key: cord-0942393-aujffkag
authors: Soons, Elsa; Bisseling, Tanya M.; van der Post, Rachel S.; Nagtegaal, Iris D.; Hazewinkel, Yark; van Kouwen, Mariette C. A.; Siersema, Peter D.
title: The Workgroup Serrated Polyps and Polyposis (WASP) classification for optical diagnosis of colorectal diminutive polyps with iScan and the impact of the revised World Health Organization (WHO) criteria
date: 2021-09-03
journal: United European Gastroenterol J
DOI: 10.1002/ueg2.12129
sha: a2425d95c3dfceeb136c72d487e43e65108c6104
doc_id: 942393
cord_uid: aujffkag

BACKGROUND AND AIMS: The Workgroup Serrated Polyps and Polyposis (WASP) developed criteria for optical diagnosis of colorectal polyps. The aims of this study were: (1) to improve optical diagnosis of diminutive colorectal polyps, especially SSLs, after training endoscopists in applying WASP criteria on videos of polyps obtained with iScan and (2) to evaluate if the WASP criteria are still useful when polyps are pathologically revised according to the World Health Organization (WHO) 2019 criteria. METHODS: Twenty‐one endoscopists participated in a training session and predicted polyp histology on 30 videos of diminutive polyps, before and after training (T(0) and T(1)). After three months, they scored another 30 videos (T(2)). Primary outcome was overall diagnostic accuracy (DA) at T(0), T(1) and T(2). Polyps were histopathologically classified according to the WHO 2010 and 2019 criteria. RESULTS: Overall DA (both diminutive adenomas and SSLs) significantly improved from 0.58 (95% CI 0.55–0.62) at T(0) to 0.63 (95% CI 0.60–0.66, p = 0.004) at T(1). For SSLs, DA did not change with 0.51 (95% CI 0.46–0.56) at T(0) and 0.55 (95% CI 0.49–0.60, p = 0.119) at T(1). After three months, overall DA was 0.58 (95% CI 0.54–0.62, p = 0.787, relative to T(0)) while DA for SSLs was 0.48 (95% CI 0.42–0.55, p = 0.520) at T(2). After pathological revision according to the WHO 2019 criteria, DA of all polyps significantly changed at all time points. CONCLUSION: A training session in applying WASP criteria on endoscopic videos made with iScan did not improve endoscopists' long‐term ability to optically diagnose diminutive polyps. The change of DA following polyp revision according to the revised WHO 2019 criteria suggests that the WASP classification may need revision.

Colorectal cancer (CRC) is an important cause of cancer related death worldwide. 1 The two most well-known precursors of CRC are adenomas (ADs) and sessile serrated lesions (SSLs). 2, 3 It is estimated that 70%-90% and 10%-20% of CRCs arise from ADs and SSLs, respectively. 4 Colonoscopy aims to early detect and remove these precursors, thereby preventing CRC.

The majority of polypectomies are performed on polyps that are innocent at the time of removal and up to 80% of all detected polyps during colonoscopy are diminutive (≤5 mm), of which 50% are non-neoplastic (e.g., hyperplastic or inflammatory).

Moreover, cancer prevalence is ≤0.1% in diminutive polyps. 5, 6 Following European and American guidelines, removal and pathological examination of all polyps is common practice. 7-10 However, because of the low rate of neoplasia in diminutive polyps, removal of these innocent diminutive polyps results in additional costs.

In an attempt to reduce costs, various classification systems for optical differentiation between neoplastic and non-neoplastic polyps have been proposed. One of these classification systems was devel- Recently the World Health Organization (WHO) published renewed criteria for pathological classification of digestive system tumors. 16 According to these criteria only one unequivocal aberrant crypt, rather than two or three, is already sufficient to diagnose a SSL.

It is estimated that following these criteria, HPs will be re-diagnosed as SSLs in approximately 7% of cases. 17 

This prospective study was conducted to compare the optical diagnosis of endoscopists with the pathological assessment of polyps. The study consisted of two phases: a training phase and a re-evaluation phase (see Figure 1 ). This study was performed in accordance with the Standards for Reporting Diagnostic Accuracy (STARD statement). 22

The training phase was performed to measure the short-and longterm effects of training in the WASP classification on the optical diagnosis of diminutive colorectal polyps using iScan-OE digital chromoendoscopy.

We developed a training module based on the WASP classification.

The training module was formulated including the following topics:

� Clinical importance of optical diagnosis of diminutive colorectal polyps, including the PIVI criteria 15 ;

� Introduction and breakdown of the WASP classification into the NICE criteria and the criteria formulated by Hazewinkel et al 11-13 ; � Differentiation between type 1 (HP or SSL) and type 2 (AD or SSL) polyps using the NICE criteria, illustrated with short videos; � Differentiation of ADs and/or HPs versus SSLs using the Hazewinkel criteria, illustrated with short videos.

The videoclips were retrieved from a prospectively collected database of short (≤10 s) videoclips of diminutive polyps in patients who had a colonoscopy following a positive immunochemical fecal occult blood test (iFOBT), or in patients who were known with serrated polyposis syndrome (SPS) during surveillance colonoscopy.

Only videos of diminutive polyps were included in the study because we specifically aimed to evaluate our results with regard to the PIVI criteria which are restricted to polyps ≤5 mm. In all videoclips, the lesion was consecutively shown using iScan 1, iScan 2 and iScan OE. 

To evaluate the short-term effects of the training on the accuracy of optical diagnosis of SSLs, senior endoscopists and endoscopists in training were invited to participate in a live training session that was Videos of polyps that were used during the training module were excluded from use in the first part of the training phase. -821 (T 2 ). Neither patient characteristics, nor polyp location or size were presented. Again, participants were unaware of the number of videos per category. No additional training was offered prior to this phase.

No videos of polyps that were used in the training module nor the first part of the training phase were used in this phase.

For the second part, an online platform (LimeSurvey GmbH) was used. Participants could log in on the platform at any time for 20 days. In the module, participants could only move forward, therefore it was impossible for participants to go back and see a previous video again or to change a previous answer.

The re-evaluation phase was performed to evaluate the effect of the revised WHO 2019 criteria for pathological diagnosis on the diagnostic accuracy of optical diagnosis using the WASP classification.

For this, the same optical diagnoses from the training phase were used in the analyses. However, this time they were compared to the revised pathological diagnosis, in accordance with the WHO 2019 criteria. 16 

The histopathological diagnosis was used as reference standard in all cases. All polyps used in this study were assessed by two dedicated gastrointestinal (GI) pathologists. All pathological diagnoses were based on morphological features on hematoxylin and eosin-stained slides. During the training phase all polyp specimens were initially assessed in accordance with the WHO 2010 criteria, as opposed to the re-evaluation phase in which all polyp specimens were assessed in accordance with the WHO 2019 criteria. 23 During both the training-and re-evaluation phase all polyp specimens were revised by two expert GI pathologists (CvdP and IN). 16 Any disagreement was resolved by discussion. Pathologists were unaware of patient characteristics, endoscopic appearance of the lesions and diagnosis made by the first pathologist.

Ethical approval for the assembling of the prospective database and hence the performance of this study was waived by the Institute Re- 

This study was powered on an expected improvement in diagnostic accuracy after participating in the training. An improvement in diagnostic accuracy of 10% was expected. With 15% discordant pares, a significance level op 5% and a power of 90%, this resulted in a calculated sample size of 154 videos to be analyzed. Since a selected group of senior endoscopists and endoscopists in training could score the same set of videos, a high inter-cluster correlation was expected.

Therefore, an inflation factor was calculated using the formula 1+(n-1)ᵨ. 24 An assumed intra-rater correlation of 0.05 together with 30 observations per participant resulted in an inflation factor of 2.45 and 378 observations (13 participants) needed for paired analysis.

Descriptive statistics were reported as median values with interquartile ranges (IQR), mean values with 95% confidence intervals (95% CI) and frequencies or percentages, when appropriate.

Histopathological diagnosis was used as reference standard to calculate the diagnostic accuracy of optical diagnosis. To compare diagnostic performance before and after training the Paired Sample t-Test was used. This test was also used to compare the diagnostic accuracy before and after revision of the polyp specimens. To investigate whether the level of experience of the participant (senior vs. in training endoscopist) influenced the outcomes an Independent Samples t-Test was used.

Analyses were performed in IBM SPSS Statistics, version 25 (SPSS Inc.). A p-value <0.05 was considered statistically significant.

Characteristics for all 60 polyps included in the three tests are shown in Table 1 . The videos were made during colonoscopies of 38 patients, with 37 (97.3%) having a positive iFOBT. A total of 34 videos (56.7%) was made of polyps located in the rectosigmoid. Mean polyp diameter was 2.9 mm, and most polyps (55%) were sessile.

Sixty-two eligible participants were contacted, but finally 11/37 senior endoscopists and 10/25 endoscopists in training agreed to participate in the study. Table 2 

Mean improvement in optical diagnosis after the training is presented in Table 3 . The mean score for all 30 optical estimations Abbreviations: 95% CI, 95% confidence interval; AD, adenoma; HC, high confidence; SSL, sessile serrated lesion.

Indication for colonoscopy, n (%) No significant differences in accuracy rates nor differences in improvement between senior endoscopists and endoscopists in training were seen at T 0 or T 1 .

Seventeen participants (81%) participated in the evaluation of longterm effects. Table 3 shows the long-term mean improvement No difference in accuracy rates nor difference in improvement between senior endoscopists and endoscopists in training were seen at T 2 .

After revision of all polyp specimens, the diagnoses of two ADs, one SSL and eight HPs were changed ( 

Diagnosis after revision AD SSL HP Table S1 .

After participating in an interactive training to apply the WASP classification using iScan, the diagnostic accuracy of endoscopists to correctly classify colorectal polyps significantly improved from 0.58 to 0.63 (p = 0.004). However, this improvement was no longer present after 3 months, as the diagnostic accuracy was again 0.58. The results of our training phase conflict with previously published results on the implementation of the WASP classification in terms of accuracy. When the WASP classification was introduced in 2016, a comparable study was conducted to validate the classification. 11 The accuracy rates were higher than we found in our study. In the original study, the accuracy was 0.63 at baseline, improved to 0.79 after the training, and remained high after six months: 0.76. The accuracy for SSLs was also better than in our study; 0.74 at baseline, 0.86 after training and 0.87 after six months. These accuracy rates were even higher when diagnoses made with high confidence were considered. In that study, two images (high-resolution white light endoscopy and NBI) rather than videos of 45-50 small and diminutive polyps were shown simultaneously for an undefined period of time to evaluate the diagnostic accuracy. In addition, only senior endoscopists participated in that study. Although we did not find differences in accuracy rates between senior endoscopists and endoscopists in training in our study, one could argue that this resulted in a higher overall accuracy in the previous study. 11 Based on promising results in 2016, the WASP classification was also assessed in real-life in 2018. High accuracy rates above 97%

were found for diminutive SSLs in the proximal colon and rectosigmoid. 14 Interestingly, in our study the accuracy rates for optical diagnosis of ADs at T 0 and T 1 were higher than in previous studies. In the two studies on the WASP classification above, the accuracy rates for all optical AD diagnoses and diagnoses made with high confidence were 76% and 82%-89%, respectively. 11, 14 As these high accuracy rates were already present before our training, it seems plausible that Our study has several strengths. First, we used videos rather than images in order to maximally resemble daily clinical practice.

Second, all pathological diagnoses were re-reviewed by two dedicated GI-pathologists. Third, by providing an online final test after 3 months, the majority (81%) of participants were able to participate in this part of the study regardless of the COVID-19 pandemic.

Nevertheless, the lower accuracy rates at T 2 might imply that this method of testing and/or the COVID-19 pandemic may have made the participants less dedicated.

Some limitations also need to be addressed. First, senior endoscopists and endoscopists in training participated in the study, which allowed us to include a relatively large cohort of endoscopists, compared to other studies. However, it may limit the ability to compare our results with previous studies as they exclusively included expert endoscopists. Additionally, the duration of 10 s per video might be too short for less experienced endoscopists to be able to correctly classify colorectal polyps.

Second, after re-reviewing all histopathological diagnoses by two dedicated GI-pathologists one AD was revised to a HP and vice versa. This cannot be attributed to the WHO 2019 criteria as no changes on this part have been introduced. It can therefore not be ruled out that, at least partly, some inter-and intra-observer variability in pathological diagnoses was introduced during the review process.

In conclusion, the findings of this study show that the overall optical diagnosis of diminutive colorectal polyps initially improved after participating in an interactive training to educate participants on the use of the WASP classification using the iScan-OE system, but this improvement was no longer present after three months. No short-or long-term improvement could be observed for optical diagnosis of SSLs. Thus, according to our study results we would argue against the optical diagnosis of diminutive polyps, especially

Elsa Soons designed and performed the study, collected, analyzed and interpreted the data and wrote the paper. Peter Siersema, Tanya Bisseling and Mariëtte van Kouwen contributed to the conception and design of the study, interpretation of the data and critically reviewing the manuscript. Yark Hazewinkel contributed to the interpretation of the data and critically reviewed the manuscript. Chella van der Post and Iris Nagtegaal re-reviewed the biopsies, interpreted the data and critically reviewed the manuscript. All authors gave final approval of this version to be published.

The data that support the findings of this study are available from the corresponding author upon reasonable request.

https://orcid.org/0000-0001-7251-9918

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The Workgroup Serrated Polyps and Polyposis (WASP) classification for optical diagnosis of colorectal diminutive polyps with iScan and the impact of the revised World Health Organization (WHO) criteria. United