Evelien Dekker

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

BACKGROUNDnScreening 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.nnnMETHODSnMembers 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.nnnFINDINGSn1276 (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.nnnINTERPRETATIONnParticipation 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.nnnFUNDINGnNetherlands Organisation for Health Research and Development, Centre for Translational Molecular Medicine, and the Nuts Ohra Foundation.

Immunochemical Fecal Occult Blood Testing Is Equally Sensitive for Proximal and Distal Advanced Neoplasia

OBJECTIVE:Fecal immunochemical testing (FIT) is increasingly used for colorectal cancer (CRC) screening. We aimed to estimate its diagnostic accuracy in invitational population screening measured against colonoscopy.METHODS:Participants (50–75 years) in an invitational primary colonoscopy screening program were asked to complete one sample FIT before colonoscopy. We estimated FIT sensitivity, specificity, and predictive values in detecting CRC and advanced neoplasia (carcinomas and advanced adenomas) for cutoff levels of 50 (FIT50), 75 (FIT75), and 100 (FIT100) ng hemoglobin (Hb)/ml, corresponding with, respectively, 10, 15 and 20u2009μg Hb/g feces.RESULTS:A total of 1,256 participants underwent a FIT and screening colonoscopy. Advanced neoplasia was detected by colonoscopy in 119 (9%), 8 (0.6%) of them had CRC. At FIT50, 121 (10%) had a positive test result; 45 (37%) had advanced neoplasia and 7 (6%) had CRC. A total of 74 of 1,135 FIT50 negatives (7%) had advanced neoplasia including 1 (0.1%) CRC. FIT50 had a sensitivity of 38% (95% confidence interval (CI): 29–47) for advanced neoplasia and 88% (95% CI: 37–99) for CRC at a specificity of 93% (95% CI: 92–95) and 91% (95% CI: 89–92), respectively. The positive and negative predictive values for FIT50 were 6% (95% CI: 3–12) and almost 100% (95% CI: 99–100) for CRC, and 37% (95% CI: 29–46) and 93% (95% CI: 92–95) for advanced neoplasia. The sensitivity and specificity of FIT75 for advanced neoplasia were 33% (95% CI: 25–42) and 96% (95% CI: 94–97). At FIT100, 71 screenees (6%) had a positive test result. The sensitivity and specificity of FIT100 were for advanced neoplasia 31% (95% CI: 23–40) and 97% (95% CI: 96–98), and for CRC 75% (95% CI: 36–96) and 95% (95% CI: 93–96). The area under curve for detecting advanced neoplasia was 0.70 (95% CI: 0.64–0.76). FIT had a similar sensitivity for proximal and distal advanced neoplasia at cutoffs of 50 (38% vs. 37%; P=0.99), 75 (33% vs. 31%; P=0.85) and 100 (33% vs. 29%; P=0.68) ng Hb/ml.DISCUSSION:Nine out of ten screening participants with CRC and four out of ten with advanced neoplasia will be detected using one single FIT at low cutoff. Sensitivity in detecting proximal and distal advanced neoplasia is comparable.

Differences in proximal serrated polyp detection among endoscopists are associated with variability in withdrawal time

BACKGROUNDnInsufficient detection of proximal serrated polyps (PSP) might explain the occurrence of a proportion of interval carcinomas in colonoscopy surveillance programs.nnnOBJECTIVEnTo compare PSP detection among endoscopists and to identify patient-related and endoscopist-related factors associated with PSP detection.nnnDESIGNnProspective study in unselected patients.nnnSETTINGnColonoscopy screening program for colorectal cancer at two academic medical centers.nnnPATIENTSnAsymptomatic consecutive screening participants (aged 50-75 years).nnnINTERVENTIONnColonoscopies were performed by 5 experienced endoscopists. All detected polyps were removed. Multiple colonoscopy quality indicators were prospectively recorded.nnnMAIN OUTCOME MEASUREMENTSnWe compared PSP detection among endoscopists by calculating odds ratios (OR) with logistic regression analysis. Logistic regression also was used to identify patient features and colonoscopy factors associated with PSP detection.nnnRESULTSnA total of 1354 patients underwent a complete screening colonoscopy: 1635 polyps were detected, of which 707 (43%) were adenomas and 685 (42%) were serrated polyps, including 215 PSPs. In 167 patients (12%) 1 or more PSPs were detected. The PSP detection rate differed significantly among endoscopists, ranging from 6% to 22% (P < .001). Longer withdrawal time (OR 1.12; 95% confidence interval, 1.10-1.16) was significantly associated with better PSP detection, whereas patient age, sex, and quality of bowel preparation were not.nnnLIMITATIONSnLimited number of highly experienced endoscopists.nnnCONCLUSIONnThe PSP detection rate differs among endoscopists. Longer withdrawal times are associated with better PSP detection, but patient features are not. (nnnCLINICAL TRIAL REGISTRATION NUMBERnNTR1888.).

Development and validation of the WASP classification system for optical diagnosis of adenomas, hyperplastic polyps and sessile serrated adenomas/polyps

Objective Accurate endoscopic differentiation would enable to resect and discard small and diminutive colonic lesions, thereby increasing cost-efficiency. Current classification systems based on narrow band imaging (NBI), however, do not include neoplastic sessile serrated adenomas/polyps (SSA/Ps). We aimed to develop and validate a new classification system for endoscopic differentiation of adenomas, hyperplastic polyps and SSA/Ps <10u2005mm. Design We developed the Workgroup serrAted polypS and Polyposis (WASP) classification, combining the NBI International Colorectal Endoscopic classification and criteria for differentiation of SSA/Ps in a stepwise approach. Ten consultant gastroenterologists predicted polyp histology, including levels of confidence, based on the endoscopic aspect of 45 polyps, before and after participation in training in the WASP classification. After 6u2005months, the same endoscopists predicted polyp histology of a new set of 50 polyps, with a ratio of lesions comparable to daily practice. Results The accuracy of optical diagnosis was 0.63 (95% CI 0.54 to 0.71) at baseline, which improved to 0.79 (95% CI 0.72 to 0.86, p<0.001) after training. For polyps diagnosed with high confidence the accuracy was 0.73 (95% CI 0.64 to 0.82), which improved to 0.87 (95% CI 0.80 to 0.95, p<0.01). The accuracy of optical diagnosis after 6u2005months was 0.76 (95% CI 0.72 to 0.80), increasing to 0.84 (95% CI 0.81 to 0.88) considering high confidence diagnosis. The combined negative predictive value with high confidence of diminutive neoplastic lesions (adenomas and SSA/Ps together) was 0.91 (95% CI 0.83 to 0.96). Conclusions We developed and validated the first integrative classification method for endoscopic differentiation of small and diminutive adenomas, hyperplastic polyps and SSA/Ps. In a still image evaluation setting, introduction of the WASP classification significantly improved the accuracy of optical diagnosis overall as well as SSA/P in particular, which proved to be sustainable after 6u2005months.

Colorectal surgeons' learning curve of transanal endoscopic microsurgery.

BackgroundTransanal endoscopic microsurgery (TEM) is a technically demanding key technique in minimally invasive rectal surgery. We investigated the learning curve of colorectal surgeons commencing with TEM.MethodsAll TEM procedures of four colorectal surgeons were analyzed. Procedures were ranked chronologically per surgeon. Outcomes included conversion, postoperative complications, procedure time, and recurrence. Backward multivariable regression analysis identified learning curve effects and other predictors.ResultsFour surgeons resected 693 rectal lesions [69.9xa0% adenoma/25.5xa0% carcinoma; median size 20xa0cm2; interquartile range (IQR) 11–35; 7xa0±xa04xa0cm ab ano]. A total of 555 resections (80.1xa0%) were histopathologically radical (R0). Conversion (4.3xa0%) was influenced by a learning curve [odds ratio (OR) 0.991 per additional procedure; 95xa0% confidence interval (CI) 0.984–0.998] and by lesion size. Postoperative complications depended only on the individual surgeon and lesion size in benign lesions (10.4xa0% complications). A learning curve (OR 0.99; 95xa0% CI 0.988–0.998) and peritoneal entrance affected complications in malignant lesions (13.3xa0%). Procedure time [median 55xa0min (IQR 30–90)] was influenced by a learning curve [B −0.11 (95xa0% CI −0.14 to −0.09)], individual surgeon, single-piece resection, peritoneal entrance, lesion size, and rectal quadrant. Recurrence of benign lesions (4.5xa0%) depended on lesion size, R0 resection, and prior resection attempts. Recurrence of malignant lesions (8.9xa0%) depended on 3D stereoscopic view, lesion size, full-thickness resection, and length of follow-up. Recurrence-free survival of patients operated during the 36th through 80th procedure per surgeon was significantly shorter than in patients operated during procedures 1–35 and 81 onwards.ConclusionsA surgical learning curve affected conversion rate, procedure time, and complication rate. It did not influence recurrence rates, possibly due to evolving patient populations. This first insight into the learning curve of TEM stresses the importance of quality monitoring and centralisation of care.

Combining risk factors with faecal immunochemical test outcome for selecting CRC screenees for colonoscopy

Objective Faecal immunochemical testing (FIT) is increasingly used in colorectal cancer (CRC) screening but has a less than perfect sensitivity. Combining risk stratification, based on established risk factors for advanced neoplasia, with the FIT result for allocating screenees to colonoscopy could increase the sensitivity and diagnostic yield of FIT-based screening. We explored the use of a risk prediction model in CRC screening. Design We collected data in the colonoscopy arm of the Colonoscopy or Colonography for Screening study, a multicentre screening trial. For this study 6600 randomly selected, asymptomatic men and women between 50 years and 75u2005years of age were invited to undergo colonoscopy. Screening participants were asked for one sample FIT (OC-sensor) and to complete a risk questionnaire prior to colonoscopy. Based on the questionnaire data and the FIT results, we developed a multivariable risk model with the following factors: total calcium intake, family history, age and FIT result. We evaluated goodness-of-fit, calibration and discrimination, and compared it with a model based on primary screening with FIT only. Results Of the 1426 screening participants, 1112 (78%) completed the questionnaire and FIT. Of these, 101 (9.1%) had advanced neoplasia. The risk based model significantly increased the goodness-of-fit compared with a model based on FIT only (p<0.001). Discrimination improved significantly with the risk-based model (area under the receiver operating characteristic (ROC) curve: from 0.69 to 0.76, (p=0.02)). Calibration was good (Hosmer-Lemeshow test; p=0.94). By offering colonoscopy to the 102 patients at highest risk, rather than to the 102 cases with a FIT result >50u2005ng/mL, 5 more cases of advanced neoplasia would be detected (net reclassification improvement 0.054, p=0.073). Conclusions Adding risk based stratification increases the accuracy FIT-based CRC screening and could be used in preselection for colonoscopy in CRC screening programmes.

Sporadic duodenal adenoma and the association with colorectal neoplasia: a case-control study.

OBJECTIVES:Sporadic duodenal adenomas are an uncommon finding. It is not clear whether patients with sporadic duodenal adenoma have a greater risk for colorectal neoplasia and should undergo colonoscopy. The aims of the present study were to estimate the prevalence of colorectal neoplasia in patients with sporadic duodenal adenoma, and to compare colorectal neoplasia rates in patients with sporadic duodenal adenomas versus those without them.METHODS:A retrospective case-control study was conducted to identify sporadic duodenal adenoma patients using the databases of two academic and one regional hospital in the Netherlands. Colonoscopic findings in the sporadic duodenal adenoma patients were compared with those of a control group of patients who underwent both gastroduodenoscopy and colonoscopy. Furthermore, the frequency of colorectal cancer in the sporadic duodenal adenoma patients was compared with the population incidence of colorectal cancer.RESULTS:During the period 1991–2006, 102 patients in total with sporadic duodenal adenomas were identified. Colonoscopy was performed in 49 patients (48%), and colorectal neoplasia was present in 21 of these patients (43%). There was a significantly higher rate of both colorectal neoplasia (43% vs 17%, odds ratio [OR] 3.6, 95% confidence interval [CI] 1.7–7.4) and advanced colorectal adenoma (18% vs 3%, OR 7.8, 95% CI 2.1–29.4) in the patients with sporadic duodenal adenoma compared to that in the control group. Also, the incidence of colorectal cancer was higher in sporadic duodenal adenoma patients compared to that in the population (P= 0.02).CONCLUSIONS:Individuals with sporadic duodenal adenomas appear to be at a significantly higher risk of colorectal neoplasia, and therefore should undergo colonoscopy.

Unit costs in population-based colorectal cancer screening using CT colonography performed in university hospitals in The Netherlands

AbstractObjectivesComputed tomography (CT) colonography cost assumptions so far ranged from €346 to €594 per procedure, based on clinical CT reimbursement rates. The aim of our study was to estimate the costs in a screening situation.MethodsData were collected within an invitational population-based CRC screening trial (nu2009=u20092,920, age 50–75xa0years) with a dedicated CT-screening setting. Unit costs were calculated per action, per invitee and per participant (depending on adherence) and per individual with detected advanced neoplasia. Sensitivity analyses were performed, and alternative scenarios were considered.ResultsOf the invitees, 47.2xa0% were reminded, 38.8xa0% scheduled for an intake, 37.2xa0% scheduled for CT colonography, 33.6xa0% underwent CT colonography and 1.1xa0% needed a re-examination. Lesions ≥10xa0mm were detected in 2.9xa0% of the invitees. Invitation costs were €5.57. Costs per CT colonography (intake to results) were €144.00. Extra costs of communication of positive results were €9.00. Average costs of invitational-based CT colonography screening were €56.97 per invitee, €169.40 per participant and €2,772.51 per individual with detected advanced neoplasia.ConclusionsDutch costs of CT-screening were substantially lower than the cost assumptions that were used in published cost-effectiveness analyses on CT colonography screening. This finding indicates that previous cost-effectiveness analyses should be updated, at least for the Dutch situation.Key Points• CT colonography screening costs have historically been based on (local) clinical reimbursement ratesn • Estimates ranged from €346–€594, based on abdominal and/or pelvic computed tomographyn • Average costs per participant within an invitational population-based screening program: €169.40n • Average CT colonography costs per individual with detected advanced neoplasia: €2,772.51n • Previous cost-effectiveness analyses should probably be updated

CT colonography polyp matching: differences between experienced readers

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.

Yield of colonoscopy after recent CT-proven uncomplicated acute diverticulitis: a comparative cohort study

BackgroundCurrent guidelines recommend routine follow-up colonoscopy after acute diverticulitis to confirm the diagnosis and exclude malignancy. Its value, however, has recently been questioned because of contradictory study results. Our objective was to compare the colonoscopic detection rate of advanced colonic neoplasia (ACN), comprising colorectal cancer (CRC) and advanced adenoma (AA), in patients after a CT-proven primary episode of uncomplicated acute diverticulitis with average risk participants in a primary colonoscopy CRC screening program.MethodsA retrospective comparison was performed of prospectively collected data from cohorts derived from two multicenter randomized clinical trials executed in the Netherlands between 2009 and 2013. 401 uncomplicated diverticulitis patients and 1,426 CRC screening participants underwent colonic evaluation by colonoscopy. Main outcome was the diagnostic yield for ACN, calculated as number of diverticulitis patients and screening participants with ACN relative to their totals, with differences expressed as odds ratios (OR). The histopathology outcome of removed lesions during colonoscopy was used as definitive diagnosis.ResultsAA detection was similar [5.5 vs. 8.7xa0%; OR 0.62 (95xa0% CI 0.38–1.01); Pxa0=xa00.053]. CRC was detected in 1.2xa0% (5/401) of diverticulitis patients versus 0.6xa0% (9/1,426) of screening participants [OR 1.30 (95xa0% CI 0.39–4.36); Pxa0=xa00.673]. ACN was diagnosed in 6.7xa0% (27/401) of diverticulitis patients versus 9.1xa0% (130/1,426) of screening participants [OR 0.71 (95xa0% CI 0.45–1.11); Pxa0=xa00.134]. ORs were adjusted for age, family history of CRC, smoking, BMI, and cecal intubation rate.ConclusionsACN detection does not differ significantly between patients with recent uncomplicated diverticulitis and average risk screening participants. Routine follow-up colonoscopy after primary CT-proven uncomplicated left-sided acute diverticulitis can be omitted; these patients can participate in CRC screening programs. Follow-up colonoscopy may be beneficial when targeted at high-risk patients, but such an approach first needs prospective evaluation.