of Surgery
      • • Department of Radiology
      Utrecht, Utrecht, Netherlands
    • Red Cross
      Washington, Washington, D.C., United States
  • 2013
    • Hubrecht Institute
      Utrecht, Utrecht, Netherlands
  • 2012
    • Koninklijke Nederlandse Akademie van Wetenschappen
      Amsterdamo, North Holland, Netherlands
  • 2000–2008
    • Utrecht University
      Utrecht, Utrecht, Netherlands
  • 1997–2006
    • Leiden University
      Leyden, South Holland, Netherlands
  • 1995–2006
    • Leiden University Medical Centre
      • • Department of Molecular Cell Biology
      • • Department of Surgery
      Leyden, South Holland, Netherlands
  • 2002
    • Diakonessen Hospital Utrecht
      Utrecht, Utrecht, Netherlands
  • 1997–1999
    • Erasmus MC
      • • Department of Oncological Surgery
      • • Department of Radiology
      Rotterdam, South Holland, Netherlands
    • Erasmus Universiteit Rotterdam
      Rotterdam, South Holland, Netherlands
  • 1990
    • Het Oogziekenhuis Rotterdam
      Rotterdam, South Holland, Netherlands