Apeldoorn, Netherlands
Apeldoorn, Netherlands

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Van Der Zaag E.S.,Gelre Ziekenhuizen | Bouma W.H.,Gelre Ziekenhuizen
Annals of Surgical Oncology | Year: 2012

Background. The clinical impact of sentinel lymph node (SN) biopsy in colorectal cancer is still controversial. The aim of our study was to determine the accuracy of this procedure from published data and to identify factors that contribute to the conflicting reports. Methods. A systematic search of the Medline, Embase, and Cochrane databases up to July 2011 revealed 98 potentially eligible studies, of which 57 were analyzed including 3,934 patients (3,944 specimens). Results. The pooled SN identification rate was 90.7 % (95 % CI 88.2-93.3), with a significant higher identification rate in studies including more than 100 patients or studies using the ex vivo SN technique. The pooled sensitivity of the SN procedure was 69.6 % (95 % CI 64.7-74.6). Including the immunohistochemical findings increased the pooled sensitivity of SN procedure to 80.2 % (95 % CI 4.7-10.7). Subgroups with significantly higher sensitivity could be identified: ≥4 SNs versus <4 SNs (85.2 vs. 66.3 %, p = 0.003), colon versus rectal cancer (77.6 vs. 65.7 %, p = 0.04), early T1 or T2 versus advanced T3 or T4 carcinomas (93.4 vs. 58.8 %, p = 0.01). Serial sectioning and immunohistochemistry resulted in a mean upstaging of 18.9 % (range 0-50 %). True upstaging defined as micrometastases (pN1mi?) rather than isolated tumor cells (pN0itc+) was 7.7 %. Conclusions. The SN procedure in colorectal cancer has an overall sensitivity of 70 %, with increased sensitivity and refined staging in early-stage colon cancer. Because the ex vivo SN mapping is an easy technique it should be considered. © Society of Surgical Oncology 2012.


Stapleton N.M.,Sanquin Research and Landsteiner Laboratory | Einarsdottir H.K.,Sanquin Research and Landsteiner Laboratory | Stemerding A.M.,Gelre Ziekenhuizen | Vidarsson G.,Sanquin Research and Landsteiner Laboratory
Immunological Reviews | Year: 2015

The neonatal Fc receptor, FcRn, is best known for its role in transporting IgG in various tissues, providing newborns with humoral immunity, and for prolonging the half-life of IgG. Recent findings implicate the involvement of FcRn in a far wider range of biological and immunological processes, as FcRn has been found to bind and extend the half-life of albumin; to be involved in IgG transport and antigen sampling at mucosal surfaces; and to be crucial for efficient IgG-mediated phagocytosis. Herein, the function of FcRn will be reviewed, with emphasis on its recently documented significance for IgG polymorphisms affecting the half-life and biodistribution of IgG3, on its role in phagocyte biology, and the subsequent role for the presentation of antigens to lymphocytes. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


Van Der Zaag E.S.,Gelre Ziekenhuizen
Gastrointestinal Endoscopy | Year: 2012

Background: In colorectal cancer (CRC), colonoscopic tattooing is performed to mark the tumor site before laparoscopic surgery. Objective: To determine whether colonoscopic tattooing can be used to refine staging accuracy by increasing the lymph node (LN) yield per specimen and to determine its accuracy as a sentinel LN procedure. Design: Retrospective, case-control study. All LNs were microscopically examined for the presence of carbon particles. Setting: A university hospital and a teaching hospital. Patients: A consecutive series of 95 tattooed patients who had surgery for CRC between 2005 and 2009. A series of 210 non-tattooed patients who had surgery in the same time period served as controls. Main Outcome Measurements: Total number of LNs retrieved, detection rate, and sensitivity of tattooing as a sentinel node procedure. Results: A higher LN yield was observed in patients with preoperative tattooing, median (interquartile range) 15 (10-20) versus 12 (9-16), (P =.014). In multivariable analysis, the presence of carbon-containing LNs was an independent predictive factor for a higher LN yield (P =.002). The detection rate was 71%, with a median of 5 carbon-containing LNs per specimen. If preoperative tattooing was used for sentinel node mapping, the overall accuracy of predicting LN status was 94%. In the 24 N1 cases, there were 4 false-negative procedures (sensitivity 83%). Limitations: Retrospective series. Conclusion: After tattooing of CRC, the LN yield was higher than in a control group, and it could be used as a sentinel node procedure with acceptable accuracy rates. Because LN yield and sentinel node mapping are associated with improved diagnostic accuracy of LN involvement, preoperative tattooing can refine staging. © 2012 American Society for Gastrointestinal Endoscopy.


Donswijk L.F.,Gelre Ziekenhuizen | Gale E.A.M.,University of Bristol
BMJ (Online) | Year: 2015

Objective: To determine whether trial publications of glucose lowering drugs are dominated by a small group of highly prolific authors ("supertrialists") and to identify some of their characteristics. Design: Bibliographic analysis of trial publications. Data sources and review methods We searched PubMed for all randomised controlled trials (RCTs) relating to glucose lowering drugs published between 1 January 1993 and 31 December 2013. From these publications we identified the 110 most prolific authors using PubReMiner. The 991 RCTs they published were examined for various characteristics such as author number, commercial sponsorship, company authorship, conflicts of interest, etc. The track record of the top 11 authors was studied in more detail. Main outco me measure: Proportion of articles published by the top 110 and the top 11 authors. Results: 3782 articles from 13 592 authors were identified. The top 110 authors were named in 1227 (32.4%) of all articles, and the top 11 authors in 397 (10.5%) of all articles. The top 110 authors published 991 RCTs for a median of 20 (range 4-77) RCTs per author; the top 11 published 354 RCTs for a median of 42 (36-77) RCTs per author. Of the 110 top authors, 48 were employed by a pharmaceutical company. Of the 991 RCTs, 906 were commercially sponsored. Of 704 articles that could be assessed for conflicts of interest, only 42 (6%) were considered fully independent. Medical writing assistance was acknowledged in 439 (44.3%) of 991 RCTs. Conclusion: The past two decades have seen an explosive increase in the number of published clinical trials regarding glucose lowering treatment. Some authors have made a disproportionate contribution to the therapeutic evidence base; one third of the RCT evidence base on glucose lowering drug treatment for diabetes was generated by less than 1% of authors. Of these, 44% were company employees and 56% were academics who work closely with the pharmaceutical companies. ©BMJ Publishing Group Ltd 2015.


Sturkenboom I.H.W.M.,Radboud University Nijmegen | Graff M.J.L.,Radboud University Nijmegen | Hendriks J.C.M.,Radboud University Nijmegen | Veenhuizen Y.,Radboud University Nijmegen | And 14 more authors.
The Lancet Neurology | Year: 2014

Background: There is insufficient evidence to support use of occupational therapy interventions for patients with Parkinson's disease. We aimed to assess the efficacy of occupational therapy in improving daily activities of patients with Parkinson's disease. Methods: We did a multicentre, assessor-masked, randomised controlled clinical trial in ten hospitals in nine Dutch regional networks of specialised health-care professionals (ParkinsonNet), with assessment at 3 months and 6 months. Patients with Parkinson's disease with self-reported difficulties in daily activities were included, along with their primary caregivers. Patients were randomly assigned (2:1) to the intervention or control group by a computer-generated minimisation algorithm. The intervention consisted of 10 weeks of home-based occupational therapy according to national practice guidelines; control individuals received usual care with no occupational therapy. The primary outcome was self-perceived performance in daily activities at 3 months, assessed with the Canadian Occupational Performance Measure (score 1-10). Data were analysed using linear mixed models for repeated measures (intention-to-treat principle). Assessors monitored safety by asking patients about any unusual health events during the preceding 3 months. This trial is registered with ClinicalTrials.gov, NCT01336127. Findings: Between April 14, 2011, and Nov 2, 2012, 191 patients were randomly assigned to the intervention group (n=124) or the control group (n=67). 117 (94%) of 124 patients in the intervention group and 63 (94%) of 67 in the control group had a participating caregiver. At baseline, the median score on the Canadian Occupational Performance Measure was 4·3 (IQR 3·5-5·0) in the intervention group and 4·4 (3·8-5·0) in the control group. At 3 months, these scores were 5·8 (5·0-6·4) and 4·6 (4·6-6·6), respectively. The adjusted mean difference in score between groups at 3 months was in favour of the intervention group (1·2; 95% CI 0·8-1·6; p<0·0001). There were no adverse events associated with the study. Interpretation: Home-based, individualised occupational therapy led to an improvement in self-perceived performance in daily activities in patients with Parkinson's disease. Further work should identify which factors related to the patient, environmental context, or therapist might predict which patients are most likely to benefit from occupational therapy. Funding: Prinses Beatrix Spierfonds and Parkinson Vereniging. © 2014 Elsevier Ltd.


Ten Voorde M.,Gelre Ziekenhuizen | Van Der Zaag-Loonen H.J.,Gelre Ziekenhuizen | Van Leeuwen R.B.,Gelre Ziekenhuizen
Quality of Life Research | Year: 2012

Purpose: Relatively little is known about the level of impairment in patients with dizziness. Research question: How much does dizziness impair the quality of life of patients referred to a multidisciplinary dizziness unit? Patients and methods: All 2,252 patients completed the Dutch version of the Dizziness Handicap Inventory (DHI-D; score 0-100 with higher scores representing more impairment). The results were classified into three categories: mild, moderate, and severe impairment. The three domains in the DHI representing physical, functional, and emotional aspects of dizziness were compared, as well as DHI scores of men versus women, between diagnoses, and the relationship between DHI and age. Results: A total of 2,242 patients (64% women, mean age 54 years) completed the DHI with a mean score of 40.6. Almost 70% of patients had moderate or severe complaints. The handicap perceived by patients was primarily caused by physical and functional factors and less by emotional factors. Female patients and patients with hyperventilation syndrome and/or anxiety disorder had significantly higher DHI scores on all subscales. There was an S-shaped relationship between DHI score and age, and older patients reported more impairment. Conclusion: Dizziness has considerable impact on health-related quality of life of dizzy patients. © 2011 Springer Science+Business Media B.V.


De Ru J.A.,Central Military Hospital | Van Benthem P.P.G.,Gelre Ziekenhuizen
Otology and Neurotology | Year: 2011

Objective: To critically appraise the topic, questioning whether administering antiviral medication in case of Ramsay Hunt syndrome improves the restoration of facial nerve function. Methods: We reviewed the literature on this subject and calculated the odds ratios for the different treatment modalities. Results: Our study clearly shows that antiviral medication in combination with corticosteroids improves the outcome for patients with Ramsay Hunt syndrome. Conclusion: Contrary to a recent Cochrane Library review, we conclude that patients with Ramsay Hunt syndrome should be treated with combination therapy including antivirals. Copyright © 2011 Otology & Neurotology, Inc.


To assess interobserver agreement between pathologists in judging photographs of lymph node preparations of occult tumour cells of patients with colon cancer. Descriptive and comparative study of interobserver variability. All lymph nodes of 82 pN0 patients with colon cancer were analysed using three monoclonal antibodies against epithelial cells. Digital pictures of the 37 lesions detected were placed on a secured website. Forty pathologists selected at random were asked to examine the pictures and to categorize the lesions into 'micro metastases', 'isolated tumour cells' or something else. The degree of agreement was calculated by the Kendall W coefficient (with a range of 0.0-1.0). Thirty-five pathologists (88%) categorized the 37 lesions. Five lesions (14%) were categorized unanimously as micro metastases or isolated tumour cells. In 26 pictures (70%) the degree of agreement was poor to moderate. When the analysis was performed only on those diagnoses of which the pathologists were confident about their judgment, the percentage of lesions with good agreement rose to 49%. Differences in agreement were principally associated with multifocal lesions, clusters of tumour cells < 0.2 mm with proliferation characteristics in the parenchyma of the lymph node and lymphangio invasion. The differentiation between micro metastases and isolated tumour cells in lymph nodes of patients with colon cancer was not uniform. If this classification has clinical relevance to colon cancer then better definitions are needed.


Bouhbouh S.,Gelre Ziekenhuizen
Nederlands tijdschrift voor geneeskunde | Year: 2011

A central venous catheter was inserted in a 37-year-old man. During placement the catheter took a route to the left side of the heart. On CT it appeared the catheter was placed in a persisting left V. cava superior.


Bouhbouh S.,Gelre Ziekenhuizen
Nederlands tijdschrift voor geneeskunde | Year: 2011

BACKGROUND: Ingestion of certain Cortinarius species may lead to renal failure. In the Netherlands, this type of poisoning has not been previously described. CASUS: A 58-year-old female presented with headache, vomiting and oliguria, preceded by a few days of burning, painful thirst and malaise. She had acute and irreversible renal failure of unknown cause. History revealed that two days before the onset of her symptoms, she had eaten a ragout prepared with mushrooms that were picked in a forest. A renal biopsy demonstrated interstitial nephritis with proximal tubular necrosis. In the leftovers of the ragout two fragments of Cortinarius mushroom, probably belonging to the complex of Cortinarius cinnamomeus (cinnamon webcap), were found. First signs and symptoms, and the course are compatible with those described in the literature on Cortinarius poisoning. Despite haemodialysis and administration of acetylcysteine and glucocorticoids, her renal function did not recover. CONCLUSION: This case is the first description of mushroom poisoning by a species of the genus Cortinarius in the Netherlands.

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