RESUMEN
Up to 30% of colorectal cancers (CRCs) develop from sessile serrated lesions (SSLs). Within the serrated neoplasia pathway, at least two principally distinct oncogenetic routes exist generating microsatellite-stable and microsatellite-instable CRCs, respectively. Aberrant DNA methylation (DNAm) is found early in the serrated pathway and might play a role in both oncogenetic routes. We studied a cohort of 23 SSLs with a small focus (<10 mm) of dysplasia or cancer, 10 of which were MLH1 deficient and 13 MLH1 proficient. By comparing, for each SSL, the methylation status of (1) the region of dysplasia or cancer (SSL-D), (2) the nondysplastic SSL (SSL), and (3) adjacent normal mucosa, differentially methylated probes (DMPs) and regions (DMRs) were assessed both genome-wide as well as in a tumor-suppressor gene-focused approach. By comparing DNAm of MLH1-deficient SSL-Ds with their corresponding SSLs, we identified five DMRs, including those annotating for PRDM2 and, not unexpectedly, MLH1. PRDM2 gene promotor methylation was associated with MLH1 expression status, as it was largely hypermethylated in MLH1-deficient SSL-Ds and hypomethylated in MLH1-proficient SSL-Ds. Significantly increased DNAm levels of PRDM2 and MLH1, in particular at 'critical' MLH1 probe sites, were to some extent already visible in SSLs as compared to normal mucosa (p = 0.02, p = 0.01, p < 0.0001, respectively). No DMRs, nor DMPs, were identified for SSLs destined to evolve into MLH1-proficient SSL-Ds. Our data indicate that, within both arms of the serrated CRC pathway, the majority of the epigenetic alterations are introduced early during SSL formation. Promoter hypermethylation of PRDM2 and MLH1 on the other hand specifically initiates in SSLs destined to transform into MLH1-deficient CRCs suggesting that the fate of SSLs may not necessarily result from a stochastic process but possibly is already imprinted and predisposed.
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Adenoma , Neoplasias Colorrectales , Humanos , Adenoma/patología , Neoplasias Colorrectales/patología , Metilación de ADN/genética , Regiones Promotoras Genéticas/genética , Transformación Celular Neoplásica/genética , Repeticiones de Microsatélite , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , N-Metiltransferasa de Histona-Lisina/genética , N-Metiltransferasa de Histona-Lisina/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
BACKGROUND: Recent studies demonstrated that a higher proximal serrated polyp detection rate (PSPDR) among endoscopists is associated with a lower risk of post-colonoscopy colorectal cancer (PCCRC) incidence and death for their patients. Our objective was to evaluate the effect of an e-learning resource on PSPDR. METHODS: We performed a multicenter randomized controlled trial within the Dutch fecal immunochemical test-based colorectal cancer screening program. Endoscopists were randomized using block randomization per center to either receive a 60-minute e-learning resource on serrated polyp detection or not. PSPDR was calculated based on all colonoscopies performed during a 27-month pre-intervention and a 17-month post-intervention period. The primary end point was difference in PSPDR between intervention and control arms (intention to treat) using mixed effect logistic regression modeling, with time (pre-intervention/post-intervention) and interaction between time and arm (intervention/control) as fixed effects, and endoscopists as random effects. RESULTS: 116 endoscopists (57 intervention, 59 controls) were included, and performed 27494 and 33888 colonoscopies, respectively. Median PSPDR pre-intervention was 13.6% (95%CI 13.0-14.1) in the intervention arm and 13.8% (95%CI 13.3-14.3) in controls. Post-intervention PSPDR was significantly higher over time in the intervention arm than in controls (17.1% vs. 15.4%, P=0.01). CONCLUSION: In an era of increased awareness and increasing PSPDRs, endoscopists who undertook a one-time e-learning course significantly accelerated the increase in PSPDR compared with endoscopists who did not undertake the e-learning. Widespread implementation might reduce PCCRC incidence.
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Pólipos del Colon , Colonoscopía , Humanos , Colonoscopía/educación , Colonoscopía/métodos , Pólipos del Colon/diagnóstico , Femenino , Masculino , Persona de Mediana Edad , Anciano , Instrucción por Computador/métodos , Neoplasias Colorrectales/diagnóstico , Competencia Clínica , Detección Precoz del Cáncer/métodos , Países BajosRESUMEN
INTRODUCTION: Patients with serrated polyposis syndrome (SPS) have an increased risk to develop colorectal cancer (CRC). Due to an abundance of serrated polyps, these CRCs are assumed to arise mainly through the serrated neoplasia pathway rather than through the classical adenoma-carcinoma pathway. We aimed to evaluate the pathogenetic routes of CRCs in patients with SPS. METHODS: We collected endoscopy and pathology data on CRCs and polyps of patients with SPS under treatment in our center. Our primary end point was the proportion of BRAFV600E mutated CRCs, indicating serrated pathway CRCs (sCRCs). CRCs lacking BRAFV600E most likely inferred a classical adenoma-carcinoma origin (aCRCs). We assessed patient, polyp, and CRC characteristics and stratified for BRAFV600E mutation status. RESULTS: Thirty-five patients with SPS harbored a total of 43 CRCs. Twenty-one CRCs (48.8%) carried a BRAFV600E mutation, 10 of which lacked MLH1 staining and 17 (81%) were located in the proximal colon. Twenty-two CRCs (51.1%) did not carry a BRAFV600E mutation and were MLH1 proficient. Of these 22 putatively aCRCs, 17 (77.3%) were located distally and one-third (36.4%) harbored a pathogenic KRAS or NRAS mutation. In patients with BRAFwt -CRCs, a higher ratio of the median number of conventional adenomas versus serrated polyps was found (4 vs 13) than patients with BRAFV600E -CRCs (1 vs 14). DISCUSSION: Our study indicates that in patients with SPS, the ratio of sCRCs:aCRCs on average is 50:50. This elevated sCRC:aCRC ratio in patients with SPS, when compared with non-SPS patients, correlates well with the differences in the ratios of the numbers of sessile serrated lesions and conventional adenomas in patients with SPS and non-SPS patients, respectively.
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Adenoma , Poliposis Adenomatosa del Colon , Carcinoma , Pólipos del Colon , Neoplasias Colorrectales , Humanos , Pólipos del Colon/patología , Neoplasias Colorrectales/patología , Adenoma/genética , Adenoma/patología , Carcinoma/genéticaRESUMEN
BACKGROUND: Serrated polyposis syndrome (SPS) is the most prevalent colonic polyposis syndrome and is associated with an increased colorectal cancer risk. A recent study in resected appendices of SPS patients reported that 6/23 (26.1â%) of identified serrated polyps had histological dysplasia. We evaluated the prevalence and clinical relevance of appendiceal lesions in a large SPS cohort. METHODS: Prospective data from 2007 to 2020 for a cohort of 199 SPS patients were analyzed. Data were retrieved from endoscopy and pathology reports. Patients who underwent (pre)clearance colonoscopies, surveillance colonoscopies, or colorectal surgery including the appendix were separately evaluated for the presence of appendiceal lesions. The primary outcome was the prevalence of adenocarcinomas and serrated polyps/adenomas with advanced histology in the surgery group. RESULTS: 171 patients were included, of whom 110 received endoscopic surveillance and 34 underwent surgery. Appendiceal lesion prevalence in the surgery group was 14â/34 (41.2â%, 95â%CI 24.7â%-59.3â%); none were advanced on histology. Detection rates in the (pre)clearance group were 1â/171 (0.6â%, 95â%CI 0.01â%-3.2â%) for advanced and 3â/171 (1.8â%, 95â%CI 0.04â%-5.0â%) for nonadvanced appendiceal lesions, all of which were sessile serrated lesions. During 522 patient-years of surveillance, no advanced appendiceal lesions were detected at endoscopy, and in 1â/110 patients (0.9â%, 95â%CI 0.02â%-5.0â%) was a nonadvanced lesion detected. CONCLUSION: Appendiceal lesions are common in SPS patients. The discrepancy between the endoscopic detection rate of appendiceal lesions and the reported prevalence in surgically resected appendices suggests a substantial miss-rate of appendiceal lesions during colonoscopy. Advanced appendiceal lesions are however rare and no appendiceal adenocarcinomas occurred, implying limited clinical relevance of these lesions.
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Adenoma , Poliposis Adenomatosa del Colon , Apéndice , Pólipos del Colon , Neoplasias Colorrectales , Pólipos , Humanos , Estudios Prospectivos , Apéndice/patología , Poliposis Adenomatosa del Colon/patología , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/patología , Colonoscopía , Pólipos/diagnóstico , Adenoma/epidemiología , Adenoma/cirugía , Adenoma/diagnóstico , Pólipos del Colon/epidemiología , Pólipos del Colon/cirugía , Pólipos del Colon/diagnósticoRESUMEN
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 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 colonoscopies 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 ≥â10âmm, sessile serrated lesion with dysplasia, or traditional serrated adenoma. The ASP detection rate was defined as the proportion of colonoscopies with ≥â1 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 : 322â882 colonoscopies were included in the analyses. The overall detection rate of ASPs was 5.9â%. ASPs were detected more often in women than men (6.3â% vs. 5.6â%; Pâ<â0.001). ASP detection rates in individuals aged 55-59, 60-64, 65-69, and 70â+âwere 5.2â%, 6.1â%, 6.1â%, and 5.9â%, respectively (Pâ<â0.001). The PPV for CRCs and advanced adenomas was 41.1â% and increased to 43.8â% when including ASPs. The PPV increase was larger in women than in men (3.2 vs. 2.4 percentage points). CONCLUSIONS : 5.9â% 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.
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Adenoma , Pólipos del Colon , Neoplasias Colorrectales , Masculino , Humanos , Femenino , Valor Predictivo de las Pruebas , Detección Precoz del Cáncer/métodos , Neoplasias Colorrectales/patología , Colonoscopía , Adenoma/patología , Pólipos del Colon/diagnóstico , Pólipos del Colon/patología , Tamizaje MasivoRESUMEN
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. 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 µg Hb/g faeces at start and changed mid-2014 to 47 µg 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<0·0001). 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<0·0001). Compared with endoscopists with a PSPDR greater than 11·9% and ADR greater than 66·3%, 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). 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. FUNDING: None.
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Adenoma , Pólipos del Colon , Neoplasias Colorrectales , Adenoma/diagnóstico , Adenoma/epidemiología , Adenoma/patología , Pólipos del Colon/diagnóstico , Pólipos del Colon/epidemiología , Pólipos del Colon/patología , Colonoscopía , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/patología , Detección Precoz del Cáncer , HumanosRESUMEN
Around 15-30% of colorectal cancers (CRC) develop from sessile serrated lesions (SSLs). After many years of indolent growth, SSLs can develop dysplasia and rapidly progress to CRC through events that are only partially understood. We studied molecular events at the very early stages of progression of SSLs via the MLH1-proficient and deficient pathways to CRC. We collected a cohort of rare SSLs with a small focus (<10 mm) of dysplasia or cancer from the pathology archives of three hospitals. Whole-exome sequencing was performed on DNA from nonprogressed and progressed components of each SSL. Putative somatic driver mutations were identified in known cancer genes that were differentially mutated in the progressed component. All analyses were stratified by MLH1 proficiency. Forty-five lesions with a focus dysplasia or cancer were included, of which 22 (49%) were MLH1-deficient. Lesions had a median diameter of 10 mm (interquartile range [IQR] 8-15), while the progressed component had a median diameter of 3.5 mm (IQR 1.75-4.75). Tumor mutational burden (TMB) was high in MLH1-deficient lesions (23.9 mutations per MB) as compared to MLH1-proficient lesions (6.3 mutations per MB). We identified 34 recurrently mutated genes in MLH1-deficient lesions. Most prominently, ACVR2A and RNF43 were affected in 18/22 lesions, with mutations clustered in three hotspots. Most lesions with RNF43 mutations had concurrent mutations in ZNRF3. In MLH1-proficient lesions APC (10/23 lesions) and TP53 (6/23 lesions) were recurrently mutated. Our results show that the mutational burden is exceptionally high even in the earliest MLH1-deficient lesions. We demonstrate that hotspot mutations in ACVR2A and in the RNF43/ZNRF3 complex are extremely common in the early progression of SSLs along the MLH1-deficient serrated pathway, while APC and TP53 mutations are early events in the the MLH1-proficient pathway. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
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Neoplasias Colorrectales , Proteínas Proto-Oncogénicas B-raf , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Exoma/genética , Humanos , Hiperplasia , Mutación , Recurrencia Local de Neoplasia/genética , Proteínas Proto-Oncogénicas B-raf/genética , Secuenciación del ExomaRESUMEN
For decades, conventional adenomas were the only known precursor lesions of colorectal cancer (CRC). Accordingly, education and research regarding CRC prevention were mainly focused on adenomas. The groundbreaking discovery that serrated polyps (SPs) also have the potential to develop into CRCs, and seem to account for a considerable proportion of sporadic CRCs, has led to a paradigm shift in the prevention, diagnosis, and treatment of CRC. Studies in recent years have led to our current understanding of SPs and associated CRC, but a lot of work is still to be done to further improve knowledge about this serrated neoplasia pathway and the clinical management of SPs and serrated polyposis syndrome (SPS). In this review, we reflect on the current understanding of SPs with respect to terminology, detection, resection, and surveillance and reflect on the management of SPS.
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Adenoma , Pólipos del Colon , Neoplasias Colorrectales , Adenoma/diagnóstico , Adenoma/patología , Adenoma/terapia , Pólipos del Colon/patología , Pólipos del Colon/cirugía , Colonoscopía/métodos , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/terapia , HumanosRESUMEN
BACKGROUND AND AIMS: Serrated polyposis syndrome (SPS) is the most prevalent colonic polyposis syndrome known and is associated with a high risk of colorectal cancer (CRC) if left untreated. Treatment consists of clearance of the initial polyp burden, followed by lifelong stringent endoscopic surveillance. However, the long-term safety and efficacy of surveillance and the natural disease course after initial clearance have not been described in detail. METHODS: We analyzed a single-center cohort of patients with SPS with over 10 years of prospective follow-up. Outcome measures were (1) CRC incidence, (2) postcolonoscopy adverse event rates, and (3) trends in polyp recurrence during endoscopic surveillance. RESULTS: The cohort included 142 patients who underwent a median of 6 colonoscopies with a median of 47 months of prospective follow-up after initial polyp clearance. During surveillance (every 1-2 years), 1 case of CRC occurred (5-year CRC incidence, 1.0%; 95% confidence interval, 0%-2.9%). During 447 surveillance colonoscopies with 1308 polypectomies, 1 episode of postpolypectomy bleeding, 1 postpolypectomy syndrome, and no perforations occurred (adverse event rate, 0.45% per colonoscopy). During up to 9 rounds of surveillance, no upward or downward trend in polyp recurrence was observed. CONCLUSIONS: In this prospective cohort with over 10 years of follow-up, endoscopic surveillance was effective and safe, with a low risk of CRC and colonoscopy-related adverse events. Furthermore, we show that the disease course of SPS is such that the polyp burden remains more or less equal during long-term surveillance, which advocates lifelong adherence to (personalized) surveillance guidelines and discourages de-intensifying surveillance intervals after multiple rounds of surveillance.
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Poliposis Adenomatosa del Colon , Pólipos del Colon , Neoplasias Colorrectales , Pólipos del Colon/epidemiología , Colonoscopía , Neoplasias Colorrectales/epidemiología , Estudios de Seguimiento , Humanos , Recurrencia Local de Neoplasia , Estudios ProspectivosRESUMEN
OBJECTIVE: Serrated polyps (SPs) are an important cause of postcolonoscopy colorectal cancers (PCCRCs), which is likely the result of suboptimal SP detection during colonoscopy. We assessed the long-term effect of a simple educational intervention focusing on optimising SP detection. DESIGN: An educational intervention, consisting of two 45 min training sessions (held 3 years apart) on serrated polyp detection, was given to endoscopists from 9 Dutch hospitals. Hundred randomly selected and untrained endoscopists from other hospitals were selected as control group. Our primary outcome measure was the proximal SP detection rate (PSPDR) in trained versus untrained endoscopists who participated in our faecal immunochemical test (FIT)-based population screening programme. RESULTS: Seventeen trained and 100 untrained endoscopists were included, who performed 11 305 and 51 039 colonoscopies, respectively. At baseline, PSPDR was equal between the groups (9.3% vs 9.3%). After training, the PSPDR of trained endoscopists gradually increased to 15.6% in 2018. This was significantly higher than the PSPDR of untrained endoscopists, which remained stable around 10% (p=0.018). All below-average (ie, PSPDR ≤6%) endoscopists at baseline improved their PSPDR after training session 1, as did 57% of endoscopists with average PSPDR (6%-12%) at baseline. The second training session further improved the PSPDR in 44% of endoscopists with average PSPDR after the first training. CONCLUSION: A simple educational intervention was associated with substantial long-term improvement of PSPDR in a prospective controlled trial within FIT-based population screening. Widespread implementation of such interventions might be an easy way to improve SP detection, which may ultimately result in fewer PCCRCs. TRIAL REGISTRATION NUMBER: NCT03902899.
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Pólipos del Colon/diagnóstico , Colonoscopía/educación , Capacitación en Servicio , Anciano , Competencia Clínica , Educación Médica , Femenino , Humanos , Masculino , Países Bajos , Estudios ProspectivosRESUMEN
The World Health Organization (WHO) recently updated the diagnostic criteria for serrated polyposis syndrome (SPS). One of the three previous diagnostic criteria (criterion II2010) is now abandoned: ≥ 1 serrated polyp (SP) proximal to the sigmoid in a first-degree relative (FDR) of a patient with SPS. Individuals fulfilling this abandoned criterion now receive the same surveillance recommendations as all FDRs of patients with SPS. We aimed to compare the incidence of advanced neoplasia (AN) in FDRs with vs. without fulfillment of the abandoned criterion II2010. We retrospectively recruited FDRs of patients with SPS who underwent a colonoscopy, and stratified them according to fulfilment of criterion II2010 at baseline. Our primary and secondary outcomes were AN incidence during surveillance and at baseline, respectively. We included 224 FDRs of patients with SPS, of whom 36 (16%) fulfilled criterion II2010 at baseline. One hundred and five underwent surveillance after baseline. Criterion II2010-positive FDRs were at increased risk of AN, both during surveillance (hazard ratio 8.94, 95% CI 2.15-37.1, p = .003) as well as at baseline (adjusted odds-ratio 9.30, 95% CI 3.7-23.3, p < .001). FDRs of patients with SPS that underwent colonoscopy and fulfilled the abandoned criterion II2010 for SPS diagnosis were at increased risk of AN at baseline and during surveillance in this small, retrospective cohort study. Our results should be interpreted with caution but suggest that adherence to surveillance recommendations for all FDRs of patients with SPS is important, especially for those that would have fulfilled the now abandoned criterion II2010.
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Poliposis Adenomatosa del Colon/diagnóstico , Familia , Poliposis Adenomatosa del Colon/epidemiología , Poliposis Adenomatosa del Colon/genética , Poliposis Adenomatosa del Colon/patología , Colonoscopía/estadística & datos numéricos , Femenino , Humanos , Incidencia , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Padres , Vigilancia de la Población , Análisis de Regresión , Estudios Retrospectivos , Hermanos , Síndrome , Organización Mundial de la SaludRESUMEN
BACKGROUND AND AIMS: Serrated polyposis syndrome (SPS) is associated with an increased risk of colorectal cancer (CRC). International guidelines recommend surveillance intervals of 1-2 years. However, yearly surveillance likely leads to overtreatment for many. We prospectively assessed a surveillance protocol aiming to safely reduce the burden of colonoscopies. METHODS: Between 2013 and 2018, we enrolled SPS patients from nine Dutch and Spanish hospitals. Patients were surveilled using a protocol appointing either a 1-year or 2-year interval after each surveillance colonoscopy, based on polyp burden. Primary endpoint was the 5-year cumulative incidence of CRC and advanced neoplasia (AN) during surveillance. RESULTS: We followed 271 SPS patients for a median of 3.6 years. During surveillance, two patients developed CRC (cumulative 5-year incidence 1.3%[95% CI 0% to 3.2%]). The 5-year AN incidence was 44% (95% CI 37% to 52%), and was lower for patients with SPS type III (26%) than for patients diagnosed with type I (53%) or type I and III (59%, p<0.001). Most patients were recommended a 2-year interval, and those recommended a 2-year interval were not at increased risk of AN: AN incidence after a 2-year recommendation was 15.6% compared with 24.4% after a 1-year recommendation (OR 0.57, p=0.08). CONCLUSION: Risk stratification substantially reduced colonoscopy burden while achieving CRC incidence similar to previous studies. AN incidence is considerable in SPS patients, but extension of surveillance intervals was not associated with increased AN in those identified as low-risk by the protocol. We identified SPS type III patients as low-risk group that might benefit from even less frequent surveillance. TRIAL REGISTRATION NUMBER: The study was registered on http://www.trialregister.nl; trial-ID NTR4609.
Asunto(s)
Poliposis Adenomatosa del Colon/diagnóstico , Neoplasias Colorrectales/diagnóstico , Poliposis Adenomatosa del Colon/epidemiología , Poliposis Adenomatosa del Colon/cirugía , Anciano , Estudios de Cohortes , Colonoscopía/métodos , Colonoscopía/estadística & datos numéricos , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/cirugía , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Uso Excesivo de los Servicios de Salud/prevención & control , Uso Excesivo de los Servicios de Salud/estadística & datos numéricos , Persona de Mediana Edad , Países Bajos/epidemiología , Vigilancia de la Población/métodos , Prevalencia , Estudios Prospectivos , Factores de Riesgo , España/epidemiologíaRESUMEN
INTRODUCTION: Because individuals with serrated polyps and adenomas are at increased risk of developing new polyps and colorectal cancer (CRC), surveillance after resection is justified. After adenoma resection, most international guidelines are consistent, but recommendations for surveillance after serrated polyp resection vary. The United States Multi-Society Taskforce on CRC (US-MSTF) base surveillance intervals on serrated polyp subtype (traditional serrated adenoma, sessile serrated polyp, hyperplastic polyps), while the European Society of Gastrointestinal Endoscopy (ESGE) guidelines do not take serrated polyp subtype into account. We evaluated the implications of this difference in a primary colonoscopy screening cohort. METHODS: We included participants from a large colonoscopy screening trial. In a post-hoc simulation, assuming full protocol adherence, we determined the surveillance interval for each subject based on their polyp burden, using the most recent US-MSTF and ESGE guidelines. RESULTS: We included 5323 participants, of whom 1228 had one or more serrated polyps. In 5201 of all participants (98â%; Cohen's kappa 0.90) and in 1106 of those with serrated polyps (90â%; Cohen's kappa 0.80), both guidelines recommended identical surveillance intervals. Recommendations for a 3-year surveillance interval were identical between the two guidelines. All 122 subjects with discordant recommendations would receive a follow-up colonoscopy after 10 years using ESGE guidance and after 5 years using US-MSTF guidance. CONCLUSION: Despite the different criteria used to determine surveillance after serrated polyp resection, most individuals are recommended identical colonoscopy surveillance intervals whether following the ESGE or US-MSTF guidelines. This suggests that surveillance recommendations do not need to consider the serrated polyp subtype.
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Adenoma/diagnóstico por imagen , Pólipos del Colon/diagnóstico por imagen , Colonoscopía , Neoplasias Colorrectales/diagnóstico por imagen , Vigilancia de la Población , Guías de Práctica Clínica como Asunto , Adenoma/epidemiología , Adenoma/patología , Pólipos del Colon/epidemiología , Pólipos del Colon/patología , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/patología , Europa (Continente)/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Both the adenoma detection rate (ADR) and proximal serrated polyp detection rate (PSPDR) vary among endoscopists. It is unclear how these variations influence colorectal cancer (CRC) screening effectiveness. We evaluated the effect of variation in these detection rates on the long-term impact of fecal immunochemical test (FIT) based screening. METHODS: The Adenoma and Serrated pathway to Colorectal CAncer (ASCCA) model was set up to simulate the Dutch national biennial FIT-based CRC screening program between 2014 and 2044. Adherence to FIT and colonoscopy was 73 and 92%. Besides a 'no screening scenario', several screening scenarios varying in ADR and PSPDR were evaluated. Using the available literature on colonoscopy miss rates led to a base-case ADR of 59% and PSPDR of 11%, which were varied with intervals of 3 and 2%. RESULTS: Compared to no screening, FIT-screening in the base-case scenario reduced long-term mortality with 51.8%. At a fixed PSPDR of 11%, an increase in ADR from 44 to 62% would result in a 10.7% difference in mortality reduction. Using a fixed ADR of 59%, changing the PSPDR from 3 to 15% did not substantially influence long-term mortality (51.0 to 52.3%). CONCLUSIONS: An increase in ADR gradually reduces CRC burden in a FIT-based screening program, whereas an increase in PSPDR only minimally influences long-term outcomes at a population-level. The limited effect of the PSPDR can be explained by the limited sensitivity of FIT for serrated polyps (SPs). Other triage modalities aiming to detect relevant SPs should be explored.
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Adenoma/epidemiología , Adenoma/patología , Pólipos del Colon/patología , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/patología , Modelos Econométricos , Adenoma/mortalidad , Anciano , Colonoscopía , Neoplasias Colorrectales/mortalidad , Detección Precoz del Cáncer , Femenino , Humanos , Incidencia , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Mortalidad , Vigilancia de la PoblaciónAsunto(s)
Pólipos del Colon , Inestabilidad de Microsatélites , Adenoma , Colonoscopía , Neoplasias Colorrectales , HumanosRESUMEN
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.
Asunto(s)
Pólipos Adenomatosos/patología , Pólipos del Colon/patología , Colonoscopía , Neoplasias Colorrectales/patología , Pólipos Adenomatosos/cirugía , Anciano , Biopsia , Pólipos del Colon/cirugía , Neoplasias Colorrectales/cirugía , Estudios Transversales , Femenino , Humanos , Hiperplasia , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Reproducibilidad de los Resultados , Carga TumoralRESUMEN
AIMS: Distinguishing premalignant sessile serrated lesions (SSLs) from hyperplastic polyps (HPs) is difficult for pathologists in daily practice. We aimed to evaluate nationwide variability within histopathology laboratories in the frequency of diagnosing an SSL as compared with an HP within the Dutch population-based screening programme for colorectal cancer and to assess the effect of an e-learning module on interlaboratory consistency. METHODS AND RESULTS: Data were retrieved from the Dutch Pathology Registry from the start of the nationwide population screening programme, January 2014, until December 2015. An obligatory e-learning module was implemented among pathologists in October 2014. The ratio between SSL and HP diagnosis was determined per laboratory. Odds ratios (ORs) for the diagnosis of an SSL per laboratory were compared with the laboratory with the median odds (median laboratory), before and after implementation of the e-learning module. In total, 14 997 individuals with 27 879 serrated polyps were included; 6665 (23.9%) were diagnosed as SSLs, and 21 214 as HPs (76.1%). The ratio of diagnosing an SSL ranged from 5% to 47% (median 23%) within 44 laboratories. Half of the laboratories showed a significantly different OR (range 3.47-0.16) for diagnosing an SSL than the median laboratory. Variability decreased after implementation of the e-learning module (P = 0.02). Of all pathology laboratories, 70% became more consistent with the median laboratory after e-learning implementation. CONCLUSIONS: We demonstrated substantial interlaboratory variability in the histopathological diagnosis of SSLs, which significantly decreased after implementation of a structured e-learning module. Widespread implementation of education might contribute to more homogeneous practice among pathologists.