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1.  Relationship between pretreatment FDG-PET and diffusion-weighted MRI biomarkers in diffuse large B-cell lymphoma 
The purpose of this study was to determine the correlation between the 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) standardized uptake value (SUV) and the diffusion-weighted magnetic resonance imaging (MRI) apparent diffusion coefficient (ADC) in newly diagnosed diffuse large B-cell lymphoma (DLBCL). Pretreatment FDG-PET and diffusion-weighted MRI of 21 patients with histologically proven DLBCL were prospectively analyzed. In each patient, maximum, mean and peak standardized uptake value (SUV) was measured in the lesion with visually highest FDG uptake and in the largest lesion. Mean ADC (ADCmean, calculated with b-values of 0 and 1000 s/mm2) was measured in the same lesions. Correlations between FDG-PET metrics (SUVmax, SUVmean, SUVpeak) and ADCmean were assessed using Pearson’s correlation coefficients. In the lesions with visually highest FDG uptake, no significant correlations were found between the SUVmax, SUVmean, SUVpeak and the ADCmean (P=0.498, P=0.609 and P=0.595, respectively). In the largest lesions, there were no significant correlations either between the SUVmax, SUVmean, SUVpeak and the ADCmean (P=0.992, P=0.843 and P=0.894, respectively). The results of this study indicate that the glycolytic rate as measured by FDG-PET and changes in water compartmentalization and water diffusion as measured by the ADC are independent biological phenomena in newly diagnosed DLBCL. Further studies are warranted to assess the complementary roles of these different imaging biomarkers in the evaluation and follow-up of DLBCL.
PMCID: PMC3999403  PMID: 24795837
FDG-PET; diffusion-weighted MRI; standardized uptake value; apparent diffusion coefficient; diffuse large B-cell lymphoma
2.  Fistulizing Crohn’s disease: Diagnosis and management 
Fistulizing Crohn’s disease represents an evolving, yet unresolved, issue for multidisciplinary management. Perianal fistulas are the most frequent findings in fistulizing Crohn’s disease. While enterocutaneous fistulas are rare, they are associated with considerable morbidity and mortality. Detailed evaluation of the fistula tract by advanced imaging techniques is required to determine the most suitable management options. The fundamentals of perianal fistula management are to evaluate the complexity of the fistula tract, and exclude proctitis and associated abscess. The main goals of the treatment are abscess drainage, which is mandatory, before initiating immunosuppressive medical therapy, resolution of fistula discharge, preservation of continence and, in the long term, avoidance of proctectomy with permanent stoma. The management of enterocutaneous fistulas comprises of sepsis control, skin care, nutritional optimization and, if needed, delayed surgery.
PMCID: PMC4040755  PMID: 24917961
Crohn’s disease; enterocutaneous fistula; perianal fistula; inflammatory bowel disease; anti-TNF therapy
3.  A multi-centre randomised double-blind placebo-controlled trial to evaluate the value of a single bolus intravenous alfentanil in CT colonography 
BMC Gastroenterology  2013;13:94.
Pain is common during colonic insufflation required for CT colonography. We therefore evaluate whether a single intravenous alfentanil bolus has a clinically relevant analgesic effect compared with placebo in patients undergoing CT colonography.
A prospective multi-centre randomised double-blind placebo-controlled trial was performed in patients scheduled for elective CT colonography. Patients were randomised to receive either a bolus of 7.5 μg/kg alfentanil (n = 45) or placebo (n = 45). The primary outcome was the difference in maximum pain during colonic insufflation on an 11-point numeric rating scale. We defined a clinically relevant effect as a maximum pain reduction of at least 1.3 points. Secondary outcomes included total pain and burden of CT colonography (5-point scale), the most burdensome aspect and side effects. Our primary outcome was tested using a one-sided independent samples t-test.
Maximum pain scores during insufflation were lower with alfentanil as compared with placebo, 5.3 versus 3.0 (P < 0.001). Total CT colonography pain and burden were also lower with alfentanil (2.0 vs. 1.6; P = 0.014 and 2.1 vs. 1.7; P = 0.007, respectively). With alfentanil fewer patients rated the insufflation as most burdensome aspect (56.1% vs. 18.6%; P = 0.001). Episodes with desaturations < 90% SpO2 were more common with alfentanil (8.1% vs. 44.4%; P < 0.001, but no clinically relevant desaturations occurred.
A low-dose intravenous alfentanil bolus provides a clinically relevant reduction of maximum pain during CT colonography and may improve the CT colonography acceptance, especially for patients with a low pain threshold.
Trial registration
Dutch Trial Register: NTR2902
PMCID: PMC3671205  PMID: 23706123
Randomised controlled trial; Colonography; Computed tomographic; Alfentanil; Analgesics; Opioid; Patient satisfaction
4.  Liver Fibrosis in Type I Gaucher Disease: Magnetic Resonance Imaging, Transient Elastography and Parameters of Iron Storage 
PLoS ONE  2013;8(3):e57507.
Long term liver-related complications of type-1 Gaucher disease (GD), a lysosomal storage disorder, include fibrosis and an increased incidence of hepatocellular carcinoma. Splenectomy has been implicated as a risk factor for the development of liver pathology in GD. High ferritin concentrations are a feature of GD and iron storage in Gaucher cells has been described, but iron storage in the liver in relation to liver fibrosis has not been studied. Alternatively, iron storage in GD may be the result of iron supplementation therapy or regular blood transfusions in patients with severe cytopenia. In this pilot study, comprising 14 type-1 GD patients (7 splenectomized, 7 non-splenectomized) and 7 healthy controls, we demonstrate that liver stiffness values, measured by Transient Elastography and MR-Elastography, are significantly higher in splenectomized GD patients when compared with non-splenectomized GD patients (p = 0.03 and p = 0.01, respectively). Liver iron concentration was elevated (>60±30 µmol/g) in 4 GD patients of whom 3 were splenectomized. No relationship was found between liver stiffness and liver iron concentration. HFE gene mutations were more frequent in splenectomized (6/7) than in non-splenectomized (2/7) participants (p = 0.10). Liver disease appeared more advanced in splenectomized than in non-splenectomized patients. We hypothesize a relationship with excessive hepatic iron accumulation in splenectomized patients. We recommend that all splenectomized patients, especially those with evidence of substantial liver fibrosis undergo regular screening for HCC, according to current guidelines.
PMCID: PMC3598804  PMID: 23554863
5.  The second ESGAR consensus statement on CT colonography 
European Radiology  2012;23(3):720-729.
To update quality standards for CT colonography based on consensus among opinion leaders within the European Society of Gastrointestinal and Abdominal Radiology (ESGAR).
Material and methods
A multinational European panel of nine members of the ESGAR CT colonography Working Group (representing six EU countries) used a modified Delphi process to rate their level of agreement on a variety of statements pertaining to the acquisition, interpretation and implementation of CT colonography. Four Delphi rounds were conducted, each at 2 months interval.
The panel elaborated 86 statements.
In the final round the panelists achieved complete consensus in 71 of 86 statements (82 %). Categories including the highest proportion of statements with excellent Cronbach's internal reliability were colon distension, scan parameters, use of intravenous contrast agents, general guidelines on patient preparation, role of CAD and lesion measurement.
Lower internal reliability was achieved for the use of a rectal tube, spasmolytics, decubitus positioning and number of CT data acquisitions, faecal tagging, 2D vs. 3D reading, and reporting.
The recommendations of the consensus should be useful for both the radiologist who is starting a CTC service and for those who have already implemented the technique but whose practice may need updating.
Key Points
• Computed tomographic colonography is the optimal radiological method of assessing the colon
• This article reviews ESGAR quality standards for CT colonography
• This article is aimed to provide CT-colonography guidelines for practising radiologists
• The recommendations should help radiologists who are starting/updating their CTC services
PMCID: PMC3563960  PMID: 22983280
CT colonography; Guidelines; Computed tomography; Colon; Polyps
6.  Can radiographers be trained to triage CT colonography for extracolonic findings? 
European Radiology  2012;22(12):2780-2789.
Radiographers have been shown to be capable CT colonography observers. We evaluated whether radiographers can be trained to triage screening CT colonography for extracolonic findings.
Eight radiographers participated in a structured training program. They subsequently evaluated extracolonic findings in 280 low-dose CT colonograms (cases). This dataset contained 66 cases with possibly important findings (E3) and 27 cases with probably important findings (E4) [classification based on the highest classified finding (C-RADS)]. The first 40 and last 40 CT colonograms were identical test cases. Immediate feedback was given after each reading, except for test cases. Radiographers triaged cases based on C-RADS classification and indicated the need for a radiologist read. We constructed learning curves for correct case triaging by calculating moving averages.
In the final test series, 84/120 (70 %) cases with E3 or E4 findings and 139/200 (70 %) without E3 or E4 findings were correctly triaged. Correct identification of cases with E3 findings improved with training from 46/88 (52 %) to 62/88 (70 %) (P < 0.0001) but not for E4 findings [both 22/32 (69 %) P = 1.00].
Radiographers improve after training in correctly triaging extracolonic findings at CT colonography but do not reach a high enough accuracy to consider their structural involvement in screening.
Key Points
• Radiographers were trained to triage CT colonography for extracolonic findings.
• After training, radiographers improved sensitivity for likely unimportant findings.
• After training, radiographers did not improve sensitivity for possibly important findings.
• Radiographers should probably not be expected to identify all extracolonic findings.
PMCID: PMC3486999  PMID: 22752462
Colonography, computed tomographic; Incidental findings; Learning curve; Radiology/education; Clinical competence
7.  Plain abdominal radiography in acute abdominal pain; past, present, and future 
Several studies have demonstrated that a diagnosis based solely on a patient’s medical history, physical examination, and laboratory tests is not reliable enough, despite the fact that these aspects are essential parts of the workup of a patient presenting with acute abdominal pain. Traditionally, imaging workup starts with abdominal radiography. However, numerous studies have demonstrated low sensitivity and accuracy for plain abdominal radiography in the evaluation of acute abdominal pain as well as various specific diseases such as perforated viscus, bowel obstruction, ingested foreign body, and ureteral stones. Computed tomography, and in particular computed tomography after negative ultrasonography, provides a better workup than plain abdominal radiography alone. The benefits of computed tomography lie in decision-making for management, planning of a surgical strategy, and possibly even avoidance of negative laparotomies. Based on abundant available evidence, major advances in diagnostic imaging, and changes in the management of certain diseases, we can conclude that there is no place for plain abdominal radiography in the workup of adult patients with acute abdominal pain presenting in the emergency department in current practice.
PMCID: PMC3396109  PMID: 22807640
abdominal x-ray; acute abdomen; acute abdominal pain; emergency department; diagnostic imaging; abdominal radiography
8.  Does CT colonography have a role for population-based colorectal cancer screening? 
European Radiology  2012;22(7):1495-1503.
Colorectal cancer (CRC) is the second most common cancer and second most common cause of cancer-related deaths in Europe. CRC screening has been proven to reduce disease-specific mortality and several European countries employ national screening programmes. These almost exclusively rely on stool tests, with endoscopy used as an adjunct in some countries. Computed tomographic colonography (CTC) is a potential screening test, with an estimated sensitivity of 88 % for advanced neoplasia ≥10 mm. Recent randomised studies have shown that CTC and colonoscopy have similar yields of advanced neoplasia per screened invitee, indicating that CTC is potentially viable as a primary screening test. However, the evidence is not fully elaborated. It is unclear whether CTC screening is cost-effective and the impact of extracolonic findings, both medical and economic, remains unknown. Furthermore, the effect of CTC screening on CRC-related mortality is unknown, as it is also unknown for colonoscopy. It is plausible that both techniques could lead to decreased mortality, as for sigmoidoscopy and gFOBT. Although radiation exposure is a drawback, this disadvantage may be over-emphasised. In conclusion, the detection characteristics and acceptability of CTC suggest it is a viable screening investigation. Implementation will depend on detection of extracolonic disease and health-economic impact.
Key Points
• Meta-analysis of CT colonographic screening showed high sensitivity for advanced neoplasia ≥10mm.
• CTC, colonoscopy and sigmoidoscopy screening all have similar yields for advanced neoplasia.
• Good quality information regarding the cost-effectiveness of CTC screening is lacking.
• There is little good quality data regarding the impact of extracolonic findings.
• CTC triage is not clinically effective in first round gFOBT/FIT positives.
PMCID: PMC3366291  PMID: 22549102
CT colonography; Screening; Colorectal cancer; Population-based; Role
9.  A computer-assisted model for detection of MRI signs of Crohn’s disease activity: future or fiction? 
Abdominal Imaging  2011;37(6):967-973.
Magnetic resonance imaging is increasingly used for abdominal evaluation and is more and more considered as the optimal imaging technique for detection of mural inflammation in patients with Crohn’s disease. Grading the disease activity is important in daily clinical practice to monitor the medical treatment and is assessed by evaluating different magnetic resonance imaging features. Unfortunately, only moderate interobserver agreement is reported for most of the subjective features and should be improved. A computer-assisted model for automatic detection of abnormalities, ability to grade disease severity, and thereby influence clinical disease management based on magnetic resonance imaging is missing. Recent techniques have focused on semi-automated methods for classification and segmentation of the bowel and also on objective measurement of bowel wall enhancement using absolute T1-values or dynamic contrast-enhanced imaging. This article reviews the available computerized techniques, as well as preferred developments.
PMCID: PMC3517801  PMID: 22134675
Crohn’s disease; Magnetic resonance imaging; Intestinal imaging; Disease activity; Computer assisted model
10.  Small bowel Crohn’s disease: MR enteroclysis and capsule endoscopy compared to balloon-assisted enteroscopy 
Abdominal Imaging  2011;37(3):397-403.
New modalities are available to visualize the small bowel in patients with Crohn’s disease (CD). The aim of this study was to compare the diagnostic yield of magnetic resonance enteroclysis (MRE) and capsule endoscopy (CE) to balloon-assisted enteroscopy (BAE) in patients with suspected or established CD of the small bowel. Consecutive, consenting patients first underwent MRE followed by CE and BAE. Patients with high-grade stenosis at MRE did not undergo CE. Reference standard for small bowel CD activity was a combination of BAE and an expert panel consensus diagnosis. Analysis included 38 patients, 27 (71%) females, mean age 36 (20–74) years, with suspected (n = 20) or established (n = 18) small bowel CD: 16 (42%) were diagnosed with active CD, and 13 (34%) by MRE with suspected high-grade stenosis, who consequently did not undergo CE. The reference standard defined high-grade stenosis in 10 (26%) patients. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value of MRE and CE for small bowel CD activity were 73 and 57%, 90 and 89%, 88 and 67%, and 78 and 84%, respectively. CE was complicated by capsule retention in one patient. MRE has a higher sensitivity and PPV than CE in small bowel CD. The use of CE is considerably limited by the high prevalence of stenotic lesions in these patients.
PMCID: PMC3345178  PMID: 22120660
Magnetic resonance imaging; Enteroclysis; Small bowel; Inflammatory small bowel disease; Capsule endoscopy; Crohn’s disease; Balloon-assisted enteroscopy; Medicine & Public Health; Hepatology; Gastroenterology; Imaging / Radiology
11.  A randomized double-blind placebo-controlled trial to evaluate the value of a single bolus intravenous alfentanil in CT colonography 
BMC Gastroenterology  2011;11:128.
Although CT colonography is a less invasive alternative for colonoscopy for the detection of colorectal polyps and cancer, procedural pain is common. In several studies, CT colonography pain and burden is higher than in colonoscopy. Apart from discomfort, anxiety and its related stress-induced peri- procedural side effects, this may influence the adherence for CT colonography as a possible screening tool for colorectal cancer. We hypothesize that a single bolus intravenous alfentanil will give a clinically relevant reduction in maximum pain defined as at least 1.3 point reduction on an 11-point numeric rating scale (NRS).
A randomized double-blind placebo-controlled trial in which patients scheduled for elective CT colonography in a single tertiary centre are eligible for inclusion. The first 90 consenting patient will be block-randomized to either the alfentanil group or the placebo group. Before bowel insufflation, the alfentanil group receives a single bolus intravenous alfentanil 7.5 μg/kg dissolved in 0.9% NaCl, while the placebo group receives an intravenous bolus injection of pure 0.9% NaCl. For both groups an equal amount of fluid per kilogram (75 μL/kg) is injected. The primary outcome is the difference in maximum pain on an 11-point NRS. Secondary outcomes include: pain and burden of different CT colonography aspects, side effects, procedural time and recovery time. For the primary outcome an independent samples t-test is performed and a P value < 0.05 is considered statistically significant.
This study will provide evidence whether a single bolus intravenous alfentanil gives a clinically relevant reduction in maximum pain during CT colonography.
Trial registration
Netherlands Trial Register (NTR): NTR2902
This trial will be conducted in accordance with the protocol and in compliance with the moral, ethical, and scientific principles governing clinical research as set out in the Declaration of Helsinki (1989) and Good Clinical Practice (GCP). The department of radiology of the Academic Medical Center of Amsterdam is responsible for the design and conduct of the trial.
PMCID: PMC3339326  PMID: 22111658
12.  Small bowel MRI in adult patients: not just Crohn’s disease—a tutorial 
Insights into Imaging  2011;2(5):501-513.
To provide an overview of less well-known small bowel and mesenteric diseases found at small bowel magnetic resonance (MR) enterography/enteroclysis and to review the imaging findings. MR enterography and enteroclysis are important techniques for evaluation of small bowel diseases. In most centres these techniques are primarily used in Crohn’s disease, and most radiologists are familiar with these MRI findings. However, the knowledge of findings in other diseases is often sparse, including diseases that may cause similar clinical symptoms to those of Crohn’s disease.
We present a spectrum of less common and less well-known bowel and mesenteric diseases (e.g. internal hernia, intussusception, neuroendocrine tumour) from our small bowel MR database of over 2,000 cases.
These diseases can be found in patients referred for bowel obstruction, abdominal pain or rectal blood loss. Further, in patients with (or suspected to have) Crohn’s disease, some of these diseases (e.g. neuroendocrine tumour, familial Mediterranean fever) may mislead radiologists to erroneously diagnose active Crohn’s disease.
Radiologists should be familiar with diseases affecting the small bowel other than Crohn’s disease, including diseases that may mimic Crohn’s disease.
PMCID: PMC3289029  PMID: 23100018
MRI; Small bowel; Tumours; Congenital; Inflammation
13.  Protocol for Translabial 3D-Ultrasonography for diagnosing levator defects (TRUDIL): a multicentre cohort study for estimating the diagnostic accuracy of translabial 3D-ultrasonography of the pelvic floor as compared to MR imaging 
BMC Women's Health  2011;11:23.
Pelvic organ prolapse (POP) is a condition affecting more than half of the women above age 40. The estimated lifetime risk of needing surgical management for POP is 11%.
In patients undergoing POP surgery of the anterior vaginal wall, the re-operation rate is 30%. The recurrence risk is especially high in women with a levator ani defect. Such defect is present if there is a partially or completely detachment of the levator ani from the inferior ramus of the symphysis. Detecting levator ani defects is relevant for counseling, and probably also for treatment. Levator ani defects can be imaged with MRI and also with Translabial 3D ultrasonography of the pelvic floor.
The primary aim of this study is to assess the diagnostic accuracy of translabial 3D ultrasonography for diagnosing levator defects in women with POP with Magnetic Resonance Imaging as the reference standard. Secondary goals of this study include quantification of the inter-observer agreement about levator ani defects and determining the association between levator defects and recurrent POP after anterior repair. In addition, the cost-effectiveness of adding translabial ultrasonography to the diagnostic work-up in patients with POP will be estimated in a decision analytic model.
A multicentre cohort study will be performed in nine Dutch hospitals. 140 consecutive women with a POPQ stage 2 or more anterior vaginal wall prolapse, who are indicated for anterior colporapphy will be included. Patients undergoing additional prolapse procedures will also be included.
Prior to surgery, patients will undergo MR imaging and translabial 3D ultrasound examination of the pelvic floor. Patients will be asked to complete validated disease specific quality of life questionnaires before surgery and at six and twelve months after surgery. Pelvic examination will be performed at the same time points.
Assuming a sensitivity and specificity of 90% of 3D ultrasound for diagnosing levator defects in a population of 120 women with POP, with a prior probability of levator ani defects of 40%, we will be able to estimate predictive values with good accuracy (i.e. confidence limits of at most 10% below or above the point estimates of positive and negative predictive values).
Anticipating 3% unclassifiable diagnostic images because of technical reasons, and a further safety margin of 10% we plan to recruit 140 patients.
Trial registration
Nederlands trial register NTR2220.
PMCID: PMC3121676  PMID: 21639876
14.  Diagnostic value of CT-colonography as compared to colonoscopy in an asymptomatic screening population: a meta-analysis 
European Radiology  2011;21(8):1747-1763.
Previous meta-analyses on CT-colonography included both average and high risk individuals, which may overestimate the diagnostic value in screening. A meta-analysis was performed to obtain the value of CT-colonography for screening.
A search was performed using PubMed, Embase and Cochrane. Article selection and critical appraisal was done by two reviewers. Inclusion criteria: prospective, randomized trials or cohort studies comparing CT-colonography with colonoscopy (≥50 participants), ≥95% average risk participants ≥50 years. Study characteristics and 2 × 2 contingency Tables were recorded. Sensitivity and specificity estimates were calculated per patient and per polyp (≥6 mm, ≥10 mm), using univariate and bivariate analyses.
Five of 1,021 studies identified were included, including 4,086 participants (<1% high risk). I2-values showed substantial heterogeneity, especially for 6–9 mm polyps and adenomas: 68.1% vs. 78.6% (sensitivity per patient). Estimated sensitivities for patients with polyps or adenomas ≥ 6 mm were 75.9% and 82.9%, corresponding specificities 94.6% and 91.4%. Estimated sensitivities for patients with polyps or adenomas ≥ 10 mm were 83.3% and 87.9%, corresponding specificities 98.7% and 97.6%. Estimated sensitivities per polyp for advanced adenomas ≥ 6 mm and ≥ 10 mm were 83.9% and 83.8%.
Compared to colonoscopy, CT-colonography has a high sensitivity for adenomas ≥ 10 mm. For (advanced) adenomas ≥ 6 mm sensitivity is somewhat lower.
PMCID: PMC3128257  PMID: 21455818
Colorectal cancer; Screening; CT-Colonography; Colonoscopy; Sensitivity and specificity
15.  A comparison of the Accuracy of Ultrasound and Computed Tomography in common diagnoses causing acute abdominal pain 
European Radiology  2011;21(7):1535-1545.
Head-to-head comparison of ultrasound and CT accuracy in common diagnoses causing acute abdominal pain.
Materials and methods
Consecutive patients with abdominal pain for >2 h and <5 days referred for imaging underwent both US and CT by different radiologists/radiological residents. An expert panel assigned a final diagnosis. Ultrasound and CT sensitivity and predictive values were calculated for frequent final diagnoses. Effect of patient characteristics and observer experience on ultrasound sensitivity was studied.
Frequent final diagnoses in the 1,021 patients (mean age 47; 55% female) were appendicitis (284; 28%), diverticulitis (118; 12%) and cholecystitis (52; 5%). The sensitivity of CT in detecting appendicitis and diverticulitis was significantly higher than that of ultrasound: 94% versus 76% (p < 0.01) and 81% versus 61% (p = 0.048), respectively. For cholecystitis, the sensitivity of both was 73% (p = 1.00). Positive predictive values did not differ significantly between ultrasound and CT for these conditions. Ultrasound sensitivity in detecting appendicitis and diverticulitis was not significantly negatively affected by patient characteristics or reader experience.
CT misses fewer cases than ultrasound, but both ultrasound and CT can reliably detect common diagnoses causing acute abdominal pain. Ultrasound sensitivity was largely not influenced by patient characteristics and reader experience.
PMCID: PMC3101356  PMID: 21365197
Acute abdominal pain; Computed tomography; Ultrasound; Appendicitis; Emergency Department
16.  Optimizing imaging in suspected appendicitis (OPTIMAP-study): A multicenter diagnostic accuracy study of MRI in patients with suspected acute appendicitis. Study Protocol 
In patients with clinically suspected appendicitis, imaging is needed to substantiate the clinical diagnosis. Imaging accuracy of ultrasonography (US) is suboptimal, while the most accurate technique (CT) is associated with cancer related deaths through exposure to ionizing radiation. MRI is a potential replacement, without associated ionizing radiation and no need for contrast medium administration. If MRI is proven to be sufficiently accurate, it could be introduced in the diagnostic pathway of patients with suspected appendicitis, increasing diagnostic accuracy and improving clinical outcomes, without the risk of radiation induced cancer or iodinated contrast medium-related drawbacks. The multicenter OPTIMAP study was designed to estimate the diagnostic accuracy of MRI in patients with suspected acute appendicitis in the general population.
Eligible for this study are consecutive patients presenting with clinically suspected appendicitis at the emergency department in six centers. All patients will undergo imaging according to the Dutch guideline for acute appendicitis: initial ultrasonography in all and subsequent CT whenever US does not confirm acute appendicitis. Then MRI is performed in all patients, but the results are not used for patient management. A final diagnosis assigned by an expert panel, based on all available information including 3-months follow-up, except MRI findings, is used as the reference standard in estimating accuracy. We will calculate the sensitivity, specificity, predictive values and inter-observer agreement of MRI, and aim to include 230 patients. Patient acceptance and total imaging costs will also be evaluated.
If MRI is found to be sufficiently accurate, it could replace CT in some or all patients. This will limit or obviate the ionizing radiation exposure associated risk of cancer induction and contrast medium induced nephropathy with CT, preventing the burden and the direct and indirect costs associated with treatment. Based on the high intrinsic contrast resolution of MRI, one might envision higher accuracy rates for MRI than for CT. If so, MRI could further decrease the number of unnecessary appendectomies and the number of missed appendicitis cases.
Trial registration
PMCID: PMC2978143  PMID: 20961412
17.  The diagnostic accuracy of US, CT, MRI and 1H-MRS for the evaluation of hepatic steatosis compared with liver biopsy: a meta-analysis 
European Radiology  2010;21(1):87-97.
To meta-analyse the diagnostic accuracy of US, CT, MRI and 1H-MRS for the evaluation of hepatic steatosis.
From a comprehensive literature search in MEDLINE, EMBASE, CINAHL and Cochrane (up to November 2009), articles were selected that investigated the diagnostic performance imaging techniques for evaluating hepatic steatosis with histopathology as the reference standard. Cut-off values for the presence of steatosis on liver biopsy were subdivided into four groups: (1) >0, >2 and >5% steatosis; (2) >10, >15 and >20%; (3) >25, >30 and >33%; (4) >50, >60 and >66%. Per group, summary estimates for sensitivity and specificity were calculated. The natural-logarithm of the diagnostic odds ratio (lnDOR) was used as a single indicator of test performance.
46 articles were included. Mean sensitivity estimates for subgroups were 73.3–90.5% (US), 46.1–72.0% (CT), 82.0–97.4% (MRI) and 72.7–88.5% (1H-MRS). Mean specificity ranges were 69.6–85.2% (US), 88.1–94.6% (CT), 76.1–95.3% (MRI) and 92.0–95.7% (1H-MRS). Overall performance (lnDOR) of MRI and 1H-MRS was better than that for US and CT for all subgroups, with significant differences in groups 1 and 2.
MRI and 1H-MRS can be considered techniques of choice for accurate evaluation of hepatic steatosis.
Electronic supplementary material
The online version of this article (doi:10.1007/s00330-010-1905-5) contains supplementary material, which is available to authorized users.
PMCID: PMC2995875  PMID: 20680289
Hepatic steatosis; Diagnostic accuracy; Magnetic resonance imaging; Magnetic resonance spectroscopy; Computed tomography; Ultrasonography
18.  Study protocol: population screening for colorectal cancer by colonoscopy or CT colonography: a randomized controlled trial 
BMC Gastroenterology  2010;10:47.
Colorectal cancer (CRC) is the second most prevalent type of cancer in Europe. Early detection and removal of CRC or its precursor lesions by population screening can reduce mortality. Colonoscopy and computed tomography colonography (CT colonography) are highly accurate exams and screening options that examine the entire colon. The success of screening depends on the participation rate. We designed a randomized trial to compare the uptake, yield and costs of direct colonoscopy population screening, using either a telephone consultation or a consultation at the outpatient clinic, versus CT colonography first, with colonoscopy in CT colonography positives.
Methods and design
7,500 persons between 50 and 75 years will be randomly selected from the electronic database of the municipal administration registration and will receive an invitation to participate in either CT colonography (2,500 persons) or colonoscopy (5,000 persons) screening. Those invited for colonoscopy screening will be randomized to a prior consultation either by telephone or a visit at the outpatient clinic. All CT colonography invitees will have a prior consultation by telephone. Invitees are instructed to consult their general practitioner and not to participate in screening if they have symptoms suggestive for CRC. After providing informed consent, participants will be scheduled for the screening procedure. The primary outcome measure of this study is the participation rate. Secondary outcomes are the diagnostic yield, the expected and perceived burden of the screening test, level of informed choice and cost-effectiveness of both screening methods.
This study will provide further evidence to enable decision making in population screening for colorectal cancer.
Trial registration
Dutch trial register: NTR1829
PMCID: PMC2889851  PMID: 20482825
19.  Polyp measurement based on CT colonography and colonoscopy: variability and systematic differences 
European Radiology  2009;20(6):1404-1413.
To assess the variability and systematic differences in polyp measurements on optical colonoscopy and CT colonography.
Gastroenterologists measured 51 polyps by visual estimation, forceps comparison and linear probe. CT colonography observers randomly assessed polyp size two-dimensionally (abdominal and intermediate window) and three-dimensionally (manually and semi-automatically). Linear mixed models were used to assess the variability and systematic differences between CT colonography and optical colonoscopy techniques.
The variability of forceps and linear probe measurements was comparable and both showed less variability than measurement by visual assessment. Measurements by linear probe were 0.7 mm smaller than measurements by visual assessment or by forceps. The variability of all CT colonography techniques was lower than for measurements by forceps or visual assessment and sometimes lower (only 2D intermediate window and manual 3D) compared with measurements by linear probe. All CT colonography measurements judged polyps to be larger than optical colonoscopy, with differences ranging from 0.7 to 2.3 mm.
A linear probe does not reduce the measurement variability of endoscopists compared with the forceps. Measurement differences between observers on CT colonography were usually smaller than at optical colonoscopy. Polyps appeared larger when using various CT colonography techniques than when measured during optical colonoscopy.
PMCID: PMC2861761  PMID: 20033180
CT colonography; Colon; Colonoscopy; Measurement; Cancer; 2D; 3D
20.  Magnetic resonance (MR) colonography in the detection of colorectal lesions: a systematic review of prospective studies 
European Radiology  2009;20(5):1031-1046.
To determine the diagnostic accuracy of MR-colonography for the detection of colorectal lesions.
A comprehensive literature search was performed for comparative MR-colonography studies, published between May 1997 and February 2009, using the MEDLINE, EMBASE and Cochrane databases. We included studies if MR-colonography findings were prospectively compared with conventional colonoscopy in (a)symptomatic patients. Two reviewers independently extracted study design characteristics and data for summarising sensitivity and specificity. Heterogeneity in findings between studies was tested using I2 test statistics. Sensitivity and specificity estimates with 95% confidence intervals (CI) were calculated on per patient basis and summary sensitivity on per polyp basis, using bivariate and univariate statistical models.
Thirty-seven studies were found to be potentially relevant and 13 fulfilled the inclusion criteria. The study population comprised 1,285 patients with a mean disease prevalence of 44% (range 22–63%). Sensitivity for the detection of CRC was 100%. Significant heterogeneity was found for overall per patient sensitivity and specificity. For polyps with a size of 10 mm or larger, per patient sensitivity and specificity estimates were 88% (95% CI 63–97%; I2 = 37%) and 99% (95% CI 95–100%; I2 = 60%). On a per polyp basis, polyps of 10 mm or larger were detected with a sensitivity of 84% (95% CI 66–94%; I2 = 51%). The data were too heterogeneous for polyps smaller than 6 mm and 6–9 mm.
MR-colonography can accurately detect colorectal polyps more than 10 mm in size
PMCID: PMC2850516  PMID: 19936754
Magnetic resonance imaging (MRI); Colorectal cancer (CRC); Colonic polyps; Systematic review; Diagnostic accuracy
21.  CT colonography with limited bowel preparation for the detection of colorectal neoplasia in an FOBT positive screening population 
Abdominal Imaging  2009;35(6):661-668.
Aim was to evaluate the accuracy of computed tomography colonography (CTC) for detection of colorectal neoplasia in a Fecal Occult Blood Test (FOBT) positive screening population.
In three different institutions, consecutive FOBT positives underwent CTC after laxative free iodine tagging bowel preparation followed by colonoscopy with segmental unblinding. Each CTC was read by two experienced observers. For CTC and for colonoscopy the per-polyp sensitivity and per-patient sensitivity and specificity were calculated for detection of carcinomas, advanced adenomas, and adenomas.
In total 22 of 302 included FOBT positive participants had a carcinoma (7%) and 137 had an adenoma or carcinoma ≥10 mm (45%). CTC sensitivity for carcinoma was 95% with one rectal carcinoma as false negative finding. CTC sensitivity for advanced adenomas was 92% (95% CI: 88–96) vs. 96% (95% CI: 93–99) for colonoscopy (P = 0.26). For adenomas and carcinomas ≥10 mm the CTC per-polyp sensitivity was 93% (95% CI: 89–97) vs. 97% (95% CI: 94–99) for colonoscopy (P = 0.17). The per-patient sensitivity for the detection of adenomas and carcinomas ≥10 mm was 95% (95% CI: 91–99) for CTC vs. 99% (95% CI: 98–100) for colonoscopy (P = 0.07), while the per-patient specificity was 90% (95% CI: 86–95) and 96% (95% CI: 94–99), respectively (P < 0.001).
CTC with limited bowel preparation performed in an FOBT positive screening population has high diagnostic accuracy for the detection of adenomas and carcinomas and a sensitivity similar to that of colonoscopy for relevant lesions.
PMCID: PMC2980629  PMID: 19888629
CT colonography; Colorectal neoplasia; Advanced adenoma; Colorectal cancer; FOBT
22.  CT colonography with limited bowel preparation: prospective assessment of patient experience and preference in comparison to optical colonoscopy with cathartic bowel preparation 
European Radiology  2009;20(1):146-156.
The purpose of this study was to prospectively compare participant experience and preference of limited preparation computed tomography colonography (CTC) with full-preparation colonoscopy in a consecutive series of patients at increased risk of colorectal cancer. CTC preparation comprised 180 ml diatrizoate meglumine, 80 ml barium and 30 mg bisacodyl. For the colonoscopy preparation 4 l of polyethylene glycol solution was used. Participants’ experience and preference were compared using the Wilcoxon signed rank test and the chi-squared test, respectively. Associations between preference and experience parameters for the 173 participants were determined by logistic regression. Diarrhoea occurred in 94% of participants during CTC preparation. This side effect was perceived as severely or extremely burdensome by 29%. Nonetheless, the total burden was significantly lower for the CTC preparation than for colonoscopy (9% rated the CTC preparation as severely or extremely burdensome compared with 59% for colonoscopy; p < 0.001). Participants experienced significantly more pain, discomfort and total burden with the colonoscopy procedure than with CTC (p < 0.001). After 5 weeks, 69% preferred CTC, 8% were indifferent and 23% preferred colonoscopy (p < 0.001). A burdensome colonoscopy preparation and pain at colonoscopy were associated with CTC preference (p < 0.04). In conclusion, participants’ experience and preference were rated in favour of CTC with limited bowel preparation compared with full-preparation colonoscopy.
PMCID: PMC2803752  PMID: 19626326
CT colonography; Gastrointestinal; Colon; Bowel preparation; Patient acceptance; Side effects; Contrast; Faecal tagging
23.  Primary uncleansed 2D versus primary electronically cleansed 3D in limited bowel preparation CT-colonography. Is there a difference for novices and experienced readers? 
European Radiology  2009;19(8):1939-1950.
The purpose of this study was to compare a primary uncleansed 2D and a primary electronically cleansed 3D reading strategy in CTC in limited prepped patients. Seventy-two patients received a low-fibre diet with oral iodine before CT-colonography. Six novices and two experienced observers reviewed both cleansed and uncleansed examinations in randomized order. Mean per-polyp sensitivity was compared between the methods by using generalized estimating equations. Mean per-patient sensitivity, and specificity were compared using the McNemar test. Results were stratified for experience (experienced observers versus novice observers). Mean per-polyp sensitivity for polyps 6 mm or larger was significantly higher for novices using cleansed 3D (65%; 95%CI 57–73%) compared with uncleansed 2D (51%; 95%CI 44–59%). For experienced observers there was no significant difference. Mean per-patient sensitivity for polyps 6 mm or larger was significantly higher for novices as well: respectively 75% (95%CI 70–80%) versus 64% (95%CI 59–70%). For experienced observers there was no statistically significant difference. Specificity for both novices and experienced observers was not significantly different. For novices primary electronically cleansed 3D is better for polyp detection than primary uncleansed 2D.
PMCID: PMC2705716  PMID: 19301011
CT-colonography; Sensitivity and specificity; Colonic polyps; Electronic cleansing; Colorectal neoplasms
24.  CT colonography polyp matching: differences between experienced readers 
European Radiology  2009;19(7):1723-1730.
The purpose of this study was to investigate if experienced readers differ when matching polyps shown by both CT colonography (CTC) and optical colonoscopy (OC) and to explore the reasons for discrepancy. Twenty-eight CTC cases with corresponding OC were presented to eight experienced CTC readers. Cases represented a broad spectrum of findings, not completely fulfilling typical matching criteria. In 21 cases there was a single polyp on CTC and OC; in seven there were multiple polyps. Agreement between readers for matching was analyzed. For the 21 single-polyp cases, the number of correct matches per reader varied from 13 to 19. Almost complete agreement between readers was observed in 15 cases (71%), but substantial discrepancy was found for the remaining six (29%) probably due to large perceived differences in polyp size between CT and OC. Readers were able to match between 27 (71%) and 35 (92%) of the 38 CTC detected polyps in the seven cases with multiple polyps. Experienced CTC readers agree to a considerable extent when matching polyps between CTC and subsequent OC, but non-negligible disagreement exists.
PMCID: PMC2691532  PMID: 19224220
CT colonography; Colorectal neoplasia; Colorectal polyps; Polyp matching; Colonoscopy
25.  NEOadjuvant therapy monitoring with PET and CT in Esophageal Cancer (NEOPEC-trial) 
Surgical resection is the preferred treatment of potentially curable esophageal cancer. To improve long term patient outcome, many institutes apply neoadjuvant chemoradiotherapy. In a large proportion of patients no response to chemoradiotherapy is achieved. These patients suffer from toxic and ineffective neoadjuvant treatment, while appropriate surgical therapy is delayed. For this reason a diagnostic test that allows for accurate prediction of tumor response early during chemoradiotherapy is of crucial importance. CT-scan and endoscopic ultrasound have limited accuracy in predicting histopathologic tumor response. Data suggest that metabolic changes in tumor tissue as measured by FDG-PET predict response better. This study aims to compare FDG-PET and CT-scan for the early prediction of non-response to preoperative chemoradiotherapy in patients with potentially curable esophageal cancer.
Prognostic accuracy study, embedded in a randomized multicenter Dutch trial comparing neoadjuvant chemoradiotherapy for 5 weeks followed by surgery versus surgery alone for esophageal cancer. This prognostic accuracy study is performed only in the neoadjuvant arm of the randomized trial. In 6 centers, 150 consecutive patients will be included over a 3 year period. FDG-PET and CT-scan will be performed before and 2 weeks after the start of the chemoradiotherapy. All patients complete the 5 weeks regimen of neoadjuvant chemoradiotherapy, regardless the test results. Pathological examination of the surgical resection specimen will be used as reference standard. Responders are defined as patients with < 10% viable residual tumor cells (Mandard-score).
Difference in accuracy (area under ROC curve) and negative predictive value between FDG-PET and CT-scan are primary endpoints. Furthermore, an economic evaluation will be performed, comparing survival and costs associated with the use of FDG-PET (or CT-scan) to predict tumor response with survival and costs of neoadjuvant chemoradiotherapy without prediction of response (reference strategy).
The NEOPEC-trial could be the first sufficiently powered study that helps justify implementation of FDG-PET for response-monitoring in patients with esophageal cancer in clinical practice.
Trial registration
PMCID: PMC3301128  PMID: 18671847

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