Risk of Cancers Proximal to the Colon in Fecal Immunochemical Test Positive Screenees in a Colorectal Cancer Screening Program.

BACKGROUND AND AIMS: In more than half of the colorectal cancer screening participants with a positive fecal immunochemical test (FIT) result, no advanced neoplasia (AN) is detected at colonoscopy. The positive FIT result could also be generated by cancers located proximal to the colon: upper gastrointestinal, oral cavity, nose, and throat cancers. We evaluated screenees' risk of being diagnosed with a cancer proximal to the colon within the 3 years and compared risks between those with a positive vs those with a negative FIT. METHODS: Data of Dutch colorectal cancer screening participants who underwent biennial FIT-based screening 2014-2018 were collected from the national screening database and linked to the National Cancer Registry. Screenees were classified into 3 groups: FIT-positives with AN (FIT+/AN+), FIT-positives without AN (FIT+/AN-), and FIT-negatives (FIT-). We compared the cumulative incidence of cancers proximal to the colon in each group 3 years after FIT. A Cox regression analysis with left truncation and right censoring, using FIT positivity as time-dependent variable and stratified for sex, was performed to compare the hazard of cancers proximal to the colon in participants who were FIT-positive vs FIT-negative. RESULTS: Three-year cumulative incidence of cancers proximal to the colon in FIT+/AN+ (n = 65,767), FIT+/AN- (n = 50,661), and FIT- (n = 1,831,647) screenees was 0.7%, 0.6%, and 0.4%, respectively (P < .001). FIT-positives were older and more frequently male than FIT-negatives (P < .001). Significantly more cancers proximal to the colon were detected among FIT-positives (P < .001; hazard ratio, 1.55; 95% CI, 1.44-1.67). CONCLUSION: FIT-positive screenees were at significantly increased risk of being diagnosed with a cancer proximal to the colon within 3 years after FIT, although the 3-year cumulative incidence was still less than 1%.

Intraductal Papillary Mucinous Neoplasms in High-Risk Individuals: Incidence, Growth Rate, and Malignancy Risk.

BACKGROUND AND AIMS: In high-risk individuals (HRIs), we aimed to assess the cumulative incidence of intraductal papillary mucinous neoplasms (IPMNs) and compare IPMN growth, neoplastic progression rate, and the value of growth as predictor for neoplastic progression to these in sporadic IPMNs. METHODS: We performed annual surveillance of Dutch HRIs, involving carriers of germline pathogenic variants (PVs) and PV-negative familial pancreatic cancer kindreds. HRIs with IPMNs were compared with Italian individuals without familial risk under surveillance for sporadic IPMNs. RESULTS: A total of 457 HRIs were followed for 48 (range 2-172) months; the estimated cumulative IPMN incidence was 46% (95% confidence interval, 28%-64%). In comparison with 442 control individuals, IPMNs in HRIs were more likely to grow ≥2.5 mm/y (31% vs 7%; P < .001) and develop worrisome features (32% vs 19%; P = .010). PV carriers with IPMNs more often displayed neoplastic progression (n = 3 [11%] vs n = 6 [1%]; P = .011), while familial pancreatic cancer kindreds did not (n = 0 [0%]; P = 1.000). The malignancy risk in a PV carrier with an IPMN was 23% for growth rates ≥2.5 mm/y (n = 13), 30% for ≥5 mm/y (n = 10), and 60% for ≥10 mm/y (n = 5). CONCLUSIONS: The cumulative incidence of IPMNs in HRIs is higher than previously reported in the general population. Compared with sporadic IPMNs, they have an increased growth rate. PV carriers with IPMNs are suggested to be at a higher malignancy risk. Intensive follow-up should be considered for PV carriers with an IPMN growing ≥2.5 mm/y, and surgical resection for those growing ≥5 mm/y.

Diagnostic yield of a risk model versus faecal immunochemical test only: a randomised controlled trial in a colorectal cancer screening programme.

BACKGROUND: Combining the faecal immunochemical test (FIT) result with risk factors for advanced neoplasia (AN) may increase the yield of colorectal cancer (CRC) screening without increasing the number of colonoscopies. We conducted a randomised controlled trial in the Dutch CRC screening programme to evaluate a previously developed risk model including FIT, age, sex, smoking status, and CRC family history. METHODS: A total of 22,748 individuals aged 56-75 years were pre-randomised to the risk-model group or the FIT-only group. Both groups received the FIT; those allocated to the risk-model group also received a single-page questionnaire. Study participants with a positive result (FIT ≥ 15 µg Hb/g faeces and/or risk ≥0.10) were referred for colonoscopy. The primary outcome measure was the proportion of invitees in whom AN was detected. RESULTS: In the risk-model group, 3113/11,364 invitees (27%) returned the FIT and questionnaire versus 3061/11,384 invitees (27%) in the FIT-only group (p = 0.40). The yield of AN was 3.70/1000 invitees in the risk-model group versus 3.43/1000 in the FIT-only group (absolute difference: 0.27/1000, 95%CI: -1.30 to 1.82, p = 0.82). CONCLUSIONS: Combining FIT with risk factors for CRC did not increase the yield of AN compared to FIT-only in an existing CRC screening programme. There was no difference in participation between groups. CLINICAL TRIAL REGISTRATION: NCT04490551 (ClinicalTrials.gov).

High quality colonoscopy: using textbook process as a composite quality measure.

BACKGROUND : High quality colonoscopy is fundamental to good patient outcomes. "Textbook outcome" has proven to be a feasible multidimensional measure for quality assurance between surgical centers. In this study, we sought to establish the "textbook process" (TP) as a new composite measure for the optimal colonoscopy process and assessed how frequently TP was attained in clinical practice and the variation in TP between endoscopists. METHODS : To reach consensus on the definition of TP, international expert endoscopists completed a modified Delphi consensus process. The achievement of TP was then applied to clinical practice. Prospectively collected data in two endoscopy services were retrospectively evaluated. Data on colonoscopies performed for symptoms or surveillance between 1 January 2018 and 1 August 2021 were analyzed. RESULTS : The Delphi consensus process was completed by 20 of 27 invited experts (74.1 %). TP was defined as a colonoscopy fulfilling the following items: explicit colonoscopy indication; successful cecal intubation; adequate bowel preparation; adequate withdrawal time; acceptable patient comfort score; provision of post-polypectomy surveillance recommendations in line with guidelines; and the absence of the use of reversal agents, early adverse events, readmission, and mortality. In the two endoscopy services studied, TP was achieved in 5962/8227 colonoscopies (72.5 %). Of 48 endoscopists performing colonoscopy, attainment of TP varied significantly, ranging per endoscopist from 41.0 % to 89.1 %. CONCLUSION : This study proposes a new composite measure for colonoscopy, namely "textbook process." TP gives a comprehensive summary of performance and demonstrates significant variation between endoscopists, illustrating the potential benefit of TP as a measure in future quality assessment programs.

Decision-making on colorectal cancer screening in Curaçao - interviews with the target population.

BACKGROUND: During the first year of the population based colorectal cancer (CRC) screening program on Curaçao, about 20% of invitees participated. This study explored the target population's perceptions and awareness on CRC (screening), beliefs on the program provision, their preferences and information needs for informed decision-making. METHODS: Semi-structured interviews with 23 individuals, who were not yet invited for CRC screening, were recorded, transcribed, coded and analyzed. RESULTS: CRC (screening) was discussed in the context of personal health, where own responsibility and food were important. Cancer was perceived as an unpredictable disease that causes suffering and leads to death and was also associated with fear. Despite being aware of the program, most respondents were not familiar with the screening procedure. Provision of the screening program was regarded positively and as an opportunity to contribute to health improvement. This seemed related to the expressed trust in the Caribbean Prevention Center (program organizer). Respondents preferred to make independent decisions about CRC screening participation. A personal approach, visual aids and media were the preferred sources of information. CONCLUSION: The results of our interviews suggest that it may be beneficial to provide information on CRC screening in Curaçao within the context of personal health. While including sensitivity to fears and respect for the autonomy of the target population. Finally, electronic media maybe useful in supporting informed decision-making.

Novel classification for adverse events in GI endoscopy: the AGREE classification.

BACKGROUND AND AIMS: Standardized registration and evaluation of adverse events (AEs) are essential to assess the safety of endoscopic procedures. We propose a novel classification system, named adverse events in GI endoscopy (AGREE), adapted from a widely accepted surgical tool. METHODS: The Clavien-Dindo classification for surgical AEs was adapted for endoscopy. To validate the novel classification, we assessed if the severity of AEs, as perceived by 10 endoscopists, 10 endoscopy nurses, and 10 patients, corresponded with the severity grading used in the AGREE classification in 10 pairwise comparisons. We additionally assessed the correlation between the AGREE classification and the American Society for Gastrointestinal Endoscopy (ASGE) classification. The acceptability of the AGREE classification was evaluated through an international questionnaire. RESULTS: The perception of endoscopists, endoscopy nurses, and patients corresponded with the severity grading of the AGREE classification in 80% of cases (238/299). The AGREE classification significantly correlated with the ASGE classification (ρ = .760). Fifty-seven of 84 experts (68%) completed a questionnaire regarding the acceptability of the AGREE classification. The experts consulted considered the AGREE classification as simple (86%), reproducible (98%), logical (98%), and useful (96%). Most case presentations (84%) were correctly graded according to the AGREE classification. CONCLUSIONS: The AGREE classification provides a standardized and reproducible approach to the assessment of AEs in diagnostic and therapeutic GI endoscopy. Broad implementation of the AGREE classification may facilitate the evaluation of AEs across different endoscopists, disciplines, endoscopy services, and regions. This standardization of AE reporting will support improved quality assurance in GI endoscopy.

Case-mix adjustment to compare colonoscopy performance between endoscopy centers: a nationwide registry study.

BACKGROUND : Nonmodifiable patient and endoscopy characteristics might influence colonoscopy performance. Differences in these so-called case-mix factors are likely to exist between endoscopy centers. This study aimed to examine the importance of case-mix adjustment when comparing performance between endoscopy centers. METHODS : Prospectively collected data recorded in the Dutch national colonoscopy registry between 2016 and 2019 were retrospectively analyzed. Cecal intubation rate (CIR) and adequate bowel preparation rate (ABPR) were analyzed. Additionally, polyp detection rate (PDR) was studied in screening colonoscopies following a positive fecal immunochemical test (FIT). Variation in case-mix factors between endoscopy centers and expected outcomes for each performance measure were calculated per endoscopy center based on case-mix factors (sex, age, American Society of Anesthesiologist [ASA] score, indication) using multivariable logistic regression. RESULTS: 363 840 colonoscopies were included from 51 endoscopy centers. Mean percentages per endoscopy center were significantly different for age > 65 years, male patients, ASA ≥ III, and diagnostic colonoscopies (all P < 0.001). In the FIT-positive screening population, significant differences were observed between endoscopy centers for age > 65 years, male patients, and ASA ≥ III (all P ≤ 0.001). The expected CIR, ABPR, and PDR ranged from 95.0 % to 96.9 %, from 93.6 % to 96.4 %, and from 76.2 % to 79.1 %, respectively. Age, sex, ASA classification, and indication were significant case-mix factors for CIR and ABPR. In the FIT-positive screening population, age, sex, and ASA classification were significant case-mix factors for PDR. CONCLUSION: Our findings emphasize the importance of considering case-mix adjustment when comparing colonoscopy performance measures between endoscopy centers.

Continuous monitoring of colonoscopy performance in the Netherlands: first results of a nationwide registry.

BACKGROUND: To optimize colonoscopy quality, several performance measures have been developed. These are usually assessed without distinction between the indications for colonoscopy. This study aimed to assess the feasibility of linking two national registries (one for colonoscopy and one for adverse events of gastrointestinal endoscopies in the Netherlands), and to describe the results of colonoscopy quality per indication. METHODS: This retrospective study was conducted with prospectively collected data of the Dutch Gastrointestinal Endoscopy Audit (DGEA) and the Dutch Registration of Complications in Endoscopy (DRCE). Data between 01-01-2016 and 01-01-2019 were analyzed. To calculate adverse event rates, data were linked at the level of endoscopy service. RESULTS: During the 3-year study period, 266 981 colonoscopies were recorded in DGEA. Of all indications, cecal intubation rate was highest in fecal immunochemical test (FIT)-positive screening colonoscopies (97.1 %), followed by surveillance (93.2 %), diagnostic (90.7 %), and therapeutic colonoscopies (83.1 %). The highest rate of adequate bowel preparation was observed in FIT-positive screening colonoscopies (97.1 %). A total of 1540 colonoscopy-related adverse events occurred (0.58 % of all colonoscopies). Bleeding and perforation and rates were highest for therapeutic (1.56 % and 0.51 %, respectively) and FIT-positive screening (0.72 % and 0.06 %, respectively) colonoscopies. The colonoscopy-related mortality was 0.006 %. CONCLUSION: This study describes the first results of the Dutch national colonoscopy registry, which was successfully linked to data from the national registry for adverse events of gastrointestinal endoscopies. In this large dataset, performance varied between indications. Our results emphasize the importance of defining benchmarks per indication in future guidelines.

Endoscopic full-thickness resection of T1 colorectal cancers: a retrospective analysis from a multicenter Dutch eFTR registry.

BACKGROUND: Complete endoscopic resection and accurate histological evaluation for T1 colorectal cancer (CRC) are critical in determining subsequent treatment. Endoscopic full-thickness resection (eFTR) is a new treatment option for T1 CRC < 2 cm. We aimed to report clinical outcomes and short-term results. METHODS: Consecutive eFTR procedures for T1 CRC, prospectively recorded in our national registry between November 2015 and April 2020, were retrospectively analyzed. Primary outcomes were technical success and R0 resection. Secondary outcomes were histological risk assessment, curative resection, adverse events, and short-term outcomes. RESULTS: We included 330 procedures: 132 primary resections and 198 secondary scar resections after incomplete T1 CRC resection. Overall technical success, R0 resection, and curative resection rates were 87.0 % (95 % confidence interval [CI] 82.7 %-90.3 %), 85.6 % (95 %CI 81.2 %-89.2 %), and 60.3 % (95 %CI 54.7 %-65.7 %). Curative resection rate was 23.7 % (95 %CI 15.9 %-33.6 %) for primary resection of T1 CRC and 60.8 % (95 %CI 50.4 %-70.4 %) after excluding deep submucosal invasion as a risk factor. Risk stratification was possible in 99.3 %. The severe adverse event rate was 2.2 %. Additional oncological surgery was performed in 49/320 (15.3 %), with residual cancer in 11/49 (22.4 %). Endoscopic follow-up was available in 200/242 (82.6 %), with a median of 4 months and residual cancer in 1 (0.5 %) following an incomplete resection. CONCLUSIONS: eFTR is relatively safe and effective for resection of small T1 CRC, both as primary and secondary treatment. eFTR can expand endoscopic treatment options for T1 CRC and could help to reduce surgical overtreatment. Future studies should focus on long-term outcomes.

What can We Learn From High-Performing Screening Programs to Increase Bowel Cancer Screening Participation in Australia?

BACKGROUND: Colorectal cancer (CRC) is the second most diagnosed cancer in men and women and second most common cause of cancer death in Australia; Australia's CRC incidence and mortality are among the world's highest. The Australian National Bowel Cancer Screening Program began in 2006; however, only 33% of those approached for the first time by the Program between 2018 and 2019 returned the kit. Of the 5.7 million kits sent during this period, only 44% were returned. Our aim was to identify practices and features of national bowel cancer screening programs in countries with similar programs but higher screening participation, to identify potential interventions for optimising Australian CRC screening participation. METHODS: We searched published and grey literature for CRC screening programs reporting at least 50% screening participation using postal invitation and free return of iFOBT home kits. Interviews were conducted with cancer registry staff and academic researchers, focused on participant and practitioner engagement in screening. RESULTS: National programs in Netherlands, Scotland, Denmark, and Finland reported over 50% screening participation rates for all invitation rounds. Shared characteristics include small populations within small geographic areas relative to Australia; relatively high literacy; a one-sample iFOBT kit; national registration systems for population cancer screening research; and screening program research including randomised trials of program features. CONCLUSIONS: Apart from the one-sample kit, we identified no single solution to persistent Australian low uptake of screening. Research including randomised trials within the program promises to increase participation. IMPACT: This screening program comparison suggests that within-program intervention trials will lead to increased Australian screening participation.

Impact of sedation on the Performance Indicator of Colonic Intubation.

BACKGROUND: The Performance Indicator of Colonic Intubation (PICI) is a new measure of high-quality colonic intubation. Adequate PICI was defined as cecal intubation without significant discomfort and use of minimal sedation. This study assessed achievement of PICI within the Dutch colorectal cancer (CRC) screening program, and determined the association between PICI and adenoma detection rate (ADR). PICI achievement when using the Dutch median midazolam dose was also assessed. METHODS: This retrospective study was conducted within the Dutch fecal immunochemical test-based CRC screening program. Colonoscopy and pathology data were prospectively collected in a national database. Data between January 2016 through January 2018 were analyzed. Adequate PICI was defined as successful cecal intubation, Gloucester Comfort Scale (GCS) of 1 - 3, and use of ≤ 2.5 mg midazolam. RESULTS: 107 328 colonoscopies were performed during the study period. Adequate PICI was achieved in 49 500 colonoscopies (46.1 %). In colonoscopies with inadequate PICI, inadequacy was due to higher sedation doses in 87.8 %. Adequate PICI was associated with higher ADR (odds ratio 1.16, 95 % confidence interval 1.12 - 1.20). When using a cutoff of 5 mg midazolam, median dose in this Dutch population, adequate PICI was achieved in 95 410 colonoscopies (88.9  %). CONCLUSION: PICI appeared to be heavily dependent on sedation practice. Because of wide variation in sedation practice between individual endoscopists and countries, the benefit of PICI as a quality indicator is limited.

Addition of an online, validated family history questionnaire to the Dutch FIT-based screening programme did not improve its diagnostic yield.

BACKGROUND: Faecal immunochemical testing (FIT) is suboptimal in detecting advanced neoplasia (AN). To increase the sensitivity and yield of a FIT-based screening programme, FIT could be combined with risk factors for AN. We evaluated the incremental yield of adding a family history questionnaire (FHQ) on colorectal cancer (CRC) and Lynch syndrome-associated tumours to the Dutch FIT-based screening programme. METHODS: Six thousand screen-naive individuals, aged 59-75 years, were invited to complete a FIT (FOB-Gold, cut-off 47 µg Hb/g faeces) and a validated online FHQ. Participants with a positive FIT and/or positive FHQ, confirmed after genetic counselling, were referred for colonoscopy. Yield of detecting AN per 1000 invitees for the combined strategy was compared with the FIT-only strategy. RESULTS: Of the 5979 invitees, 1952 (32.6%) completed the FIT only, 2379 (39.8%) completed both the FIT and FHQ and 95 (1.6%) completed the FHQ only. Addition of the FHQ to FIT-based screening resulted in one extra case of AN detected after 16 additional colonoscopies, resulting in a yield of 19.6 (95% CI, 16.4-23.5) for the combined strategy versus 19.5 (95% CI, 16.3-23.3) for the FIT-only strategy (p = 1.0). CONCLUSIONS: The addition of an FHQ to one round of FIT screening did not increase the detection of AN compared with FIT only (ClinicalTrials.gov NCT02698462).

Diagnostic Yield of One-Time Colonoscopy vs One-Time Flexible Sigmoidoscopy vs Multiple Rounds of Mailed Fecal Immunohistochemical Tests in Colorectal Cancer Screening.

BACKGROUND & AIMS: We compared the diagnostic yields of colonoscopy, flexible sigmoidoscopy, and fecal immunochemical tests (FITs) in colorectal cancer (CRC) screening. METHODS: A total of 30,007 asymptomatic persons, 50-74 years old, were invited for CRC screening in the Netherlands. Participants were assigned to groups that received 4 rounds of FIT (mailed to 15,046 participants), once-only flexible sigmoidoscopy (n = 8407), or once-only colonoscopy (n = 6600). Patients with positive results from the FIT (≥10 µg Hb/g feces) were referred for colonoscopy. Patients who underwent flexible sigmoidoscopy were referred for colonoscopy if they had a polyp of ≥10 mm; adenoma with ≥25% villous histology or high-grade dysplasia; sessile serrated adenoma; ≥3 adenomas; ≥20 hyperplastic polyps; or invasive CRC. The primary outcome was number of advanced neoplasia detected (diagnostic yield) by each test. Secondary outcomes were number of colonoscopies needed to detect advanced neoplasia and number of interval CRCs found during each primary screening test. Patients with interval CRCs were found through linkage with Netherlands Cancer Registry. Advanced neoplasia were defined as CRC, adenomas ≥ 10 mm, adenomas with high-grade dysplasia, or adenomas with a villous component of at least 25%. RESULTS: The cumulative participation rate was significantly higher for FIT screening (73%) than for flexible sigmoidoscopy (31%; P < .001) or colonoscopy (24%; P < .001). The percentage of colonoscopies among invitees was higher for colonoscopy (24%) compared to FIT (13%; P < .001) or flexible sigmoidoscopy (3%; P < .001). In the intention to screen analysis, the cumulative diagnostic yield of advanced neoplasia was higher with FIT screening (4.5%; 95% CI 4.2-4.9) than with colonoscopy (2.2%; 95% CI, 1.8-2.6) or flexible sigmoidoscopy (2.3%; 95% CI, 2.0-2.7). In the as-screened analysis, the cumulative yield of advanced neoplasia was higher for endoscopic screening with colonoscopy (9.1%; 95% CI, 7.7-10.7) or flexible sigmoidoscopy (7.4%; 95% CI, 6.5-8.5) than with the FIT (6.1%; 95% CI, 5.7-6.6). All 3 screening strategies detected a similar proportion of patients with CRC. Follow-up times differed for each test (median 8.3 years for FIT and flexible sigmoidoscopy and 5.8 years for colonoscopy). Proportions of patients that developed interval CRC were 0.13% for persons with a negative result from FIT, 0.09% for persons with a negative result from flexible sigmoidoscopy, and 0.01% for persons with a negative result from colonoscopy. CONCLUSIONS: Mailed multiple-round FITs detect significantly more advanced neoplasia, on a population level, compared with once-only flexible sigmoidoscopy or colonoscopy screening. Significantly fewer colonoscopies are required by individuals screened by multiple FITs. Trialregister.nl numbers: first round, NTR1096; second round and additional invitees, NTR1512; fourth round, NTR5874; COCOS trial NTR1829.

Interval Colorectal Cancer Incidence Among Subjects Undergoing Multiple Rounds of Fecal Immunochemical Testing.

BACKGROUND & AIMS: Among subjects screened for colorectal cancer (CRC) by the guaiac fecal occult blood test, interval cancers develop in 48% to 55% of the subjects. Data are limited on how many persons screened by fecal immunochemical tests (FIT), over multiple rounds, develop interval cancers. In the Netherlands, a pilot FIT-based biennial CRC screening program was conducted between 2006 and 2014. We collected and analyzed data from the program on CRCs detected during screening (SD-CRC) and CRCs not detected within the screening program (non-SD-CRC; such as FIT interval cancers, colonoscopy interval cancers, and cancer in nonparticipants). METHODS: Screenees with a negative FIT result received a letter explaining that no blood had been detected in the stool sample and were re-invited, if eligible, for screening biennially. Screenees with a positive FIT result (hemoglobin concentration of 10 µg Hb/g feces) were invited for consultation and scheduled for colonoscopy; results were collected. After the fourth round of FIT screening, the cohort was linked to the Netherlands Cancer Registry, through March 31, 2015; participant characteristics, data on tumor stage, location (at time of resection), and survival status were collected for all identified CRC cases. A reference group comprised all persons with CRC diagnosed in the Netherlands general population during the same period, in the same age range (50-76 years), who had not been offered CRC screening. The median time between invitations (2.37 years) was used as a cutoff to categorize participants within the FIT interval cancer category. We compared participant characteristics, tumor characteristics, and mortality among subjects with SD-CRC and with non-SD-CRC. RESULTS: A total of 27,304 eligible individuals were invited for FIT screening, of whom 18,716 (69%) participated at least once. Of these, 3005 (16%) had a positive result from the FIT in 1 of the 4 screening rounds. In total, CRC was detected in 261 participants: 116 SD-CRCs and 145 non-SD-CRCs (27 FIT interval cancers, 9 colonoscopy interval cancers, and 109 CRCs in nonparticipants). The FIT interval cancer proportion after 3 completed screening rounds was 23%. Participants with SD-CRC had more early-stage tumors than participants with non-SD-CRCs (P < .001). Of persons with SD-CRC and FIT interval cancers, significantly higher proportions survived (89% and 81%, respectively) compared with persons with colonoscopy interval cancers (44% survival) and nonparticipants with CRC (60% survival) (P < .001). CONCLUSIONS: In an analysis of data from a pilot FIT-based biennial screening program, we found that among persons screened by FIT, 23% developed FIT interval cancer. FIT therefore detects CRC with 77% sensitivity. The proportion of FIT interval cancers in FIT screening appears to be lower than that with guaiac fecal occult blood testing. Clinical trial registry: yes, www.trialregister.nl, trial number: NTR5385.

Risk of Oral and Upper Gastrointestinal Cancers in Persons With Positive Results From a Fecal Immunochemical Test in a Colorectal Cancer Screening Program.

BACKGROUND & AIMS: European guidelines recommend screening for colorectal cancer (CRC) using the fecal immunochemical test (FIT), with follow-up colonoscopies for individuals with positive test results. However, more than half of participants with positive results from the FIT are not found to have advanced neoplasia in the colonoscopy examination. Fecal occult blood might also come from the upper gastrointestinal (GI) tract, so perhaps we should consider esophagogastroduodenoscopy (EGD), to detect upper GI cancers. We aimed to determine how many individuals are found to have oral or upper GI cancers (oral cavity, throat, esophageal, gastric, or small bowel cancer) within 3 years after a positive or negative result from a FIT in a CRC screening program. METHODS: We performed a retrospective analysis of data from a pilot study of 3 rounds of biennial FIT-based screening for CRC in 2 regions in the west of the Netherlands, from 2006 through October 2012. Participants who developed oral or upper GI cancers were identified through linkage with the National Cancer Registry. We classified these cancers into 3 groups: those that developed in individuals with a positive result from a FIT but negative findings from colonoscopy (no advanced neoplasia), those that developed in individuals with a positive result from a FIT and a positive finding from colonoscopy (advanced neoplasia), and those that developed in individuals with negative results from a FIT. We compared oral and upper GI cancer incidence among groups. RESULTS: Among 16,165 screening participants, linkage identified 52 persons who developed an oral or upper GI cancer within 3 years after a FIT. We found no significant difference in incidence values between individuals with a positive vs a negative FIT result: 8 cancers developed in individuals with a positive result from a FIT (0.37%; 95% CI, 0.19-0.76) and 44 developed in individuals with a negative result from a FIT (0.31%; 95% CI, 0.23-0.42) (P = .65). Of the 8 individuals with a positive result from a FIT and an oral or upper GI cancer, 6 were diagnosed after negative findings from colonoscopy and 2 after positive findings from colonoscopy. We found that only 0.14% of all persons with a positive result from a FIT were diagnosed with a gastric or esophageal cancer within 3 years. CONCLUSION: In a study of individuals in the Netherlands undergoing screening for CRC by FIT, we found fewer than 1% of patients with a positive result from the FIT to receive a diagnosis of upper GI cancers within 3 years. Routine EGD investigation of individuals with positive results from a FIT and negative findings from colonoscopy is therefore not recommended. TrialRegister.nl, Number: NTR5385.

Adherence to colorectal cancer screening: four rounds of faecal immunochemical test-based screening.

BACKGROUND: The effectiveness of faecal immunochemical test (FIT)-based screening programs is highly dependent on consistent participation over multiple rounds. We evaluated adherence to FIT screening over four rounds and aimed to identify determinants of participation behaviour. METHODS: A total of 23 339 randomly selected asymptomatic persons aged 50-74 years were invited for biennial FIT-based colorectal cancer screening between 2006 and 2014. All were invited for every consecutive round, except for those who had moved out of the area, passed the upper age limit, or had tested positive in a previous screening round. A reminder letter was sent to non-responders. We calculated participation rates per round, response rates to a reminder letter, and differences in participation between subgroups defined by age, sex, and socioeconomic status (SES). RESULTS: Over the four rounds, participation rates increased significantly, from 60% (95% CI 60-61), 60% (95% CI 59-60), 62% (95% CI 61-63) to 63% (95% CI 62-64; P for trend<0.001) with significantly higher participation rates in women in all rounds (P<0.001). Of the 17 312 invitees eligible for at least two rounds of FIT screening, 12 455 (72%) participated at least once, whereas 4857 (28%) never participated; 8271 (48%) attended all rounds when eligible. Consistent participation was associated with older age, female sex, and higher SES. Offering a reminder letter after the initial invite in the first round increased uptake with 12%; in subsequent screening rounds this resulted in an additional uptake of up to 10%. CONCLUSIONS: In four rounds of a pilot biennial FIT-screening program, we observed a consistently high and increasing participation rate, whereas sending reminders remain effective. The substantial proportion of inconsistent participants suggests the existence of incidental barriers to participation, which, if possible, should be identified and removed.

Optical Diagnosis of Sessile Serrated Polyps: Bottleneck for the Optical Diagnosis Paradigm?

BACKGROUND: Optical diagnosis of diminutive (1 to 5 mm) polyps could result in a more cost-effective colonoscopy practice. Previous optical diagnosis studies did not incorporate the differentiation of sessile serrated polyps (SSPs). This study aimed to evaluate the impact of optical diagnosis of diminutive SSPs on the overall performance of endoscopic polyp differentiation in daily colonoscopy practice. METHODS: Endoscopy data were prospectively collected between 2011 and 2014 in a colonoscopy center. Each endoscopist reported a real-time optical diagnosis (SSP, adenoma or hyperplastic polyp) for all lesions in a structured colonoscopy reporting system, using narrow band imaging at their discretion. Study outcomes were accuracy of optical diagnosis, surveillance interval agreement and negative predictive value for diminutive rectosigmoid neoplastic histology based on the optical diagnosis of diminutive polyps compared to histopathology. RESULTS: Of 2853 removed diminutive polyps, 202 (7.1%) were histologically proven SSPs. Optical diagnosis of diminutive SSPs was accurate in 24.4%. Diminutive SSPs determined 6.9% of postpolypectomy surveillance assignments. Inaccurate optical diagnosis of diminutive SSPs led to lower surveillance interval agreement (78.1% vs. 53.3%, P<0.01) and pooled negative predictive value per polyp (84.3% vs. 50.0%; P<0.01) in patients with diminutive SSPs when compared to patients without diminutive SSPs. Accurate endoscopic identification of diminutive SSPs improved from 0% in 2011 to 47% in 2014 (P=0.02). CONCLUSIONS: Endoscopic characterization of diminutive SSPs is difficult, impairing overall performance of optical diagnosis in patients with diminutive SSPs. Future optical diagnosis studies should use validated trainings and classification algorithms that include differentiation of SSPs.

Prevalence, distribution and risk of sessile serrated adenomas/polyps at a center with a high adenoma detection rate and experienced pathologists.

BACKGROUND AND STUDY AIMS: Sessile serrated adenomas/polyps (SSA/Ps) are the precursors of 15 % - 30 % of colorectal cancers (CRC). We aimed to determine the prevalence and distribution of SSA/Ps and to evaluate the association between SSA/Ps and the risk of synchronous advanced neoplasia at a high quality colonoscopy center. METHODS: Data from all colonoscopies performed within one dedicated colonoscopy center between 2011 and 2015 were prospectively retrieved using an automated reporting system. All lesions were assessed by an experienced gastrointestinal pathologist. Multiple logistic regression was used to evaluate influence of age, gender, and colonoscopy indication on prevalence of SSA/Ps, and to assess the association between SSA/Ps and synchronous advanced neoplasia. RESULTS: In total 4251 histologically confirmed polyps were resected in 3364 patients; 399 polyps were SSA/Ps (9.4 %). The prevalence of SSA/Ps was 8.2 % overall, increasing to 9.0 % for individuals older than 50 years. SSA/P detection rate varied between 2.5 % and 13.6 % among endoscopists. Increased SSA/P prevalence was associated with colonoscopy indications "familial CRC risk" (odds ratio [OR] 1.52, 95 % confidence interval [95 %CI] 1.05 - 2.22; P = 0.03) and "surveillance" (OR 1.73, 95 %CI 1.20 - 2.49; P < 0.01), when compared with the indication "symptoms." The presence of synchronous advanced neoplasia was associated with SSA/Ps overall (OR 1.71, 95 %CI 1.25 - 2.34; P = 0.001), as well as with high risk SSA/Ps (defined as ≥ 10 mm and/or with dysplasia) (OR 2.70, 95 %CI 1.56 - 4.67; P < 0.001) CONCLUSION: SSA/Ps are more common than previously reported and are associated with the presence of synchronous advanced neoplasia. Endoscopists should be assiduous in identifying SSA/Ps in daily practice and should carefully look for synchronous advanced neoplasia when an SSA/P has been recognized. RESULTS from this study can guide detection standards in general colonoscopy practice adapted to the type of patient that may predominate in an individual department.