Sjoerd G Elias

cipto mangunkusumo hospital, Batavia, Jakarta Raya, Indonesia

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Publications (84)285.9 Total impact

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    ABSTRACT: Breast cancer imaging phenotype is diverse and may relate to molecular alterations driving cancer behavior. We systematically reviewed and meta-analyzed relations between breast cancer imaging features and HER2 overexpression as a marker of breast cancer aggressiveness. MEDLINE and EMBASE were searched for mammography, breast ultrasound, magnetic resonance imaging (MRI) and/or [18F]fluorodeoxyglucose positron emission tomography studies through February 2013. Of 68 imaging features that could be pooled (85 papers, 23,255 cancers; random-effects meta-analysis), 11 significantly related to HER2 overexpression. Results based on ≥5 studies and robustness in subgroup analyses: presence of microcalcifications on mammography (pooled odds ratio (pOR) 3.14, 95% confidence interval (CI): 2.46-4.00) or ultrasound (mass-associated pOR 2.95, 95%CI: 2.34-3.71), branching or fine linear microcalcifications (pOR 2.11, 95%CI: 1.07-4.14) or extremely dense breasts on mammography (pOR 1.37, 95%CI: 1.07-1.76), and washout (pOR 1.57, 95%CI: 1.11-2.21) or fast initial kinetics (pOR 2.60, 95%CI: 1.43-4.73) on MRI. Maximum [18F]fluorodeoxyglucose standardized uptake value (SUVmax) was higher upon HER2 overexpression (pooled mean difference +0.76, 95%CI: 0.10-1.42). These results show that several imaging features relate to HER2 overexpression, lending credibility to the hypothesis that imaging phenotype reflects cancer behavior. This implies prognostic relevance, which is especially relevant as imaging is readily available during diagnostic work-up.
    Cancer Epidemiology Biomarkers &amp Prevention 05/2014; · 4.56 Impact Factor
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    ABSTRACT: Molecular imaging of breast cancer is a promising emerging technology, potentially able to improve clinical care. Valid imaging targets for molecular imaging tracer development are membrane-bound hypoxia-related proteins, expressed when tumor growth outpaces neo-angiogenesis. We performed a systematic literature review and meta-analysis of such hypoxia marker expression rates in human breast cancer to evaluate their potential as clinically relevant molecular imaging targets. We searched MEDLINE and EMBASE for articles describing membrane-bound proteins that are related to hypoxia inducible factor 1alpha (HIF-1alpha), the key regulator of the hypoxia response. We extracted expression rates of carbonic anhydrase-IX (CAIX), glucose transporter-1 (GLUT1), C-X-C chemokine receptor type-4 (CXCR4), or insulin-like growth factor-1 receptor (IGF1R) in human breast disease, evaluated by immunohistochemistry. We pooled study results using random-effects models and applied meta-regression to identify associations with clinicopathological variables. Of 1,705 identified articles, 117 matched our selection criteria, totaling 30,216 immunohistochemistry results. We found substantial between-study variability in expression rates. Invasive cancer showed pooled expression rates of 35% for CAIX (95% confidence interval (CI): 26-46%), 51% for GLUT1 (CI: 40-61%), 46% for CXCR4 (CI: 33-59%), and 46% for IGF1R (CI: 35-70%). Expression rates increased with tumor grade for GLUT1, CAIX, and CXCR4 (all p < 0.001), but decreased for IGF1R (p < 0.001). GLUT1 showed the highest expression rate in grade III cancers with 58% (45-69%). CXCR4 showed the highest expression rate in small T1 tumors with 48% (CI: 28-69%), but associations with size were only significant for CAIX (p < 0.001; positive association) and IGF1R (p = 0.047; negative association). Although based on few studies, CAIX, GLUT1, and CXCR4 showed profound lower expression rates in normal breast tissue and benign breast disease (p < 0.001), and high rates in carcinoma in situ. Invasive lobular carcinoma consistently showed lower expression rates (p < 0.001). Our results support the potential of hypoxia-related markers as breast cancer molecular imaging targets. Although specificity is promising, combining targets would be necessary for optimal sensitivity. These data could help guide the choice of imaging targets for tracer development depending on the envisioned clinical application.
    BMC Cancer 11/2013; 13(1):538. · 3.33 Impact Factor
  • International journal of cardiology 08/2013; · 6.18 Impact Factor
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    ABSTRACT: Purpose:To assess the relationship between parameters measured on dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging and fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) in primary invasive breast cancer.Materials and Methods:This HIPAA-compliant study was a retrospective review of medical records and therefore approved by the institutional review board without the requirement for informed consent. Patients with a diagnosis of invasive breast cancer from January 2005 through December 2009 who underwent both DCE MR imaging and FDG PET/CT before treatment initiation were retrospectively identified. Fractional volumes were measured for ranges of signal enhancement ratio (SER) values from DCE MR imaging data and compared with maximum standardized uptake values (SUVmax) from FDG PET/CT data. Linear regression analysis was performed to clarify the relationship between SER and SUVmax, adjusting for tumor size, pathologic grade, and receptor status.Results:Analyzed were 117 invasive breast cancers in 117 patients. Overall, a higher percentage of high washout kinetics was positively associated with SUVmax (1.57% increase in SUVmax per 1% increase in high washout; P = .020), and a higher percentage of low plateau kinetics was negatively associated with SUVmax (1.19% decrease in SUVmax per 1% increase in low plateau; P = .003). These relationships were strongest among triple-negative (TN) tumors (4.34% increase in SUVmax per 1% increase in high washout and 2.65% decrease in SUVmax per 1% increase in low plateau; P = .018 and .004, respectively).Conclusion:In invasive breast carcinoma, there is a positive relationship between the percentage of high washout and SUVmax and a negative relationship between the percentage of low plateau and SUVmax. These results are stronger in TN tumors.© RSNA, 2013Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13130058/-/DC1.
    Radiology 07/2013; · 6.34 Impact Factor
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    ABSTRACT: Desmoid-type fibromatosis is a locally aggressive soft tissue tumour with a biological behaviour that varies between relatively indolent and progressive growth. Although there is a trend towards conservative treatment, surgery remains the standard treatment for extra-abdominal desmoid tumours. Databases of three hospitals were searched to identify patients who had been treated for desmoid-type fibromatosis between November 1989 and May 2011. The risk of local recurrence was evaluated and predictive factors were assessed in patients who underwent surgical resection as initial treatment for a primary tumour. A total of 132 patients had surgical treatment for a primary tumour. A complete resection (R0) was achieved in 87 patients (65·9 per cent). In addition to surgery, 54 patients received radiotherapy. During a median follow-up of 38 months, 18 local recurrences were detected. The estimated 5-year cumulative risk of local recurrence was 17·6 per cent. Univariable Cox regression analysis demonstrated that the risk of local recurrence increased for extremity lesions compared with desmoids on the trunk (odds ratio 6·69, 95 per cent confidence interval 1·42 to 31·54). No significant influence of age, resection margins or adjuvant radiotherapy on the risk for local recurrence was observed. Following surgical treatment of a primary extra-abdominal desmoid tumour, the 5-year risk of local recurrence is modest and not influenced by microscopically clear resection margins or adjuvant radiotherapy.
    British Journal of Surgery 06/2013; · 4.84 Impact Factor
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    ABSTRACT: The aim of this study is to evaluate Breast Imaging Reporting and Data Systems (BI-RADS) 4A/B subcategory risk estimates for ductal carcinoma in situ (DCIS) and invasive cancer (IC), determining whether changing the proposed cutoffs to a higher biopsy threshold could safely increase cancer-to-biopsy yields while minimizing false-positive biopsies. A prospective clinical trial was performed to evaluate BI-RADS 4 lesions from women seen in clinic between January 2006 and March 2007. An experienced radiologist prospectively estimated a percent risk-estimate for DCIS and IC. Truth was determined by histopathology or 4-year follow-up negative for malignancy. Risk estimates were used to generate receiver-operating characteristic (ROC) curves. Biopsy rates, cancer-to-biopsy yields, and type of malignancies missed were then calculated across postulated risk thresholds. A total of 124 breast lesions were evaluated from 213 women. An experienced radiologist gave highly accurate risk estimates for IC, DCIS alone, or the combination with an area under ROC curve of 0.91 (95 % CI 0.84-0.99) (p < 0.001), 0.81 (95 % CI 0.69-0.93) (p = 0.011), and 0.89 (95 % CI 0.83-0.95) (p < 0.001), respectively. The cancer-to-biopsy yield was 30 %. Three hypothetical thresholds for intervention were analyzed: (1) DCIS or IC ≥ 10 %; (2) DCIS ≥ 50 % or IC ≥ 10 %; and (3) IC ≥ 10 %, which translated to 22, 48, and 56 % of biopsies avoided; cancer-to-biopsy yields of 36, 47, and 46 %; and associated chance of missing an IC of 0, 1, and 2 %, respectively. Expert radiologists estimate risk of IC and DCIS with a high degree of accuracy. Increasing the cut off point for recommending biopsy, substituting with a short-term follow-up protocol with biopsy if any change, may safely reduce the number of false-positive biopsies.
    Breast Cancer Research and Treatment 06/2013; · 4.47 Impact Factor
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    ABSTRACT: OBJECTIVE: To determine to what extent the Rome III criteria for irritable bowel syndrome can contribute towards safely reducing unnecessary referrals for colonoscopy in primary care patients with lower gastrointestinal (GI) complaints. DESIGN: Data from the CEDAR study were used: a cross-sectional study in 810 patients with lower GI complaints suggestive for organic bowel disease who were referred by their general practitioner for secondary care colonoscopy. Fulfilment of the Rome III criteria was ascertained by a questionnaire. General practitioners recorded the presence or absence of alarm symptoms. Outcome was determined by colonoscopy and histology. RESULTS: Of 810 participants, 222 fulfilled the Rome III criteria [27%, 95% confidence interval (CI) 24-31%]. The majority of these patients presented with alarm symptoms. Only 39 participants fulfilled the Rome III criteria and lacked alarm symptoms (overall frequency 5%, 95% CI 4-7). Overall, organic bowel disease was diagnosed in 141 participants (17%). Participants who fulfilled the Rome III criteria had a significantly lower risk of organic bowel disease compared with participants who did not [12% (95% CI 8-17) vs. 20% (95% CI 17-23), P<0.01]. The lowest risk was observed in patients without alarm symptoms who fulfilled the Rome III criteria (3%, 95% CI 0-14). CONCLUSION: A minority of referred primary care patients with lower GI complaints both fulfilled the Rome III criteria for irritable bowel syndrome and lacked alarm symptoms. Although organic bowel disease could be ruled out safely in this small group, application of the Rome III criteria is not likely to lead to a considerable reduction in unnecessary referrals for colonoscopy in these patients.
    European journal of gastroenterology & hepatology 01/2013; · 1.66 Impact Factor
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    ABSTRACT: INTRODUCTION: Since the introduction of the sentinel lymph node biopsy (SLNB) in patients with breast cancer, micrometastases and isolated tumor cells are detected frequently in the SLN. As such, they offer an opportunity to study the development of regional metastases in breast cancer. PATIENTS AND METHODS: Between June 1999 and November 2010 1418 patients with cT1-2N0 breast cancer underwent SLNB. Primary tumor characteristics and information regarding regional lymph node involvement were collected prospectively. Patients were categorized into four levels of lymph node involvement: pN0, pN0(i+), pN1mi and pN ≥ 1a. An univariate analysis and a binary logistic regression analysis were performed to assess the relation between patient- and tumor characteristics and lymph node involvement. RESULTS: Increasing tumor size and younger age were associated with a higher risk of pN1mi and pN ≥ 1a and a lower chance of pN0 and pN0(i+). Triple negative molecular subtype was associated with a decreased risk of pN1mi and pN ≥ 1a. Tumor size was positively related to overall occurrence of regional lymph node metastases in a linear manner. CONCLUSION: Patients with larger tumors, no triple negative disease, and younger age showed a decreased chance of both pN0 and pN0(i+) and an increased risk of both pN1mi and pN ≥ 1a. There seems to be a gradual shift in risk pattern from pN0 to pN0(i+) to pN1mi and to pN ≥ 1a-disease. The presence of the smallest metastases remained fairly constant over time when compared to macrometastases. This constant presence suggests that the risk of seeding and outgrowth of metastases remains constant over time.
    Breast (Edinburgh, Scotland) 01/2013; · 2.09 Impact Factor
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    ABSTRACT: To assess the effects of famine exposure during childhood on coronary calcium deposition and, secondarily, on cardiac valve and aortic calcifications. Retrospective cohort. Community. 286 postmenopausal women with individual measurements of famine exposure during childhood in the Netherlands during World War II. Famine exposure during childhood. Coronary artery calcifications measured by CT scan and scored using the Agatston method; calcifications of the aorta and cardiac valves (mitral and/or aortic) measured semiquantitatively. Logistic regression was used for coronary Agatston score of >100 or ≤100, valve or aortic calcifications as the dependent variable and an indicator for famine exposure as the independent variable. These models were also used for confounder adjustment and stratification based on age groups of 0-9 and 10-17 years. In the overall analysis, no statistically significant association was found between severe famine exposure in childhood and a high coronary calcium score (OR 1.80, 95% CI 0.87 to 3.78). However, when looking at specific risk periods, severe famine exposure during adolescence was related to a higher risk for a high coronary calcium score than non-exposure to famine, both in crude (OR 3.47, 95% CI 1.00 to 12.07) and adjusted analyses (OR 4.62, 95% CI 1.16 to 18.43). No statistically significant association was found between childhood famine exposure and valve or aortic calcification (OR 1.66, 95% CI 0.69 to 4.10). Famine exposure in childhood, especially during adolescence, seems to be associated with a higher risk of coronary artery calcification in late adulthood. However, the association between childhood famine exposure and cardiac valve/aortic calcification is less clear.
    BMJ Open 01/2013; 3(11):e003818. · 1.58 Impact Factor
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    ABSTRACT: Undernutrition during critical periods of growth and development may permanently affect lung physiology and function. To investigate whether acute undernutrition in childhood or young adulthood increases the risk of later hospitalization for obstructive airways disease, chronic obstructive pulmonary disease (COPD), or asthma. We studied 7,841 women from Prospect-EPIC who experienced the 1944-45 Dutch famine between ages 0 and 21. Pulmonary outcomes were measured by registered hospital admissions and exposure-blinded computed tomography (CT) in a subgroup of 295 women. With Cox proportional hazard regression we explored effects of famine exposure on risk of hospitalization for obstructive airways disease, COPD, and asthma. With logistic regression we explored effects of famine on risk of CT evidence of pulmonary disease. RISKS OF HOSPITALIZATION FOR OBSTRUCTIVE AIRWAYS DISEASE, COPD, AND ASTHMA WERE INCREASED AFTER MODERATE FAMINE EXPOSURE, AND SIGNIFICANTLY INCREASED AFTER SEVERE FAMINE EXPOSURE: hazard ratios for obstructive airways disease were 1.31 (95% CI: 0.97 to 1.77) and 1.57 (95% CI: 1.10 to 2.23) respectively. Associations between famine exposure and hospitalization for COPD were stronger in ever-smokers than in never-smokers. Acute undernutrition in childhood or young adulthood is associated with an increased risk of later COPD and asthma hospitalization, possibly through increased sensitivity for tobacco smoke.
    PLoS ONE 01/2013; 8(12):e82636. · 3.53 Impact Factor
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    ABSTRACT: We aimed to develop a multivariable model for prediction of underestimated invasiveness in women with ductal carcinoma in situ at stereotactic large core needle biopsy, that can be used to select patients for sentinel node biopsy at primary surgery. From the literature, we selected potential preoperative predictors of underestimated invasive breast cancer. Data of patients with nonpalpable breast lesions who were diagnosed with ductal carcinoma in situ at stereotactic large core needle biopsy, drawn from the prospective COBRA (Core Biopsy after RAdiological localization) and COBRA2000 cohort studies, were used to fit the multivariable model and assess its overall performance, discrimination, and calibration. 348 women with large core needle biopsy-proven ductal carcinoma in situ were available for analysis. In 100 (28.7%) patients invasive carcinoma was found at subsequent surgery. Nine predictors were included in the model. In the multivariable analysis, the predictors with the strongest association were lesion size (OR 1.12 per cm, 95% CI 0.98-1.28), number of cores retrieved at biopsy (OR per core 0.87, 95% CI 0.75-1.01), presence of lobular cancerization (OR 5.29, 95% CI 1.25-26.77), and microinvasion (OR 3.75, 95% CI 1.42-9.87). The overall performance of the multivariable model was poor with an explained variation of 9% (Nagelkerke's R (2) ), mediocre discrimination with area under the receiver operating characteristic curve of 0.66 (95% confidence interval 0.58-0.73), and fairly good calibration. The evaluation of our multivariable prediction model in a large, clinically representative study population proves that routine clinical and pathological variables are not suitable to select patients with large core needle biopsy-proven ductal carcinoma in situ for sentinel node biopsy during primary surgery.
    PLoS ONE 01/2013; 8(10):e77826. · 3.53 Impact Factor
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    ABSTRACT: PURPOSE To assess how dynamic-contrast-enhanced magnetic resonance imaging (DCE-MRI) kinetics relate to 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in invasive breast cancer, and to determine the degree of this association for tumors of the “triple negative” phenotype. METHOD AND MATERIALS After obtaining IRB approval, patients diagnosed with invasive breast cancer between 1/2005 through 12/2009 who underwent both DCE-MRI and FDG-PET/CT before initiation of treatment were retrospectively identified. DCE-MRI was acquired using a three time-point method. Enhancement kinetics was quantified by computing the signal enhancement ratio (SER), defined as the ratio of early-to-late signal enhancement at each pixel. Fractional tumor volumes of washout (SER > 1.3), plateau (0.9< SER≤1.3) and persistent (0< SER≤0.9) were calculated, as a percentage of the whole tumor SER volume. FDG PET/CT studies were reviewed to obtain SUV max values of the tumor; partial-volume correction was performed using a mathematical look-up table for each PET/CT scanner. Linear regression analysis was performed to assess the relationship between SER and SUV max, correcting for overall tumor size, pathologic grade, hormone receptor and her2-neu status. RESULTS 118 invasive breast cancers in 117 patients were analyzed. Increasing percentage “washout” kinetics was positively and independently associated with increasing percentages of SUV max (1.17% increase in SUV max per 1% increase in washout; p=0.016), while increasing percentage “plateau” and “persistent” kinetics was not. This relationship was strongest among triple-negative tumors (2.43% increase in SUV max per 1% increase in washout; p=0.011). CONCLUSION In invasive breast carcinoma, there is a positive correlation between percentage washout and SUV max. This correlation is greatest and most significant for the triple negative phenotype, after correcting for tumor volume, pathologic grade and biomarker status. CLINICAL RELEVANCE/APPLICATION This study suggests a small but significant association between washout on MRI and PET SUV max, which differs among subtypes, potentially reflecting differences in underlying intrinsic biology.
    Radiological Society of North America 2012 Scientific Assembly and Annual Meeting; 11/2012
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    ABSTRACT: BACKGROUND: We describe a new method for biodistribution studies with IRDye800CW fluorescent antibody probes. This method allows the quantification of the IRDye800CW fluorescent tracer in percentage of injected dose per gram of tissue (% ID/g), and it is herein compared to the generally used reference method that makes use of radioactivity. METHODS: Cetuximab was conjugated to both the near-infrared fluorophore IRDye800CW and/or the positron emitter 89-zirconium, which was injected in nude mice bearing A431 human tumor xenografts. Positron emission tomography (PET) and optical imaging were performed 24 h post-injection (p.i.). For the biodistribution study, organs and tumors were collected 24 h p.i., and each of these was halved. One half was used for the determination of probe uptake by radioactivity measurement. The other half was homogenized, and the content of the fluorescent probe was determined by extrapolation from a calibration curve made with the injected probe. RESULTS: Tumors were clearly visualized with both modalities, and the calculated tumor-to-normal tissue ratios were very similar for optical and PET imaging: 3.31 +/- 1.09 and 3.15 +/- 0.99, respectively. Although some variations were observed in ex vivo analyses, tumor uptake was within the same range for IRDye800CW and gamma ray quantification: 15.07 +/- 3.66% ID/g and 13.92 +/- 2.59% ID/g, respectively. CONCLUSIONS: The novel method for quantification of the optical tracer IRDye800CW gives similar results as the reference method of gamma ray quantification. This new method is considered very useful in the context of the preclinical development of IRDye800CW fluorescent probes for optical molecular imaging, likely contributing to the selection of lead compounds that are the most promising for clinical translation.
    EJNMMI research. 09/2012; 2(1):50.
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    ABSTRACT: OBJECTIVE:: Numerous experiments in animals have been performed to investigate the effect of prenatal undernutrition on the development of hypertension in later life, with inconclusive results. We systematically reviewed animal studies examining the effects of maternal undernutrition on SBP, DBP, and mean arterial blood pressure (BP) in offspring. METHODS:: A search was performed in Medline and Embase to identify articles that reported on maternal undernutrition and hypertension in experimental animal studies. Summary estimates of the effect of undernutrition on SBP, DBP, and mean arterial BP were obtained through meta-analysis. RESULTS:: Of the 6151 articles identified, 194 were considered eligible after screening titles and abstracts. After detailed evaluation, 101 met the inclusion criteria and were included in the review. Both maternal general and protein undernutrition increased SBP [general undernutrition: 14.5 mmHg, 95% confidence interval (CI) 10.8-18.3; protein undernutrition: 18.9 mmHg, 95% CI 16.1-21.8] and mean arterial BP (general undernutrition: 5.0 mmHg, 95% CI 1.4-8.6; protein undernutrition: 10.5 mmHg, 95% CI 6.7-14.2). There was substantial heterogeneity in the results. DBP was increased by protein undernutrition (9.5 mmHg, 95% CI 2.6-16.3), whereas general undernutrition had no significant effect. CONCLUSION:: The results of this meta-analysis generally support the view that in animals, maternal undernutrition - both general and protein - results in increased SBP and mean arterial BP. DBP was only increased after protein undernutrition. The results depended strongly on the applied measurement technique and animal model.
    Journal of Hypertension 09/2012; · 4.22 Impact Factor
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    ABSTRACT: Optical breast imaging offers the possibility of noninvasive, low cost, and high sensitivity imaging of breast cancers. Poor spatial resolution and a lack of anatomical landmarks in optical images of the breast make interpretation difficult and motivate registration and fusion of these data with subsequent optical images and other breast imaging modalities. Methods used for registration and fusion of optical breast images are reviewed. Imaging concerns relevant to the registration problem are first highlighted, followed by a focus on both monomodal and multimodal registration of optical breast imaging. Where relevant, methods pertaining to other imaging modalities or imaged anatomies are presented. The multimodal registration discussion concerns digital x-ray mammography, ultrasound, magnetic resonance imaging, and positron emission tomography.
    Journal of Biomedical Optics 08/2012; 17(8):80901-1. · 2.75 Impact Factor
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    ABSTRACT: To evaluate if clinical fluorescence imaging of IRDye800CW is feasible on our fluorescence optical mammography system by estimating detection limits assessed by breast-cancer-simulating phantom experiments. Phantoms (2.1 cm(3), 0.9 cm(3)) with IRDye800CW concentrations of 0.5 to 120 nM were suspended in a 550 cm(3) measurement cup containing 507 surface-mounted source and detector fibers. The cup was filled with optical matching fluid containing IRDye800CW concentrations of 0, 5, 10, or 20 nM. Tomographic fluorescence images were acquired by exciting IRDye800CW at 730 nm; wavelengths above 750 nm were filtered. Signal intensities were calculated over a volume of interest corresponding to the size and location of the phantom in the reconstructed images. Correlations (R(2)) were calculated, and detection limits with associated upper 95% prediction interval were estimated. Between-day reproducibility was assessed with intraclass correlation coefficients (ICC). Fluorescent intensities were strongly correlated with phantom IRDye800CW concentrations (R(2)0.983 to 0.999). IRDye800CW detection limits ranged from 0.14 to 2.46 nM (upper 95% prediction limit 4.63 to 18.63 nM). ICC ranged from 0.88 to 1.00. The estimated detection limits for IRDye800CW were in the low-nanomolar range. These results support the start of clinical trials to evaluate the fluorescence optical mammography system using IRDye800CW labeled breast cancer targeting ligands.
    Journal of Biomedical Optics 07/2012; 17(7):076022. · 2.75 Impact Factor
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    ABSTRACT: The purpose of this study was to describe the rationale and design of a randomized controlled trial analyzing the effects of mesh type (Ultrapro versus Prolene mesh) on postoperative pain and well-being following an endoscopic Totally Extraperitoneal (TEP) repair for inguinal hernias (short: TULP trial). The TULP trial is a prospective, two arm, double blind, randomized controlled trial to assess chronic postoperative pain and quality of life following implantation of a lightweight (Ultrapro) and heavyweight (Prolene) mesh in endoscopic TEP hernia repair. The setting is a high-volume single center hospital, specializing in TEP hernia repair. All patients are operated on by one of four surgeons. Adult male patients (≥18 years of age) with primary, reducible, unilateral inguinal hernias and no contraindications for TEP repair are eligible for inclusion in the study. The primary outcome is substantial chronic postoperative pain, defined as moderate to severe pain persisting ≥ 3 months postoperatively (Numerical Rating Scale, NRS 4-10). Secondary endpoints are the individual development of pain until three years after the TEP procedure, the quality of life (QoL), recurrence rate, patient satisfaction and complications. Large prospective randomized controlled studies with a long follow-up evaluating the incidence of chronic postoperative pain following implantation of lightweight and heavyweight mesh in endoscopic (TEP) hernia repair are limited. By studying the presence of pain and quality of life, but also complications and recurrences in a large patient population, a complete efficiency and feasibility assessment of both mesh types in TEP hernia repair will be performed. The TULP study is registered in the Dutch Trial Register (NTR2131).
    Trials 06/2012; 13:76. · 2.21 Impact Factor
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    ABSTRACT: The developmental origins hypothesis proposes that undernutrition during early development is associated with an increased type 2 diabetes risk in adulthood. We investigated the association between undernutrition during childhood and young adulthood and type 2 diabetes in adulthood. We studied 7,837 women from Prospect-EPIC (European Prospective Investigation Into Cancer and Nutrition) who were exposed to the 1944-1945 Dutch famine when they were between age 0 and 21 years. We used Cox proportional hazards regression models to explore the effect of famine on the risk of subsequent type 2 diabetes in adulthood. We adjusted for potential confounders, including age at famine exposure, smoking, and level of education. Self-reported famine exposure during childhood and young adulthood was associated with an increased type 2 diabetes risk in a dose-dependent manner. In those who reported moderate famine exposure, the age-adjusted type 2 diabetes hazard ratio (HR) was 1.36 (95% CI [1.09-1.70]); in those who reported severe famine exposure, the age-adjusted HR was 1.64 (1.26-2.14) relative to unexposed women. These effects did not change after adjustment for confounders. This study provides the first direct evidence, using individual famine exposure data, that a short period of moderate or severe undernutrition during postnatal development increases type 2 diabetes risk in adulthood.
    Diabetes 05/2012; 61(9):2255-60. · 7.90 Impact Factor
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    ABSTRACT: To describe the rationale and design of an observational cohort study analyzing the effects of endoscopic Totally Extraperitoneal (TEP) hernia repair on male fertility (MAIN study). The MAIN study is an observational cohort study designed to assess fertility after endoscopic TEP hernia repair. The setting is a high-volume single center hospital, specialized in TEP hernia repair. Male patients of 18-60 years of age, with primary, reducible, bilateral inguinal hernias and no contraindications for endoscopic TEP repair are eligible for inclusion in this study. Patients with an ASA-classification≥III and patients with recurrent and/or scrotal hernias and/or a medical history of pelvic surgery and/or radiotherapy, known fertility problems, diabetes and/or other diseases associated with a risk of fertility problems, will be excluded. The primary outcome is the testicular perfusion before and 6 months after TEP hernia repair (assessed by means of a scrotal ultrasonography). Secondary endpoints are the testicular volume (Ultrasound), semen quality and quantity and the endocrinological status, based on serum levels of the sexual hormones follicle-stimulating hormone (FSH), luteinizing hormone (LSH), testosterone and inhibin B before and 6 months after TEP hernia repair. The use of polypropylene mesh is associated with a strong foreign body reaction which could play a role in chronic groin pain development. Since the mesh in (endoscopic) inguinal hernia repair is placed in close contact to the vas deferens and spermatic vessels, the mesh-induced inflammatory reaction could lead to a dysfunction of these structures. Relevant large and prospective clinical studies on the problem are limited. This study will provide a complete assessment of fertility in male patients who undergo simultaneous bilateral endoscopic TEP hernia repair, by analyzing testicular perfusion and volume, semen quantity and quality and endocrinological status before and 6 months after TEP repair. The MAIN study is registered in the Dutch Trial Register (NTR2208).
    BMC Surgery 05/2012; 12:7. · 1.97 Impact Factor
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    ABSTRACT: Fecal biomarker tests that differentiate between organic bowel disease (OBD) and non-OBD in primary care patients with persistent lower-abdomen complaints could reduce the number of unnecessary referrals for endoscopy. We quantified the accuracy of fecal calprotectin and immunochemical occult blood (iFOBT) point-of-care (POC) tests and a calprotectin ELISA in primary care patients with suspected OBD. We performed biomarker tests on fecal samples from 386 patients with lower-abdomen complaints suggestive for OBD. Endoscopic and histological diagnosis served as reference. OBD was diagnosed in 99 patients (prevalence 25.9%); 19 had adenocarcinoma, 53 adenoma, and 27 inflammatory bowel disease. Sensitivity for OBD was 0.64 (95% CI 0.54-0.72) for calprotectin POC, 0.56 (0.46-0.66) for iFOBT POC, and 0.74 (0.65-0.82) for calprotectin ELISA; specificities were 0.53 (0.48-0.59), 0.83 (0.78-0.87), and 0.47 (0.41-0.53), respectively. Negative predictive values (NPVs) were 0.81 (0.74-0.86), 0.85 (0.80-0.88), and 0.84 (0.78-0.89); positive predictive values (PPVs) varied from 0.32 (0.26-0.39) and 0.33 (0.27-0.39) (calprotectin tests) to 0.53 (0.44-0.63) (iFOBT POC). Combining the 2 POC tests improved sensitivity [0.79 (0.69-0.86)] and NPV [0.87 (0.81-0.91)] but lowered specificity [0.49 (0.44-0.55)] and PPV [0.35 (0.29-0.42)]. When adenomas ≤1 cm were considered non-OBD, the NPV of all tests improved to >0.90 [combined POC tests, 0.97 (0.93-0.99)]. Diagnostic accuracy of the tests alone or combined was insufficient when all adenomas were considered OBD. When only adenomas >1 cm were considered OBD, all tests could rule out OBD to a reasonable extent, particularly the combined POC tests. The tests were less useful for inclusion of OBD.
    Clinical Chemistry 03/2012; 58(6):989-98. · 7.15 Impact Factor