Abstract Near-Focus Versus Normal-Focus Narrow Band Imaging Colonoscopy in Diagnosis of ColorectalPolyps Based on Combined NICE and WASP Classification in Routine Colonoscopy: A Randomized Controlled Trial

doi:10.21203/rs.3.rs-809507/v1

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Abstract Near-Focus Versus Normal-Focus Narrow Band Imaging Colonoscopy in Diagnosis of ColorectalPolyps Based on Combined NICE and WASP Classification in Routine Colonoscopy: A Randomized Controlled Trial

https://doi.org/10.21203/rs.3.rs-809507/v1

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Near-focus versus Normal-focus Narrow Band Imaging Colonoscopy in Diagnosis of Colorectal Polyps based on Combined NICE and WASP Classification in routine colonoscopy: a Randomized Controlled Trial

Nisa Netinatsunton¹, Natcha Cheewasereechon¹Tanawat Pattarapuntakul¹, Jaksin Sottisuporn¹, Kanet Kanjanapradit², Bancha Ovartlarnporn¹

Background: NICE (NBI International Colorectal Endoscopic) and WASP (Workgroup on Serrated Polyps and Polyposis) classification were developed for optical diagnosis of adenoma and sessile serrated polyps, respectively. Near focus NBI with NICE combined with WASP criteria for optical diagnosis of colonic polyps has not been assessed formerly.

Aims: To compare the accuracy of near focus NBI (group A) with normal focus NBI (group B) in real time optical diagnosis of colorectal polyps using combined NICE and WASP criteria.

Methods: 118 out of 362 patients with 227 polyps were recruited. 62 patients with 130 polyps (3 lost polyps) were assigned to group A and 56 patients with 106 polyps (6 lost polyps) were assigned to group B. Optical diagnoses were compared with pathological reports.

Results: The performance of optical diagnosis of neoplastic polyps in group A compared with group B in terms of accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) was not significantly difference (76%, 72%, 81%, 86%, 64%, in group A, and 71%, 66%, 83%, 90%, 51%, in group B, respectively). Combined NICE and WASP criteria provided all false positive diagnosis of sessile polyps as serrated polyps in 31 (15.9%).

Conclusions: Near-focus NBI was not superior to normal-focus NBI in in optical diagnostic of neoplastic polyps using NICE criteria. Combined NICE and WASP classification yielded all false positive in the diagnosis SSAPs in our study. Routine real life optical diagnosis of polyps is still not recommended.

Trial registration: Clinical Trials.gov, NCT 04831814, was retrospectively registered on 04/01/2021.

Gastroenterology & Hepatology

Colorectal polyp

NICE classification

WASP classification

Near-focus narrow band imaging

Optical diagnosis

Colorectal cancer is the third most common cancer and the second most common cause of cancer-related death worldwide, whereas screening colonoscopy with adenoma resection had been reported to reduce the risk of colorectal cancer along with the cancer associated mortality by approximately 53% − 80% (1, 2). However, nearly half of the small polyps are non-neoplastic with negligible potential to transform to cancer, so polypectomies of these polyps that imposed patients to the risks of bleeding as well as perforation together with the increased cost incurred by tissue processing, are unnecessary (2, 3). Image enhancing technologies have been developed to help endoscopist differentiating neoplastic from non-neoplastic lesions. Narrow Band Imaging (NBI) is an image enhancing technology utilizing narrow-band light filters to improve visualization of mucosal surface architecture and vascular pattern (4). There were many studies including multiple meta-analyses assessing the accuracy of colonoscopy with NBI imaging for differentiating between neoplastic and non-neoplastic polyps in the literature with variable results (5–14). The efficacy of NBI for optical diagnosis of polyp in terms of sensitivity varied from 85–92.2% (10–13) and one meta-analysis showed the higher accuracy of studies from academic centers, with experienced endoscopists and high confidence optical diagnosis (14).

The NBI International Colorectal Endoscopic had proposed the NICE criteria to differentiate neoplastic lesions, namely, adenoma and deep submucosal invasive cancer from hyperplastic polyp (15, 16). Although, this classification system showed good correlation between the optical diagnosis and histopathological diagnosis in some pilot studies by expert endoscopists, while other study in community setting showed inferior result (3, 17, 18).

Furthermore, NICE classification does not address neoplastic sessile serrated adenomas/polyps (SSAPs), which is difficult to differentiate from hyperplastic polyps by colonoscopy even using NBI with NICE criteria (19–21). A meta-analysis of 10 studies (8 with magnifying NBI and 2 with standard NBI) showed pooled sensitivity of 0.6 and pooled specificity of 0.75 for optical diagnosis of SSAPs (22). Endoscopic features of SSAPs as validated by international experts for NBI included the following characters, 1 cloud like surface, 2 indistinct borders, 3 irregular shapes, and 4 dark spots inside the crypts (23), and this study showed that implementation of all 4 criteria yielded 93% accuracy. The Workgroup serrAted polypS and Polyposis (WASP) had developed a classification combining the NICE classification and the criteria for SSAPs mentioned above to distinguish between hyperplastic and SSAPs and this study showed WASP criteria significantly improved the accuracy of optical diagnosis despite the using of 2 out of 4 features of SSAPs (24). One study evaluated the accuracy of optical diagnosis of NBI without optic magnification by using combined NICE and WASP classification by nonexpert endoscopists showed moderate accuracy for real-time optical diagnosis of colorectal lesions (25). However, WASP has not been widely validated.

The introduction of a novel dual focus capability (Olympus Co., Tokyo, Japan) enables optical magnification of up to 65x in near focus (NF) with a push of a button of the endoscope compared with 52x in normal standard focus (SF) (26). There were a few studies assessing diagnostic accuracy of NF NBI with or without comparing with SF NBI (26–30) and the performance of NF NBI were reported to have high accuracy in series reports or better than SF NBI in other reports and be similar to SF NBI in one study. To the best of our knowledge, there is no study of NF NBI that incorporated NICE and WASP in optical diagnosis of colonic polyps. We, therefore, aim to compare the accuracy of optical diagnosis between NF and SF NBI by using combined NICE and WASP criteria by NBI-non-expert endoscopists.

Patients selection.

This study was a prospective-randomized trial conducted at the NKC institute, a tertiary center, Faculty of Medicine, Prince of Songkla University. Patients aged 18–75 years who were scheduled for colonoscopy at NKC institute from April 2019 to January 2020 were enrolled. Patients with inflammatory bowel disease, polyposis syndrome, documented colonic mass, active gastrointestinal bleeding, pregnancy, inadequate bowel preparation (Boston bowel preparation score (BBPS) < 5) (31) and any contraindications for polypectomy were excluded.

Study designs and colonoscopy procedure.

The study protocol was approved by the Ethics Committee of Faculty of Medicine, Prince of Songkla University (registered no. 61355143), and was registered with Clinical Trials.gov (ID: NCT 04831814) on 04/01/2021. The study was conducted in accordance with the Helsinki Declaration. Informed consent was obtained from each patient prior to entry to the study. Randomization codes were generated by a computer using a block of two and concealed in envelopes. Endoscopist enrolled by using the sealed envelope previously prepared before the entry. Patients who consented to the study were randomized to either the NF NBI (group A) or the SF NBI (group B) according to the randomization codes in the sealed envelopes at the start of the procedure.

Bowel preparation.

Either a split dose of 90 ml. solution of monobasic sodium phosphate + dibasic sodium phosphate (Swiff®) or a hospital prepared formula of polyethylene glycol solution were used for bowel preparation. The quality of bowel preparation was assessed according to BBPS scale (31).

Colonoscopy procedure.

All the procedures were performed with a high definition colonoscope (Evis Exera III CF HQ 190 L/I with DF capability, Olympus, Tokyo, Japan). NF mode provides 2–6 mm. depth of field with 65X zoom at 2 mm distance and SF mode provides 5-100 mm. depth of field with 52X zoom at 5 mm distance (26). No prior formal training for NBI image interpretation was done for the endoscopists participating in the study and all the endoscopists were not blinded to the model of NBI colonoscope. All the staff-endoscopists are familiar with NICE criteria but not quite familiar with WASP criteria during routine colonoscopy. Colonoscopy was performed by a trainee under supervision of a staff or by a staff under conscious sedation using midazolam and pethidine or fentanyl according to our institute sedation protocol. All colonoscopies were performed initially with high-definition white light, and if a polyp was detected it was further evaluated with NBI mode. The optical diagnoses of polyps were aided by using colour images charts of NICE and WASP classification in each endoscopic room as the reference standards (16, 24). The confidence of the endoscopists in making optical diagnosis was not assessed in this study. In group A, optical diagnosis of polyps was performed by the NF NBI mode and in group B, by the SF NBI mode. Each polyp was evaluated in real time by the best image captured then stored in a computer by the Endo-Smart Program® version 7. The size of polyp was estimated using the width of an opened biopsy forceps as the reference. The morphology of polyp was described as pedunculated (O-Ip), sessile (O-Is), and flat polyp (O-IIb) (32). The diminutive polyp was defined as polyp smaller than 5 millimetres (26). The location, size, number, morphology, and optical diagnosis of polyps were recorded in a data recording form. The follow up schedule was based on clinical context and the discretion of the endoscopists.

Polyp characterization.

The optical diagnosis of each polyp was made according to the NICE and WASP classification. Based on the NICE guideline (16), polyps were classified according to the lesion colour, microvascular architecture, and pit pattern of mucosa as: Type 1- hyperplastic, Type 2 – adenomatous and superficial mucosal invasive cancer (< 1000 µm) and Type 3 – deep mucosal invasive cancer (> 1000 µm). For sessile polyps, additional assessment was done based on the WASP classification (24). SSAPs was diagnosed if two of the following features, 1) clouded surface, 2) indistinctive border, 3) irregular shape and 4) dark spots inside crypts, were present (24)

Pathological polyp evaluation.

All polyps were removed by using a biopsy forceps, a cold snare or a hot snare at the discretion of the attending staff and the resected specimens were sent for histopathological examination. All the histology assessments were done by one pathologist (KK) according to WHO criteria (33). No validation for pathologist accuracy by an independent pathologist was done in this study.

End points.

The primary outcome was the performance of NF NBI compared with SF NBI in, 1 the optical diagnosis of polyps and 2 in distinguishing serrated adenoma from hyperplastic polyp for sessile polyps, by using histologic evaluation as the gold standard. The performance was assessed by accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of NF NBI compared with SF NBI in optical diagnosis of polyps.

Sample size calculation.

Sample size was calculated with the assumption that NF NBI was 10% superior to SF NBI. The number of polyps required were 252 in each group in order to detect a difference in accuracy with the power of 80% at the significant level α = 0.05, calculated by using comparison of two proportions based on the accuracy of SF NBI = 75% (34, 35).

Statistical analyses.

Continuous variables were presented as mean ± (SD) and statistical analysis was performed by using Student’s T test. Discrete variables were presented as percentage. Accuracy, sensitivity, specificity, PPV and NPV were presented as percentage and Chi-square test, or Fischer exact test was done for analysis where appropriate. P-value less than 0.05 was considered statistically significant. All statistical analyses were conducted by using R-program version 3.6.1.

There were 362 patients recruited from April 2019 till January 2020 and 118 cases of these 362 patients with polyp(s) detected at colonoscopy were eventually randomized into the study (Fig. 1). A total number of 236 polyps were detected for the whole group, but 9 polyps (3 of 130 polyps in group A, 6 of 106 polyps in group B) were lost during the process of retrieval leaving 227 polyps eventually available for pathological assessment. The missing polyps were not significantly difference between the two groups (Chi-square p = 0.345).

Among the 227 polyps, 144 (63.4%) of the polyps were adenoma, 79 (34.8%) were hyperplastic polyps and 4 (1.7%) were cancer according to histological results. There were no SSAPs detected in this study. The most common site of polyps’ location was sigmoid colon (30%) and 188 of 227 (82.8%) polyps were diminutive type. The polyp detection rate (PDR) and adenoma detection rate (ADR) for the whole group of 362 patients were 118 of 362 (32.5%) and 86 of 362 (23.7 %) respectively.

Sixty-two patients with 130 polyps including 3 lost polyps leaving 127 polyps available were assigned to group A and 56 patients with 106 polyps including 6 lost polyps leaving 100 polyps available were allocated to group B (Fig. 1). There was no significant difference between the two groups regarding age, sex, indications for colonoscopy, total procedure time, withdrawal time, cecal intubation rate, complication rate, polyp size, polyp morphology, polyp histology and polyp locations (Table 1). The quality of bowel preparation in group A was significantly better than group B (P = 0.01). There were 76 adenomatous polyps and 2 cancers by histology in group A and 68 adenomatous polyps and 2 cancers in group B, but the differences were not statistically significant (P = 0.433).

Table 1

Baseline characteristics, colonoscopic procedure details and polyp’s characteristics of group A and B.
	Near-focus(n = 62) (A)	Norma-focus(n = 56) (B)	p-value
Age (year) (mean ± SD)	59.3 ± 8.7	60 ± 8	0.631
Sex (male/female)	40/22	34/22	0.814
Indication CRC screening (%) Diagnosis (%)	38 (61.3) 24 (38.7)	29 (51.8) 27 (48.2)	0.557
Boston bowel preparation score (mean) (%) BBPS = 6 (%) BBPS = 7 (%) BBPS = 8 (%) BBPS = 9 (%)	0 (0) 1 (1.6) 0 (0) 61 (98.4)	2 (3.6) 0 (0) 4 (7.1) 50 (89.3)	0.01
Total procedure time (minute)(mean ± SD)	52.9 ± 22	54.5 ± 27.3	0.732
Withdrawal time (minute) (mean ± SD)	19.6 ± 11.3	24.2 ± 20.9	0.134
Cecal intubation (n) (%)	59 (95.2)	52 (92.9)	0.707
Complications (n) (%)	0 (0)	1 (1.8)	0.475
Polyp number (n)*	127	100	0.125
Polyp size (mm) (mean ± SD)	3.8 (2.1)	4.6 (5.2)	0.318
Polyp morphology (n) (%) Sessile Pedunculated Flat	113 (89) 12 (9.4) 2(1.6)	82 (82) 17 (17) 1(1)	0.314
Polyp location (n) (%) Cecum Ascending colon Transverse colon Descending colon Sigmoid colon Rectum	10 (7.9) 23 (18.1) 24 (18.9) 18 (14.2) 35 (27.6) 17 (13.4)	11 (11) 14 (14) 16 (16) 17 (17) 33 (33) 9(9)	0.666
Histopathology (n) (%) Hyperplastic Adenomatous Cancer	49 (38.5) 76 (59.8) 2 (2.4)	30 (30) 68 (68) 2 (2)	0.433
CRC: colorectal cancer; BBPS: Boston bowel preparation scores. * Available for histologic assessment.

Primary end point (Table 2.)

Table 2

Accuracy, sensitivity, specificity, PPV and NPV of NICE criteria in group A and B.
	Near-focus (A) n = 127	95% CI	Normal-focus (B) n = 100	95% CI	p-value
Neoplastic (n = 149)	79		70
Accuracy	76	67–83	71	61–80	0.522
Sensitivity	72	61–82	66	53–77	0.445
Specificity	81	67–91	83	65–94	0.854
PPV	86	76–94	90	79–97	0.514
NPV	64	51–76	51	36–66	0.086
Hyperplastic polyp (n = 78)	48		30
Accuracy	76	67–83	71	61–80	0.522
Sensitivity	81	67–91	83	65–94	0.854
Specificity	72	61–82	66	53–77	0.445
PPV	64	51–76	51	36–66	0.086
NPV	86	76–94	90	79–97	0.514
Adenomatous polyp (n = 144)	76		68
Accuracy	75	66–82	69	59–78	0.431
Sensitivity	70	58–80	62	49–73	0.296
Specificity	82	69–92	84	67–95	0.851
PPV	85	74–93	89	77–96	0.528
NPV	65	52–76	51	37–65	0.063
PPV: positive predictive value; NPV: negative predictive value

The accuracy, sensitivity, specificity, PPV, and NPV of NICE in optical diagnosis of neoplastic polyps were 76%, 72%, 81%, 86%, 64%, respectively in group A and 71%, 66%, 83%, 90%, 51%, respectively in group B. The performance of NF NBI was not better than SF NBI in optical diagnosis of neoplastic polyps (p = 0.522, p = 0.445, p = 0.854, p = 0.514 and p = 0.086, respectively). NPV in NF NBI was higher than SF NBI, even though, it was statistically not significantly different (p = 0.086).

The accuracy, sensitivity, specificity, PPV, and NPV of NICE to diagnose hyperplastic polyps were 76%, 81%, 72%, 64%, 86% in group A and 71%, 83%, 66%, 51%, 90% in group B, however, there were no significant difference in performance between NF NBI and SF NBI in terms of optical diagnosis (p = 0.522, p = 0.854, 0.445, 0.086, 0.514, respectively).

The accuracy, sensitivity, specificity, PPV, and NPV of NICE in diagnosis of adenomatous polyps were 75%, 70%, 82%, 85%, 65% in group A and 69%, 62%, 84%, 89%, 51% in group B, even though, there were no significant difference between NF NBI compared with SF NBI (p = 0.431, p = 0.296, 0.851, 0.528, 0.063, respectively), but the NPV of NF NBI was higher than SF NBI showing a trend of NF NBI superior to SF NBI (p = 0.063).

Outcome measure according to interobserver variations.

The capability of each endoscopist in optical diagnosis of polyps using the NICE classification (excluding WASP for SSAPs) compared with histological analysis by using Cohen’s K-coefficient was 79.21% (Kappa = 0.579) for endoscopist I, 64.58% (Kappa = 0.431) for endoscopist II, 54.55% (Kappa = -0.009) for endoscopist III, and 50% (Kappa = 0.213) for endoscopist IV.

The accuracy of NICE classification for optical diagnosis of neoplastic polyps of the whole group (A and B) by the endoscopists with higher Kappa (Kappa 0.579 and 0.431) was 76%, it was significantly higher than 57% by the endoscopists with lower Kappa (Kappa 0.0213 and − 0.0009) (p = 0.007). The accuracy of the NICE classification in optical diagnosis of neoplastic polyps by the endoscopists with higher Kappa was 79 % in group A, and was higher than 71 % in group B, however the difference was not significant (p = 0.253) (Table 3), whereas the accuracy of optical diagnosis by the NICE classification for neoplastic polyps by the endoscopists with lower Kappa was 55 % in group A that was lower than 60 % in group B, but the difference failed to reach statistical significance (p = 0.567) (Table 4).

Table 3

Accuracy, sensitivity, specificity, PPV and NPV by NICE criteria of the endoscopists with higher Kappa in optical diagnosis of polyps.
	Near-focus (A) n = 95	95% CI	Normal-focus (B) n = 82	95% CI	p-value
Neoplastic (n = 113)	58		55
Accuracy	79	71–86	71	60–80	0.253
Sensitivity	75	63–84	65	52–77	0.165
Specificity	86	72–95	83	65–94	0.696
PPV	90	79–96	89	75–96	1.000
NPV	67	53–79	54	39–69	0.083
Hyperplastic polyp (n = 64)	37		27
Accuracy	79	70–86	71	61–80	0.253
Sensitivity	86	72–95	83	65–94	0.696
Specificity	75	63–84	65	52–77	0.165
PPV	67	53–79	54	39–69	0.083
NPV	90	79–96	89	75–96	1.000
Adenomatous polyp (n = 108)	55		53
Accuracy	78	70–85	69	58–78	0.199
Sensitivity	72	60–83	60	47–73	0.101
Specificity	87	74–95	84	67–95	0.688
PPV	89	78–96	88	73–96	1.000
NPV	68	54–79	54	39–68	0.059
PPV: positive predictive value; NPV: negative predictive value

Table 4

Accuracy, sensitivity, specificity, PPV and NPV by NICE criteria of the endoscopists with lower Kappa in optical diagnosis of polyps.
	Near-focus (A) n = 32	95% CI	Normal-focus (B) n = 18	95% CI	p-value
Neoplastic (n = 36)	21		15
Accuracy	55	35–75	60	32–84	0.567
Sensitivity	41	18–67	58	28–85	0.023
Specificity	80	44–97	67	9–99	0.054
PPV	78	40–97	88	47–100	0.090
NPV	44	22–69	29	4–71	0.039
Hyperplastic polyp (n = 14)	11		3
Accuracy	55	35–74	60	32–84	0.567
Sensitivity	80	44–97	67	9–99	0.054
Specificity	41	18–67	58	28–85	0.024
PPV	44	22–69	29	4–71	0.039
NPV	78	40–97	88	47–100	0.090
Adenomatous polyp (n = 36)	21		15
Accuracy	55	35–75	57	41–72	0.567
Sensitivity	41	18–67	48	29–67	0.024
Specificity	80	44–97	77	46–95	0.054
PPV	78	40–97	82	57–96	0.090
NPV	44	22–69	40	21–61	0.039
PPV: positive predictive value; NPV: negative predictive value

The sensitivity and NPV of NICE classification in predicting neoplastic polyps of the whole group (A and B) by the endoscopist with higher Kappa were 72 % and 62 %, these were significantly higher than 48 % and 49 % by the endoscopists with lower Kappa (p = 0.002 and p = 0.004, respectively), but the specificity and PPV were not different between the two groups of endoscopists, namely 83 % and 88 % for the endoscopists with higher Kappa compared with 77 % and 82 % for the endoscopists with lower Kappa; (p = 0.207 and p = 0.228, respectively).

The sensitivity, specificity, PPV, and NPV of NICE classification in predicting neoplastic polyps by the endoscopists with higher Kappa were 75%, 86%, 90%, 67% in group A and 65%, 83%, 89%, 54% in group B, respectively, but they were not significantly difference. (p = 0.165, p = 0.696, p = 1.000 and p = 0.083, respectively). The sensitivity, specificity, PPV, and NPV of NICE classification in predicting neoplastic polyps by the endoscopists with lower Kappa were 41%, 80%, 78%, 44% in group A and 58%, 67%, 88%, 29% in group B, respectively. The 41% sensitivity in group A was significantly lower than 58% in group B, in contrary, the 44% NPV of group A was significantly higher than 29% NPV in group B (p = 0.023 and p = 0.039, respectively), however, there were no significant difference of specificity and PPV between the two groups (p = 0.054 and p = 0.090, respectively).

For diminutive polyps.

There were no statistical differences regarding accuracy, sensitivity, specificity, PPV and NPV in optical diagnosis of diminutive neoplastic polyps, hyperplastic polyps and adenomas between group A and group B (Table 5.) When performance was assessed by comparing the whole group (A and B) with diminutive group (A and B), the accuracy, sensitivity, specificity, PPV and NPV of NICE classification in predicting neoplastic polyps were 74%, 69%, 82%, 88%, 58% for the whole group and were 68%, 59%, 82%, 82%, 58% for the diminutive group, nevertheless, the differences were not significant (Chi-square test, p = 0.436, p = 0.185, p = 1.000, p = 0.322, and p = 1.000, respectively).

Table 5

Accuracy, sensitivity, specificity, PPV and NPV by NICE criteria in the polyps ≤ 5 mm.
	Near-focus (A) n = 109	95%CI	Normal-focus (B) n = 78	95%CI	p-value
Neoplastic (n = 110)	61		49
Accuracy	72	62–79	64	52–74	0.289
Sensitivity	64	51–76	53	38–67	0.151
Specificity	81	67–91	83	64–94	0.854
PPV	81	67–91	84	66–95	0.709
NPV	64	51–76	51	36–66	0.086
Hyperplastic polyp (n = 77)	48		29
Accuracy	72	62–79	64	52–75	0.289
Sensitivity	81	67–91	83	64–94	0.854
Specificity	64	51–76	53	38–67	0.151
PPV	64	51–76	51	66–95	0.709
NPV	72	62–79	64	52–75	0.289
Adenomatous polyp (n = 108)	59		49
Accuracy	71	62–79	61	49–72	0.179
Sensitivity	63	49–75	49	34–64	0.064
Specificity	82	69–91	83	64–94	1.000
PPV	80	66–91	83	64–94	0.716
NPV	65	52–77	49	34–64	0.032

Outcome of WASP criteria in sessile polyps.

The WASP criteria classified polyps as serrated polyps in 31 (15.9%), however, the histology did not confirm the diagnosis in all 31 polyps. The pathological examinations of polyps classified as serrated polyps by WASP criteria were hyperplastic polyps in 11 and adenomatous polyps in 20. In group A, WASP criteria falsely diagnosed 22% (25 out of 113 polyps) SSAPs whereas in group B, false diagnoses were 7.4% (6 out of 81 polyps) and the difference was statistically significant (p = 0.011). Of these 31 polyps classified as serrated polyps by WASP criteria, 25 polyps had 2 features and 6 polyps had 4 features of SSAPs.

Optical Diagnosis Missed classification (Table 6.).

Table 6

Optical diagnostic accuracy of polyps by NICE classification in group A and group B.
		Hyperplastic polyp	Adenomatous polyp	Deep invasive cancer	p-value
Group A	NICEI (n = 61)	40 (65.6)	20 (32.8)	1 (1.6)
Group B	NICEI (n = 49)	25 (51)	24 (49)	0 (0)	0.164
Group A	NICEII(n = 62)	9 (14.5)	53 (85.5)	0 (0)
Group B	NICEII(n = 47)	5 (10.6)	42 (89.4)	0 (0)	0.756
Group A	NICEIII (n = 4)	0 (0)	3 (75)	1 (25)
Group B	NICEIII (n = 4)	0 (0)	2 (50)	2 (50)	NA

NICE I misclassified adenomatous polyps as hyperplastic polyps in 20 (32.8%) in group A and 24 (49%) polyps in group B and 1 cancer as hyperplastic polyps (1.6%) in group A (Chi’s square test, p < 0.164).

NICE II misclassified hyperplastic polyps as adenomatous polyps in 9 (14.5%) polyps in group A and 5 (10.6%) polyps in group B. (Chi’s square test, p < 0.756).

NICE III misclassified 3 adenomatous polyp as malignant lesions in group A and misclassified 2 adenomatous polyps as malignant lesions in group B. No statistical analysis was attempted since the number of misclassifications were too small.

Complications

Post-polypectomy bleeding that required application of hemostatic clips to stop occurred in one patient in group B.

Our study showed that NF NBI did not increase the diagnostic accuracy compared with SF NBI (76% vs 71%) in distinguishing neoplastic and non-neoplastic polyps based on the NICE criteria by the non-expert endoscopists, but the findings must be interpreted with caution since we recruited patients with polyps less than half the calculated sample size so this may be under-power to detect the difference. The efficacy of NF NBI in optical diagnosis of polyps were reported in multiple studies with variable results. In two series reports from academic centers showed high accuracy of NF NBI, one report by Wiessner JR, et al. (27) in 63 polyps in 55 patients showed that the combination NF NBI with acetic acid had 85.5% accuracy in the prediction of polyp histology when the confidence in optical diagnosis of the endoscopists was high and another report using NF NBI with a transparent cap combined with digital magnification in 164 polyps of 87 patients with overall accuracy of 97% if the optical diagnosis was made with high confidence (30). In comparative studies, one study was a prospective multi-centers randomized study with all participating endoscopists trained for NBI to attain 90% accuracy prior to the study and compared NF NBI with old model SF NBI (180 series) and showed that NF NBI yielded more high confidence optical diagnosis than SF NBI (85.1 vs 72.6) (28), in another series study compared white light, SF NBI and NF NBI sequentially in the same patient demonstrated that NF NBI improved accuracy more than SF NBI (29) whereas another study by Wallace et, al (26) reported similar accuracy of NF NBI (79%) compared old model SF NBI (180 series) (78%) in optical diagnosis of colorectal polyps, despite prior training of endoscopists to attain 90% accuracy. Our study showed the accuracy of 76% for NF NBI in optical diagnosis of neoplastic polyps was comparable to that reported by Wallace et al. (26) using NF NBI, but lower than 89% reported by Hewett et al. (15) using SF NBI. No formal training for the endoscopists was done in our study and the endoscopists relied on the color images chart of NICE criteria as reference. The NPV of 51% − 64% in our study were below the 90% PIVI as recommended by ASGE as an acceptable capability to implement optical diagnosis (14). We did not assess the level of confidence in optical diagnosis, high confidence optical diagnosis may improve the outcome of this study as reported in some studies (27, 28, 29, 30).

This study showed no difference for NF NBI compared to SF NBI to assess diminutive polyps < 5 mm compared with those larger than 5 mm, however, number of the polyps > 5 mm was small. In one study, NF NBI performance was better in small polyps < 5 mm with accuracy of 88% and NPV of 96% when the optical diagnosis was made with high confidence (28), in contrast, another retrospective study by Hattori et al. (36) using NBI with magnification showed that NICE I optical diagnosis for small polyps ≤ 1 cm misclassified 20% of adenomatous polyps as hyperplastic polyps and 42% of diminutive adenomas as hyperplastic polyps.

The accuracy of endoscopists with high capability (higher Kappa) was superior to that of endoscopists with lower Kappa implying that the skill of endoscopist is an important contributing factor for the accuracy in our study which was in line with the findings of one meta-analysis (14), however, the number of cases performed by endoscopist with lower Kappa were small. DISCARD2 study by using NICE criteria in non-academic centers showed a sensitivity of 83% for the presence of adenoma (3), in contrary to our study, endoscopist expertise in DISCARD2 study did not improve performance.

Histologic and optical diagnosis discrepancy were reported to vary from 3.4% − 19.3% (3, 28). We did not assess the accuracy of our pathologist so the effect on the outcome due to variation of accuracy by pathological diagnosis could not be assessed.

The combination of NICE and WASP criteria providing all false optical diagnosis for SSAPs. The WASP criteria to detect SSAPs for non-expert endoscopist without prior proper training was un-reliable in this study and NF NBI did not provide additional advantage. In our study, only 2 out of 4 WASP criteria were used for diagnosis of SSAPs, in one study that validated the NBI for SSAPs using all 4 features showed accuracy of 93% (23), however, in our study 25 out of 31 polyps had only 2 features and these may account for low accuracy of WASP criteria. Surprisingly, NF NBI leading to significantly more false positives (25/113) than SF NBI (6/81). This may be due to a narrow focal length of NF NBI compared to longer focal length in SF NBI and no measure to stabilize the distance from tip of the endoscope to the polyp lending more blurred margin and/or blurred surface by NF NBI than SF NBI so these may be contributing to more false positives in NF NBI group. Further Study with a larger number of polyps and prior training of the endoscopists with measure to stabilize the distance of the endoscope and polyp as well as using all 4 features of WASP criteria may clarify the role of WASP criteria using NF NBI in differentiating SSAPs from hyperplastic polyps.

There were some limitations in our study; 1) inadequate sample size due to time constraint, 2) no assessment of endoscopist confidence in optical diagnosis that may alter the outcome in our study, 3) no prior training and assessment of endoscopists participating in the study, 4) small number of polyps included in the assessment of WASP criteria, 5) no validation of the accuracy of pathological reports of sessile serrated polyp and 6) no measure to keep the constant focal length from the tip of the endoscope and polyp that may affect image sharpness of NF NBI .

Near-focus NBI was not superior to normal-focus NBI in in optical diagnostic of polyps using NICE criteria. Combined NICE and WASP classification yielded all false positive in the diagnosis SSAPs in our study. With current capability of image enhancing technology, routine use of optical diagnosis of polyp in real life practise is still unadvisable.

NBI: Narrow band imaging; NF: Near focus; NPV: Negative predictive value; PPV: Positive predictive value; SF: Standard focus; SSAPs: Sessile serrated adenomas/polyps; WASP; The Workgroup serrAted polypS and Polyposis.

Acknowledgements

The authors would like to thank Miss Nannapat Pruphetkaew, Department of Epidemiology for calculation of statistical analysis.

Funding

There was no financial support provided for this study.

Availability of data and materials

All data generated or analyzed during this study are available from the corresponding author on reasonable request.

Declarations

Authors’ contributions

NN and NC designed the study, enrolled patients, data correction, analysis and interpretation of data, drafting the article and write the manuscript, TW and JS helped to enrolled patients, KK reviewed and reported of polyp histology, BO enrolled patients and critically reviewed as well as edited the manuscript. All authors read and approved the final manuscript.

Ethics approval and consent to participate.

The study protocol was approved by the Ethics Committee of Faculty of Medicine, Prince of Songkla University (61355143) on February 2019.

Clinical Trial Registration

This study protocol was retrospectively registered on Clinical Trials.gov (ID: NCT 04831814) on 04/01/2021.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no conflict of interest.

Author details

¹NKC Institute of Gastroenterology and Hepatology, Faculty of Medicine, Prince of Songkla university

²Division of pathology Prince of Songkla university, Faculty of Medicine, Prince of Songkla university

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No competing interests reported.

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Abstract Near-Focus Versus Normal-Focus Narrow Band Imaging Colonoscopy in Diagnosis of ColorectalPolyps Based on Combined NICE and WASP Classification in Routine Colonoscopy: A Randomized Controlled Trial

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