Introduction
Colorectal cancer (CRC) develops from at least two types of precursor lesions, adenomas
and serrated polyps, together referred to as polyps. Early detection and removal of
these polyps during colonoscopy decreases the incidence of CRC [1 ]. Current practice is to send all detected and resected colorectal polyps for histopathological
assessment by the pathologist to determine the interval for a surveillance colonoscopy.
Diminutive polyps (1 to 5 mm), which constitute up to 60 % of all polyps, are rarely
malignant [2 ]
[3 ]. Accurate endoscopic characterization of these polyps would allow resecting and
discarding diminutive polyps without histopathologic assessment. Furthermore, all
diminutive harmless hyperplastic polyps (HPs) in the rectosigmoid could be characterized
and left in situ [4 ]. Application of this strategy could result in a more cost-effective practice [5 ]
[6 ].
To reach this goal, enhancements in endoscopic imaging have been made in the last
two decades. Especially, the development of virtual chromoendoscopy (e. g. blue light
imaging [BLI], narrow band imaging [NBI]) revolutionized the field of endoscopic imaging.
The main advantage of virtual chromoendoscopy is that it is available in all new generations
of endoscopy systems and that it is easy to activate with a button on the handle of
the endoscope. Virtual chromoendoscopy improved the endoscopist’s ability to accurately
differentiate between diminutive and small adenomas, HPs, and sessile serrated lesions
(SSLs) [7 ].
Since 2017–2018, Fujifilm has marketed the ELUXEO 7000 endoscope system that employs
four different wavelength light-emitting diodes (LEDs) as light sources. By changing
the intensity of each of the four LEDs, a BLI, linked color imaging (LCI), and high-definition
white-light endoscopy (HD-WLE) can be obtained. The white-light mode is similar to
conventional endoscopy using a Xenon lamp. In both BLI and LCI mode, the peak intensity
of the LEDs is set at 410 nm ± 10 nm. As this is the peak absorption of light of hemoglobin,
microvascular structures at the surface of the mucosa can be distinguished more clearly
from blood vessels in the deep mucosa. Thereby, mucosal surface patterns are better
visualized and clarify the boundaries of the mucosal pit. In this way, both BLI and
LCI could potentially increase the accuracy for polyp characterization. To date, data
on LCI and BLI for the characterization of polyps are scarce but promising [8 ]
[9 ]
[10 ]
[11 ]
[12 ].
The aim of this study was to assess the diagnostic accuracy of real-time colorectal
polyp characterization using BLI, LCI and HD-WLE (ELUXEO 7000 endoscope system).
Patient and methods
Study design
This prospective study is a prespecified post-hoc analysis of the LCI-LYNCH trial
[13 ]. The study was conducted in in eight centers in Belgium, Italy, the Netherlands,
Poland, Spain, and the United Kingdom. Methods and outcomes of this trial are described
in detail elsewhere. The trial is registered at ClinicalTrials.gov (NCT03344289).
The Standards for Reporting of Diagnostic Accuracy (STARD) guideline was followed
in reporting the diagnostic test accuracies with respect to lesion characterization
[14 ].
Patients
Patients were considered eligible for participation in the trial if they were aged
18 or older, provided informed consent, were scheduled for polyp surveillance, and
had been diagnosed with a Lynch syndrome-associated pathogenic gene variant in one
of the MMR genes (MLH1, MSH2, MSH6, PMS2 ) or deletions in the 3’ region of the EpCAM gene. Exclusion criteria included surveillance colonoscopy within 1 year from current exam,
colonoscopy planned for the evaluation of symptoms, total proctocolectomy, known colonic
neoplasia (referred patients), or a concurrent diagnosis of (serrated) polyposis syndrome
or inflammatory bowel disease. In line with the LCI-LYNCH trial patients with a Boston
Bowel Preparation Scale (BBPS) [15 ] < 6 or an incomplete colonoscopy were excluded.
Endoscopists
All participating endoscopists had extensive experience with colonoscopy (> 2,000
colonoscopies). At the start of the study, participating endoscopists had performed
at least 10 procedures with the ELUXEO 7000 system. Endoscopists were not formally
trained in the NBI International Colorectal Endoscopic classification (NICE) [16 ] or the Workgroup on serrAted polypS and Polyposis (WASP) classification [17 ] for purpose of this study.
Endoscopy equipment
Colonoscopies were performed with the ELUXEO 7000 system, which consists of a light
source, a processor, and special scope series developed by Fujifilm (EC-760ZP and
EC-760 R, Fujifilm, Tokyo, Japan). Switching between the three different imaging modes
(LCI, BLI and HD-WLE) in the ELUXEO 7000 system was performed by pressing a button
on the shaft of the colonoscope. High-definition monitor output was used at appropriate
viewing distances at the discretion of the endoscopist.
Real-time lesion characterization (index test)
When the patient was eligible for inclusion, the endoscope was advanced to the cecum.
Cecal intubation was confirmed by identification of the appendiceal orifice and ileocecal
valve or by intubation of the terminal ileum. Upon reaching the cecum, the quality
of the bowel preparation was assessed using the BBPS [15 ]. During withdrawal from the cecum or terminal ileum, the colon was scrutinized for
the presence of lesions. If a lesion was detected, the segment of the colon was registered,
the size was estimated by using a reference of known diameter, e. g. open biopsy forceps,
and the morphology of the lesion was described according to the Paris classification
[18 ]. In addition, digital still images of all detected lesions were taken in LCI, BLI,
and HD-WLE imaging mode. The endoscopist could use all three imaging modes (LCI, BLI
and HD-WLE) to predict the endoscopic diagnosis of the lesion including a high- or
low-confidence statement. Endoscopists could choose between hyperplastic polyp, SSL,
adenoma, carcinoma, or other. In addition, endoscopists assessed each lesion using
the WASP classification [17 ], which includes the NICE classification and the Hazewinkel criteria (Supplementary Fig. 1 ) [16 ]
[19 ]. First, endoscopists assessed the three criteria of the NICE classification (color/vessel/surface
pattern) aiming to differentiate between non-adenomas (type 1), adenomas or superficial
carcinoma (type 2) and deep invasive carcinoma (type 3). Using these criteria, the
presence of at least one adenoma-like feature was sufficient to diagnose a type 2
polyp. Subsequently, the four Hazewinkel criteria (i. e. clouded surface, indistinctive
border, irregular shape, and darks spots inside the crypts) were used to differentiate
between SSLs and HPs for type 1 polyps and between SSLs and adenomas for type 2 polyps.
The presence of at least two SSL-like features was hereby considered sufficient to
diagnose a SSL. Subsequently, all detected lesions and their adjacent mucosa were
removed for histopathologic evaluation. Obvious hyperplastic lesions of 1 to 5 mm
in the rectosigmoid could be left in situ, at the discretion of the endoscopist.
Histopathology (reference test)
At each center, an experienced gastrointestinal pathologist was designated for this
study. Pathologists were blinded for optical diagnosis of the lesions detected during
colonoscopy. Histological samples were collected in paraffin and processed using standard
procedures. Histological findings were reported according to the Vienna classification
of gastrointestinal neoplasia [20 ]. SSLs were defined as serrated lesions with at least two irregular, dilated crypts,
including dilatation of the base of the crypts that often have a boot, L- or inverted
T-shape [21 ]. Adenomas and SSLs were categorized as neoplastic. HPs and SSLs were grouped as
serrated polyps. An advanced adenoma was defined as an adenoma ≥ 10 mm, had villous
morphology, or contained high-grade dysplasia.
Study outcomes
The primary outcome of this study was the diagnostic test accuracies (e. g. accuracy,
sensitivity, specificity, positive and negative predictive values) for endoscopic
characterization of colorectal polyps using a combination of BLI, LCI and HD-WLE (ELUXEO
7000 endoscope system). Accuracy was defined as the percentage of correctly predicted
endoscopic diagnoses compared to the reference standard pathology. For the calculation
of the overall accuracy, adenomas, SSLs and HPs were considered as different histological
subtypes.
Secondary outcomes included a description of detected colorectal polyps; diagnostic
test accuracies for polyps ≤ 5 mm and > 5mm; diagnostic test accuracies according
to the level of confidence; predictors for accurate endoscopic characterization of
polyps.
Statistical methods
Diagnostic test accuracies of endoscopic characterization with BLI, LCI and HD-WLE
(index test) were calculated with the outcomes of histopathology as the reference
standard (reference test). Diagnostic test accuracies included sensitivity, specificity,
and predictive values. If histopathology outcome was carcinoma, traditional serrated
adenoma, normal mucosa, inflammatory lesion or missing, the lesion was excluded from
the diagnostic accuracy analysis. In addition, lesions with no endoscopic characterization
were excluded. Answers were dichotomized to a positive outcome for each histological
subtype of interest and a negative outcome for the other histological subtypes. For
all outcomes on diagnostic test accuracies, 95 % confidence intervals (CIs) were calculated.
Diagnostic test accuracy also was calculated for each participating center. Owing
to the limited number of histopathology predictions per individual endoscopist, we
decided not to separately analyze the diagnostic test accuracies.
Generalized estimating equations modeling using binary logistic regression adjusted
for clustering of polyps and patients per endoscopist was performed to evaluate predictors
of accuracy. The outcome variable of the model was accurate histology prediction of
a polyp. Potential predictors included confidence level, polyp size, polyp block,
and polyp location. Polyp block was defined as the number of polyps endoscopically
characterized by and endoscopist during the study duration. The association between
predictors and accuracy were summarized as odds ratios, including the 95 %CI and corresponding
P value. Analysis was performed in statistical software R (version 3.6.1) using the
EpiR and lme4 packages, with the function of glmer. P < 0.05 was considered statistically significant.
Ethical approval and role of the funding source
The study was conducted according to the ethical principles of the Declaration of
Helsinki and was approved by the ethics committees of each participating center. Fujifilm
Europe GmbH provided research equipment on loan for this study and an unrestricted
research grant that partially supported a research fellow to help execute the study.
The sponsor had no role in the trial design, execution, data analysis, interpretation,
decision to submit the paper, or manuscript preparation. All contributing authors
had access to the study data and reviewed and approved the final manuscript.
Results
Between January 2018 and March 2020, 357 patients were eligible for randomization.
Nineteen patients were excluded because of poor bowel preparation (BBPS < 6) and six
because of incomplete colonoscopy. After excluding these patients, the total number
of patients was 332 ([Fig. 1 ]). Their mean age was 48.4 years (SD 14.1), 141 (42 %) were male and 72 (22 %) had
a personal history of CRC. A total of 22 endoscopists from eight centers participated
in the study. The number of colonoscopies per center ranged from 15 to 81. [Table 1 ] shows the clinicopathological characteristics of the detected and included lesions
polyps. Overall, 341 lesions were detected. Of these 341 lesions, 176 (54 %) were
adenomas, 28 (9 %) were SSLs, 79 (24 %) were HPs, four (1 %) were traditional serrated
adenomas, five (1 %) were carcinomas, 33 (10 %) lesions were reported as normal mucosa
or other non-neoplastic lesions (e. g. inflammatory lesions), and 16 (5 %) lesions
were not retrieved for histology.
Fig. 1 Flow diagram.
Table 1
Characteristics of the detected and included lesions.
Detected lesions
(N = 341)
Included polyps[1 ]
(N = 269)
Included diminutive polyps
[1 ]
(N = 220)
Location
237 (70 %)
188 (70 %)
148 (67 %)
104 (30 %)
81 (30 %)
72 (33 %)
Morphology
159 (47 %)
127 (47 %)
112 (51 %)
171 (50 %)
142 (53 %)
108 (49 %)
11 (3 %)
0 (0 %)
0 (0 %)
Endoscopic characterisation
2 (0 %)
0 (0 %)
0 (0 %)
172 (51 %)
146 (55 %)
119 (54 %)
31 (9 %)
28 (15 %)
12 (5 %)
118 (35 %)
95 (30 %)
89 (41 %)
18 (5 %)
0 (0 %)
0 (0 %)
Confidence level
267 (82 %)
223 (83 %)
178 (81 %)
69 (17 %)
46 (17 %)
42 (19 %)
5 (1 %)
0 (0 %)
0 (0 %)
Histopathology
5 (1 %)
–
–
176 (52 %)
165 (61 %)
137 (62 %)
5
5
4
0
0
0
28 (8 %)
27 (10 %)
14 (6 %)
0
0
0
4 (1 %)
0
0
79 (23 %)
77 (29 %)
69 (31 %)
27 (8 %)
0
0
6 (2 %)
0
0
16 (5 %)
0
0
1 Histologically confirmed adenomas, SSL and hyperplastic polyps with as well an optical
diagnosis were included; Data are n or n (%)
2 Polypoid was defined as Paris classification Ip, Isp and Is.
3 Non-polypoid was defined as Paris classification IIa and IIb.
In the diagnostic accuracy analysis, only histologically confirmed adenomas, SSLs
and HPs for which also an optical diagnosis was recorded were included ([Fig. 1 ] and [Table 1 ]). A total of 269 polyps were included, of which 165 (61 %%) were adenoma, 27 (10 %)
SSL and 77 (29 %) hyperplastic polyp. Of all polyps included, 220 (82 %) were diminutive
(≤ 5 mm), 33 (12%) were small (6–9 mm), and 15 (6 %) were ≥ 10 mm. Of the 220 diminutive
polyps, 72 (33 %) were located in the rectosigmoid. Thirty-eight (53 %) of them were
neoplastic (i. e. adenoma or SSL) while 34 (47 %) were non-neoplastic (i. e. hyperplastic
polyp).Overall, a high-confidence optical diagnosis was made in 223 (82.9 %) of the
269 polyps. Of the 220 diminutive polyps, 179 (81.3 %) were predicted with high confidence.
The proportion of polyps with a high-confidence optical diagnosis varied between the
participating centers (range 58–100 %, median = 84 %).
Five histologically confirmed adenocarcinomas were detected during the study period.
These carcinomas were not included in the diagnostic accuracy analysis, but did have
an optical diagnosis. Three of these carcinomas were correctly recognized as a carcinoma,
while two carcinomas were not recognized (one was optically diagnosed as an adenoma
and one as a hyperplastic polyp). As well, one adenoma was incorrectly optically diagnosed
as a carcinoma.
Diagnostic test accuracies for polyp characterization
Diagnostic test accuracies for polyp characterization for overall and high-confidence
predictions of polyps are shown in [Table 2 ] and Supplementary Table 1 . The overall accuracy for endoscopic characterization for all polyps was 75.1 % (95 %CI
69.5–80.1 %), compared with an accuracy of 78.0 % (95 % CI 72.0–83.2 %) when endoscopic
characterization was assigned with high confidence. The overall sensitivity of characterizing
adenomas (adenomas vs. serrated polyps) was 80.0 % (95 % CI 73.1–85.8 %) and increased
to 84.9 % (95 % CI 77.8–90.4 %) for high-confidence predictions.
Table 2
Diagnostic test accuracies for endoscopic characterization with histopathology as
reference standard.
Endoscopic characterization
All polyps, % (95 % CI)
(N = 269)
High confidence all polyps, % (95 % CI)
(N = 223)
Diminutive polyps, % (95 % CI)
(N = 220)
Diminutive polyps with high confidence, % (95 %CI)
(N = 178)
Overall accuracy[1 ]
75.1 (69.4–80.1)
78.0 (72.0–83.2)
74.7 (68.4–80.3)
78.2 (71.4–84.0)
Adenomas vs serrated polyps
82.5 (77.5–86.9)
86.1 (80.9–90.3)
81.9 (76.2–86.7)
86.0 (80.1–90.8)
80.0 (73.1–85.8)
84.9 (77.8–90.4)
79.0 (71.2–85.5)
84.8 (76.8–90.9)
86.5 (78.4–92.4)
88.1 (79.2–94.1)
86.8 (77.5–93.2)
88.1 (77.8–94.7)
90.4 (84.4–94.7)
92.2 (86.1–96.2)
90.8 (84.2–95.3)
92.2 (95.3–96.6)
73.2 (64.4–80.8)
77.9 (68.2–85.8)
71.3 (61.4–79.9)
77.6 (66.6–86.4)
SSLs vs non-SSLs
88.5 (84.0–92.0)
87.9 (82.9–91.9)
91.0 (86.4–94.4)
90.5 (85.2–94.4)
44.4 (25.5–64.7)
47.8 (26.8–69.4)
21.4 (4.7–50.8)
25.0 (5.5–57.2)
93.3 (89.5–96.2)
92.5 (87.9–95.7)
95.6 (91.9–98.0)
95.2 (90.8–97.9)
42.9 (24.5–62.8)
42.3 (23.3–63.1)
25.0 (5.5–57.2)
27.3 (6.0–61.0)
93.8 (90.0–96.5)
93.9 (89.6–96.8)
94.7 (90.8–97.3)
94.6 (90.0–97.5)
HPs vs non-HPs
79.2 (73.8–83.9)
82.1 (76.4–86.9)
76.5 (70.3–81.9)
79.9 (73.3–85.5)
75.3 (64.2–84.4)
73.8 (60.9–84.2)
76.8 (65.1–86.1)
76.4 (63.0–86.8)
80.7 (74.4–86.1)
85.2 (78.8–90.3)
76.3 (68.8–82.8)
81.5 (73.5–87.9)
61.1 (50.5–70.9)
65.2 (52.8–76.3)
59.6 (48.6–69.8)
64.6 (51.8–76.1)
89.1 (83.5–93.3)
89.6 (83.7–93.9)
87.9 (81.1–92.9)
88.6 (81.3–93.8)
PPV, positive predictive value; CI, confidence interval; NPV, negative predictive
value; SSL, sessile serrated lesion; HP, hyperplastic polyp.
1 For the calculation of the overall accuracy adenomas, SSLs and HPs were considered
different histological subtypes.
The overall accuracy for endoscopic characterization for all diminutive polyps was
74.7 % (95 % CI 68.4–80.3 %), compared with an accuracy of 78.2 % (95 % CI 71.4–84.0 %)
when characterization was assigned with high confidence. Overall sensitivity for diminutive
adenomas (adenomas vs. serrated polyps) was 79.0 % (95 % CI 71.2–85.5 %) and increased
to 84.8 % (95 % CI 76.8–90.9 %) for high-confidence predictions.
Only 12 of 27 SSLs were assessed with at least two Hazewinkel criteria, corresponding
to a sensitivity of 44.4 % (95 % CI% 25.5–64.7 %), specificity of 93.3 % (95 % CI
89.5–96.2 %), PPV of 42.9 % (95 % CI 24.5–62.8 %), NPV of 93.8 % (95 % CI 90.0–96.5 %).
When only diminutive SSLs were taken into account the diagnostic accuracies decreased
to a sensitivity of 21.4 % (95 % CI% 4.7–50.8 %), specificity of 95.6 % (95 % CI 91.9–98.0%),
PPV of 25.0 % (95 % CI 5.5–27.2 %), NPV of 94.7 % (95 % CI 90.8–97.3 %).
Diagnostic test accuracies for polyp characterization per center
Diagnostic test accuracies for polyp characterization for overall and high-confidence
predictions of polyps per center are shown in [Fig. 2 ]
. This figure shows the wide variation in accuracies for polyp characterization for
overall and high-confidence predictions of the individual centers.
Fig. 2 Overall accuracies for endoscopic characterization per center with histopathology
as reference standard (overall accuracies along with its 95% confidence intervals).
*For the calculation of the overall accuracy adenomas, SSLs and HPs were considered
different histological subtypes.
Predictors for accurate endoscopic polyp characterization
Outcomes of univariate and multivariate logistic regression analysis to find predictors
for accurate prediction of histology are shown in [Table 3 ]. For accurate prediction of histology, only high-confidence predictions were independently
associated with accurate histology prediction in multivariate analysis.
Table 3
Outcomes of multilevel logistic regression analysis to find predictors for accurate
endoscopic prediction of histology.
Predictors
Univariate logistic regression odds ratio
(95 % CI)
P
Multivariate logistic regression odds ratio (95 % CI)
P
Confidence level
Reference
Reference
3.02 (1.20–7.59)
0.02
2.25 (1.13–4.42)
0.02
Polyp location
Reference
Reference
0.53 (0.21–1.34)
0.29
0.87 (0.49–1.52)
0.55
Polyp size, mm
Reference
Reference
1.97 (0.79–4.96)
0.15
1.08 (0.59–2.04)
0.81
Polyp block[1 ]
Reference
0.90 (0.36–2.25)
0.89
0.98 (0.41–2.34)
0.98
Morphology
Reference
0.93 (0.37–2.33)
0.85
1 Polyp block was defined as the number of polyps an endoscopist had endoscopically
characterized during the study.
2 Polypoid was defined as Paris classification Ip, Isp and Is.
3 Non-polypoid was defined as Paris classification IIa and IIb
Discussion
In this post-hoc analysis of a prospective multicenter trial, diagnostic accuracy
for real-time polyp characterization using BLI, LCI and HD-WLE appears to be suboptimal.
Participating endoscopists were experienced endoscopists and familiar with endoscopic
polyp characterization, but did not follow a specific training for purpose of this
study. Using a combination of BLI, LCI and HD-WLE the lesions were endoscopically
characterized with an overall accuracy of 75 %, which increased to 78 % for high-confidence
assignments only. The overall sensitivity of characterizing adenomas (adenomas vs.
serrated polyps) was 80.0 % compared with an accuracy of 84.8 % when optical diagnosis
was assigned with high confidence. For diminutive adenoma characterization (adenomas
vs serrated polyps), sensitivities were respectively 79.0 % and 84.8 % for high-confidence
assessments only. There are two plausible reasons for these relatively low diagnostic
accuracies. First, the different light techniques used in this study were simply not
sufficient enough to highlight the specific endoscopic features of the assessed polyps,
leading to suboptimal results. In addition, the WASP classification used in this study
has not been validated for BLI or LCI [22 ]. A second explanation could be that the study did not primarily focus on polyp characterization
and that endoscopists were not formally trained prior to the start of the study.
As concerns SSLs, the present study shows suboptimal results, with an overall sensitivity
of 44 % for all sized SSLs and even a lower sensitivity of 21 % for diminutive SSLs.
Almost 90% of the detected SSLs were small in size (< 1 cm). This is in line with
a previous post-hoc analysis from prospective multicentre study of NBI characterization
by community endoscopists in daily practice. Vleugels and colleagues described that
only 24.4.% of 202 diminutive SSLs were accurately diagnosed when using the WASP classification
[23 ]. Of the 202 diminutive SSLs, 83 were misclassified as HPs. Kumar and colleagues
described also that up to one third of the SSLs were misclassified as HPs when applying
the NICE classification [24 ]. Apparently, many morphological features typical of SSLs, such as the presence of
mucus cap, clouded surface, indistinctive borders or irregular shape cannot be recognized
easily in small lesions. This was confirmed by Bustamante-Balén et al, who showed
that the presence of two or more Hazewinkel criteria are not reliable for a positive
diagnosis of SSL (sensitivity 32.9%, PPV 30.6 %), particularly not for diminutive
SSLs (sensitivity 14.7 %, PPV 14.3 %) [25 ]. Another explanation for the suboptimal accuracy for diagnosing SSL might be that
there was no revision of histopathology in this study, while there is considerable
interobserver variability in the histopathological diagnosis of SSLs [26 ]. The discordances in histological evaluation (especially between SSL and HP and
in diminutive polyps) may explain low accuracy. However, we performed a sub-analysis
for adenomas versus serrated polyps, which showed similar diagnostic accuracies. To
increase the probability for correct diagnosing SSLs, it might be considered use the
presence of three or more Hazewinkel criteria instead of two or more.
As reported in a recent meta-analysis and reaffirmed by our study, high-confidence
assignment is the most significant predictor of optical diagnostic accuracy [27 ]. High-confidence predictions are a crucial factor for the implementation of optical
diagnosis and for cost savings while following the “resect and discard” strategy.
Although the concept of high confidence is easy to understand, a uniform definition
of high-confidence diagnosis is lacking. Therefore, setting the confidence level is
inherently subjective. The ESGE recently insisted on the importance of developing
more uniform criteria for high-confidence assignments [22 ]. As well, little is known about the optimal high-confidence rate. Cost effectiveness
analyses showed a cost saving of € 6–22 per individual when 79–84 % of the diminutive
polyp are characterized with high confidence [5 ]
[6 ]. In this study, the proportion of high-confidence assignments was reasonably comparable
(81.3 %). Therefore, a minimum rate of approximately 75 % of high confidence predictions
might be appropriate, although a higher rate would expand the economic benefits of
the strategy.
The main strength of our study is that polyp characterization was performed during
real-time colonoscopy in eight different hospitals with 22 endoscopists, which allows
externalization of results. Several limitations of this study have to be acknowledged.
As mentioned before, endoscopists in this study were not formally trained, while dedicated
training is required to improve and maintain optical diagnosis competence. On the
other hand, a setting without a formal training reflects daily clinical practice and
is therefore all the more worthwhile to investigate [22 ]. Second, diminutive polyps of the rectosigmoid that looked as HPs were not removed
and were not included in the analysis. This “under-detection” could have artificially
increased the proportion of adenomas and SSLs among diminutive rectosigmoid lesions
in our study (53 %), which is higher than the prevalence found in another large cohort
of patients with Lynch syndrome (23 %) [28 ]. If all polyps would have been included leaving no polyps in situ, the results might
have been better. Another aspect that could limit generalizability is that this study
was performed in patients with Lynch syndrome. However, there is no reason to assume
a difference in polyp phenotypes from this patient group compared with polyp phenotypes
from sporadic patients [29 ]. In addition, the polyp subtype distribution in this Lynch cohort is comparable
to a screening or polyp surveillance cohort [30 ]. Therefore, we think that our data can be extrapolated to the general population.
Another aspect that may limit generalizability is that endoscopists participating
in this study were specialist endoscopists, devoted to high-risk CRC conditions and
with interest in performing endoscopy research. This may have also caused selection
bias, as it is unclear how less experienced endoscopists would have performed. However,
based on previous literature we anticipate that if characterization proves difficult
among specialists, this can be extrapolated to endoscopists with less experience in
optical diagnosis of lesions. Since no uniform definition of high-confidence diagnosis
was available, this might have caused differences in accuracy between endoscopists.
As polyps were evaluated with the combination of BLI, LCI and HD-WLE it was not possible
to investigate the sensitivity and accuracy of each light modality independently.
Last, the number of lesions assessed per single endoscopist participating in our study
was quite small. Our study findings should therefore be confirmed in larger sample
studies performed in daily clinical practice.
Conclusions
This study illustrates that in a real-time setting experienced endoscopists were not
able to achieve a high diagnostic accuracy using a combination of BLI, LCI and HD-WLE.
Ongoing monitoring and development of artificial intelligences systems are needed
to improve endoscopistsʼ polyp characterization with this system.
