Hjalmar C van Santvoort

Radboud University Medical Centre (Radboudumc), Nymegen, Gelderland, Netherlands

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Publications (129)770.16 Total impact

  • [Show abstract] [Hide abstract]
    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: Chronic pancreatitis is a complex disease with many unanswered questions regarding the natural history and therapy. Prospective longitudinal studies with long-term follow-up are warranted. The Dutch Chronic Pancreatitis Registry (CARE) is a nationwide registry aimed at prospective evaluation and follow-up of patients with chronic pancreatitis. All patients with (suspected) chronic or recurrent pancreatitis are eligible for CARE. Patients are followed-up by yearly questionnaires and review of medical records. Study outcomes are pain, disease complications, quality of life, and pancreatic function. The target sample size was set at 500 for the first year and 1000 patients within 3 years. A total of 1218 patients were included from February 2010 until June 2013 by 76 participating surgeons and gastroenterologist from 33 hospitals. Participation rate was 90% of eligible patients. Eight academic centers included 761 (62%) patients, while 25 community hospitals included 457 (38%). Patient centered outcomes were assessed by yearly questionnaires, which had a response rate of 85 and 82% for year 1 and 2, respectively. The median age of patients was 58 years, 814 (67%) were male, and 38% had symptoms for less than 5 years. The CARE registry has successfully recruited over 1200 patients with chronic and recurrent pancreatitis in about 3 years. The defined inclusion criteria ensure patients are included at an early disease stage. Participation and compliance rates are high. CARE offers a unique opportunity with sufficient power to investigate many clinical questions regarding natural course, complications, and efficacy and timing of treatment strategies. Copyright © 2014 IAP and EPC. Published by Elsevier B.V. All rights reserved.
    Pancreatology 11/2014; · 2.50 Impact Factor
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    ABSTRACT: Background Early enteral feeding through a nasoenteric feeding tube is often used in patients with severe acute pancreatitis to prevent gut-derived infections, but evidence to support this strategy is limited. We conducted a multicenter, randomized trial comparing early nasoenteric tube feeding with an oral diet at 72 hours after presentation to the emergency department in patients with acute pancreatitis. Methods We enrolled patients with acute pancreatitis who were at high risk for complications on the basis of an Acute Physiology and Chronic Health Evaluation II score of 8 or higher (on a scale of 0 to 71, with higher scores indicating more severe disease), an Imrie or modified Glasgow score of 3 or higher (on a scale of 0 to 8, with higher scores indicating more severe disease), or a serum C-reactive protein level of more than 150 mg per liter. Patients were randomly assigned to nasoenteric tube feeding within 24 hours after randomization (early group) or to an oral diet initiated 72 hours after presentation (on-demand group), with tube feeding provided if the oral diet was not tolerated. The primary end point was a composite of major infection (infected pancreatic necrosis, bacteremia, or pneumonia) or death during 6 months of follow-up. Results A total of 208 patients were enrolled at 19 Dutch hospitals. The primary end point occurred in 30 of 101 patients (30%) in the early group and in 28 of 104 (27%) in the on-demand group (risk ratio, 1.07; 95% confidence interval, 0.79 to 1.44; P=0.76). There were no significant differences between the early group and the on-demand group in the rate of major infection (25% and 26%, respectively; P=0.87) or death (11% and 7%, respectively; P=0.33). In the on-demand group, 72 patients (69%) tolerated an oral diet and did not require tube feeding. Conclusions This trial did not show the superiority of early nasoenteric tube feeding, as compared with an oral diet after 72 hours, in reducing the rate of infection or death in patients with acute pancreatitis at high risk for complications. (Funded by the Netherlands Organization for Health Research and Development and others; PYTHON Current Controlled Trials number, ISRCTN18170985 .).
    New England Journal of Medicine 11/2014; 371:1983-1993. · 54.42 Impact Factor
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    ABSTRACT: Cohort studies from expert centers suggest that laparoscopic distal pancreatectomy (LDP) is superior to open distal pancreatectomy (ODP) regarding postoperative morbidity and length of hospital stay. The generalizability of these findings is however unknown since nationwide data on LDP are lacking.Study DesignAdults who had undergone distal pancreatectomy in 17 centers between 2005 and 2013 were analyzed retrospectively. First, all LDPs were compared with all open distal pancreatectomies (ODPs). Second, groups were matched using a propensity score. Third, the attitudes of pancreatic surgeons towards LDP were surveyed. Primary outcome was major complications (Clavien-Dindo grade ≥III).ResultsAmongst 633 included patients, 64 patients (10%) had undergone LDP and 569 patients (90%) ODP. Baseline characteristics were comparable, except for previous abdominal surgery and mean tumor size. In the full cohort, LDP was associated with fewer major complications (16% vs. 29%; P=0.02) and a shorter median [IQR] hospital stay (8 days [7-12] vs. 10 days [8-14]; P=0.03). Of all LDPs, 33% was converted to ODP. Matching succeeded for 63 LDP patients. After matching, the differences in major complications (9 patients [14%] vs. 19 patients [30%]; P=0.06) and median [IQR] length of hospital stay (8 days [7-12] vs. 10 days [8-13]; P=0.48) were not statistically significant. The survey demonstrated that 85% of surgeons welcomed LDP-training.Conclusions Despite a nationwide underutilization and an impact of selection bias, outcomes of LDP seemed to be at least non-inferior to ODP. Specific training is welcomed and could improve both the use and outcomes of LDP.
    Journal of the American College of Surgeons 11/2014; · 4.45 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. · 2.37 Impact Factor
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    ABSTRACT: Background/Objectives Acute pancreatitis has a highly variable clinical course. Early and reliable predictors for the severity of acute pancreatitis are lacking. Proteinuria appears to be a useful predictor of disease severity and outcome in a variety of clinical conditions. This study aims to investigate the predictive value of proteinuria on admission for the severity of acute pancreatitis compared with other commonly used predictors; the APACHE II score, Modified Glasgow score and C-reactive protein (CRP). Methods This is a post-hoc analysis of 64 patients admitted with acute pancreatitis treated in one teaching hospital, who participated in a previous randomized trial. Proteinuria was defined as a Protein/Creatinine (P/C) ratio >23 mg/mmol. The primary endpoint was severe acute pancreatitis. Secondary endpoints included infectious complications, need for invasive intervention, ICU stay and in hospital mortality. Results Proteinuria was present in 30/64 patients (47%). Eleven patients (17%) had severe acute pancreatitis. There was no difference in incidence of severe acute pancreatitis between patients with and without proteinuria: 6/30 patients (20%) versus 5/34 patients (15%) respectively (p=0.58). Likewise, the occurrence of infectious complications, need for intervention and ICU stay and mortality did not differ significantly (p=0.58, p=0.99, p=0.33 and p=0.60 respectively). The diagnostic performance of the P/C ratio for the prediction of severe pancreatitis was inferior to the Modified Glasgow score (p=0.04) and CRP (p=0.03). Conclusion Proteinuria on admission does not seem to be a reliable predictor for disease severity in acute pancreatitis. The diagnostic performance of the P/C ratio is inferior to the Modified Glasgow score and CRP.
    Pancreatology 09/2014; · 2.50 Impact Factor
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    ABSTRACT: Introduction In acute pancreatitis, enteral nutrition (EN) reduces the rate of complications, such as infected pancreatic necrosis, organ failure, and mortality, as compared to parenteral nutrition (PN). Starting EN within 24 hours of admission might further reduce complications. Methods A literature search for trials of EN in acute pancreatitis was performed. Authors of eligible trials were requested to provide the data of all patients in the EN-arm of their trials. A meta-analysis of individual patient data was performed. The cohort of patients with EN was divided into patients receiving EN within 24 hours or after 24 hours of admission. Multivariable logistic regression, adjusting for predicted disease severity and trial, was used to study the effect of timing of EN on a composite endpoint of infected pancreatic necrosis, organ failure, or mortality. Results Observational data from 165 individuals from 8 randomised trials were obtained; 100 patients with EN within 24 hours and 65 patients with EN after 24 hours of admission. In the multivariable model, EN started within 24 hours of admission compared to EN started after 24 hours of admission, reduced the composite endpoint from 45% to 19% (adjusted odds ratio [OR] of 0.44; 95% confidence interval [CI] 0.20 – 0.96). Within the composite endpoint, organ failure was reduced from 42% to 16% (adjusted OR 0.42; 95% CI 0.19 – 0.94). Conclusions In this meta-analysis of observational data from individuals with acute pancreatitis, starting EN within 24 hours after hospital admission, compared with after 24 hours, was associated with a reduction in complications.
    Pancreatology 09/2014; · 2.50 Impact Factor
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    ABSTRACT: Infected necrosis is the main indication for invasive intervention in acute necrotizing pancreatitis. The 2013 IAP/APA guidelines state that percutaneous catheter drainage should be the first step in the treatment of infected necrosis. In 50–65% of patients, additional necrosectomy is required after catheter drainage, which was traditionally done by open necrosectomy. Driven by the perceived lower complication rate, there is an increasing trend toward minimally invasive percutaneous and endoscopic transluminal necrosectomy. The authors present an overview of current minimally invasive treatment options for necrotizing pancreatitis and review recent developments in clinical studies.
    Expert Review of Medical Devices 08/2014; · 2.43 Impact Factor
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    ABSTRACT: This Review covers the latest developments in the treatment options for chronic pancreatitis. Pain is the most frequent and dominant symptom in patients with chronic pancreatitis, which ranges from severe disabling continuous pain to mild pain attacks and pain-free periods. Conventional treatment strategies and recent changes in the treatment of pain in patients with chronic pancreatitis are outlined. The different treatment options for pain consist of medical therapy, endoscopy or surgery. Their related merits and drawbacks are discussed. Finally, novel insights in the field of genetics and microbiota are summarized, and future perspectives are discussed.
    Nature Reviews Gastroenterology &#38 Hepatology 06/2014; · 10.81 Impact Factor
  • Pancreatology 06/2014; 14(3):S10. · 2.50 Impact Factor
  • Pancreatology 06/2014; 14(3):S9–S10. · 2.50 Impact Factor
  • Pancreatology 06/2014; 14(3):S11. · 2.50 Impact Factor
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    ABSTRACT: Preoperative differentiation between malignant and benign pancreatic tumors can be difficult. Consequently, a proportion of patients undergoing pancreatoduodenectomy for suspected malignancy will ultimately have benign disease. The aim of this study was to compare preoperative clinical and diagnostic characteristics of patients with unexpected benign disease after pancreatoduodenectomy with those of patients with confirmed (pre)malignant disease.
    Pancreatology 05/2014; 13(3):S11. · 2.50 Impact Factor
  • Nicolien J Schepers, Hjalmar C van Santvoort, Marco J Bruno
    New England Journal of Medicine 05/2014; 370(20):1955. · 54.42 Impact Factor
  • Article: Reply.
    Journal of the American College of Surgeons 05/2014; 218(5):1075. · 4.45 Impact Factor
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    ABSTRACT: We sought association of genetic variants in the renin-angiotensin system (RAS) and vitamin D system with acute pancreatitis (AP) development and severity. The endocrine RAS is involved in circulatory homeostasis through the pressor action of angiotensin II at its AT1 receptor. However, local RAS regulate growth and inflammation in diverse cells and tissues, and their activity may be suppressed by vitamin D. Intrapancreatic angiotensin II generation has been implicated in the development of AP. Five hundred forty-four white patients with AP from 3 countries (United Kingdom, 22; Germany, 136; and The Netherlands 386) and 8487 control subjects (United Kingdom 7833, The Netherlands 717) were genotyped for 8 polymorphisms of the RAS/vitamin D systems, chosen on the basis of likely functionality. The angiotensin-converting enzyme I (rather than D) allele was significantly associated with alcohol-related AP when all cohorts were combined (P = 0.03). The renin rs5707 G (rather than A) allele was associated with AP (P = 0.002), infected necrosis (P = 0.025) and mortality (P = 0.046). The association of 2 RAS polymorphisms with AP suggests the need for further detailed analysis of the role of RAS/vitamin D in the genesis or severity of AP, particularly given the ready potential for pharmacological manipulation of this system using existing marketed agents. However, further replication studies will be required before any such association is considered robust, particularly given the significant heterogeneity of AP causation and clinical course.
    Annals of surgery 04/2014; · 7.19 Impact Factor
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    ABSTRACT: To characterize pancreatic tumor motion and to develop a gating scheme for radiotherapy in pancreatic cancer. Two cine MRIs of 60s each were performed in fifteen pancreatic cancer patients, one in sagittal direction and one in coronal direction. A Minimum Output Sum of Squared Error (MOSSE) adaptive correlation filter was used to quantify tumor motion in craniocaudal, lateral and anteroposterior directions. To develop a gating scheme, stability of the breathing phases was examined and a gating window assessment was created, incorporating tumor motion, treatment time and motion margins. The largest tumor motion was found in craniocaudal direction, with an average peak-to-peak amplitude of 15mm (range 6-34mm). Amplitude of the tumor in the anteroposterior direction was on average 5mm (range 1-13mm). The least motion was seen in lateral direction (average 3mm, range 2-5mm). The end exhale position was the most stable position in the breathing cycle and tumors spent more time closer to the end exhale position than to the end inhale position. On average, a margin of 25% of the maximum craniocaudal breathing amplitude was needed to achieve full target coverage with a duty cycle of 50%. When reducing the duty cycle to 50%, a margin of 5mm was sufficient to cover the target in 11 out of 15 patients. Gated delivery for radiotherapy of pancreatic cancer is best performed around the end exhale position as this is the most stable position in the breathing cycle. Considerable margin reduction can be established at moderate duty cycles, yielding acceptable treatment efficiency. However, motion patterns and amplitude do substantially differ between individual patients. Therefore, individual treatment strategies should be considered for radiotherapy in pancreatic cancer.
    Radiotherapy and Oncology 04/2014; · 4.86 Impact Factor
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    ABSTRACT: This Review covers the latest developments in the treatment of acute pancreatitis. The Atlanta Classification of acute pancreatitis has been revised, proposing several new terms and abandoning some of the old and confusing terminology. The 2012 Revised Atlanta Classification and the determinant-based classification aim to universally define the different local and systemic complications and predict outcome. The most important differences between these classifications are discussed. Several promising treatment options for the early management of acute pancreatitis have been tested, including the use of enteral nutrition and antibiotics as well as novel therapies such as haemofiltration and protease inhibitors. The results are summarized and the quality of evidence is discussed. Finally, new developments in the management of patients with infected pancreatic necrosis are addressed, including the use of the 'step-up approach' and results of minimally invasive necrosectomy.
    Nature Reviews Gastroenterology &#38 Hepatology 03/2014; · 10.43 Impact Factor
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    ABSTRACT: Background In patients suspected of pancreatic or periampullary cancer, abdominal contrast-enhanced computed tomography (CT) is the standard diagnostic modality. A supplementary endoscopic ultrasonography (EUS) is often performed, although there is only limited evidence of its additional diagnostic value. The aim of the study is to evaluate the additional diagnostic value of EUS over CT in deciding on exploratory laparotomy in patients suspected of pancreatic or periampullary cancer. Methods We retrospectively analyzed 86 consecutive patients who routinely underwent CT and EUS before exploratory laparotomy with or without pancreatoduodenectomy for suspected pancreatic or periampullary carcinoma between 2007 and 2010. Primary outcomes were visibility of a mass, resectability on CT/EUS and resection with curative intent. Results A mass was visible on CT in 72/86 (84%) patients. In these 72 patients, EUS demonstrated a mass in 64/72 (89%) patients. Resectability was accurately predicted by CT in 65/72 (90%) and by EUS in 58/72 (81%) patients. In 14/86 (16%) patients no mass was seen on CT. EUS showed a mass in 12/14 (86%) of these patients. A malignant lesion was histological proven in 11/12 (92%) of these patients. Overall, resectability was accurately predicted by CT and EUS in 90% (77/86) and 84% (72/86), respectively. Conclusions In patients with a visible mass on CT, suspected for pancreatic or periampullary cancer, EUS has no additional diagnostic value, does not influence the decision to perform laparotomy and should therefore not be performed routinely. In patients without a visible mass on CT, EUS is useful to confirm the presence of a tumor.
    Pancreatology 03/2014; · 2.50 Impact Factor
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    ABSTRACT: Background Diagnosing infected necrotizing pancreatitis (INP) may be challenging. The aim of this study was to determine the added value of routine fine-needle aspiration (FNA) in addition to clinical and imaging signs of infection in patients who underwent intervention for suspected INP. Methods We conducted a post hoc analysis of 208 consecutive patients from a prospective, multicenter database who underwent intervention because of suspected INP. In retrospect, 3 groups were constructed based on the patients preoperative characteristics: Clinical, imaging, and FNA. Patients in the clinical group had clinical signs of infection but no gas on preoperative computed tomography (CT) and no FNA performed before intervention. Patients in the imaging group had gas bubbles on the preoperative CT but no was FNA performed, whereas patients in the FNA group had a positive FNA before intervention. The reference standard for infection was the culture taken during the first intervention (either catheter drainage or necrosectomy). Results The initial intervention for INP was performed a median of 27 days (interquartile range, 20–39) after admission without difference between the 3 groups (P = .15). Infection was confirmed in 80% of 92 patients of the clinical group, in 94% of 88 patients of the imaging group, and in 86% of 28 patients of the FNA group (P = .07). Mortality was 19% and was not different between groups (P = .39). Conclusion INP can generally be diagnosed based on clinical or imaging signs of infection. FNA may be useful in patients with unclear clinical signs and no imaging signs of INP.
    Surgery 03/2014; 155(3):442–448. · 3.11 Impact Factor

Publication Stats

2k Citations
770.16 Total Impact Points


  • 2011–2014
    • Radboud University Medical Centre (Radboudumc)
      Nymegen, Gelderland, Netherlands
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • Department of Surgery
      Amsterdam, North Holland, Netherlands
  • 2006–2014
    • St. Antonius Ziekenhuis
      • • Department of Surgery
      • • Department of Radiology
      • • Department of Vascular Surgery
      Nieuwegen, Utrecht, Netherlands
    • University Medical Center Utrecht
      • Department of Surgery
      Utrecht, Utrecht, Netherlands
  • 2009
    • Universität Heidelberg
      Heidelburg, Baden-Württemberg, Germany
  • 2008
    • Nizhny Novgorod State Medical Academy
      Gorkey, Nizjnij Novgorod, Russia