Current Approaches in Managing Colonic Serrated Polyps and Serrated Polyposis.

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.

Effect of an E-learning resource on endoscopists' proximal serrated polyp detection rate: a randomized controlled trial.

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.

Appendiceal lesions in serrated polyposis patients are easily overlooked but only seldomly lead to colorectal cancer.

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 (26.1 %) 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 14 /34 (41.2 %, 95 %CI 24.7 %-59.3 %); none were advanced on histology. Detection rates in the (pre)clearance group were 1 /171 (0.6 %, 95 %CI 0.01 %-3.2 %) for advanced and 3 /171 (1.8 %, 95 %CI 0.04 %-5.0 %) 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 1 /110 patients (0.9 %, 95 %CI 0.02 %-5.0 %) 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.

Advanced serrated polyps as a target of screening: detection rate and positive predictive value within a fecal immunochemical test-based colorectal cancer screening population.

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 ≥ 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.

The earliest events in BRAF-mutant colorectal cancer: exome sequencing of sessile serrated lesions with a tiny focus dysplasia or cancer reveals recurring mutations in two distinct progression pathways.

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.

Substantial and sustained improvement of serrated polyp detection after a simple educational intervention: results from a prospective controlled trial.

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.

Personalised surveillance for serrated polyposis syndrome: results from a prospective 5-year international cohort study.

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.

The long-term outcomes and natural disease course of serrated polyposis syndrome: over 10 years of prospective follow-up in a specialized center.

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.

Implications of different guidelines for surveillance after serrated polyp resection in United States of America and Europe.

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 (98 %; Cohen's kappa 0.90) and in 1106 of those with serrated polyps (90 %; 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.

Impact of differences in adenoma and proximal serrated polyp detection rate on the long-term effectiveness of FIT-based colorectal cancer screening.

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.

Implementation of an e-learning module improves consistency in the histopathological diagnosis of sessile serrated lesions within a nationwide population screening programme.

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.

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.

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

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

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.

The proximal serrated polyp detection rate is an easy-to-measure proxy for the detection rate of clinically relevant serrated polyps.

BACKGROUND AND AIMS: The adenoma detection rate (ADR) is the most important surrogate quality parameter for colorectal cancer (CRC) prevention. However, serrated polyps also are precursors of CRC. Large, prospective studies comparing the detection rate of serrated polyps among endoscopists in an era of awareness about the malignant potential of serrated polyps have not yet been performed. We aimed to compare the proximal serrated polyp (PSP) detection rate and the clinically relevant serrated polyp (RSP) detection rate among endoscopists and to analyze the association between these parameters and the ADR. METHODS: Colonoscopy data were retrieved in one expert center between January 2011 and July 2014 by using a structured reporting system, enabling prospective and automatic quality assessment. Endoscopists who performed at least 50 colonoscopies within the timeframe were included for analysis. Multivariate logistic regression was used to compare the ADR, PSP detection rate, and RSP detection rate among endoscopists. The association among these parameters was calculated by using the Pearson r correlation coefficient. All lesions were assessed by an expert pathologist. RESULTS: In total, 16 endoscopists and 2088 colonoscopies were included for analysis. The PSP detection rate ranged from 2.9% to 18.6% (mean 10.4%) among endoscopists. Corrected for confounders, the odds ratio to detect ≥1 PSP, compared with endoscopists with the highest detection rate, ranged from 0.79 (95% confidence interval [CI], 0.41-1.52) to 0.12 (95% CI, 0.03-0.55). The PSP detection rate was highly correlated with the RSP detection rate (ρ 0.94; P < .001), ranging from 4.3% to 20.9% (mean 13.9%). The PSP detection rate moderately correlated with the ADR (0.55; P = .03), which ranged from 23.2% to 49.2% (mean 35.2%). CONCLUSIONS: The PSP detection rate is widely variable among endoscopists, strongly correlated with the RSP detection rate, and moderately correlated with the ADR. These results suggest a high miss rate of RSPs among endoscopists with low rates of PSP detection. Future research should determine the association between endoscopists' PSP detection rates and the risk of interval cancer.

Low prevalence of serrated polyposis syndrome in screening populations: a systematic review.

BACKGROUND AND STUDY AIMS: The most frequently cited prevalence for serrated polyposis syndrome (SPS) is 1 in every 3000 people screened, but this value is debated. Additionally, changes in 2010 in the World Health Organization (WHO) diagnostic criteria for SPS might affect reported prevalence. An updated estimate of SPS prevalence is necessary to predict the number of cases in screening programs. PATIENTS AND METHODS: A systematic literature search was conducted in the PubMed, EMBASE, and Web of Science databases up to February 2014. Studies reporting the prevalence of SPS, as defined by WHO criteria, in screening populations were selected. RESULTS: Six studies reported prevalence of SPS in screening populations, varying from 0 to 0.66 %. The highest prevalences (0.34 % and 0.66 %) were seen in studies from screening programs with patients pre-selected by fecal blood test. Primary colonoscopy-based screening programs, that have the lowest risk of bias, reported SPS prevalences ranging from 0 to 0.09 %. Across studies, 56 patients were diagnosed with SPS of whom 3 presented with synchronous colorectal cancer at index endoscopy. CONCLUSION: The true prevalence of SPS is unclear because of the risk of bias across studies, but is likely to be below 0.09 % as derived from primary colonoscopy screening programs. The prevalence in pre-selected screening populations after positive fecal testing is higher, with reported values of 0.34 % and 0.66 %. Large and high quality primary colonoscopy screening studies, reporting SPS prevalence in adequately described populations, are necessary for better estimation of the true prevalence of SPS in average-risk patients.

Gel instillation sonohysterography (GIS) using Endosgel versus ExEmgel, comparison of pain and image quality and cost benefit analysis: A double blind randomised controlled trial. GISPAIN trial.

INTRODUCTION: Pain experience, physical reaction, image quality and adverse events during Gel Instillation Sonohysterography (GIS) can differ using gels with different compositions. As a result, patient satisfaction can also be affected. The effect of two instillation gels, Endosgel versus ExEmgel, using both the Visual Analogue Scale (VAS) and a Continuous Pain Score Meter (CPSM) was therefore compared. METHODS: This single centre double blind randomised controlled trial included 80 women planned for outpatient GIS, diagnosed with abnormal intrauterine bleeding or fertility disorders and suspicion on an intrauterine abnormality. Patients were randomly allocated to the instillation of Endosgel containing chlorhexidine or ExEmgel without chlorhexidine. Primary outcome was reported pain during the procedure using VAS. Secondary outcomes included pain score measured using CPSM, satisfaction to the procedure and preference at 3 weeks and 3 months after the procedure and image quality. A cost benefit analysis was also performed. RESULTS: The reported median VAS concerning pain during gel instillation was comparable in the Endosgel and ExEmgel group, 2.50 (IQR 0.00-5.00) and 2.00 (IQR 0.00-5.75) respectively (p = 0.69). The median VAS of the entire procedure was also similar: both 2.00 (IQR 0.00-5.00) (p = 0.86). CPSM-scores were not significantly different either. Both groups were similar in image quality (p = 0.83) and patient's satisfaction (p = 0.36). CONCLUSION: Concerning the pain experienced during a GIS procedure and patients' satisfaction, the ExEmgel was not proven to be superior to the Endosgel. Our advice is to use the gel that is available at the lowest costs, as the image quality is the same for both Endosgel and ExEmgel.

Aberrant PRDM2 methylation as an early event in serrated lesions destined to evolve into microsatellite-instable colorectal cancers.

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.