Richard van Hillegersberg

University Medical Center Utrecht, Utrecht, Utrecht, Netherlands

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Publications (252)710.09 Total impact

  • [Show abstract] [Hide abstract]
    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; · 3.94 Impact Factor
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    ABSTRACT: Locally advanced pancreatic cancer (LAPC) is associated with a very poor prognosis. Current palliative (radio)chemotherapy provides only a marginal survival benefit of 2-3 months. Several innovative local ablative therapies have been explored as new treatment options. This systematic review aims to provide an overview of the clinical outcomes of these ablative therapies. A systematic search in PubMed, Embase and the Cochrane Library was performed to identify clinical studies, published before 1 June 2014, involving ablative therapies in LAPC. Outcomes of interest were safety, survival, quality of life and pain. After screening 1037 articles, 38 clinical studies involving 1164 patients with LAPC, treated with ablative therapies, were included. These studies concerned radiofrequency ablation (RFA) (7 studies), irreversible electroporation (IRE) (4), stereotactic body radiation therapy (SBRT) (16), high-intensity focused ultrasound (HIFU) (5), iodine-125 (2), iodine-125-cryosurgery (2), photodynamic therapy (1) and microwave ablation (1). All strategies appeared to be feasible and safe. Outcomes for postoperative, procedure-related morbidity and mortality were reported only for RFA (4-22 and 0-11 per cent respectively), IRE (9-15 and 0-4 per cent) and SBRT (0-25 and 0 per cent). Median survival of up to 25·6, 20·2, 24·0 and 12·6 months was reported for RFA, IRE, SBRT and HIFU respectively. Pain relief was demonstrated for RFA, IRE, SBRT and HIFU. Quality-of-life outcomes were reported only for SBRT, and showed promising results. Ablative therapies in patients with LAPC appear to be feasible and safe. © 2014 BJS Society Ltd Published by John Wiley & Sons Ltd.
    British Journal of Surgery 12/2014; · 5.21 Impact Factor
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    ABSTRACT: Occasionally incurable cancer is encountered after completion of the thoracic (first) phase of a three-phase esophagectomy. The outcome of aborting the operation at this stage, leaving the mobilized thoracic esophagus in situ, is unknown. A multicenter retrospective analysis was performed of patients in whom a completely mobilized thoracic esophagus was left in situ when incurable disease was discovered intraoperatively. The occurrence of esophageal necrosis or perforation, mortality, and all other adverse events were recorded and graded by severity. Some 18 patients were included. The median admission time was 9 days. All patients had resumed oral intake at discharge, except for 1 patient who was fed through a nasojejunal tube. After the operation, the median overall survival was 2.9 months. Postoperatively, 7 patients (39%) experienced major surgical adverse events, and 11 patients (61%) had no or only minor adverse events. Major adverse events were associated with the patient's death in 6 patients (33%), within 5 to 34 days postoperatively. Esophageal perforation or ischemia developed in 4 patients (22%) and 1 patient (6%), respectively. No predictive factors could be identified. Leaving a completely mobilized thoracic esophagus in situ when incurable cancer was discovered intraoperatively was a successful strategy in more than half of the patients. However, one third experienced major adverse events leading to mortality. Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
    The Annals of Thoracic Surgery 12/2014; · 3.63 Impact Factor
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    ABSTRACT: During thoracoscopic oesophageal surgery, we observed not previously described fascia-like structures. Description of similar structures in rectal cancer surgery was of paramount importance in improving the quality of resection. Therefore, we aimed to describe a new comprehensive concept of the surgical anatomy of the thoracic oesophagus with definition of the meso-oesophagus. We retrospectively evaluated 35 consecutive unedited videos of thoracoscopic oesophageal resections for cancer, to determine the surgical anatomy of the oesophageal fascia's vessels and lymphatic drainage. The resulting concept was validated in a prospective study, including 20 patients at three different centres. Additional confirmation was sought by a histologic study of a cadaver's thorax. A thin layer of connective tissue around the infracarinal oesophagus, involving the lymph nodes at the level of the carina, was observed during thoracoscopic esophagectomy in 32 of the 35 patients included in the retrospective study and in 19 of the 20 patients included in the prospective study. A thick fascia-like structure from the upper thoracic aperture to the lower thoracic aperture was visualized in all patients. This fascia is encountered between the descending aorta and left aspect of the infracarinal oesophagus. Above the carina it expands on both sides of the oesophagus to lateral mediastinal structures. This fascia contains oesophageal vessels, lymph vessels and nodes and nerves. The histologic study confirmed these findings. Here we described the concept of the "meso-oesophagus". Applying the description of the meso-oesophagus will create a better understanding of the oesophageal anatomy, leading to more adequate and reproducible surgery.
    Surgical Endoscopy 12/2014; · 3.31 Impact Factor
  • Peter S N van Rossum, Richard van Hillegersberg, Onne Reerink, Jelle P Ruurda
    Journal of Clinical Oncology 12/2014; · 17.88 Impact Factor
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    ABSTRACT: The optimal surgical treatment of patients with adenocarcinoma of the gastroesophageal junction has not been established yet. To evaluate the surgical strategies to treat adenocarcinoma of the gastroesophageal junction. Databases Pubmed, Cochrane, and Embase were searched for "adenocarcinoma of the gastroesophageal junction" AND ("surgery" OR "esophagectomy" OR "gastrectomy") or its synonyms or abbreviations. Only comparative studies that evaluated gastrectomy versus esophagectomy were included. In total 10 cohort studies comparing esophagectomy versus gastrectomy fulfilled the quality criteria. The R0 resection rates varied between 72-93% for esophagectomy and 62%-93% for gastrectomy. Morbidity was 33-39% after esophagectomy versus 11-54% after gastrectomy. The 30-day mortality ranged between 1.0-2.3 after esophagectomy and 1.8-2.7% after gastrectomy. At 6 months after surgery, health-related quality of life was higher after total gastrectomy than after esophagectomy. The 5-year survival rates varied between 30-42% for esophagectomy and 18-38% for gastrectomy, but were not significantly different. No clear oncologic benefit of either esophagectomy or gastrectomy in patients with adenomacarcinoma of gastroesophageal junction could be observed. However, gastrectomy seems to be accompanied with better quality of life. Future research should preferably consist of a multicenter RCT comparing esophagectomy and gastrectomy for adenocarcinomas of the gastroesophageal junction. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Surgical Oncology 10/2014; 23(4):222-228. · 2.37 Impact Factor
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    ABSTRACT: Background Although radiofrequency ablation (RFA) is promising for the local treatment of breast cancer, burns are a frequent complication. The safety and efficacy of a new technique with a bipolar RFA electrode was evaluated. Methods Dosimetry was assessed ex vivo in bovine mammary tissue, applying power settings of 5-15 W with 10-20 minutes exposure and 3.0-12.0 kJ to a 20-mm active length bipolar internally cooled needle-electrode. Subsequently, in 15 women with invasive breast carcinoma ≤2.0 cm diameter ultrasound-guided RFA was performed followed by immediate resection. Results An ablation zone of 2.5 cm was reached in the ex vivo experiments at 15 W at 9.0 kJ administered energy. Histopathology revealed complete cell death in 10 of 13 patients (77%); in 3 patients partial ablation was due to inaccurate probe positioning. In 1 patient a pneumothorax was caused by the probe placement, treated conservatively. No burns occurred. Conclusions Ultrasound-guided RFA with a bipolar needle-electrode appears to be a safe local treatment technique for invasive breast cancer up to 2 cm. Ways to improve placement of the probe and direct monitoring of the ablation-effect should be the aim of further research.
    European Journal of Surgical Oncology 10/2014; · 2.89 Impact Factor
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    ABSTRACT: The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on the distinction between adenocarcinomas above, below, or within the gastroesophageal junction; combined modality therapy; tumor markers for use in personalized medicine; PET-CT and endoscopic biopsies in the evaluation of response to neoadjuvant chemoradiation therapy; a standardized grading system for tumor regression in squamous cell cancer and adenocarcinoma; the experimental basis for new approaches to medical treatment; the criteria measuring response in esophageal cancer; and the impact of novel imaging on staging and response assessment.
    Annals of the New York Academy of Sciences 10/2014; 1325(1):197-210. · 4.31 Impact Factor
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    ABSTRACT: Patients with adenocarcinoma of the gastro-esophageal junction (GEJ) may undergo either esophagectomy or gastrectomy. The aim of this study was to evaluate the outcome of surgical therapy with regard to postoperative outcome and survival in patients with Siewert type II tumors.
    Annals of Surgical Oncology 09/2014; · 3.94 Impact Factor
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    ABSTRACT: Background In patients undergoing breast conserving surgery for non-palpable breast cancer, obtaining tumour free resection margins is important to prevent reexcision and local recurrence. We developed a model to predict positive resection margins in patients undergoing breast conserving surgery for non-palpable invasive breast cancer. Methods A total of 576 patients with non-palpable invasive breast cancer underwent breast conserving surgery in five hospitals in the Netherlands. A prediction model for positive resection margins was developed using multivariate logistic regression. Calibration and discrimination of the model were assessed and the model was internally validated by bootstrapping. Results Positive resection margins were present in 69/576 (12%) patients. Factors independently associated with positive resection margins included mammographic microcalcifications (OR 2.14, 1.22-3.77), tumour size (OR 1.75, 1.20-2.56), presence of DCIS (OR 2.61, 1.41-4.82), Bloom and Richardson grade 2/3 (OR 1.82, 1.05-3.14), and caudal location of the lesion (OR 2.4, 1.35-4.27). The model was well calibrated and moderately able to discriminate between patients with positive versus negative resection margins (AUC 0.70, 95% CI, 0.63 – 0.77, and 0.69 after internal validation). Conclusion The presented prediction model is moderately able to differentiate between women with high versus low risk of positive margins, and may be useful for surgical planning and preoperative patient counselling.
    European Journal of Surgical Oncology 09/2014; · 2.89 Impact Factor
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    ABSTRACT: The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on the role of the nurse in preparation of esophageal resection (ER); the management of patients who develop high-grade dysplasia after having undergone Nissen fundoplication; the trajectory of care for the patient with esophageal cancer; the influence of the site of tumor in the choice of treatment; the best location for esophagogastrostomy; management of chylous leak after esophagectomy; the optimal approach to manage thoracic esophageal leak after esophagectomy; the choice for operational approach in surgery of cardioesophageal crossing; the advantages of robot esophagectomy; the place of open esophagectomy; the advantages of esophagectomy compared to definitive chemoradiotherapy; the pathologist report in the resected specimen; the best way to manage patients with unsuspected positive microscopic margin after ER; enhanced recovery after surgery for ER: expedited care protocols; and long-term quality of life in patients following esophagectomy.
    Annals of the New York Academy of Sciences 09/2014; 1325(1). · 4.38 Impact Factor
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    ABSTRACT: Integrated 2-[(18)F]-fluoro-2-deoxy-d-glucose (FDG) PET/CT and magnetic resonance imaging (MRI) with functional features of diffusion-weighted imaging (DWI) are advancing imaging technologies that have current and future potential to overcome important limitations of conventional staging methods in the management of patients with oesophageal cancer. PET/CT has emerged as an important part of the standard work-up of patients with oesophageal cancer. Besides its important ability to detect unsuspected metastatic disease, PET/CT may be useful in the assessment of treatment response, radiation treatment planning, and detection of recurrent disease. In addition, high-resolution T2-weighted MRI and DWI have potential complementary roles. Recent improvements in MRI protocols and techniques have resulted in better imaging quality with the potential to bring improvement in staging, radiation treatment planning, and the assessment of treatment response. Optimal use and understanding of PET/CT and MRI in oesophageal cancer will contribute to the impact of these advancing technologies in tailoring treatment to the individual patient and achieving best possible outcomes. In this article, we graphically outline the current and potential future roles of PET/CT and MRI in the multidisciplinary management of oesophageal cancer.
    Clinical Radiology 08/2014; · 1.66 Impact Factor
  • Ronald D L Akkerman, Leonie Haverkamp, Richard van Hillegersberg, Jelle P Ruurda
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    ABSTRACT: Delayed gastric emptying is observed in 10% to 50% of patients after esophagectomy with gastric interposition. The effects of gastric interposition diameter, pyloric drainage, reconstructive route, and anastomotic site on postoperative gastric emptying were systematically reviewed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Most studies showed superior passage of the gastric tube compared with the whole stomach. Pyloric drainage is not significantly associated with the risk of developing delayed gastric emptying after esophagectomy. For reconstructive route and anastomotic site, available evidence on delayed gastric emptying is limited. Prospectively randomized studies with standardized outcome measurements are recommended.
    The Annals of Thoracic Surgery 08/2014; · 3.63 Impact Factor
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    ABSTRACT: Purpose To evaluate the association between the amount and location of calcifications of the supplying arteries of the gastric tube, as determined with a vascular calcification scoring system, and the occurrence of anastomotic leakage after esophagectomy with gastric tube reconstruction in patients with esophageal cancer. Materials and Methods Institutional review board approval was obtained, and the informed consent requirement was waived for this retrospective study. Consecutive patients who underwent elective esophagectomy for cancer with gastric tube reconstruction and cervical anastomosis between 2003 and 2012 were identified from a prospective database. Vascular calcification scores were retrospectively assigned by reviewing the routine preoperative computed tomographic (CT) images. In patients with anastomotic leakage, presence and severity of calcifications of the aorta (score of 0-2), celiac axis (score of 0-2), right postceliac arteries (common hepatic, gastroduodenal, and right gastroepiploic arteries; score of 0-1), and left postceliac arteries (splenic and left gastroepiploic arteries, score of 0-1) along with patient- and procedure-related characteristics were compared with those of patients without leakage by using multivariate logistic regression analysis. Results Of 246 patients, 58 (24%) experienced anastomotic leakage. No significant differences in patient-related factors were found between patients with leakage and those without leakage, with the exception of more chronic use of steroids in the leakage group (7% [four of 58] vs 0% [0 of 188], P = .003). At univariate analysis, leakage was more common in patients with calcification of the aorta (27% [28 of 102] and 35% [13 of 37] vs 16% [17 of 107], P = .029) and the right postceliac arteries (55% [six of 11] vs 22% [52 of 235], P = .013). At multivariate analysis, both minor (odds ratio, 2.00; 95% confidence interval: 1.02, 3.94) and major (odds ratio, 2.87; 95% confidence interval: 1.22, 6.72) aortic calcifications were associated with leakage. Also, an independent association with leakage was found for calcifications of the right postceliac arteries (odds ratio, 4.22; 95% confidence interval: 1.24, 14.4). Conclusion Atherosclerotic calcification of the aorta and right postceliac arteries that supply the gastric tube is an independent risk factor for anastomotic leakage after esophagectomy. © RSNA, 2014.
    Radiology 08/2014; · 6.21 Impact Factor
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    ABSTRACT: Background Early enteral feeding following surgery can be given orally, via a jejunostomy or via a nasojejunal tube. However, the best feeding route following esophagectomy is unclear. Objectives To determine the best route for enteral nutrition following esophagectomy regarding anastomotic leakage, pneumonia, percentage meeting the nutritional requirements, weight loss, complications of tube feeding, mortality, patient satisfaction and length of hospital stay. Design A systematic literature review following PRISMA and MOOSE guidelines. Results There were 17 eligible studies on early oral intake, jejunostomy or nasojejunal tube feeding. Only one nonrandomized study (N = 133) investigated early oral feeding specifically following esophagectomy. Early oral feeding was associated with a reduced length of stay with delayed oral feeding, without increased complication rates. Postoperative nasojejunal tube feeding was not significantly different from jejunostomy tube feeding regarding complications or catheter efficacy in the only randomised trial on this subject (N = 150). Jejunostomy tube feeding outcome was reported in 12 non-comparative studies (N = 3293). It was effective in meeting short-term nutritional requirements, but major tube-related complications necessitated relaparotomy in 0-2.9% of patients. In three non-comparative studies (N = 135) on nasojejunal tube feeding only minor complications were reported, data on nutritional outcome was lacking. Data on patient satisfaction and long-term nutritional outcome were not found for any of the feeding routes investigated. Conclusion It is unclear what the best route for early enteral nutrition is after esophagectomy. Especially data regarding early oral intake are scarce, and phase 2 trials are needed for further investigation. Registration International prospective register of systematic reviews, CRD42013004032.
    Clinical Nutrition 08/2014; · 3.94 Impact Factor
  • Gastrointestinal Endoscopy 07/2014; · 4.90 Impact Factor
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    ABSTRACT: OBJECTIVES:Barrett's esophagus (BE) is associated with an increased risk of developing esophageal adenocarcinoma (EAC). Patients with a known diagnosis of BE are usually advised to participate in an endoscopic surveillance program, but its clinical value is unproven. Our objective was to compare patients participating in a surveillance program for BE before EAC diagnosis with those not participating in such a program, and to determine predictive factors for mortality from EAC.METHODS:All patients diagnosed with EAC between 1999 and 2009 were identified in the nationwide Netherlands Cancer Registry. These data were linked to Pathologisch-Anatomisch Landelijk Geautomatiseerd Archief, the Dutch Pathology Registry. Prior surveillance was evaluated, and multivariable Cox proportional hazards regression analysis was performed to identify predictors for all-cause mortality at 2-year and 5-year follow-up.RESULTS:In total, 9,780 EAC patients were included. Of these, 791 (8%) patients were known with a prior diagnosis of BE, of which 452 (57%) patients participated in an adequate endoscopic surveillance program, 120 (15%) patients in an inadequate program, and 219 (28%) patients had a prior BE diagnosis without participating. Two-year (and five-year) mortality rates were lower in patients undergoing adequate surveillance (adjusted hazard ratio (HR)=0.79, 95% confidence interval (CI)=0.64-0.92) when compared with patients with a prior BE diagnosis who were not participating. Other factors associated with lower mortality from EAC were lower tumor stage (stage I vs. IV, HR=0.19, 95% CI=0.16-0.23) and combining surgery with neoadjuvant chemo/radiotherapy (HR=0.66, 95% CI=0.58-0.76).CONCLUSIONS:Participation in a surveillance program for BE, but only if adequately performed, reduces mortality from EAC. Nevertheless, it remains to be determined whether such a program is cost-effective, as more than 90% of all EAC patients were not known to have BE before diagnosis.Am J Gastroenterol advance online publication, 1 July 2014; doi:10.1038/ajg.2014.156.
    The American journal of gastroenterology. 07/2014;
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    ABSTRACT: Background: Pneumonia is a frequently observed complication following esophagectomy. The lack of a uniform definition of pneumonia leads to large variations of pneumonia rates in literature. This study was designed to develop a scoring system for diagnosing pneumonia following esophagectomy at the hospital ward. Methods: In a prospective cohort study of esophagectomy patients, known risk factors for pneumonia, temperature, leukocyte count, pulmonary radiography and sputum culture added were evaluated. Primary outcome was defined as the decision to treat suspected pneumonia. Multivariate Cox regression analysis with backward selection was used to identify predictors of pneumonia treatment. Results: The majority of postoperative pneumonia treatments (88.2%) occurred at the hospital ward, where treatment was observed in 67 (36.2%) of 185 patients. Independent diagnostic determinants for pneumonia treatment were temperature (hazard ratio (HR) = 1.283, p = 0.073), leukocyte count (HR = 1.040, p = 0.078) and pulmonary radiography (HR >11.0, p = 0.000). Sputum culture did not influence the decision to treat pneumonia. These findings were used to develop a scoring system which includes temperature, leukocyte count and pulmonary radiography. Conclusion: The decision to treat pneumonia is based on temperature, leukocyte count and pulmonary radiography findings. The proposed clinical scoring system for pneumonia following esophagectomy at the hospital ward has the potential to aid clinical practice and improve comparability of future research in esophageal cancer surgery. © 2014 S. Karger AG, Basel.
    Digestive surgery 06/2014; 31(2):108-116. · 1.37 Impact Factor
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    ABSTRACT: The best route of feeding for patients undergoing an oesophagectomy is unclear. Concerns exist that early oral intake would increase the incidence and severity of pneumonia and anastomotic leakage. However, in studies including patients after many other types of gastrointestinal surgery and in animal experiments, early oral intake has been shown to be beneficial and enhance recovery. Therefore, we aim to determine the feasibility of early oral intake after oesophagectomy.
    BMJ Open 06/2014; 4(6):e004557. · 2.06 Impact Factor
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    ABSTRACT: Severe pulmonary complications occur frequently following transthoracic oesophagectomy. An exaggerated immunological response is probably a main driving factor, and this might be prevented by perioperative administration of a glucocorticoid.
    European Journal of Anaesthesiology 05/2014; · 3.01 Impact Factor

Publication Stats

2k Citations
710.09 Total Impact Points

Institutions

  • 2007–2014
    • University Medical Center Utrecht
      • • Department of Surgery
      • • Department of Gastroenterology and Hepatology
      • • Department of Pathology
      Utrecht, Utrecht, Netherlands
  • 2012
    • University of Malaya
      • Department of Surgery
      Kuala Lumpur, Kuala Lumpur, Malaysia
  • 2005–2009
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • • Department of Surgery
      • • Academic Medical Center
      Amsterdam, North Holland, Netherlands
  • 2008
    • St. Antonius Ziekenhuis
      Nieuwegen, Utrecht, Netherlands
  • 2002–2003
    • Erasmus MC
      • Department of Surgery
      Rotterdam, South Holland, Netherlands
    • University of Amsterdam
      Amsterdamo, North Holland, Netherlands
  • 1991–2001
    • Erasmus Universiteit Rotterdam
      • Department of Surgery
      Rotterdam, South Holland, Netherlands