Maarten Thomeer

Resurgence of Lymphogranuloma Venereum in Western Europe: An Outbreak of Chlamydia trachomatis Serovar L2 Proctitis in The Netherlands among Men Who Have Sex with Men

BACKGROUND Lymphogranuloma venereum (LGV) is a sexually transmitted disease (STD) and is rare in the Western world. Recently, 3 men who have sex with men presented with LGV proctitis at the Erasmus Medical Center, Rotterdam, The Netherlands. We investigated a possible outbreak in a sexual network of men who have sex with men (MSM). METHODS After active case finding, a total of 15 men presented and were investigated. Serum antibody titers to Chlamydia trachomatis were determined. Urine and rectum specimens were analyzed by polymerase chain reaction (PCR) for the presence of C. trachomatis. C. trachomatis-positive specimens were genotyped to detect the specific C. trachomatis serovars. All subjects underwent routine STD screening. Sociodemographic, clinical, and endoscopic characteristics were evaluated. RESULTS Thirteen subjects had high immunoglobulin (Ig) G and IgA titers to C. trachomatis, suggesting an invasive infection. Rectal specimens of 12 subjects were PCR-positive for C. trachomatis. All urine specimens were negative. Genotyping revealed serovars L(2) (n=8) and L(1) (n=1). An ulcerative proctitis was found in all subjects obtaining sigmoidoscopy (n=9). Eleven of 13 subjects with an LGV diagnosis were seropositive for human immunodeficiency virus (HIV), 6 had another concomitant STD, and 1 had recently acquired a hepatitis C virus infection. Further sexual contacts were reported from The Netherlands, Germany, Belgium, the United Kingdom, and France. CONCLUSIONS We revealed an outbreak of LGV proctitis among MSM in The Netherlands. The ulcerous character favors transmission of HIV, other STDs, and blood-borne diseases. From a public health perspective, it seems important to increase the awareness of possible LGV in MSM with symptomatic proctitis.

Participation and yield of colonoscopy versus non-cathartic CT colonography in population-based screening for colorectal cancer: a randomised controlled trial

BACKGROUND Screening for colorectal cancer is widely recommended, but the preferred strategy remains unidentified. We aimed to compare participation and diagnostic yield between screening with colonoscopy and with non-cathartic CT colonography. METHODS Members of the general population, aged 50-75 years, and living in the regions of Amsterdam or Rotterdam, identified via the registries of the regional municipal administration, were randomly allocated (2:1) to be invited for primary screening for colorectal cancer by colonoscopy or by CT colonography. Randomisation was done per household with a minimisation algorithm based on age, sex, and socioeconomic status. Invitations were sent between June 8, 2009, and Aug 16, 2010. Participants assigned to CT colonography who were found to have one or more large lesions (≥10 mm) were offered colonoscopy; those with 6-9 mm lesions were offered surveillance CT colonography. The primary outcome was the participation rate, defined as number of invitees undergoing the examination relative to the total number of invitees. Diagnostic yield was calculated as number of participants with advanced neoplasia relative to the total number of invitees. Invitees and screening centre employees were not masked to allocation. This trial is registered in the Dutch trial register, number NTR1829. FINDINGS 1276 (22%) of 5924 colonoscopy invitees participated, compared with 982 (34%) of 2920 CT colonography invitees (relative risk [RR] 1·56, 95% CI 1·46-1·68; p<0·0001). Of the participants in the colonoscopy group, 111 (9%) had advanced neoplasia of whom seven (<1%) had a carcinoma. Of CT colonography participants, 84 (9%) were offered colonoscopy, of whom 60 (6%) had advanced neoplasia of whom five (<1%) had a carcinoma; 82 (8%) were offered surveillance. The diagnostic yield for all advanced neoplasia was 8·7 per 100 participants for colonoscopy versus 6·1 per 100 for CT colonography (RR 1·46, 95% CI 1·06-2·03; p=0·02) and 1·9 per 100 invitees for colonoscopy and 2·1 per 100 invitees for CT colonography (RR 0·91, 0·66-2·03; p=0·56). The diagnostic yield for advanced neoplasia of 10 mm or more was 1·5 per 100 invitees for colonoscopy and 2·0 per 100 invitees for CT colonography, respectively (RR 0·74, 95% CI 0·53-1·03; p=0·07). Serious adverse events related to the screening procedure were post-polypectomy bleedings: two in the colonoscopy group and three in the CT colonography group. INTERPRETATION Participation in colorectal cancer screening with CT colonography was significantly better than with colonoscopy, but colonoscopy identified significantly more advanced neoplasia per 100 participants than did CT colonography. The diagnostic yield for advanced neoplasia per 100 invitees was similar for both strategies, indicating that both techniques can be used for population-based screening for colorectal cancer. Other factors such as cost-effectiveness and perceived burden should be taken into account when deciding which technique is preferable. FUNDING Netherlands Organisation for Health Research and Development, Centre for Translational Molecular Medicine, and the Nuts Ohra Foundation.

Hepatocellular Adenomas: Correlation of MR Imaging Findings with Pathologic Subtype Classification

PURPOSE To investigate the correlation between magnetic resonance (MR) imaging findings and pathologic subtype classification of hepatocellular adenoma (HCA). MATERIALS AND METHODS This retrospective study was approved by the institutional review board, and the requirement for informed consent was waived. MR imaging studies of 61 lesions (48 patients; median age, 36 years) were available and were independently reviewed by two radiologists. Consensus readings on all morphologic and signal-intensity imaging features were obtained. Previously, these lesions had been classified on the basis of pathologic findings and immunohistochemical analysis. Fisher exact and χ² tests were performed to compare the results between the different subtypes. A Bonferroni correction was applied to correct for multiple testing (α < .0033). RESULTS MR imaging signs of diffuse intratumoral fat deposition were present in seven (78%) of nine liver-fatty acid binding protein (L-FABP)-negative HCAs compared with five (17%) of 29 inflammatory HCAs (P = .001). Steatosis within the nontumoral liver was present in 11 (38%) of 29 inflammatory HCAs compared with none of the L-FABP-negative HCAs (P = .038). A characteristic atoll sign was only seen in the inflammatory group (P = .027). Presence of a typical vaguely defined type of scar was seen in five (71%) of seven β-catenin-positive HCAs (P = .003). No specific MR imaging features were identified for the unclassified cases. CONCLUSION L-FABP-negative, inflammatory, and β-catenin-positive HCAs were related to MR imaging signs of diffuse intratumoral fat deposition, an atoll sign, and a typical vaguely defined scar, respectively. Since β-catenin-positive HCAs are considered premalignant, closer follow-up with MR imaging or resection may be preferred.

Stool tagging applied in thin-slice multidetector computed tomography colonography.

Objective To compare thin-slice multidetector computed tomography colonography (CTC) that uses stool tagging with colonoscopy. Method One hundred fifty patients scheduled for colonoscopy underwent high-resolution CTC. An iodinated contrast agent was added to the preparation to tag the residual colonic fluid and stool. The effect of fluid tagging was assessed first. Sensitivity and specificity were calculated for two independent readers. In addition, values were recalculated separately for the first and last 75 patients. Results Tagging was optimal in 95.3% of the cases, and reader confidence was high. Sensitivities were 64.1%–66.7% (for the 2 readers) for 5- to 9-mm polyps and 91.7% for larger polyps. The overall specificity was 94.2% and 95%. Sensitivity improved during the study for both 5- to 9-mm polyps (from 54.2%–58.3% to 80%) and polyps larger than 9 mm (from 50% to 100%). Specificity changed nonuniformly. Conclusion The combination of fluid tagging and high-resolution scanning in CTC showed high sensitivity and specificity, especially concerning sensitivity for polyps of 10 mm and larger.

Burden of colonoscopy compared to non-cathartic CT-colonography in a colorectal cancer screening programme: randomised controlled trial

Objective CT-colonography has been suggested to be less burdensome for primary colorectal cancer (CRC) screening than colonoscopy. To compare the expected and perceived burden of both in a randomised trial. Design 8844 Dutch citizens aged 50–74 years were randomly invited for CRC screening with colonoscopy (n=5924) or CT-colonography (n=2920). Colonoscopy was performed after full colon lavage, or CT-colonography after limited bowel preparation (non-cathartic). All invitees were asked to complete the expected burden questionnaire before the procedure. All participants were invited to complete the perceived burden questionnaire 14 days later. Mean scores were calculated on 5-point scales. Results Expected burden: 2111 (36%) colonoscopy and 1199 (41%) CT-colonography invitees completed the expected burden questionnaire. Colonoscopy invitees expected the bowel preparation and screening procedure to be more burdensome than CT-colonography invitees: mean scores 3.0±1.1 vs 2.3±0.9 (p<0.001) and 3.1±1.1 vs 2.2±0.9 (p<0.001). Perceived burden: 1009/1276 (79%) colonoscopy and 801/982 (82%) CT-colonography participants completed the perceived burden questionnaire. The full screening procedure was reported as more burdensome in CT-colonography than in colonoscopy: 1.8±0.9 vs 2.0±0.9 (p<0.001). Drinking the bowel preparation resulted in a higher burden score in colonoscopy (3.0±1.3 vs 1.7±1.0, p<0.001) while related bowel movements were scored more burdensome in CT-colonography (2.0±1.0 vs 2.2±1.1, p<0.001). Most participants would probably or definitely take part in a next screening round: 96% for colonoscopy and 93% for CT-colonography (p=0.99). Conclusion In a CRC screening programme, colonoscopy invitees expected the screening procedure and bowel preparation to be more burdensome than CT-colonography invitees. In participants, CT-colonography was scored as more burdensome than colonoscopy. Intended participation in a next screening round was comparable.

Study protocol: population screening for colorectal cancer by colonoscopy or CT colonography: a randomized controlled trial.

BackgroundColorectal 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 design7,500 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.DiscussionThis study will provide further evidence to enable decision making in population screening for colorectal cancer.Trial registrationDutch trial register: NTR1829

Using CT colonography as a triage technique after a positive faecal occult blood test in colorectal cancer screening

Objective: The purpose of this study was to evaluate the effectiveness of CT colonography (CTC) as a triage technique in faecal occult blood test (FOBT)-positive screening participants. Methods: Consecutive guaiac (G-FOBT) and immunochemical (I-FOBT) FOBT-positive patients scheduled for colonoscopy underwent CTC with iodine tagging bowel preparation. Each CTC was read independently by two experienced observers. Per patient sensitivity, specificity and positive and negative predictive values (PPV and NPV) were calculated based on double reading with different CTC cut-off lesion sizes using segmental unblinded colonoscopy as the reference standard. The acceptability of the technique to patients was evaluated with questionnaires. Results: 302 FOBT-positive patients were included (54 G-FOBT and 248 I-FOBT). 22 FOBT-positive patients (7%) had a colorectal carcinoma and 211 (70%) had a lesion ⩾6 mm. Participants considered colonoscopy more burdensome than CTC (p<0.05). Using a 6 mm CTC size cut-off, per patient sensitivity for CTC was 91% (95% CI 85% to 91%) and specificity was 69% (95% CI 60% to 89%) for the detection of colonoscopy lesions ⩾6 mm. The PPV of CTC was 87% (95% CI 80% to 93%) and NPV 77% (95% CI 69% to 85%). Using CTC as a triage technique in 100 FOBT-positive patients would mean that colonoscopy could be prevented in 28 patients while missing ⩾10 mm lesions in 2 patients. Conclusion: CTC with limited bowel preparation has reasonable predictive values in an FOBT-positive population and a higher acceptability to patients than colonoscopy. However, due to the high prevalence of clinically relevant lesions in FOBT-positive patients, CTC is unlikely to be an efficient triage technique in a first round FOBT population screening programme.

Evaluation of a standardized CT colonography training program for novice readers.

PURPOSE To determine how many computed tomographic (CT) colonography training studies have to be evaluated by novice readers to obtain an adequate level of competence in polyp detection. MATERIALS AND METHODS The study was approved by the Institutional Review Board. Informed consent was obtained from all participants. Six physicians (one radiologist, three radiology residents, two researchers) and three technicians completed a CT colonography training program. Two hundred CT colonographic examinations with colonoscopic verification were selected from a research database, with 100 CT colonographic examinations with at least one polyp 6 mm or larger. After a lecture session and short individual hands-on training, CT colonography training was done individually with immediate feedback of colonoscopy outcome. Per-polyp sensitivity was calculated for four sets of 50 CT colonographic examinations for lesions 6 mm or larger. By using logistic regression analyses, the number of CT colonographic examinations to reach 90% sensitivity for lesions 6 mm or larger was estimated. Reading times were registered. RESULTS The average per-polyp sensitivity for lesions 6 mm or larger was 76% (207 of 270) in the first set of 50 CT colonographic examinations, 77% (262 of 342) in the second (P = .96 vs first set), 80% (310 of 387) in the third (P = .67 vs first set), and 91% (261 of 288) in the fourth (P = .018). The estimated number of CT colonographic examinations for a sufficient sensitivity was 164. Six of nine readers reached this level of competence within 175 CT colonographic examinations. Reading times decreased significantly from the first to the second set of 50 CT colonographic examinations for six readers. CONCLUSION Novice CT colonography readers obtained sensitivity equal to that of experienced readers after practicing on average 164 CT colonographic studies.

Reasons for participation and nonparticipation in colorectal cancer screening: a randomized trial of colonoscopy and CT colonography.

Objectives:We compared reported reasons for participation and nonparticipation in colorectal cancer (CRC) screening between colonoscopy and computed tomographic (CT) colonography in a randomized controlled trial.Methods:We randomly invited 8,844 people for screening by colonoscopy or CT colonography. On a questionnaire, invitees indicated reasons for participation or nonparticipation and indicated the most decisive reason.Results:The most frequently cited reasons to accept screening were early detection of precursor lesions and CRC, and contribution to science. The most frequently cited reasons to decline were the unpleasantness of the examination, the inconvenience of the preparation, a lack of symptoms, and “no time/too much effort.” Among colonoscopy nonparticipants, elderly invitees cited inconvenience less often, and absence of symptoms more often, than did the group overall. The reason reported most frequently as the most decisive reason not to participate was the unpleasantness of the examination among colonoscopy nonparticipants, and “no time/too much effort” and lack of symptoms among CT colonography nonparticipants.Conclusions:In light of these results, future screening programs could tailor the information provided to invitees.

CT-Colonography vs. Colonoscopy for Detection of High-Risk Sessile Serrated Polyps.

Objectives:Sessile serrated polyps (SSPs) are suggested to be the precursors of 15–30% of all colorectal cancers (CRCs). Therefore, CRC screening modalities should also be designed to detect high-risk SSPs. We compared computed tomography colonography (CTC) with colonoscopy-based screening for the detection of high-risk SSPs in average-risk individuals.Methods:Data from a randomized controlled trial that compared CTC with colonoscopy for population screening were used for the analysis. Individuals diagnosed at CTC with a lesion ≥10 mm in size were referred for colonoscopy. Individuals with only 6–9 mm lesions were offered surveillance CTC. This surveillance CTC was followed by a colonoscopy when a lesion ≥6 mm was detected. Yield of both was accumulated to mimic current American College of Radiology CTC referral strategy (referral of individuals with any lesion ≥6 mm). Per participant detection of ≥1 high-risk (dysplastic and/or ≥10 mm) SSP was compared with colonoscopy using multiple logistic regression analysis.Results:In total, 8,844 individuals were invited to participate (in 2:1 allocation), of which 1,276 colonoscopy and 982 CTC invitees participated in the study. In the colonoscopy arm, 4.3% of individuals were diagnosed with ≥1 high-risk SSP, compared with 0.8% in the CTC arm (odds ratio (OR) 5.5; 95% confidence interval (CI) 2.6–11.6; P<0.001). In total, 3.1% of individuals in the colonoscopy arm were diagnosed with high-risk SSPs as most advanced lesion, compared with 0.4% in the CTC arm (OR 7.7; 95% CI 2.7–21.6; P<0.001). The current CTC strategy showed a marked lower detection for especially flat high-risk SSPs (17 vs. 0), high-risk SSP located in the proximal colon (32 vs. 1), and SSPs with dysplasia (30 vs. 1).Conclusions:In a randomized controlled setting, the detection rate of high-risk SSPs was significantly higher with colonoscopy than CTC. These results might have implications for CTC as a CRC modality for opportunistic screening in average-risk adults.