Riu Pons et al. BMC Gastroenterology (2020) 20:111 https://doi.org/10.1186/s12876-020-01257-4 RESEARCH ARTICLE Open Access Narrow-band imaging and high-definition white-light endoscopy in patients with serrated lesions not fulfilling criteria for serrated polyposis syndrome: a randomized controlled trial with tandem colonoscopy Fausto Riu Pons1,2,3*, Montserrat Andreu1,2,3,4, Dolores Naranjo5, Marco Antonio Álvarez-González1,2,3, Agustín Seoane1,2, Josep Maria Dedeu1,2,3, Luis Barranco1,2 and Xavier Bessa1,2,3 Abstract Background: It is unknown whether narrow-band imaging (NBI) could be more effective than high-definition white-light endoscopy (HD-WLE) in detecting serrated lesions in patients with prior serrated lesions > 5 mm not completely fulfilling serrated polyposis syndrome (SPS) criteria. Methods: We conducted a randomized, cross-over trial in consecutive patients with prior detection of at least one serrated polyp ≥10 mm or ≥ 3 serrated polyps larger than 5 mm, both proximal to the sigmoid colon. Five experienced endoscopists performed same-day tandem colonoscopies, with the order being randomized 1:1 to NBI—HD-WLE or HD-WLE—NBI. All tandem colonoscopies were performed by the same endoscopist. Results: We included 41 patients. Baseline characteristics were similar in the two cohorts: NBI—HD-WLE (n = 21) and HD-WLE—NBI (n = 20). No differences were observed in the serrated lesion detection rate of NBI versus HD- WLE: 47.4% versus 51.9% (OR 0.84, 95% CI: 0.37–1.91) for the first and second withdrawal, respectively. Equally, no differences were found in the polyp miss rate of NBI versus HD-WLE: 21.3% versus 26.1% (OR 0.77, 95% CI: 0.43–1.38). Follow-up colonoscopy in nine patients (22%) allowed them to be reclassified as having SPS. Conclusions: In patients with previous serrated lesions, the serrated lesion detection rate was similar with NBI and HD- WLE. A shorter surveillance colonoscopy interval increases the detection of missed serrated polyps and could change the diagnosis of SPS in approximately one in every five patients. Trial registration: ClinicalTrials.gov NCT02406547, registered on April 2, 2015. Keywords: Colonoscopy, Colonic polyps, Optical imaging, Narrow-band imaging * Correspondence: FRiu@parcdesalutmar.cat 1 Gastroenterology Department, Hospital del Mar, Passeig Marítim 25-29, 08003 Barcelona, Spain 2 IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Riu Pons et al. BMC Gastroenterology (2020) 20:111 Page 2 of 9 Background patients with prior relevant (larger than 5 mm) serrated Colorectal cancer (CRC) is the second leading cause of lesions not fulfilling the SPS criteria. Therefore, this cancer death in western countries [1, 2]. Conventional study was designed to compare the serrated polyp detec- polyps are considered to be precursor lesions of sporadic tion rate of NBI versus HD-WLE in a randomized, CRC. Serrated polyps cause 20 to 35% of all CRC cases cross-over trial of tandem colonoscopy. and are associated with interval CRC, especially when they involve microsatellite instability and the CpG island Methods methylator phenotype [3]. These polyps are difficult to Study design and population identify on endoscopy due to their location in the right We performed a randomized, cross-over trial of tandem colon, their sessile or flat morphology, and their pale colonoscopy to compare NBI versus HD-WLE in the de- color with mucus capping [4]. tection of serrated lesions in patients with previously According to the World Health Organization (WHO) of resected serrated lesions not fulfilling SPS criteria be- 2010, serrated polyposis syndrome (SPS) was defined by tween March 2015 and April 2016 at Hospital del Mar, the presence of one out of the following criteria: [5] 1) at Barcelona (Spain). least five serrated polyps proximal to the sigmoid colon, In compliance with the ethical guidelines of the Dec- with two or more of these larger than 10 mm in diameter; laration of Helsinki, the study protocol was approved by 2) any number of serrated polyps occurring proximal to the institutional review board of Parc de Salut Mar on 6 the sigmoid colon in an individual with a first-degree rela- February 2015 (2014/5964/I) and was registered at Clini- tive with SPS; and 3) more than 20 serrated polyps of any calTrials.gov (NCT02406547). Written informed consent size distributed throughout the colon. In June 2019, a new was obtained from all patients before study inclusion. update on the WHO SPS criteria was made with small dif- We included consecutive patients from the electronic ferences between criteria 1 and 3, and the abandonment database of the Endoscopy Unit who had undergone a of criterion 2: 1) five or more serrated polyps proximal to complete baseline colonoscopy in the previous year, with the rectum, all being ≥5 mm in size, with at least two be- any of the following findings: ≥ 1 serrated polyp prox- ing ≥10 mm in size; and 2) more than 20 serrated polyps imal to the sigmoid colon larger than ≥10 mm in diam- of any size distributed throughout the large bowel, with eter; or ≥ 3 serrated polyps proximal to the sigmoid ≥5 being proximal to the rectum [6]. Therefore, patients colon larger than 5 mm. All detected polyps were with SPS are considered to be at increased risk of CRC. resected at the baseline colonoscopy. We used the pro- Because of the substantial risk of polyp recurrence in these posed United Kingdom terminology, based on World patients, surveillance is mandatory with 1- to 2-yearly col- Health Organization criteria, to define serrated lesions, onoscopies [7]. including hyperplastic polyp (HP), sessile serrated le- The European Society of Gastrointestinal Endoscopy sions (SSL) with or without dysplasia (also known as ses- has published the first Guideline of Advanced Endo- sile serrated polyp/adenoma), traditional serrated scopic Imaging for the detection and differentiation of adenoma, and mixed polyp [13]. colorectal neoplasia and recommends conventional Patients were excluded if: 1) CRC was found at the chromoendoscopy or narrow-band imaging (NBI) in pa- baseline colonoscopy; 2) they did not attend follow-up tients with SPS (strong recommendation, low quality evi- or refused to provide informed consent; 3) they had a dence) [8]. A pilot study in patients with SPS showed a high risk of complications due to sedation (patients with significantly lower polyp miss rate with NBI than with high comorbidities considered by the American Society high-definition white-light endoscopy (HD-WLE). How- of Anesthesiologists to be grade IV and higher); 4) they ever, this finding was not confirmed in a subsequent had an incomplete colonoscopy; and 5) they had inad- multicentre randomized trial by the same group [9, 10]. equate bowel preparation for colonoscopy defined by the A randomized controlled trial in patients undergoing Boston Bowel Preparation Score (BBPS): 0–1 points in their first colonoscopy reported a non-significant trend any of the three segments of the colon [14, 15]. toward detection of more proximal colon serrated le- sions with NBI than with HD-WLE [11]. Finally, in a Procedure and randomization retrospective selected case series [12] of individuals in a Patients were evaluated by the same endoscopist with population-based screening program with proximal ser- tandem (“back-to-back”) colonoscopy. In this proced- rated lesions at the baseline colonoscopy, colonoscopy ure, two withdrawals from the cecum to sigmoid reassessment within 1 year using chromoendoscopy and colon were performed using the two techniques con- high-definition endoscopes led to a three-fold increase secutively. At the first cecal intubation with HD- in the diagnosis of SPS. WLE, a sealed envelope was opened and each patient We hypothesized that NBI could improve the detec- was randomly assigned 1:1 to the NBI—HD-WLE or tion of serrated polyps compared with HD-WLE in the HD-WLE—NBI withdrawal group. All detected Riu Pons et al. BMC Gastroenterology (2020) 20:111 Page 3 of 9 polyps were classified macroscopically and were localization, morphology, Paris classification [17], and the resected at each withdrawal (Fig. 1). After detecting a BBPS. Localization of polyps was divided into five anatom- polyp on NBI withdrawal, the endoscopist could ical segments: cecum, ascending, transverse (including the switch from NBI to HD-WLE to perform the poly- hepatic and splenic flexures) and descending colon (from pectomy and then resume NBI. Each polyp was re- the splenic flexure to the sigmoid colon). corded on a data sheet by nursing staff from the endoscopy room. All diminutive HPs resected from Outcome measures the rectosigmoid colon were excluded from the ana- The primary outcome was to measure the number of lysis. The endoscopists and study participants were serrated polyps detected with NBI and HD-WLE. Sec- blinded to the randomization list, which was ondary outcomes were the number of missed lesions computer-generated by the biomedical research con- from the first technique used for each group (NBI or sulting service of Hospital del Mar Medical Research HD-WLE), defined as the proportion of polyps detected Institute (IMIM), Barcelona. on the second withdrawal relative to the number of Patients underwent a bowel preparation of 4 L split-dose polyps found during the two examinations, and to assess polyethylene glycol solution. The level of sedation was the number of patients reclassified as having SPS after monitored mostly by propofol alone or combined with the scheduled colonoscopy. midazolam and fentanyl at the discretion of the endosco- pist. An anesthesia specialist was required in one patient. Statistical analysis and sample size High-definition colonoscopes (EVIS EXERA III CV- All data were prospectively recorded and stored in a 190; Olympus Inc., Tokyo, Japan) were used by five ex- database. Continuous variables are expressed as the perienced senior endoscopists (experience with > 4000 mean and standard deviation (SD) or median and inter- colonoscopies). These endoscopes utilize high-definition quartile range (IQR) for skewed data and categorical var- images to produce NBI with a brighter quality than that iables as frequencies (%). Continuous variables were obtained with 180 series colonoscopies [16]. compared using the t-test if normally distributed and Histological specimens were collected and revised by the Mann-Whitney U test if not. Categorical variables blinded expert gastrointestinal pathologists. They were were compared using the chi-square test or Fisher not informed which sample was received from the study exact test. Associations with the polyp, serrated polyp protocol. and adenoma miss rates were calculated using odds Patient data included age, sex, weight and height, co- ratios with 95% confidence intervals. Two-tailed P morbidities, personal and family history of CRC and values < 0.05 were considered to be statistically sig- smoking habits. Data from the study protocol included nificant. Statistical analyses were performed using median time to evaluation, time for each withdrawal (ex- STATA/IC software (version 13.1. StataCorp Lp, Col- cluding time of therapeutic polypectomy), lesion histology, lege Station, TX, United States). Fig. 1 Study protocol. Back-to-back colonoscopy study with two randomized groups HD-WLE—NBI and NBI—HD-WLE Riu Pons et al. BMC Gastroenterology (2020) 20:111 Page 4 of 9 In a previous study in SPS patients, NBI showed an in- in 19 patients (46.3%), followed by polyp surveillance in 10 crease of up to three-fold in the detection of HPs com- patients (24.4%). pared with HD-WLE. Assuming a polyp miss rate on At the baseline colonoscopy, 26 of the 41 patients colonoscopy of around 22% [18]. we hypothesized that (63.4%) had at least one serrated polyp larger than 10 NBI would decrease this ratio from 22 to 7% [9]. To de- mm and 15 of the 41 patients (36.6%) had three or more tect this difference with an 80% power and a significance serrated polyps proximal to the sigmoid colon. In the level of 0.05, 81 polyps were required. We assumed that latter 15 patients, both inclusion criteria were present in at least two polyps would be found in these patients and 10 patients. therefore 41 patients (81/2) were required for the study. Comparison of NBI and HD-WLE Results Patient characteristics were similar in the two groups Baseline characteristics (Table 2). There were no major complications due to the Of 60 patients assessed for eligibility, 12 patients were colonoscopy intervention. The mean time from baseline excluded before intervention (eight due to exclusion cri- to colonoscopy review was 6.7 months (95% CI, 5.2–8.3) teria, two declined to participate, and two patients had with no differences between groups. The median time high comorbidity) and seven patients were excluded required for the first withdrawal was similar (11.1 vs after allocation (six were lost to follow-up and one pa- 12.9 min, for HD-WLE and NBI, respectively, P = 0.2). tient had inadequate bowel preparation). Forty-one pa- Statistically significant differences were found for the tients were finally included and randomly assigned: 20 second withdrawal, which was 2 min longer for NBI in patients in the HD-WLE—NBI group and 21 in the the HD-WLE—NBI group than in HD-WLE in the NBI—HD-WLE group (Fig. 2). NBI—HD-WLE group, (9.1 vs 7.1 min, P = 0.05). The patients’ baseline characteristics are shown in A total of 246 suspected polyps were detected with a Table 1. Patients were mostly men (53.7%) with no median size of 3 mm (IQR: 2–4). Histology was obtained major comorbidities. Smoking habits were reported by 25/ in 228: 113 (49.6%) HPs, 28 (12.3%) SSL with no dyspla- 41 patients (60.9%), and current smokers (34.2%) had a sia, 57 (25.0%) adenomas, 29 (12.7%) with normal hist- smoking history of a median of 17.5 pack-years. A family ology and one lipoma (0.4%) (Table 3, Fig. 3). The history of CRC was present in 12 (29.3%) patients with no median number of polyps detected was similar with HD- personal history of CRC or family history of SPS. The in- WLE and NBI on the first withdrawal for each group, dication for the first colonoscopy was mainly due to CRC HD-WLE—NBI group: 2.5 polyps (IQR: 1–4) versus screening based on a positive fecal immunochemical test NBI—HD-WLE group: 3 polyps (IQR: 2–8), P = 0.15. No Fig. 2 CONSORT flow chart diagram of study selection Riu Pons et al. BMC Gastroenterology (2020) 20:111 Page 5 of 9 Table 1 Patient baseline characteristics Table 2 Characteristics between groups Total number of patients (n) 41 HD-WLE—NBI NBI—HD-WLE P value (n = 20) (n = 21) Mean age, years (SD) 59.6 (8.6) Males (n, %) 9 (45) 13 (61.9) 0.35 Male sex (%) 53.7 Age (years, mean) 59.9 59.3 0.84 BMI (Kg/m2, SD) 26.9 (4.2) BMI (Kg/m2, mean) 26.1 27.7 0.24 Diabetes mellitus (n, %) 4 (9.8) Median number of detected 2.5 (1–4) 3 (2–8) 0.15 Smoking habits (n, %) polyps on 1st withdrawal Non-smokers 16 (39.0) (n, IQR) Former smoker 11 (26.8) Median size of resected polyps 3 (2–4) 3 (2–4) 0.8 on 1st withdrawal (mm, IQR) Current smoker 14 (34.2) Mean time 1st withdrawal 11.1 (3.9) 12.9 (4.4) 0.2 Smoking pack-years (median, IQR) 17.5 (14–31) (min, SD) Comorbidities (n, %) Mean time 2nd withdrawal 9.1 (3.7) 7.1 (2.1) 0.05 None 21 (51.2) (min, SD) Obesity 2 (4.9) Mean time from baseline 7.2 (4.4–10.0) 6.2 (4.5–7.9) 0.53 colonoscopy (months, 95% CI) Cardiovascular 9 (22.0) Colonoscope at baseline 0.99 Respiratory 4 (9.8) examination (n, %) Any cancer 2 (4.9) 165 Olympus series 2 (10.0) 2 (9.5) Multiple pathology 3 (7.3) 180 Olympus series 7 (35.0) 7 (33.3) Family history of CRC (n, %) 12 (29.3) 190 Olympus series 11 (55.0) 12 (57.1) Personal history of CRC (n, %) 0 HD-WLE high-definition white light endoscopy, NBI narrow-band imaging, BMI body mass index, SD standard deviation, IQR interquartile range Personal history of abdominal surgery (n, %) 17 (41.5) Colonoscopy indication (n, %) NBI—HD-WLE group. Only two were detected with CRC screening 19 (46.3) HD-WLE on the first withdrawal from the HD-WLE— Surveillance for colonic neoplasia 10 (24.4) NBI group, and the remaining five were detected by NBI Diagnosis or clinical symptoms 6 (14.6) (three on first withdrawal and two on the second). Family history of CRC screening 5 (12.2) No differences were observed in the polyp miss rate Therapeutic colonoscopy 1 (2.4) between HD-WLE and NBI, calculated as the percentage Baseline inclusion criteria (n, %) a of missed polyps at the second withdrawal with regard to the first: 21.3 and 26.1% (OR 0.77, 95% CI: 0.43–1.38) One or more serrated polyp larger than 10 mm 26 (63.4) for NBI and HD-WLE, respectively. The serrated polyp Three or more serrated polyps 15 (36.6) miss rate (including proximal hyperplastic and serrated Type of colonoscope at baseline examination lesions, both larger than 5 mm) was 25.0 and 28.6% (OR 165 Olympus series 4 (9.8) 0.83, 95% CI: 0.19–3.63) for NBI and HD-WLE, and the 180 Olympus series 14 (34.1) adenoma miss rate was 21.2 and 29.2% (OR 0.65, 95% 190 Olympus series 23 (56.1) CI: 0.2–2.13) for NBI and HD-WLE, respectively. After reassessment, nine patients were reclassified as Mean time from baseline to colonoscopy 6.7 (5.2–8.3) review (months, 95% CI) having SPS based on 2010’s criteria and the new 2019’s BMI body mass index, SD standard deviation, IQR interquartile range, CRC criteria: six patients had criterion 1 (at least five prox- colorectal cancer, CI confidence interval imal serrated polyps, all being ≥5 mm in size, two of a All polyps were proximal to the sigmoid colon which were larger than 10 mm in diameter), and three patients had criterion 2 (more than 20 serrated polyps of differences were observed in the detection rate of ser- any size distributed throughout the colon, with ≥5 being rated lesions by NBI versus HD-WLE: 47.4% vs 51.9% proximal to the rectum). These patients represented (OR 0.84, 95% CI: 0.37–1.91) for the first and second 21.95% (9/41) of the individuals reassessed (Table 4). withdrawal, respectively. Thirty-four relevant serrated lesions, defined as any Discussion polyp larger than 5 mm, were detected proximal to the In this randomized cross-over study, we found that the sigmoid junction, with no differences between groups use of NBI versus HD-WLE in patients with a history of (P = 0.33). Seven serrated lesions were larger than 10 relevant serrated lesions not fulfilling SPS criteria was mm: four in the HD-WLE—NBI group and three in the not superior in detecting polyps, including serrated Riu Pons et al. BMC Gastroenterology (2020) 20:111 Page 6 of 9 Table 3 Histology of all resected polyps in the two groups HD-WLE—NBI group NBI—HD-WLE group HD-WLE (n, %) NBI (n, %) NBI (n, %) HD-WLE (n, %) Total (n, %) First withdrawal Second withdrawal First withdrawal Second withdrawal Hyperplastic 55 (64.7) 12 (52.2) 35 (36.1) 11 (47.8) 113 (49.6) Sessile serrated lesion 5 (5.9) 2 (8.7) 19 (19.6) 2 (8.7) 28 (12.3) Adenoma 17 (20.0) 7 (30.4) 26 (26.8) 7 (30.4) 57 (25) Normal 8 (9.4) 2 (8.7) 17 (17.5) 2 (9.3) 29 (12.7) Other (lipoma) – – – 1 (4.4) 1 (0.4) Total (n) 85 23 P = 0.23 97 23 228 P = 0.32 HD-WLE high-definition white light endoscopy, NBI narrow-band imaging lesions. However, reassessment of these patients, inde- differences, but found a trend toward higher detection of pendently of the evaluated technique, allowed one-fifth serrated lesions with NBI than with HD-WLE (0.51 versus of them to be reclassified as having SPS. In addition, we 0.39 serrated lesions per patient, P = 0.085) [11]. found no differences in the polyp miss rate on first One of the most salient findings of our randomized evaluation with NBI or HD-WLE (21.3% versus 26.1%). controlled study is that after the scheduled follow-up This prospective study confirms previously published colonoscopy, nine patients (22%) were reassessed as results on the non-superiority of NBI in the detection of meeting SPS criteria, both the 2010’s and the recently serrated lesions compared with HD-WLE. A multicenter updated 2019’s criteria, with important clinical implica- randomized cross-over trial of NBI and HD-WLE in 51 tions in these patients. A similar finding was observed in patients with SPS concluded that the two techniques a retrospective study of a fecal immunochemical test were similar, showing a non-significant trend in the (FIT)-based CRC screening program [12], in which a 1- polyp miss rate: 20% with NBI (95% CI, 15–27) versus year reassessment colonoscopy of arbitrary selected 29% with HD-WLE (95% CI, 22–36), P = 0.065. This dif- participants with previous serrated polyps detected by ference was driven by the lower HP miss rate with NBI chromoendoscopy and high-definition endoscopes sub- [10]. Moreover, a recent randomized controlled trial stantially improved SPS detection in those with proximal with NBI and HD-WLE using the Olympus 190 series for serrated lesions. the detection of proximal colon serrated lesions in routine Without endoscopic reevaluation, most societies, such colonoscopy patients showed no statistically significant as the US Multi-Society Task Force, the European Fig. 3 Percentage of polyps detected for each group (HD-WLE—NBI and NBI—HD-WLE) and technique distributed by localization and withdrawal. The x-axis shows withdrawals with the two techniques for each anatomical location. The first column shows the first withdrawal with HD-WLE for HD-WLE—NBI group (a) or with NBI for NBI—HD-WLE group (b) and the second column shows the results of the second withdrawal with the opposite. The y-axis shows the polyp detection rate distributed by histology. Abbreviations: HD-WLE: high-definition white light endoscopy; NBI: narrow-band imaging; SSL: sessile serrated lesion; HP: hyperplastic polyp Riu Pons et al. BMC Gastroenterology (2020) 20:111 Page 7 of 9 Table 4 Characteristics of patients with reassessment of SPS criteria Patient Baseline colonoscopy Follow-up colonoscopy SPS 2010’s criteria SPS 2019’s criteria #1 2 SSL (10 and 15 mm) 1 SSL (10 mm) No. 1 No. 1 1 TVA HGD (35 mm) 4 HP (3, 3, 6 and 8 mm) 1 TA LGD (< 10 mm) 1 TA LGD (< 10 mm) #2 2 SSL (11 and 12 mm) 1 SSL (5 mm) No. 1 No. 1 1 SSL (8 mm) 2 HP (4 and 9 mm) 1 HP (7 mm) 1 TA LGD (< 10 mm) #3 2 SSL (5 and 8 mm) 2 SSL (10 and 15 mm) No. 1 No. 1 1 HP (6 mm) 4 HP (2, 4, 6 and 10 mm) 3 TA LGD (< 10 mm) 1 TA LGD (< 10 mm) #4 2 SSL (13 and 15 mm) 2 HP (6 and 10 mm) No. 1 No. 1 2 SSL (8 and 10 mm) 2 TA LGD (< 10 mm) 1 TVA HGD (20 mm) #5 1 SSL (10 mm) 1 SSL (20 mm) No. 1 No. 1 1 SSL (6 mm) 5 SSL (2, 2, 4, 4 and 8 mm) 4 HP (4, 5, 5 and 8 mm) 3 HP (3, 5 and 8 mm) 3 TA LGD (< 10 mm) 3 TA LGD (< 10 mm) #6 1 SSL (< 10 mm) 1 SSL (< 10 mm) No. 3 No. 2 11 HP (< 10 mm) 9 HP (< 10 mm) 4 TA LGD (< 10 mm) 4 TA LGD (< 10 mm) #7 15 HP (< 10 mm) 1 SSL (< 10 mm) No. 3 No. 2 1 TSA (15 mm) 7 HP (< 10 mm) 5 TA LGD (< 10 mm) #8 1 SSL (< 10 mm) 2 SSL (< 10 mm) No. 3 No. 2 1 TSA (11 mm) 8 HP (< 10 mm) 10 HP (< 10 mm) #9 1 SSL (20 mm) 1 SSL (12 mm) No. 1 No. 1 1 HP (4 mm) 2 SSL (5 and 6 mm) 2 TA LGD (< 10 mm) 3 HP (3, 3 and 5 mm) 1 TA LGD (< 10 mm) SPS serrated polyposis syndrome, SSL sessile serrated lesion, HP hyperplastic polyp, TVA tubulovillous adenoma, TA tubular adenoma, TSA traditional serrated adenoma, LGD low grade dysplasia, HGD high grade dysplasia. The World Health Organization (WHO) for diagnosis SPS of 2010’s criteria: criterion no.1 refers to at least five serrated polyps proximal to the sigmoid colon, two of which are larger than 10 mm in diameter; SPS criterion no. 2 refers to any number of serrated polyps occurring proximal to the sigmoid colon in an individual with a first-degree relative with SPS; SPS criterion no. 3 refers to more than 20 serrated polyps of any size distributed throughout the colon. The WHO’s 2019 criteria: SPS criterion no. 1 refers to five or more serrated lesions/polyps proximal to the rectum, all being ≥5 mm in size, with at least two of which are larger than 10 mm in diameter; SPS criterion no. 2 refers to more than 20 serrated lesions/polyps of any size distributed throughout the colon, with ≥5 being proximal to the rectum Society of Gastrointestinal Endoscopy and recently the we applied these criteria to our study, only 12 of our 41 British Society of Gastroenterology, classify these pa- (29.3%) patients met the threshold for endoscopic re- tients as high risk and recommend they undergo surveil- evaluation, and two of the nine patients with SPS were lance colonoscopy at a 3-yearly interval (patients with at misclassified. least one sessile serrated lesion or a traditional serrated These results have implications for participants in adenoma ≥10 mm or with a dysplastic component (weak CRC screening programs. In a study of five European recommendation, low quality evidence) [7, 19, 20]. The cohorts, the rate of any serrated lesion was between results of our study emphasize the clinical implications 15.1 and 27.2% (1.1 and 2.6% with at least one ser- of the addition of high-quality endoscopic reassessment rated lesion larger than 10 mm), with SPS being diag- in patients with relevant serrated lesions, allowing nosed in 0.4 to 0.8% after a follow-up colonoscopy (1: around 20% of them to be reclassified as having SPS and 127 individuals were diagnosed with SPS during col- to undergo close surveillance. onoscopy follow-up in the Spanish FIT-based CRC Of note, our inclusion criteria (more than one serrated screening cohort) [21]. Identification of patients with lesion ≥10 mm or more than three serrated lesions prox- SPS has important implications related to the higher imal to the sigmoid colon) were not based on pre- risk of CRC. Indeed, in a large multicenter study con- established criteria but involved a high-risk group ac- ducted in Spain, CRC was diagnosed in 15.8% of all cording to clinical guidelines. In the aforementioned patients with SPS with a cumulative risk of CRC of retrospective study [12], the factors associated with SPS 1.9% at 5 years [22]. Therefore, identifying patients reassessment were five or more proximal serrated lesions who require close surveillance is essential to decrease or two or more sessile serrated polyps ≥ 10 mm. When the incidence of CRC. Riu Pons et al. BMC Gastroenterology (2020) 20:111 Page 8 of 9 This study has some limitations. First, it is a single- Authors’ contributions center study in a small number of patients based on a FRP – Procedural endoscopist, collected data, analyzed data, wrote manuscript. MA – Study design, analyzed data, critical revision of the sample size calculation. However, given that we found manuscript. DN – Supervised histophatological samples. MAAG – Procedural no statistically significant differences, it is likely that a endoscopist, collected data, critical revision of the manuscript. AS – larger study would probably yield similar results. In Procedural endoscopist, collected data. JMD – Procedural endoscopist, collected data. LB – Procedural endoscopist, collected data. XB – Study addition, the study was underpowered to show differ- design, analyzed data, critical revision of the manuscript. All the co-authors ences in the detection of large SSL > 10 mm. Secondly, had access to the study data, they had reviewed and approved the final back-to-back colonoscopies were performed by the same manuscript. endoscopist. Although it would have been better if two Funding different endoscopists had performed each withdrawal This work has not been supported by any financial grant. colonoscopy, we considered this study design to be the Availability of data and materials most effective way to reduce interobserver variation [18] The dataset generated and analyzed during the study is stored in a secure and to be the most feasible in practice. The main advan- localized database but is available from the corresponding author in an tages are that the presence of a single endoscopist in the anonymous format on reasonable request. room eliminates other confounders such as differences Ethics approval and consent to participate in skill or experience between distinct endoscopists. The study protocol was done in accordance to the ethical guidelines of the Therefore, the withdrawal time and polyp/adenoma de- 1975 Helsinki Declaration. The study protocol was approved by the tection rate were identical for each endoscopist. Finally, institutional review board of Parc de Salut Mar on 6 February 2015 (2014/ 5964/I) and was registered at ClinicalTrials.gov (Identifier: NCT02406547) on 2 although NBI is designed for use at a close distance from April 2015. A written informed consent was obtained from all included the mucosa to visualize vascular and pit patterns, our patients before study inclusion. Our study adheres to CONSORT guidelines. study was not designed to evaluate the accuracy of the Consent for publication endoscopists in characterizing detected lesions. Not applicable. Competing interests Conclusion The authors declare that they have no competing interests. Our study shows that in patients with previously Author details resected relevant serrated lesions there were no differ- 1 Gastroenterology Department, Hospital del Mar, Passeig Marítim 25-29, ences in the use of NBI or HD-WLE in the detection of 08003 Barcelona, Spain. 2IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain. 3Department of Medicine, Autonomous University of serrated lesions, with the two techniques having a simi- Barcelona, Barcelona, Spain. 4Pompeu Fabra University, Barcelona, Spain. lar polyp miss rate. We suggest that NBI is an option in 5 Pathology Department, Hospital del Mar-IMIM, Barcelona, Spain. clinical practice but not necessarily as a matter of rou- Received: 6 March 2019 Accepted: 31 March 2020 tine. Notably, the results of our study emphasize the im- portance of an exhaustive examination in patients with suspicion of relevant serrated lesions. Although further References 1. 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