Artificial Intelligence in the Characterization of Small and Diminutive Colorectal Polyps: A Prospective Study in a Clinical Setting Using CAD EYE®
Conditions: Colonic Polyps
Sponsor: Unidade Local de Saúde de Coimbra, EPE

 
Artificial intelligence in the characterization of 
colorectal polyps: A prospective study in a clinical 
setting using CAD EYE® 
 
 
 
 
 
STUDY PROTOCOL 
 
 
 
 
Elisa Gravito-Soares, Marta Gravito-Soares, Pedro Amaro 
October 29th, 2020 

Artificial intelligence in the characterization of colorectal polyps: A prospective study in a 
clinical setting using CAD EYE® 
Elisa Gravito-Soares, Marta Gravito-Soares, Pedro Amaro 
Gastroenterology Department, Centro Hospitalar e Universitário de Coimbra, E.P.E., 
Coimbra, Portugal 
 
STUDY PROTOCOL 
 
Brief summary 
Current guidelines recommend resection and histopathological analyses of all colorectal polyps. 
Real-time optical diagnosis can obviate non-neoplastic polyp resection (“diagnose-and-leave-
behind”) and histopathological analyses of diminutive polyps (“predict-resect-and-discard”) 
reducing healthcare and cost burden. The investigators aimed to evaluate the diagnostic 
accuracy of computer-aided diagnosis using CAD EYE® (Fujifilm,Germany) in real-time optical 
characterization of colorectal polyps compared to endoscopic diagnosis with histopathology as 
the gold-standard. For this purpose, a single-centre prospective study of diminutive/small 
colorectal polyps is ongoing.  
 
Introduction 
Worldwide, colorectal cancer (CRC) is the 4th most frequent cancer and the 3rd cause of cancer-
related death. In Portugal, CRC is the 3rd most common cause and the 2nd leading cause of 
cancer-related mortality. In colorectal carcinogenesis, colorectal polyps (adenomatous or 
serrated polyps) are considered premalignant lesions. The detection of colorectal polyps and 
subsequent resection is effective in reducing CRC incidence and mortality and the risk of interval 
CRC, and is the crucial aspect of CRC prevention. Considering the detection of colorectal polyps, 
there is a wide variation among endoscopists in terms of skills for the detection of adenomas, 
the major premalignant lesions of CRC, translated into the detection rate of adenomas (ADR). 
ADR is considered a marker of careful inspection of colorectal mucosa, translating quality in 
colonoscopy, which is inversely associated with the risk of interval CRC or cancer-related death. 
In the context of screening colonoscopy, the minimum ADR is 25% to reduce the risk of interval 

CRC and death, being predictably higher if a positive fecal occult blood test is found, although 
the exact value still remains to be elucidated. The detection rate of serrated polyps has been 
strongly correlated with ADR.  
About 50% of small polyps are non-adenomatous and these polyps have no malignancy 
potential, especially for small polyps, whose cancer risk is extremely low (0-0.6%). The resection 
of these non-adenomatous polyps may increase medical costs and risks related to post-
polypectomy complications (bleeding, perforation). 
Real time optical diagnosis by artificial intelligence can improve the cost-benefit and efficiency 
of colonoscopy as an auxiliary tool in the decision making of which polyps should be resected 
and which polyps should be recovered for histological characterization. However, its practical 
application implies a negative predictive value ≥ 90% in optical diagnosis in order to don´t have 
implications in terms of interval CRC and medico-legal issues. 
CAD EYE® (Fujifilm, Europe, Gesellschaft mit beschränkter Haftung, Dusseldorf, Germany) is a 
fully-automated computer program, which allows the detection of colorectal polyps as well as 
their histological classification using the artificial intelligence technology using deep learning, 
so-called REilI. When applied in a high-quality colonoscopy, it seems to improve the detection 
rate of polyps and the ADR in real time, during colonoscopy course. In fact, the detection of 
difficult lesions remains one of the major challenges in the endoscopy field in last years, 
particularly for flat lesions, multiple polyps and polyps located at the image periphery. The 
detection of colorectal polyps is shown by 3 simultaneous identifiers, 2 visual and 1 auditory. 
The visual identifiers correspond to a detection box in the area of suspected polyps and a 
semicircle at the periphery of the image, corresponding to the quadrant where the suspect 
polyps are located. The auditory stimulus corresponds to a volume adjustable sound signal 
emitted when a suspect polyps is detected. Regarding the optical characterization of 
histopathology, colo-rectal polyps are classified into 2 types, hyperplastic (green colour), which 
include hyperplastic and serrated polyps, and neoplastic (yellow colour), for adenomas and 
adenocarcinomas. In addition, it allows to perform this characterization in 3 confidence levels 
and the mapping of the position of the suspected area. 
This system allows the storage of videos related to both detection and characterization of 
colorectal polyps, one of the recognized quality tools in colonoscopy. 
The detection mode of colorectal polyps is performed in white light imaging (WLI) or Linked 
Colour Imaging (LCI), while the optical characterization is performed in Blue Light Imaging (BLI) 

mode, without the need to fix or zoom the image. This tool is user-friendly, simple, intuitive and 
does not interfere with colonoscopy images. 
 
Objectives 
Primary objectives 
- To evaluate the diagnostic accuracy of computer-aided diagnosis using CAD EYE® system in 
real-time optical characterization of colorectal polyps compared to digital chromoendoscopy; 
- To evaluate the diagnostic accuracy of computer-aided diagnosis using CAD EYE® system in 
real-time optical characterization of colorectal polyps by comparison with histopathological 
analysis. 
Secondary objectives 
- To evaluate the diagnostic accuracy of computer-aided diagnosis using CAD EYE® system in 
real-time optical characterization of colorectal polyps in terms of dimension (≤5, 6-9mm and 
≥10mm), location and histological type (hyperplastic, serrated sessile lesion, adenoma, 
adenocarcinoma); 
- To evaluate the diagnostic accuracy of computer-aided diagnosis using CAD EYE® system in 
real-time optical characterization of colorectal polyps according to the experience of the 
endoscopist. 
 
Population and methodology 
 
Type of study 
Prospective observational cohort study 
 
Type of sample 
The total number of consecutive patients who underwent elective colonoscopy with high quality 
of bowel preparation (at least two points per segment and at least of six points at the total score 
of Boston Bowel Preparation), performed at the Gastroenterology Department of the Centro 

Hospitalar e Universitário de Coimbra, E.P.E., Coimbra, Portugal, with at least one identified 
colorectal polyp, regardless the indication for its performance. 
 
Inclusion criteria 
- Age ≥18 years 
- The presence of at least one polyp in an elective colonoscopy 
 
Exclusion criteria 
- Poor bowel preparation (Boston Bowel Preparation Score <6 at the total score or <2 at one of 
colorectal segment) 
- No recovery of excised polyps for histopathological analysis 
- The presence of polyps not amenable to endoscopic excision or with contraindication for their 
excision at the time of colonoscopy 
- The absence of explicit indication for colonoscopy 
 
Study design 
All colonoscopies will be performed by the endoscopist (trainee and experienced endoscopist) 
using CAD EYE® in detection mode (WLI or LCI), during colonoscopy retrieval. When a suspected 
polyp is identified by the endoscopist, optical characterization is performed by the endoscopist 
in WLI and BLI modes, in a first phase and by the CAD EYE® with BLI, in a second phase. 
 
Methods plan 
Phase 1. Brief virtual chromoendoscopy training on the characterization of colorectal polyps 
(WLI, LCI and BLI) 
Phase 2. CAD EYE® system applied during colonoscopy retrieval: 
2.1. CAD EYE® system OFF: Virtual chromoendoscopy (BLI) – independently characterization of a 
suspected polyp in WLI and BLI by the first endoscopist and by the second endoscopist 
(iconographic record) 

2.2. CAD EYE® system ON: Characterization mode (BLI): Characterization of a suspected polyp by 
CAD EYE® and respectively level of characterization (1 to 3) (iconographic record) 
Phase 3. Histopathological evaluation (pathologist with gastrointestinal expertise): Resection 
and recovery of a suspected polyp for anatomopathological characterization 
 
Detailed explanation of Methods phases 
Phase 1. Brief virtual chromoendoscopy training on the characterization of colorectal polyps 
(WLI, LCI and BLI) 
Virtual chromoendoscopy training should be performed online through the BASIC e-learning 
platform (bli.eu/category/e-learning/). This training should be carried out by all participants 
enrolled in the project (trainees and experienced endoscopists) before its practical application, 
which will allow skills acquisition on the characterization of virtual chromoendoscopy of 
colorectal polyps using BLI. Additionally, a brief review of the Kudo classification of pit pattern 
of colorectal polyps should be carried out. 
 
Phase 2. Evaluation of colorectal polyps in real-time - Optical characterization of colorectal 
polyps 
The first approach on optical characterization of an identified polyp consists in the evaluation of 
the polyp, first in WLI mode and then in BLI mode, with CAD EYE® OFF. This evaluation should 
be systematically performed by two independent endoscopists in the exam room, and the 
evaluation of both should be recorded on a separate record sheet by the endoscopist who is not 
performing the examination. The two endoscopists should preferably (but not necessarily) be 
an experienced endoscopist and a trainee from the last few years, and the presence of at least 
one experienced endoscopist is mandatory. The independent evaluation is guaranteed by a 
phased and recorded approach: 1st step - The 1st endoscopist (endoscopist performing 
colonoscopy) request the polyp evaluation and written record by the 2nd endoscopist (the one 
who is not performing the colonoscopy) -  blinded evaluation because the 1st endoscopist 
doesn’t verbalize his evaluation); 2nd moment - when the 2nd endoscopist signals that he has 
completed his record, the 1st endoscopist verbally explicit his classification, which is recorded by 
the 2nd endoscopist. This evaluation should include the histopathological type of polyp 
(hyperplastic, adenoma, sessile serrated lesion or other type) and the level of confidence of the 

evaluation performed (high or low). Kudo classification of pit pattern can also be recorded 
(optional). 
Afterwards, optical characterization mode of CAD EYE® (CAD EYE® ON) in BLI mode should be 
activated for the evaluation of CAD EYE® optical characterization, in hyperplastic or neoplastic 
polyps, as well as the level of characterization (graduated from 1 to 3). The evaluation of the 
CAD EYE® should also be recorded by the endoscopist in the exam room who is not performing 
the colonoscopy, on its own record sheet. 
The iconographic record of evaluated polyps in WLI and BLI modes and the evaluation video 
using CAD EYE® in BLI characterization mode should be done. 
 
Phase 3. Histopathological evaluation (by pathologist with gastrointestinal expertise) 
After detection and optical characterization of identified colorectal polyps, their resection 
should be performed by the most appropriate technique according to the size and type of polyp 
(cold forceps polypectomy if dimensions <3mm), cold snare polypectomy if dimension between 
3-10mm and diathermic snare polypectomy/endoscopic mucosal resection if lesions >10mm) 
and recovery of colorectal polyp for anatomopathological characterization. Each colorectal 
polyp should be recovered to a separate vial. Unrecovered polyps will not be counted for 
comparative evaluation of optical characterization. 
 
Statistical analysis 
The diagnostic performance of CAD EYE® will be evaluated by comparison with the gold standard 
(histological characterization in the optical characterization phase), in terms of diagnostic 
accuracy, sensitivity, specificity, positive predictive value and negative predictive value. Sub-
analysis can be performed regarding the size, location and histological type of polyp, as well as 
the expertise of the endoscopist. 
 
Sample size calculation 
For an alpha risk of 0.05 and beta risk of 0.2 for a bilateral test, it will be necessary to include 
197 colorectal polyps assuming the initial pre-intervention diagnostic ratio is 0.7 and the final 
after-intervention ratio is 0.82. 

Expected Results 
It is expected that the new CAD EYE® system will have a diagnostic accuracy in the optical 
characterization of colorectal polyps around 78.4%, comparable to experienced endoscopists 
(78.4% vs 79.6%) and superior to less experienced endoscopists (70.7% vs 79.6%).(14) Thus, the 
new CAD EYE® system will allow optical characterization with high accuracy impacting as a 
decision making tool for the endoscopist in strategies based on optical diagnosis such as 
"diagnosis and leave behind" for diminutive polyps from sigmoid colon and rectum with high 
degree of confidence in hyperplastic histology and "predict, resect and discard" for diminutive 
polyps. 
 
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Links 
URL: https://gco.iarc.fr 
Description: World Health Organization International Agency for Research on Cancer (IARC). 
Global Cancer Observatory 2018: estimated cancer incidence and mortality worldwide in 2018. 
[homepage on the internet]. Available from: https://gco.iarc.fr 
URL: https://www.fujifilm.eu/eu/cadeye 
Description: CAD EYE® (Fujifilm,Germany) 
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