Jasper L.A. Vleugels

Colorectal cancer screening by colonoscopy: putting it into perspective

Implementation of nationwide screening programs aims to decrease the disease burden of colorectal cancer (CRC) in the general population. Globally, most population screening programs for CRC are carried out by either fecal occult blood test, flexible sigmoidoscopy or colonoscopy. For screening programs with colonoscopy as the primary method, only circumstantial evidence from observational studies is available to prove its effectiveness, suggesting that colonoscopy effectively reduces CRC incidence and mortality. Currently, large randomized trials are being conducted to corroborate these findings. Besides the direct effect of a screening program for CRC, its protective effect is further enhanced by enrolment of patients that underwent polypectomy in surveillance programs. However, despite CRC screening and surveillance colonoscopies, interval CRC still occur. Those are predominantly located in the right‐sided colon and potential explanations, besides unfavorable tumor characteristics, are preventable operator‐dependent factors relating to the quality of the colonoscopy procedure. In an effort to reduce differences in endoscopists’ performance and thereby the occurrence of interval CRC, quality indicators of colonoscopy have been introduced. In addition, emerging advanced colonoscopy techniques might contribute to improvement in polyp detection and removal. Meticulous inspection of the colonic mucosa not only results in the detection of advanced and relevant lesions, but also in the removal of many diminutive and small lesions leading to an increasing number of surveillance colonoscopies, known as the ‘high‐detection paradox’. More data on the cost‐effectiveness of high‐quality colonoscopy as a primary screening method and surveillance programs with intervals based on optimal risk stratification are eagerly awaited.

Morphological classifications of gastrointestinal lesions

In the era of spreading adoption of gastrointestinal endoscopy screening worldwide, endoscopists encounter an increasing number of complex lesions in the gastrointestinal tract. For decision-making on optimal treatment, precise lesion characterization is crucial. Especially the assessment of potential submucosal invasion is of utmost importance as this determines whether endoscopic removal is an option and which technique should be used. To describe a lesion and stratify for the risk of submucosal invasion, several morphological classification systems have been developed. In this manuscript, we thoroughly discuss a systematic approach for the endoscopic assessment of a lesion, which include location, size, Paris classification, lateral spreading tumor classification if applicable and evaluation of the surface pattern with advanced endoscopic imaging techniques. The use of advanced imaging techniques improves the characterization of mucosal surface patterns and helps to determine whether lesions are amenable to endoscopic resection.

Chromoendoscopy versus autofluorescence imaging for neoplasia detection in patients with longstanding ulcerative colitis (FIND-UC): an international, multicentre, randomised controlled trial

BACKGROUND Patients with longstanding ulcerative colitis undergo regular dysplasia surveillance because they have an increased colorectal cancer risk. Autofluorescence imaging and chromoendoscopy improve dysplasia detection. The aim of this study was to determine whether autofluorescence imaging should be further studied as an alternative method for dysplasia surveillance in patients with longstanding ulcerative colitis. METHODS This prospective, international, randomised controlled trial included patients from an ulcerative colitis-dysplasia surveillance cohort from five centres in the Netherlands and the UK. Eligible patients were aged 18 years or older who were undergoing dysplasia surveillance after being diagnosed with extensive colitis (Montreal E3) at least 8 years before study start or with left-sided colitis (Montreal E2) at least 15 years before study start. Randomisation (1:1) was minimised for a previous personal history of histologically proven dysplasia and concomitant primary sclerosing cholangitis. The coprimary outcomes were the proportion of patients in whom at least one dysplastic lesion was detected and the mean number of dysplastic lesions per patient. The relative dysplasia detection rate, calculated as the ratio of the detection rates by autofluorescence imaging and chromoendoscopy, needed to be more than 0·67 (using an 80% CI) for both primary outcomes to support a subsequent large non-inferiority trial. Outcomes were analysed on a per-protocol basis. The trial is registered at the Netherlands Trial Register, number NTR4062. FINDINGS Between Aug 1, 2013, and March 10, 2017, 210 patients undergoing colonoscopy surveillance for longstanding ulcerative colitis were randomised for inspection with either autofluorescence imaging (n=105) or chromoendoscopy (n=105). Dysplasia was detected in 13 (12%) patients by autofluorescence imaging and in 20 patients (19%) by chromoendoscopy. The relative dysplasia detection rate of autofluorescence imaging versus chromoendoscopy for the proportion of patients with ulcerative colitis with at least one dysplastic lesion was 0·65 (80% CI 0·43-0·99). The mean number of detected dysplastic lesions per patient was 0·13 (SD 0·37) for autofluorescence imaging and 0·37 (1·02) for chromoendoscopy (relative dysplasia detection rate 0·36, 80% CI 0·21-0·61). Adverse events were reported for two patients in the autofluorescence imaging group (one patient had intraprocedural mild bleeding, and one patient had abdominal pain) and for three patients in the chromoendoscopy group (two patients had intraprocedural mild bleeding, and one patient had perforation). INTERPRETATION Autofluorescence imaging did not meet criteria for proceeding to a large non-inferiority trial. Therefore, existing autofluorescence imaging technology should not be further investigated as an alternative dysplasia surveillance method. FUNDING Olympus Europe and Olympus Keymed.

Serrated lesions of the colon and rectum: the role of advanced endoscopic imaging

Conventional adenomas were traditionally thought to be the only precursors to colorectal cancer (CRC). Nowadays, also serrated polyps are acknowledged as precursor lesions for CRC, responsible for up to 30% of all CRCs and probably a larger percentage of interval CRCs after colonoscopy. In recent years, much research is being done to unravel the serrated neoplasia pathway. Endoscopic detection of serrated polyps is still a challenge for gastroenterologists, which is illustrated by large variations in detection rates of serrated polyps in the proximal colon. Clinical practice is further inhibited by poor optical differentiation of SSA/Ps from conventional adenomas and HPs and difficult delineation of those lesions, resulting in incomplete resection. The main focus of this review is to highlight recent advancements in endoscopic imaging techniques with regards to detection, differentiation and resection of serrated polyps.

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.

Adding family history to faecal immunochemical testing increases the detection of advanced neoplasia in a colorectal cancer screening programme

Faecal immunochemical testing (FIT) for colorectal cancer (CRC) screening has suboptimal sensitivity for detecting advanced neoplasia. To increase its performance, FIT could be combined with other risk factors.

Implementation of an optical diagnosis strategy saves costs and does not impair clinical outcomes of a fecal immunochemical test-based colorectal cancer screening program

Background and study aims  In an optical diagnosis strategy, diminutive polyps that are endoscopically characterized with high confidence are removed without histopathological analysis and distal hyperplastic polyps are left in situ. We evaluated the effectiveness and costs of optical diagnosis. Methods  Using the Adenoma and Serrated pathway to Colorectal CAncer (ASCCA) model, we simulated biennial fecal immunochemical test (FIT) screening in individuals aged 55 – 75 years. In this program, we compared an optical diagnosis strategy with current histopathology assessment of all diminutive polyps. Base-case assumptions included 76 % high-confidence predictions and sensitivities of 88 %, 91 %, and 88 % for endoscopically characterizing adenomas, sessile serrated polyps, and hyperplastic polyps, respectively. Outcomes were colorectal cancer burden, number of colonoscopies, life-years, and costs. Results  Both the histopathology strategy and the optical diagnosis strategy resulted in 21 life-days gained per simulated individual compared with no screening. For optical diagnosis, €6 per individual was saved compared with the current histopathology strategy. These cost savings were related to a 31 % reduction in colonoscopies in which histopathology was needed for diminutive polyps. Projecting these results onto the Netherlands (17 million inhabitants), assuming a fully implemented FIT-based screening program, resulted in an annual undiscounted cost saving of € 1.7 – 2.2 million for optical diagnosis. Conclusion  Implementation of optical diagnosis in a FIT-based screening program saves costs without decreasing program effectiveness when compared with current histopathology analysis of all diminutive polyps. Further work is required to evaluate how endoscopists participating in a screening program should be trained, audited, and monitored to achieve adequate competence in optical diagnosis.

Diagnostic Accuracy of Endoscopic Trimodal Imaging and Chromoendoscopy for Lesion Characterization in Ulcerative Colitis

Background During surveillance colonoscopy of patients with long-standing ulcerative colitis [UC], a variety of dysplastic and non-dysplastic lesions are detected. The aim of this study was to address the diagnostic accuracy of endoscopic characterization of endoscopic trimodal imaging [ETMI] and chromoendoscopy [CE]. ETMI includes the combination of autofluorescence imaging [AFI], narrow band imaging [NBI] and white light endoscopy [WLE]. Methods This is a pre-specified additional analysis of a multi-centre, randomized controlled trial that compared AFI with CE for dysplasia detection in 210 patients with long-standing UC [FIND-UC trial]. In the AFI arm, endoscopists used the ETMI system to record AFI colour, Kudo pit pattern using NBI and WLE for lesion characterization. For AFI, purple colour and ambiguous colour combined with pit pattern type III-V on NBI was considered dysplastic. Kudo pit pattern was described in the CE arm. For pit pattern description using NBI and CE, type III-V was considered dysplastic. Histology was the reference standard. Results In total, 52 dysplastic and 255 non-dysplastic lesions were detected. Overall sensitivity for real-time prediction of dysplasia was 76.9% (95% confidence interval [CI] 46.2-95.0) for ETMI, and 81.6% [95% CI 65.7-92.3] for CE. Overall negative predictive value [NPV] for ETMI was 96.9% [95% CI 92.0-98.8] and 94.7% [90.2-97.2] for CE. Conclusions Sensitivity for endoscopic differentiation of dysplastic lesions detected during surveillance of patients with long-standing UC seems limited using ETMI and CE. Future research is warranted as the high NPV indicates that these techniques are valuable for the exclusion of dysplastic lesions [NTR4062].

Does polyp size matter

morbidity and mortality of colorectal cancer (CRC) by implementing screening programs [1, 2]. Besides early detection, colonoscopy could also reduce the incidence and long-term mortality of CRC because of removal precancerous polyps during the procedure [3]. Furthermore, previous research has shown that individuals who undergo adenoma-removal are at increased risk of developing future CRC [4, 5]. In CRC prevention, size matters because polyp characteristics that contribute to estimated risk of future CRC relate to histology, multiplicity and also size of polyps at index colonoscopy [6]. For example, most current international guidelines advise a 3-year surveillance interval for individuals diagnosed with adenomatous and serrated polyps ≥10mm and 5-year intervals for smaller polyps [7, 8]. Thus, endoscopic polyp size measurement contributes importantly to the assigned surveillance interval. Besides this important 10-mm cut-off, polyp size is also correlated with the chance that a lesion harbors invasive growth [9], and therefore is important in decision-making on treatment options. Last but not least, polyp size is also crucial for safe implementation of an optical diagnosis strategy, in which 1to 5-mm polyps are characterized during endoscopy and resected and discarded without histopathological analysis [10]. Although polyp size measurement is crucial for clinical decision-making, no reference standard is available. In current clinical practice, both endoscopists and pathologists estimate polyp size and their measurements are subject to variability. Endoscopists rely on their “carpenters’ eye” for estimating polyp size prior to endoscopic treatment. In a retrospective analysis of endoscopic size measurements of more than 90,000 polyps, endoscopists performing colonoscopies in the UK bowel cancer screening program clustered their measurements of polyps at 5mm, 10mm and 15mm endings, thereby having a preference for “pleasing” numbers [11]. Furthermore, the fish eye lenses of colonoscopes distort the displayed polyp images. Objects located at the center of the displayed view appear magnified compared to objects located at the periphery, leading to overestimation and underestimation of polyp size. Previous studies using artificial colon models with polyps have reported rates accuracy for endoscopic polyp size measurements ranging between 25% and 60% [12, 13]. In studies of real-time endoscopy, polyp size measurement has a great interobserver variability, which was not reduced by placing a ruler or biopsy forceps adjacent to the polyp [14, 15]. Pathologists measure polyp size after resection and use a ruler. Because this measurement is not influenced by image distortion or endoscopist preferences, this method may seem more reproducible and objective. However, there are also several reasons for inaccuracy of pathologists’ size measurements. Coagulation during polypectomy may lead to specimen shrinkage, as may the fixing method in formalin. Besides, suctioning a polyp through the working channel of the endoscope might distort and disintegrate it. Also, a polyp may have been lifted with submucosal fluid before resection or resected including a rim of normal tissue, both of which could potentially lead to overestimation of its original size. Lastly, resection may have been incomplete or performed in a piecemeal fashion, making size measurement by the pathologist clearly impossible. In this issue of Endoscopy International Open, Elwir and colleagues aimed to identify patientand physician-related factors associated with endoscopic size measurement in a large community-based endoscopy practice [16]. In more than 16,000 colonoscopies performed between January 2013 and December 2013, the endoscopic size was recorded for 1 or more Does polyp size matter?