Background In the Dutch colorectal (CRC) screening program, fecal immunochemical test (FIT)-positive individuals are referred for colonoscopy. If no relevant findings are detected at colonoscopy,... Show moreBackground In the Dutch colorectal (CRC) screening program, fecal immunochemical test (FIT)-positive individuals are referred for colonoscopy. If no relevant findings are detected at colonoscopy, individuals are reinvited for FIT screening after 10 years. We aimed to assess CRC risk after a negative colonoscopy in FIT-positive individuals.Methods In this cross-sectional cohort study, data were extracted from the Dutch national screening information system. Participants with a positive FIT followed by a negative colonoscopy between 2014 and 2018 were included. A negative colonoscopy was defined as a colonoscopy during which no more than one nonvillous, nonproximal adenoma < 10 mm or serrated polyp < 10 mm was found. The main outcome was interval post-colonoscopy CRC (iPCCRC) risk. iPCCRC risk was reviewed against the risk of interval CRC after a negative FIT (FIT IC) with a 2-year screening interval.Results 35 052 FIT-positive participants had a negative colonoscopy and 24 iPCCRCs were diagnosed, resulting in an iPCCRC risk of 6.85 (95 %CI 4.60–10.19) per 10 000 individuals after a median follow-up of 1.4 years. After 2.5 years of follow-up, age-adjusted iPCCRC risk was approximately equal to FIT IC risk at 2 years.Conclusion Risk of iPCCRC within a FIT-based CRC screening program was low during the first years after colonos-copy but, after 2.5 years, was the same as the risk in FIT-negative individuals at 2 years, when they are reinvited for screening. Colonoscopy quality may therefore require further improvement and FIT screening interval may need to be reduced after negative colonoscopy. Show less
Background Extensive colectomy (subtotal or total colectomy) is often advised for carriers of Lynch syndrome with colorectal cancer. However, the risk of metachronous colorectal cancer might differ... Show moreBackground Extensive colectomy (subtotal or total colectomy) is often advised for carriers of Lynch syndrome with colorectal cancer. However, the risk of metachronous colorectal cancer might differ by Lynch syndrome variant, meaning that partial colectomy, which has better functional outcomes, might be adequate for some patients with lowrisk variants. We aimed to assess the risk of metachronous colorectal cancer after partial colectomy and extensive colectomy in carriers of Lynch syndrome with different pathogenic variants. Methods For this retrospective cohort study, carriers of Lynch syndrome with colorectal cancer in the Netherlands were identified by linkage of the Dutch Foundation for the Detection of Hereditary Tumors (StOET) database and the Dutch Nationwide Network and Registry of Histopathology and Cytopathology (PALGA) database. Data on demographics, Lynch syndrome variants, colorectal cancers, surgery types, mortality, and surveillance colonoscopies were extracted. Data on colorectal cancer and surveillance colonoscopies were updated until Feb 28, 2022. Data on survival status was updated until Feb 7, 2022. MLH1, MSH2, and EPCAM were classified as high-risk variants and MSH6 and PMS2 as low-risk variants. Patients for whom the type of surgery was unknown were excluded. Cox regression time-to-event analyses were done to assess the risk of metachronous colorectal cancer in four subgroups based on pathogenic variant (high-risk vs low-risk variants) and the extent of surgery (extensive colectomy vs partial colectomy). Sex, age at the time of primary colorectal cancer, primary colorectal cancer stage, performance of surveillance colonoscopies, adherence to the surveillance guidelines, and time period of primary colorectal cancer diagnosis were added to the model as possible confounders. Metachronous colorectal cancer was defined as colorectal cancer diagnosed more than 6 months after the primary colorectal cancer. Patients were censored at time of death or assembly of the database. Findings Of 1908 carriers of Lynch syndrome registered in StOET, 532 with a history of colorectal cancer were identified after linkage with PALGA. Five carriers were excluded because of an unknown surgery type, leaving 527 in our sample (mean age at primary colorectal cancer 48·7 years [SD 12·1]; 274 [52%] male and 253 [48%] female). 121 (23%) patients developed metachronous colorectal cancer (median time from primary colorectal cancer to metachronous colorectal cancer 11·0 years [IQR 2·1–17·8]). Metachronous colorectal cancer occurred in 12 (12%) of 97 patients with high-risk variants and extensive colectomy, in 85 (32%) of 267 patients with high-risk variants and partial colectomy, in zero (0%) of 11 patients with low-risk variants and extensive colectomy, and in 24 (16%) of 152 patients with low-risk variants and partial colectomy. Partial colectomy was associated with a higher risk of metachronous colorectal cancer than extensive colectomy in the high-risk variant group (hazard ratio 1·97, 95% CI 1·04–3·73; p=0·039). The risk of metachronous colorectal cancer did not differ between carriers of low-risk variants who had partial colectomy and those of high-risk variants who had extensive colectomy (1·14, 0·55–2·36; p=0·72). Interpretation The risk of metachronous colorectal cancer after partial colectomy in carriers of low-risk variants is similar to the risk after extensive colectomy in carriers of high-risk variants. This finding suggests that partial colectomy followed by endoscopic surveillance is an appropriate management approach to treat colorectal cancer in carriers of low-risk Lynch syndrome variants. Show less
Jodal, H.C.; Akwiwu, E.U.; Lemmens, M.; Delis-van Diemen, P.M.; Klotz, D.; Leon, L.G.; ... ; Carvalho, B. 2023
Current morphologic features defining advanced adenomas (size ≥10 mm, high-grade dysplasia or ≥25% villous component) cannot optimally distinguish individuals at high risk or low risk of... Show moreCurrent morphologic features defining advanced adenomas (size ≥10 mm, high-grade dysplasia or ≥25% villous component) cannot optimally distinguish individuals at high risk or low risk of metachronous colorectal cancer (me-CRC), which may result in suboptimal surveillance. Certain DNA copy-number alterations (CNAs) are associated with adenoma-to-carcinoma progression. We aimed to evaluate whether these molecular features can better predict an individual's risk of me-CRC than the morphologic advanced adenoma features.In this nested case–control study, 529 individuals with a single adenoma at first colonoscopy were selected from a Norwegian adenoma cohort. DNA copy-number profiles were determined, by low-coverage whole-genome sequencing. Prevalence of CNAs in advanced and non-advanced adenomas and its association (OR) with me-CRC was assessed. For the latter, cases (with me-CRC) were matched to controls (without me-CRC) on follow-up, age and sex.CNAs associated with adenoma-to-carcinoma progression were observed in 85/267 (32%) of advanced adenomas and in 27/262 (10%) of non-advanced adenomas. me-CRC was statistically significantly associated, also after adjustment for other variables, with age at baseline [OR, 1.14; 95% confidence interval CI), 1.03–1.26; P = 0.012], advanced adenomas (OR, 2.46; 95% CI, 1.50–4.01; P < 0.001) and with the presence of ≥3 DNA copy-number losses (OR, 1.90; 95% CI. 1.02–3.54; P = 0.043).Molecularly-defined high-risk adenomas were associated with me-CRC, but the association of advanced adenoma with me-CRC was stronger.Significance:Identifying new biomarkers may improve prediction of me-CRC for individuals with adenomas and optimize surveillance intervals to reduce risk of colorectal cancer and reduce oversurveillance of patients with low risk of colorectal cancer. Use of DNA CNAs alone does not improve prediction of me-CRC. Further research to improve risk classification is required. Show less
Aelvoet, A.S.; Karstensen, J.G.; Bastiaansen, B.A.J.; Leerdam, M.E. van; Balaguer, F.; Kaminski, M.; ... ; European FAP Consortium 2023
Background and study aims In patients with familial adenomatous polyposis (FAP), endoscopic resection of duodenal adenomas is commonly performed to prevent cancer and prevent or defer duodenal... Show moreBackground and study aims In patients with familial adenomatous polyposis (FAP), endoscopic resection of duodenal adenomas is commonly performed to prevent cancer and prevent or defer duodenal surgery. However, based on studies using different resection techniques, adverse events (AEs) of polypectomy in the duodenum can be significant. We hypothesized that cold snare polypectomy (CSP) is a safe technique for duodenal adenomas in FAP and evaluated its outcomes in our centers.Patients and methods We performed a prospective international cohort study including FAP patients who underwent CSP for one or more superficial non-ampullary duodenal adenomas of any size between 2020 and 2022. At that time, this technique was common practice in our centers for superficial duodenal adenomas. The primary outcome was the occurrence of intraprocedural and post-procedural AEs.ResultsIn total, 133 CSPs were performed in 39 patients with FAP (1–18 per session). Median adenoma size was 10 mm (interquartile range 8–15 mm), ranging from 5 to 40 mm; 27 adenomas were ≥20 mm (20%). Of the 133 polypectomies, 109 (82%) were performed after submucosal injection. Sixty-one adenomas (46%) were resected en bloc and 72 (54%) piecemeal. Macroscopic radical resection was achieved for 129 polypectomies (97%). Deep mural injury type II occurred in three polyps (2%) with no delayed perforation after prophylactic clipping. There were no clinically significant bleeds, perforations or other post-procedural AEs. Histopathology showed low-grade dysplasia in all 133 adenomas.Conclusions CSP for (multiple) superficial non-ampullary duodenal adenomas in FAP seems feasible and safe. Long-term prospective research is needed to evaluate whether protocolized duodenal polypectomies prevent cancer and surgery. Show less
Jodal, H.C.; Akwiwu, E.U.; Lemmens, M.; Diemen, P.M.D.V.; Klotz, D.; Leon, L.G.; ... ; Carvalho, B. 2023
Current morphologic features defining advanced adenomas (size >= 10 mm, high-grade dysplasia or >= 25% villous component) cannot optimally distinguish individuals at high risk or low risk of... Show moreCurrent morphologic features defining advanced adenomas (size >= 10 mm, high-grade dysplasia or >= 25% villous component) cannot optimally distinguish individuals at high risk or low risk of metachronous colorectal cancer (me-CRC), which may result in suboptimal surveillance. Certain DNA copy-number alterations (CNAs) are associated with adenoma-to-carcinoma progression. We aimed to evaluate whether these molecular features can better predict an individual's risk of me-CRC than the morphologic advanced adenoma features.In this nested case-control study, 529 individuals with a single adenoma at first colonoscopy were selected from a Norwegian adenoma cohort. DNA copy-number profiles were determined, by low-coverage whole-genome sequencing. Prevalence of CNAs in advanced and non-advanced adenomas and its association (OR) with me-CRC was assessed. For the latter, cases (with me-CRC) were matched to controls (without me-CRC) on follow-up, age and sex.CNAs associated with adenoma-to-carcinoma progression were observed in 85/267 (32%) of advanced adenomas and in 27/262 (10%) of non-advanced adenomas. me-CRC was statistically significantly associated, also after adjustment for other variables, with age at baseline [OR, 1.14; 95% confidence interval CI), 1.03-1.26; P = 0.012], advanced adenomas (OR, 2.46; 95% CI, 1.50-4.01; P < 0.001) and with the presence of >= 3 DNA copy-number losses (OR, 1.90; 95% CI. 1.02-3.54; P = 0.043).Molecularly-defined high-risk adenomas were associated with me-CRC, but the association of advanced adenoma with me-CRC was stronger. Show less
Background and AimsPrior studies on the effect of smoking on the risk of colitis-associated colorectal neoplasia (CRN) have reported conflicting results. We aimed to further elucidate the... Show moreBackground and AimsPrior studies on the effect of smoking on the risk of colitis-associated colorectal neoplasia (CRN) have reported conflicting results. We aimed to further elucidate the association between smoking, including possible dose-effects, and the development of colorectal neoplasia in patients with inflammatory bowel disease (IBD).MethodsWe performed a prospective multicenter cohort study including patients with colonic IBD enrolled in a surveillance program in four academic hospitals between 2011 and 2021. The effects of smoking status and pack-years at study entry on subsequent recurrent events of CRN (including indefinite, low- and high-grade dysplasia, and colorectal cancer [CRC]) were evaluated using uni- and multivariable Prentice, Williams, and Peterson total-time Cox proportional hazard models. Adjustment was performed for extensive disease, prior/index dysplasia, sex, age, first-degree relative with CRC, primary sclerosing cholangitis, and endoscopic inflammation.ResultsIn 501 of the enrolled 576 patients, at least one follow-up surveillance was performed after the study index (median follow-up 5 years). CRN occurred at least once in 105 patients. Ever smoking was not associated with recurrent CRN risk (adjusted hazard ratio [aHR] 1.04, 95% confidence interval [CI] 0.75–1.44), but an increasing number of pack-years was associated with an increased risk of recurrent CRN (aHR per 10 pack-years 1.17, 95% CI 1.03–1.32; p < 0.05). Separate analyses per IBD type did not reveal differences.ConclusionsThis study found that an increase in pack-years is associated with a higher risk of recurrent CRN in patients with IBD, independent of established CRN risk factors (NCT01464151). Show less
Schootbrugge-Vandermeer, H.J. van de; Lansdorp-Vogelaar, I.; Jonge, L. de; Vuuren, A.J. van; Dekker, E.; Spaander, M.C.W.; ... ; Toes-Zoutendijk, E. 2023
BackgroundHigh participation rates are essential for a screening programme to be beneficial. To reach non-participants in a targeted manner, insight in characteristics of non-participants is needed... Show moreBackgroundHigh participation rates are essential for a screening programme to be beneficial. To reach non-participants in a targeted manner, insight in characteristics of non-participants is needed. We investigated demographic differences between participants and non-participants in the Dutch faecal immunochemical test-based colorectal cancer (CRC) screening programme.MethodsIn this population-based cohort study, we included all invitees for CRC screening in 2018 and 2019. Participation status, birth year, and sex were extracted from the Dutch national screening information system and linked to demographic characteristics from Statistics Netherlands, including migration background, level of education, socioeconomic category, household composition, and household income. A multivariable logistic regression was used to assess the association between demographic factors and participation.ResultsA total of 4,383,861 individuals were invited for CRC screening in 2018 and 2019, of which 3,170,349 (72.3%) participated. Individuals were less likely to participate when they were single and/or living with others (single with other residents versus couple: odds ratio [OR] 0.34, 95% confidence interval [CI]: 0.31–0.38), had a migration background (e.g. Moroccan migrant versus Dutch background: OR 0.43, 95% CI: 0.42–0.44), or had a low income (lowest versus highest quintile: OR 0.45, 95% CI: 0.44–0.45). Although to a lesser extent, non-participation was also significantly associated with being male, being younger, receiving social welfare benefits and having a low level of education.ConclusionWe found that individuals who were single and/or living with others, immigrants from Morocco or individuals with low income were the least likely to participate in the Dutch CRC screening programme. Targeted interventions are needed to minimise inequities in CRC screening. Show less
Toes-Zoutendijk, E.; Jonge, L. de; Iersel, C.A. van; Spaander, M.C.W.; Vuuren, A.J. van; Kemenade, F. van; ... ; Lansdorp-Vogelaar, I. 2023
Objective: To assess the impact of delayed invitation on screen-detected and interval colorectal cancers (CRC) within a faecal immunochemical testing (FIT)-based CRC screening programme. Design:... Show moreObjective: To assess the impact of delayed invitation on screen-detected and interval colorectal cancers (CRC) within a faecal immunochemical testing (FIT)-based CRC screening programme. Design: All individuals that participated in 2017 and 2018 with a negative FIT and were eligible for CRC screening in 2019 and 2020 were included using individual-level data. Multivariable logistic regression analyses were used to assess the association between either the different time periods (ie, 'before', 'during' and 'after' the first COVID-19 wave) or the invitation interval on screen-detected and interval CRCs. Results: Positive predictive value for advanced neoplasia (AN) was slightly lower during (OR=0.83) and after (OR=0.92) the first COVID-19 wave, but no significant difference was observed for the different invitation intervals. Out of all individuals that previously tested negative, 84 (0.004%) had an interval CRC beyond the 24 months since their last invitation. The time period of invitation as well as the extended invitation interval was not associated with detection rates for AN and interval CRC rate. Conclusion: The impact of the first COVID-19 wave on screening yield was modest. A very small proportion of the FIT negatives had an interval CRC possibly due to an extended interval, which potentially could have been prevented if they had received the invitation earlier. Nonetheless, no increase in interval CRC rate was observed, indicating that an extended invitation interval up to 30 months had no negative impact on the performance of the CRC screening programme and a modest extension of the invitation interval seems an appropriate intervention. Show less
Aelvoet, A.S.; Pellise, M.; Bastiaansen, B.A.J.; Leerdam, M.E. van; Jover, R.; Balaguer, F.; ... ; European FAP Consortium 2023
Background and study aims: Patients with familial adenomatous polyposis (FAP) undergo colectomy and lifelong endoscopic surveillance to prevent colorectal, duodenal and gastric cancer. Endoscopy... Show moreBackground and study aims: Patients with familial adenomatous polyposis (FAP) undergo colectomy and lifelong endoscopic surveillance to prevent colorectal, duodenal and gastric cancer. Endoscopy has advanced significantly in recent years, including both detection technology as well as treatment options. For the lower gastrointestinal tract, current guidelines do not provide clear recommendations for surveillance intervals. Furthermore, the Spigelman staging system for duodenal polyposis has its limitations. We present a newly developed personalized endoscopic surveillance strategy for the lower and upper gastrointestinal tract, aiming to improve the care for patients with FAP. We aim to inform centers caring for FAP patients and encourage the discussion on optimizing endoscopic surveillance and treatment in this high-risk population. Methods: The European FAP Consortium, consisting of endoscopists with expertise in FAP, collaboratively developed new surveillance protocols. The proposed strategy was consensus-based and a result of several consortium meetings, discussing current evidence and limitations of existing systems. This strategy provides clear indications for endoscopic polypectomy in the rectum, pouch, duodenum and stomach and defines new criteria for surveillance intervals. This strategy will be evaluated in a 5-year prospective study in nine FAP expert centers in Europe. Results: We present a newly developed personalized endoscopic surveillance and endoscopic treatment strategy for patients with FAP aiming to prevent cancer, optimize endoscopic resources and limit the number of surgical interventions. Following this new strategy, prospectively collected data in a large cohort of patients will inform us on the efficacy and safety of the proposed approaches. Show less
Breekveldt, E.C.H.; Toes-Zoutendijk, E.; Jonge, L. de; Spaander, M.C.W.; Dekker, E.; Kemenade, F.J. van; ... ; Lansdorp-Vogelaar, I. 2023
Background In 2014, the national population-based colorectal cancer (CRC) screening program was implemented in the Netherlands. Biennial fecal immunochemical testing (FIT) for hemoglobin (Hb) is... Show moreBackground In 2014, the national population-based colorectal cancer (CRC) screening program was implemented in the Netherlands. Biennial fecal immunochemical testing (FIT) for hemoglobin (Hb) is used at a cut-off of 47 mu g Hb per gram feces. The CRC screening program successfully started, with high participation rates and yield of screening. Now that the program has reached a steady state, there is potential to further optimize the program. Previous studies showed that prior fecal Hb (f-Hb) concentrations just below the FIT cut-off are associated with a higher risk for detection of advanced neoplasia (AN) at subsequent screening rounds. We aim to achieve a better balance between the harms and benefits of CRC screening by offering participants tailored invitation intervals based on prior f-Hb concentrations after negative FIT. Methods This mixed-methods study will be performed within the Dutch national CRC screening program and will consist of: (1) a randomized controlled trial (RCT), (2) focus group studies, and (3) decision modelling. The primary outcome is the yield of AN per screened individual in personalized screening vs. uniform screening. Secondary outcomes are perspectives on, acceptability of and adherence to personalized screening, as well as long-term outcomes of personalized vs. uniform screening. The RCT will include 20,000 participants of the Dutch CRC screening program; 10,000 in the intervention and 10,000 in the control arm. The intervention arm will receive a personalized screening interval based on the prior f-Hb concentration (1, 2 or 3 years). The control arm will receive a screening interval according to current practice (2 years). The focus group studies are designed to understand individuals' perspectives on and acceptability of personalized CRC screening. Results of the RCT will be incorporated into the MISCAN-Colon model to determine long-term benefits, harms, and costs of personalized vs. uniform CRC screening. Discussion The aim of this study is to evaluate the yield, feasibility, acceptability and (cost-) effectiveness of personalized CRC screening through tailored invitation intervals based on prior f-Hb concentrations. This knowledge may be of guidance for health policy makers and may provide evidence for implementing personalized CRC screening in The Netherlands and/or other countries using FIT as screening modality. Show less
Background: Advanced serrated polyps (ASPs) have a comparable risk to advanced adenomas for progression to colorectal cancer (CRC). The yield of most CRC screening programs, however, is based on... Show moreBackground: Advanced serrated polyps (ASPs) have a comparable risk to advanced adenomas for progression to colorectal cancer (CRC). The yield of most CRC screening programs, however, is based on advanced adenomas and CRC only. We assessed the ASP detection rate, and positive predictive value (PPV) including ASPs in a fecal immunochemical test (FIT)-based screening program. Methods: We analyzed the findings of follow-up colonosco pies of FIT-positive screenees in the Dutch CRC screening program from 2014 until 2020. Data were retrieved from the national screening and pathology database. An ASP was defined as any serrated polyp of z 10 mm, sessile serrated lesion with dysplasia, or traditional serrated adenoma. The ASP detection rate was defined as the proportion of colonoscopies with >= 1 ASP. PPV was originally defined as the proportion of individuals with a CRC or advanced adenoma. The updated PPV definition included CRCs, advanced adenomas, and/or ASPs. Results: 322 882 colonoscopies were included in the analyses. The overall detection rate of ASPs was 5.9%. ASPs were detected more often in women than men (6.3% vs. 5.6%; P < 0.001). ASP detection rates in individuals aged 55-59, 60-64, 65-69, and 70+ were 5.2%, 6.1 %, 6.1 %, and 5.9%, respectively (P < 0.001). The PPV for CRCs and advanced adenomas was 41.1 % and increased to 43.8% when including ASPs. The PPV increase was larger in women than in men (3.2 vs. 2.4 percentage points). Conclusions: 5.9% of FIT-positive screenees had ASPs, but half of these were detected in combination with a CRC or advanced adenoma. Therefore, including ASPs results in a small increase in the yield of FIT-based screening. Show less
Background and aims: From 2014, the Dutch colorectal cancer (CRC) faecal immunochemical testing-based screening programme was gradually rolled out by birth cohort. We evaluated changes in advanced... Show moreBackground and aims: From 2014, the Dutch colorectal cancer (CRC) faecal immunochemical testing-based screening programme was gradually rolled out by birth cohort. We evaluated changes in advanced-stage CRC incidence by timing of invitation to further strengthen the evidence for the effectiveness of CRC screening. Methods: Data on advanced-stage CRC incidence in the period 2010-2019 by invitation cohort were collected through the Netherlands Cancer Registry. Crude rates of advanced -stage CRC incidence and cumulative advanced-stage CRC incidence were calculated. Observed advanced-stage CRC incidence and cumulative advanced-stage CRC incidence were compared with expected advanced-stage CRC incidence and cumulative advanced-stage CRC incidence by invitation cohort using trend lines extrapolating data prior to the introduction of screening. Results: For the invitation cohort that was first invited for screening in 2014, advanced-stage CRC incidence increased before the introduction of screening from 94.1 to 124.7 per 100,000 individuals in the period 2010-2013. In 2014, the observed increase was higher than in preceding years, to 184.9 per 100,000 individuals. Hereafter, a decrease in incidence was observed to levels below expected incidence based on trends before the introduction of screening. A similar pattern was observed for invitation cohorts in subsequent years, coinciding with the first invitation to the screening pro-gramme. In 2019, the observed incidence for all invitation cohorts remained below expected inci-dence. The cumulative advanced-stage CRC incidence in the 2014-2016 invitation cohorts was significantly lower than the expected cumulative CRC incidence in the period 2010-2019. Conclusions: In the period 2014-2019, an increase in advanced-stage CRC incidence was observed for all invitation cohorts first invited for screening, followed by a decrease below expected incidence, following the pattern of the phased implementation. The cumulative advanced-stage CRC inci-dence in invitation cohorts invited for screening multiple times was lower than expected based on trends from the pre-screening era. These findings support a causal relationship between the intro-duction of the Dutch screening programme and a decrease in advanced-stage CRC incidence.(c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
Zwager, L.W.; Moons, L.M.G.; Sarasqueta, A.F.; Lacle, M.M.; Albers, S.C.; Hompes, R.; ... ; Dutch eFTR Working Group 2022
Background: T1 colorectal cancer (CRC) without histological high-risk factors for lymph node metastasis (LNM) can potentially be cured by endoscopic resection, which is associated with... Show moreBackground: T1 colorectal cancer (CRC) without histological high-risk factors for lymph node metastasis (LNM) can potentially be cured by endoscopic resection, which is associated with significantly lower morbidity, mortality and costs compared to radical surgery. An important prerequisite for endoscopic resection as definite treatment is the histological confirmation of tumour-free resection margins. Incomplete resection with involved (R1) or indeterminate (Rx) margins is considered a strong risk factor for residual disease and local recurrence. Therefore, international guidelines recommend additional surgery in case of R1/Rx resection, even in absence of high-risk factors for LNM. Endoscopic full-thickness resection (eFTR) is a relatively new technique that allows transmural resection of colorectal lesions. Local scar excision after prior R1/Rx resection of low-risk T1 CRC could offer an attractive minimal invasive strategy to achieve confirmation about radicality of the previous resection or a second attempt for radical resection of residual luminal cancer. However, oncologic safety has not been established and long-term data are lacking. Besides, surveillance varies widely and requires standardization. Methods/design: In this nationwide, multicenter, prospective cohort study we aim to assess feasibility and oncological safety of completion eFTR following incomplete resection of low-risk T1 CRC. The primary endpoint is to assess the 2 and 5 year luminal local tumor recurrence rate. Secondary study endpoints are to assess feasibility, percentage of curative eFTR-resections, presence of scar tissue and/or complete scar excision at histopathology, safety of eFTR compared to surgery, 2 and 5 year nodal and/or distant tumor recurrence rate and 5-year disease-specific and overall-survival rate. Discussion: Since the implementation of CRC screening programs, the diagnostic rate of T1 CRC is steadily increasing. A significant proportion is not recognized as cancer before endoscopic resection and is therefore resected through conventional techniques primarily reserved for benign polyps. As such, precise histological assessment is often hampered due to cauterization and fragmentation and frequently leads to treatment dilemmas. This first prospective trial will potentially demonstrate the effectiveness and oncological safety of completion eFTR for patients who have undergone a previous incomplete T1 CRC resection. Hereby, substantial surgical overtreatment may be avoided, leading to treatment optimization and organ preservation. Show less
BackgroundT1 colorectal cancer (CRC) without histological high-risk factors for lymph node metastasis (LNM) can potentially be cured by endoscopic resection, which is associated with significantly... Show moreBackgroundT1 colorectal cancer (CRC) without histological high-risk factors for lymph node metastasis (LNM) can potentially be cured by endoscopic resection, which is associated with significantly lower morbidity, mortality and costs compared to radical surgery. An important prerequisite for endoscopic resection as definite treatment is the histological confirmation of tumour-free resection margins. Incomplete resection with involved (R1) or indeterminate (Rx) margins is considered a strong risk factor for residual disease and local recurrence. Therefore, international guidelines recommend additional surgery in case of R1/Rx resection, even in absence of high-risk factors for LNM. Endoscopic full-thickness resection (eFTR) is a relatively new technique that allows transmural resection of colorectal lesions. Local scar excision after prior R1/Rx resection of low-risk T1 CRC could offer an attractive minimal invasive strategy to achieve confirmation about radicality of the previous resection or a second attempt for radical resection of residual luminal cancer. However, oncologic safety has not been established and long-term data are lacking. Besides, surveillance varies widely and requires standardization.Methods/designIn this nationwide, multicenter, prospective cohort study we aim to assess feasibility and oncological safety of completion eFTR following incomplete resection of low-risk T1 CRC. The primary endpoint is to assess the 2 and 5 year luminal local tumor recurrence rate. Secondary study endpoints are to assess feasibility, percentage of curative eFTR-resections, presence of scar tissue and/or complete scar excision at histopathology, safety of eFTR compared to surgery, 2 and 5 year nodal and/or distant tumor recurrence rate and 5-year disease-specific and overall-survival rate.DiscussionSince the implementation of CRC screening programs, the diagnostic rate of T1 CRC is steadily increasing. A significant proportion is not recognized as cancer before endoscopic resection and is therefore resected through conventional techniques primarily reserved for benign polyps. As such, precise histological assessment is often hampered due to cauterization and fragmentation and frequently leads to treatment dilemmas. This first prospective trial will potentially demonstrate the effectiveness and oncological safety of completion eFTR for patients who have undergone a previous incomplete T1 CRC resection. Hereby, substantial surgical overtreatment may be avoided, leading to treatment optimization and organ preservation. Show less
Breekveldt, E.C.H.; Toes-Zoutendijk, E.; Schootbrugge-vandermeer, H.J. van de; Jonge, L. de; Kooyker, A.I.; Spaander, M.C.W.; ... ; Lansdorp-Vogelaar, I. 2022
The interval colorectal cancer (CRC) rate after negative fecal immunochemical testing (FIT) is an important quality indicator of CRC screening programs. We analyzed the outcomes of two rounds of... Show moreThe interval colorectal cancer (CRC) rate after negative fecal immunochemical testing (FIT) is an important quality indicator of CRC screening programs. We analyzed the outcomes of two rounds of the FIT-based CRC screening program in the Netherlands, using data from individuals who participated in FIT-screening from 2014 to 2017. Data of individuals with one prior negative FIT (first round) or two prior negative FITs (first and second round) were included. Outcomes included the incidence of interval CRC in FIT-negative participants (< 47 mu g Hb/g feces [mu g/g]), FIT-sensitivity, and the probability of detecting an interval CRC by fecal hemoglobin concentration (f-Hb). FIT-sensitivity was estimated using the detection method and the proportional incidence method (based on expected CRC incidence). Logistic regression analysis was performed to estimate whether f-Hb affects probability of detecting interval CRC, adjusted for sex- and age-differences. Incidence of interval CRC was 10.4 per 10 000 participants after the first and 9.6 after the second screening round. FIT-sensitivity based on the detection method was 84.4% (95%CI 83.8-85.0) in the first and 73.5% (95% CI 71.8-75.2) in the second screening round. The proportional incidence method resulted in a FIT-sensitivity of 76.4% (95%CI 73.3-79.6) in the first and 79.1% (95%CI 73.7-85.3) in the second screening round. After one negative FIT, participants with f-Hb just below the cut-off (> 40-46.9 mu g/g) had a higher probability of detecting an interval CRC (OR 16.9; 95%CI: 14.0-20.4) than had participants with unmeasurable f-Hb (0-2.6 mu g/g). After two screening rounds, the odds ratio for interval CRC was 12.0 (95%CI: 7.8-17.6) for participants with f-Hb just below the cut-off compared with participants with unmeasurable f-Hb. After both screening rounds, the Dutch CRC screening program had a low incidence of interval CRC and an associated high FIT-sensitivity. Our findings suggest there is a potential for further optimizing CRC screening programs with the use of risk-stratified CRC screening based on prior f-Hb. Show less
Breekveldt, E.C.H.; Toes-Zoutendijk, E.; Schootbrugge-vandermeer, H.J. van de; Jonge, L. de; Kooyker, A.I.; Spaander, M.C.W.; ... ; Lansdorp-Vogelaar, I. 2022
The interval colorectal cancer (CRC) rate after negative fecal immunochemical testing (FIT) is an important quality indicator of CRC screening programs. We analyzed the outcomes of two rounds of... Show moreThe interval colorectal cancer (CRC) rate after negative fecal immunochemical testing (FIT) is an important quality indicator of CRC screening programs. We analyzed the outcomes of two rounds of the FIT-based CRC screening program in the Netherlands, using data from individuals who participated in FIT-screening from 2014 to 2017. Data of individuals with one prior negative FIT (first round) or two prior negative FITs (first and second round) were included. Outcomes included the incidence of interval CRC in FIT-negative participants (<47 μg Hb/g feces [μg/g]), FIT-sensitivity, and the probability of detecting an interval CRC by fecal hemoglobin concentration (f-Hb). FIT-sensitivity was estimated using the detection method and the proportional incidence method (based on expected CRC incidence). Logistic regression analysis was performed to estimate whether f-Hb affects probability of detecting interval CRC, adjusted for sex- and age-differences. Incidence of interval CRC was 10.4 per 10 000 participants after the first and 9.6 after the second screening round. FIT-sensitivity based on the detection method was 84.4% (95%CI 83.8-85.0) in the first and 73.5% (95% CI 71.8-75.2) in the second screening round. The proportional incidence method resulted in a FIT-sensitivity of 76.4% (95%CI 73.3-79.6) in the first and 79.1% (95%CI 73.7-85.3) in the second screening round. After one negative FIT, participants with f-Hb just below the cut-off (>40-46.9 μg/g) had a higher probability of detecting an interval CRC (OR 16.9; 95%CI: 14.0-20.4) than had participants with unmeasurable f-Hb (0-2.6 μg/g). After two screening rounds, the odds ratio for interval CRC was 12.0 (95%CI: 7.8-17.6) for participants with f-Hb just below the cut-off compared with participants with unmeasurable f-Hb. After both screening rounds, the Dutch CRC screening program had a low incidence of interval CRC and an associated high FIT-sensitivity. Our findings suggest there is a potential for further optimizing CRC screening programs with the use of risk-stratified CRC screening based on prior f-Hb. Show less
Introduction Many methodological papers report a comparison of methods for LCA, for instance comparing different impact assessment systems, or developing streamlined methods. A popular way to do so... Show moreIntroduction Many methodological papers report a comparison of methods for LCA, for instance comparing different impact assessment systems, or developing streamlined methods. A popular way to do so is by studying the differences of results for a number of products. We refer to such studies as quasi-empirical meta-comparisons. Review of existing approaches A scan of the literature reveals that many different methods and indicators are employed: contribution analyses, Pearson correlations, Spearman correlations, regression, significance tests, neural networks, etc. Critical discussion We critically examine the current practice and conclude that some of the widely used methods are associated with important deficits. A new approach Inspired by the critical analysis, we develop a new approach for meta-comparative LCA, based on directional statistics. We apply it to several real-world test cases, and analyze its performance vis-a-vis traditional regression-based approaches. Conclusion The method on the basis of directional statistics withstands the tests of changing the scale and unit of the training data. As such, it holds a promise for improved method comparisons. Show less
Toledo, D.E.F.W.M. van; IJspeert, J.E.G.; Bossuyt, P.M.M.; Bleijenberg, A.G.C.; Leerdam, M.E. van; Vlugt, M. van der; ... ; Dekker, E. 2022
Background Adenoma detection rate (ADR) is a well-established quality indicator for colonoscopy and is inversely associated with the incidence of interval post-colonoscopy colorectal cancer.... Show moreBackground Adenoma detection rate (ADR) is a well-established quality indicator for colonoscopy and is inversely associated with the incidence of interval post-colonoscopy colorectal cancer. However, interval post-colonoscopy colorectal cancers frequently develop from serrated polyps, which are not included in the ADR. Therefore, the proximal serrated polyp detection rate (PSPDR) has been proposed as a quality indicator, but its association with interval post-colonoscopy colorectal cancer has not been studied. We aimed to evaluate this potential association based on data collected in the Dutch colorectal cancer screening programme. Methods In this population-based study, using colonoscopy data from the Dutch faecal immunochemical test-based colorectal cancer screening programme and cancer data from the Netherlands Cancer Registry, we evaluated the association between endoscopists' individual PSPDR and their patients' risk of interval post-colonoscopy colorectal cancer with a shared frailty Cox proportional-hazard regression analysis. Participants in the screening programme who were eligible for inclusion were aged 55-76 years, had a positive faecal immunochemical test (cutoff 15 mu g Hb/g faeces at start and changed mid-2014 to 47 mu g Hb/g faeces), were asymptomatic, and underwent a colonoscopy between Jan 1, 2014, and Dec 31, 2020. The PSPDR was defined as the proportion of colonoscopies in which at least one serrated polyp proximal to the descending colon was detected, confirmed by histopathology. The ADR was defined as the proportion of all colonoscopies in which at least one conventional adenoma was detected, confirmed by histopathology. Detection rates were determined for each endoscopist individually. We additionally evaluated the risk of interval post-colonoscopy colorectal cancer for endoscopists with a PSPDR and ADR above the median versus endoscopists with either one or both parameters below the median. This study is registered with the Netherlands Trial Registry, NL8350. Findings During the study period, 329 104 colonoscopies were done, of which 277 555, done by 441 endoscopists, were included in the PSPDR calculations. The median PSPDR was 11.9% (IQR 8.3-15.8) and median ADR was 66.3% (61.4-69.9). The correlation between the PSDPR and ADR was moderate (r=0.59; p < 0middot0001). During a median follow-up of 33 months (IQR 21-42), 305 interval post-colonoscopy colorectal cancers were detected. For each percentage point increase in PSPDR, the adjusted interval post-colonoscopy colorectal cancer hazard was 7% lower (hazard ratio [HR] 0.93, 95% CI 0.90-0.95; p < 0middot0001). Compared with endoscopists with a PSPDR greater than 11middot9% and ADR greater than 66middot3%, the HR of interval post-colonoscopy colorectal cancer for endoscopists with a low PSPDR and high ADR was 1.79 (95% CI 1.22-2.63), for endoscopists with a high PSPDR and low ADR was 1.97 (1.19-3.24), and for endoscopists with a low PSPDR and low ADR was 2.55 (1.89-3.45). Gastroenterology, (Prof Gastroenterology the (Prof Interpretation The PSPDR of an endoscopist is inversely associated with the incidence of interval post-colonoscopy colorectal cancer. Implementation of PSPDR monitoring, in addition to ADR monitoring, could optimise colorectal cancer prevention. Copyright (C) 2022 Elsevier Ltd. All rights reserved. Show less
Jonge, L. de; Schootbrugge-Vandermeer, H.J. van de; Breekveldt, E.C.H.; Spaander, M.C.W.; Vuuren, H.J. van; Kemenade, F.J. van; ... ; Lansdorp-Vogelaar, I. 2022
Objective: The COVID-19 pandemic forced colorectal cancer (CRC) screening programs to downscale their colonoscopy capacity. In this study, we assessed strategies to deal with temporary restricted... Show moreObjective: The COVID-19 pandemic forced colorectal cancer (CRC) screening programs to downscale their colonoscopy capacity. In this study, we assessed strategies to deal with temporary restricted colonoscopy capacity in a FIT-based CRC screening program while aiming to retain the maximum possible preventive effect of the screening program. Design: We simulated the Dutch national CRC screening program inviting individuals between ages 55 and 75 for biennial FIT using the MISCAN-Colon model including the 3-month disruption in the first half of 2020 due to the COVID-19 pandemic. For the second half of 2020 and 2021, we simulated three different strategies for the total target population: 1) increasing the FIT cut-off, 2) skipping one screening for specific screening ages, and 3) extending the screening interval. We estimated the impact on required colonoscopy capacity in 2020-2021 and life years (LYs) lost in the long-term. Results: Increasing the FIT cut-off, skipping screening ages and extending the screening interval resulted in a maximum reduction of 25,100 (-17.0%), 16,100(-10.9%) and 19,000 (-12.9%) colonoscopies, respectively. Modelling an increased FIT cut-off, the number of LYs lost ranged between 1,400 and 4,400. Skipping just a single screening age resulted in approximately 2,700 LYs lost and this was doubled in case of skipping two screening ages. Extending the screening interval up to 34 months had the smallest impact on LYs lost (up to 1,100 LYs lost). Conclusion: This modelling study shows that to anticipate on restricted colonoscopy capacity, temporarily extending the screening interval retains the maximum possible preventive effect of the CRC screening program. Show less
