Keywords Endoscopy Lower GI Tract - Inflammatory bowel disease - CRC screening - Diagnosis
and imaging (inc chromoendoscopy, NBI, iSCAN, FICE, CLE...)
Introduction
Inflammatory bowel disease (IBD) is a risk factor for colorectal cancer (CRC) [1 ]. Early studies in patients with
long-standing disease suggested a progressive risk of malignancies in the colon and
rectum,
with a cumulative incidence of 1% at 10 years, and 7% at 30 years [2 ]
[3 ]. In ulcerative colitis (UC), the incidence is higher, reaching 18% at
30 years [4 ]. Population-based
studies, however, suggest this risk to be lower, particularly for patients who were
diagnosed in the biological era [5 ]
[6 ]. On the
other hand, patients with primary sclerosing cholangitis (PSC) and IBD concomitantly,
PSC-IBD, have a higher risk of CRC. A Scandinavian study suggested that risk in those
with
PSC-UC may be as high as nine times that of the general population [7 ]. Moreover, a meta-analysis with more
than 13,000 subjects observed that these patients have a 3-fold increase in risk of
CRC
compared with IBD-only patients [1 ].
Incidence of PSC is about 1.0 per 105 person-years [6 ], about 70% have IBD, of which 80% are
UC and 20% Crohn’s disease (CD) [8 ].
Patients with PSC-IBD have a distinct phenotype of IBD that causes mildly symptomatic
or
even asymptomatic disease, often with rectal sparing, pancolitis, and backwash ileitis
[9 ]. However, in a composite endpoint of
cancer, liver transplantation, and death, patients with PSC-CD have a less severe
course
than those with PSC-UC, 9% vs 27% [10 ]. Moreover, patients with PSC-UC have a 3-fold increase in risk of
dysplasia and cancer compared with patients with UC only, which has not been observed
between patients with CD [11 ]
[12 ]. Recent studies have pointed to an
increased risk of nonconventional neoplasia (i.e., different from the intestinal type
and
sporadic adenomas) in patients with PSC-IBD [13 ]
[14 ]. These
changes can be macroscopically similar to the adjacent mucosa and result in suboptimal
results of surveillance, with increased risk of progression to colectomy [15 ]
[16 ]. Among these, sessile serrated
lesions (SSLs) represent an early stage of the serrated neoplasia pathway, marked
by
development of CRC with characteristically high levels of microsatellite instability
[17 ].
There is an unmet need for defining the best strategy for CRC surveillance in the
IBD
population. In conventional IBD, CRC screening is recommended after 6 to 10 years
of IBD
onset [18 ]
[19 ]
[20 ]. All patients with PSC should be
offered an index colonoscopy at time of diagnosis with biopsies to detect subclinical
IBD
and repeat colonoscopy at 5-yearly intervals in the absence of clinically apparent
IBD, or
annual colonoscopic surveillance in the presence of IBD. Advanced endoscopic imaging
may
increase neoplasia detection rate and reduce unnecessary biopsies [21 ]. Chromoendoscopy (CE) has been
recommended as the preferred method over white light endoscopy (WLE) [18 ]
[19 ]
[20 ]
[21 ]
[22 ], despite the poor quality of
evidence. With the advent of high-definition (HD) WLE, some have questioned the added
value
of CE with extra costs and time, with meta-analyses failing to show a statistically
significant advantage of chromoendoscopy when HD-WLE is the comparator [23 ]. Thus, it is essential that we
define the best surveillance technique for patients with PSC-IBD, more so for those
with
PSC-UC, who have a higher risk of CRC than others.
The aim of the present study was to use real-world data to analyze differences in
detection
of neoplasia using CE and HD-WLE in contrast to standard definition (SD) in the surveillance
of CRC among patients with PSC-IBD of a tertiary referral center in the United Kingdom.
We
hypothesize that colonoscopy with CE and HD-WLE have higher neoplasia detection rates
than
SD-WLE.
Patients and methods
Study design
This was a single-center, retrospective, observational cohort study to analyze the
difference in neoplasia detection between CE, HD-WLE, and SD-WLE among patients with
PSC-IBD undergoing annual CRC surveillance with colonoscopy between January 2010 and
March
2020 at the Oxford University Hospitals NHS Foundation Trust in the United Kingdom.
This study was approved by the Clinical Audit Division at Oxford University Hospitals
Trust (reference number 8299). Patients in this study have consented to have their
data
collected and used in research developed by the biobank and the researchers from the
Translational Gastroenterology Unit, Division of Experimental Medicine, Nuffield
Department of Medicine, University of Oxford (REC 09/H1204/30, and 16/YH/0247).
Patient characteristics
Patients in the study were between 18 and 85 years of age, with a diagnosis of PSC
and
IBD, who were seen at specialist IBD and PSC clinics, and had at least one colonoscopy
for
CRC surveillance. Patients with a history of neoplasia in previous screenings were
excluded from subsequent analysis.
Data collection
Data were collected from electronic patient records and included gender, age in years
at
PSC and IBD diagnosis, subtype of IBD, date of first colonoscopy and subsequent scopes,
use of dye spray, use of HD scope, bowel preparation, if random or targeted biopsies
were
collected, and histology of lesion (adenomatous polyps, serrated lesions, hyperplastic
polyps).
Endoscopic techniques
Procedures were performed under conscious sedation using intravenous benzodiazepines
and
opiates as needed. Carbon dioxide insufflation was used for all colonoscopies. Patients
received bowel preparation with Citramag and senna, or Moviprep, scored as: inadequate;
adequate; good; excellent. Olympus SD colonoscopes (CF-260DL) or HD colonoscopes
(CF-H290DL) were used for procedures. Dye spray was applied with a spray catheter
(Olympus
PW-205V) in a segmental fashion with 0.2% indigo carmine. Targeted biopsies were taken
of
suspected lesions, or they were resected. Pairs of segmental biopsies were taken for
activity and extent, without the intent to detect dysplasia. Random biopsies could
also be
taken at the discretion of the endoscopist but were not mandated. Use of chromoendoscopy
and HD endoscopes was encouraged through the study period via mentorship, departmental
presentations, and highlighting new guidelines (e.g., SCENIC 2015). Narrow band imaging
was not used.
Pathology
Pathology was reported according to the Vienna criteria. Neoplastic lesions were defined
as: all adenomatous polyps plus all serrated lesions (sessile serrated lesion and
hyperplastic polyps) proximal to the rectum and serrated polyps in the rectum > 5
mm in
size. Rectal hyperplastic polyps ≤5 mm were not considered neoplastic. This is in
line
with the British Society of Gastroenterology 2020 post-polypectomy guidelines which
uses
this definition for premalignant polyps [24 ].
Outcomes
The primary outcome measure was the odds ratio (OR) for neoplasia detection with use
of
chromoendoscopy or HD colonoscope, adjusted for other confounding factors.
Preplanned secondary outcomes included: primary outcomes subdivided into HD versus
chromoendoscopy; adenomatous lesions and serrated lesions; and rate of adoption of
both HD
and chromoendoscopy over the study period. We performed a sensitivity analysis to
look at
the primary outcome subdivided into PSC-UC and PSC-CD groups.
Statistical analysis
Patients were categorized according to use of CE and HD-WLE or SD-WLE at each
colonoscopy. Data were censored after the first diagnosis of neoplasia, last follow-up,
or
at the end of the study period (31 March 2020). Continuous data are presented as median
and interquartile range. Categorical data are described using number and percentage.
Patient-level demographic measures were compared using the Chi-square test for categorical
variables and the Kruskal-Wallis test for continuous variables. Multilevel logistic
regression examined the association between each technique and occurrence of neoplasia
in
the entire cohort, and it was also used to perform subgroup analyses according to
IBD
subtype. For each technique, three different analyses were carried out (unadjusted;
adjusted for demographic factors associated with first analysis; adjusted for factors
associated with the first analysis and for the other technique). Two-side P =0.05
was considered statistically significant (Stata 15.1, Stata Corp.). All comparisons
were
done on a base of complete-case analysis. Patients were censored at the time that
neoplasia was detected during annual surveillance or at the end of the study. There
were
no strategies to prevent loss to follow-up, given the nature of a retrospective analysis.
Percentages are rounded to the nearest integer. This cohort study is reported according
to
STROBE guidelines for reporting observational studies [25 ].
Confounders and bias
The long follow-up of these patients exposes this cohort to confounders due to new
developments in CRC surveillance that happened throughout the study period. Furthermore,
there are several factors that might affect occurrence of neoplasia among these patients,
such as age at diagnosis of PSC, age at diagnosis of IBD, use of CE and/or HD-WLE,
bowel
preparation, use of aminosalicylates, and use of biologicals. The statistical analysis
adjusted for possible confounding factors, which were found to vary between groups.
Finally, collection of data from electronic patient records is effective against
recollection bias.
Results
Demographics
Ninety-one patients with PSC-IBD met the eligibility criteria for this study, resulting
in an average follow-up of 3.95 person-years and a total follow-up of 360 person-years
([Fig. 1 ]). There were 58 men (64%), median
age at diagnosis of PSC was 39.2 years, and median age at diagnosis of IBD was 29.4
years.
Sixty-three patients (70%) had UC, of whom 56 (90%) had pan-colonic inflammation,
six (9%)
had active disease only in the left side, and one (1%) had no inflammation detected.
There
were 17 patients with CD, 16 (94%) had pan-colonic inflammation, six (35%) had active
disease in the ileum, and two (12%) had perianal disease. Among the 10 patients (11%)
with
unclassified IBD, all of them had pan-colonic inflammation and one (10%) had ileal
disease. Data on IBD type were unavailable for one patient.
Fig. 1 Number of patients and colonoscopies that met the eligibility criteria and how the
outcome was analyzed.
Aminosalicylates (5-ASA) were used as monotherapy in 36 patients (40%) and as dual
therapy with immunosuppressants and with biologics in 24 (26%) and 17 (19%), respectively.
Intrahepatic strictures were the only manifestation of PSC in 55 patients (60%), while
23
(25%) had both intrahepatic and extrahepatic strictures. Fifty-seven patients (63%)
used
ursodeoxycholic acid for PSC. The 91 PSC-IBD patients had 422 colonoscopies in total,
but
63 were excluded from analysis because there was evidence of neoplasia in a previous
exam,
leaving 359 colonoscopies to be analyzed.
Identification of neoplasia
Twenty-two patients (24%) had at least one neoplastic lesion identified. Random biopsies
were used in 340 colonoscopies and in one occasion, identified dysplasia; however,
targeted biopsies also identified dysplasia in this patient. The mean neoplastic lesion
rate was much higher for the PSC-UC patients 0.87 (54/63) than for the PSC-CD patients
0.24 (4/17); however, the PSC-UC group includes one patient who had 20 hyperplastic
polyps
resected in the right colon, a potential case of PSC-UC with serrated polyposis syndrome.
Removing this outlier gives a revised rate of PSC-UC mean neoplastic lesion rate of
0.55
(34/62). No SSLs with dysplasia were observed in this cohort. There was one case of
moderately differentiated adenocarcinoma identified in the cecum 25 × 50 mm pT3 pN0
pM0
R0, managed by subtotal colectomy with ileorectal anastomosis; the patient is alive
8
years post-operatively ([Table 1 ]).
Table 1 Distribution of lesions among patients and IBD
subtype.
Category
All PSC-IBD
PSC-UC
PSC-CD
PSC-IBDU
*Data about IBD subtype were unavailable for one patient.
†This includes one patient who had 20 hyperplastic polyps in the right
colon.
IBD, inflammatory bowel disease; HP, hyperplastic polyp; IBDU, IBD
unclassified; PSC, primary sclerosing cholangitis; SSL, sessile serrated lesion;
UC, ulcerative colitis.
Per patient with neoplasia
22/91* (24%)
18/63 (29%)
3/17 (17%)
1/10 (10%)
Dysplasia (all adenomas)
10/91 (11%)
8/63 (13%)
2/17 (12%)
0/10 (0%)
Serrated lesions (SSL and HP)
14/91 (15%)
11/63 (17%)
2/17 (12%)
1/10 (10%)
SSL
5/91 (5 %)
5/63 (8%)
0/17 (0%)
0/10 (0%)
Hyperplastic
11/91 (12%)
8/63 (13%)
2/17 (12%)
1 (10%)
Adenocarcinoma
1/91 (1%)
1/63 (2%)
0/17 (0%)
0/10 (0%)
Total neoplastic lesions
59
54
4
1
Dysplasia (all adenomas)
13
11
2
0
Serrated lesions (SSL and HP)
45
42
2
1
SSL
8
8
0
0
Hyperplastic
37†
34†
2
1
Adenocarcinoma
1
1
0
0
Choice of endoscopic technique
Chromoendoscopy (CE)
PSC-IBD patients were divided into three categories: those where CE was never used
“never”; those where CE was used for some surveillance procedures “sometimes”; and
those
patients where CE was used for all surveillance procedures “always” ([Table 2 ]). There was a significant difference
between year of first colonoscopy and use of CE; patients who had a mix of techniques
were recruited earlier (median 2012) than those who had their surveillance with CE
or
with SD-WLE only (median 2015) (P =0.002). Age at PSC diagnosis, age at IBD
diagnosis, gender, type of IBD, and adequacy of bowel preparation were not significantly
associated with endoscopic technique used ([Table 2 ] and [Table 3 ]).
Although we recommended that CE should not be performed in patients with fair or
inadequate bowel preparation, at the discretion of the endoscopist, in three patients
with inadequate preparation, CE was still used.
Table 2 Patient-level demographics between dye spray groups.
Variable
Category
Never
Sometimes
Always
P value
Figures are median interquartile range or number (percentage).
IBD, inflammatory bowel disease; IBDU, IBD unclassified; PSC, primary
sclerosing cholangitis: UC, ulcerative colitis.
Year of first procedure
–
2015
2012
2015
0.002
Age PSC diagnosed
–
23 (16–55)
40 (26–55)
33 (26–48)
0.21
Age IBD diagnosed
–
26 (15–37)
34 (22–52)
27 (21–41)
0.14
Gender
Female
8 (42%)
19 (35%)
6 (33%)
0.83
Male
11 (58%)
35 (65%)
12 (67%)
Type IBD
UC
13 (72%)
35 (65%)
15 (83%)
0.68
Crohn’s
3 (17%)
12 (22%)
2 (11%)
IBDU
2 (11%)
7 (13%)
1 (6%)
Table 3 Procedure-level demographics between dye spray
groups.
Variable
Category
No dye spray
Dye spray
P value
Bowel preparation
Inadequate
19 (11%)
3 (2%)
0.21
Adequate
66 (37%)
81 (45%)
Good
52 (29%)
38 (21%)
Excellent
41 (23%)
58 (32%)
High-definition and standard definition white light endoscopy
PSC-IBD patients were divided into three categories: never used, sometimes done, all
surveillance was done using HD-WLE or SD-WLE ([Table 4 ]). Patients who had all procedures performed with SD-WLE were
recruited to the screening program earlier (median 2010) than those who had all
surveillance investigations done with HD-WLE (median 2017) (P <0.001).
Table 4 Patient-level demographics between HD scope groups.
Variable
Category
Never
Sometimes
Always
P value
Figures are median interquartile range or number (percentage).
HD, high definition; IBD, inflammatory bowel disease; IBDU, IBD unclassified;
UC, ulcerative colitis.
Year of first procedure
–
2010
2013
2017
<0.001
Age PSC diagnosed
–
39 23, 54
41 26, 54
25 15, 37
0.10
Age IBD diagnosed
–
26 21, 51
36 24, 50
18 13, 28
0.02
Gender
Female
5 (23%)
20 (37%)
7 (50%)
0.23
Male
17 (77%)
34 (63%)
7 (50%)
Type IBD
UC
15 (68%)
35 (66%)
12 (86%)
0.51
Crohn’s
5 (23%)
10 (19%)
2 (14%)
IBDU
2 (9%)
8 (15%)
0 (0%)
Those who had a mix of HD and SD-WLE received the IBD diagnosis at an older age (median
36 years) than those who always were screened with HD-WLE (median 18 years)
(P =0.02).
Quality of bowel preparation was associated with use of SD or HD-WLE. Twenty percent
of
patients with excellent bowel preparation had colonoscopies with SD-WLE, while 37%
of
those with excellent bowel preparation used HD-WLE technology (P <0.001), as
seen in [Table 5 ].
Table 5 Procedure-level demographics between HD scope
groups.
Variable
Category
No HD scope
HD scope
P value
HD, high definition.
Bowel prep
Inadequate
16 (8%)
2 (2%)
<0.001
Adequate
87 (44%)
51 (39%)
Good
56 (28%)
30 (23%)
Excellent
39 (20%)
49 (37%)
Logistic regression of endoscopic technique and neoplasia detection
Unadjusted multilevel logistic regression suggests that CE detected more neoplasia
than
just WLE (13.9% vs. 2.8%, OR 5.58, 95% CI 2.08–14.9, P =0.001) ([Table 6 ]). When the analysis factored year of
colonoscopy and age at diagnosis of IBD, CE maintained a significant difference (OR
5.95,
95% CI 1.55–22.8, P =0.009). After adjusting for previous confounders and for use of
HD colonoscopes, CE was still significantly better at detecting neoplasia (OR 5.02,
95% CI
1.43–17.7, P =0.01).
Table 6 Association between endoscopic technique and
neoplasia.
Factor
Analysis
All neoplasia-n/N (%)
Odds ratio*
P
*Odds ratio expressed as odds of dysplasia when dye spray/HD scope used
relative
to odds when it was not used.
† Adjusted for year of procedure and age at IBD diagnosis.
‡ As Adjusted Analysis 1, plus additional adjustment for use of HD
scope.
§ Adjusted for year of procedure, age of IBD diagnosis, age of PSC
diagnosis and bowel
prep quality.
¶ As Adjusted Analysis 1, plus additional adjustment for use of dye
spray.
CI, confidence interval; HD, high definition; IBD, inflammatory bowel disease;
PSC, primary
sclerosing cholangitis.
Not used
Used
(95% CI)
value
Dye spray
Unadjusted
5/178 (2.8%)
25/180 (13.9%)
5.58 (2.08–14.9)
0.001
Adjusted 1†
–
–
5.95 (1.55–22.8)
0.009
Adjusted 2‡
–
–
5.02 (1.43–17.7)
0.01
HD scope
Unadjusted
12/199 (6.0%)
18/132 (13.6%)
2.46 (1.14–5.30)
0.02
Adjusted 1§
-
-
1.87 (0.72–4.83)
0.20
Adjusted 2¶
-
-
1.93 (0.69–5.40)
0.21
Unadjusted multilevel logistic regression suggests that HD-WLE detected more neoplasia
than SD (OR 2.46, 95% CI 1.14–5.30, P =0.02). Nevertheless, the differences were no
longer significant when adjusted for year of procedure, age of IBD diagnosis, age
of PSC
diagnosis, and bowel preparation quality (OR 1.87, 95% CI 0.72–4.83, P =0.20), and
for use of dye spray on top of the previous confounders (OR 1.93, 95% CI 0.69–5.40,
P =0.21).
Logistic regression of endoscopic technique and type of neoplasia
Unadjusted multilevel logistic regression suggests that CE (8.9%) identified more
serrated neoplasia than WLE (1.7%) (OR 5.69, 95% CI 1.62–19.8, P =0.006), and HD-WLE
detected more serrated neoplasia (9.1%) than SD (3.5%) (OR 2.74, 95% CI 1.05–7.16,
P =0.04) ([Table 7 ]). However, when
adjusting for confounders including year of procedure, age at IBD and PSC diagnosis,
and
quality of bowel preparation, there was no significant difference.
Table 7 Association between endoscopic technique and serrated
neoplasia.
Factor
Analysis
Serrated neoplasia-n/N (%)
Odds ratio*
P
*Odds ratio expressed as odds of dysplasia when dye spray/HD scope used
relative
to odds when it was not used.
† Adjusted for year of procedure and age of IBD diagnosis.
‡ As Adjusted Analysis 1, plus additional adjustment for use of HD
scope.
§ Adjusted for year of procedure, age of IBD diagnosis, age of PSC
diagnosis and
bowel prep quality.
¶ As Adjusted Analysis 1, plus additional adjustment for use of dye
spray.
HD, high definition; IBD, inflammatory bowel disease; PSC, primary sclerosing
cholangitis.
Not used
Used
(95% CI)
value
Dye spray
Unadjusted
3/178 (1.7%)
16/180 (8.9%)
5.69 (1.62–19.8)
0.006
Adjusted 1†
–
–
3.67 (0.79–17.0)
0.10
Adjusted 2‡
–
–
3.50 (0.87–14.1)
0.08
HD scope
Unadjusted
7/199 (3.5%)
12/132 (9.1%)
2.74 (1.05–7.16)
0.04
Adjusted§
-
-
2.09 (0.65–6.72)
0.22
Adjusted 2¶
-
-
2.01 (0.62–6.57)
0.24
Unadjusted multilevel logistic regression suggests that CE (6.1%) detected more
adenomatous polyps than WLE (1.1%) (OR 12.8, 95% CI 1.24–132, P =0.03) ([Table 8 ]). This difference remained significant
after accounting for year of procedure and age at IBD diagnosis (OR 14.7 (95% CI 1.41–153,
P =0.02) and use of HD-WLE (OR 12.0, 95% CI 1.08–134, P =0.04).
Table 8 Association between endoscopic technique and adenomatous
neoplasia.
Factor
Analysis
Adenomatous neoplasia-n/N (%)
Odds ratio*
P
*Odds ratio expressed as odds of dysplasia when dye spray/HD scope used
relative
to odds when it was not used.
† Adjusted for year of procedure and age of IBD diagnosis.
‡ Adjusted Analysis 1, plus additional adjustment for use of HD
scope.
§ Adjusted for year of procedure, age of IBD diagnosis, age of PSC
diagnosis and bowel
prep quality.
¶ As Adjusted Analysis 1, plus additional adjustment for use of dye
spray.
HD, high definition; IBD, inflammatory bowel disease; PSC, primary sclerosing
cholangitis.
Not used
Used
(95% CI)
value
Dye spray
Unadjusted
2/178 (1.1%)
11/180 (6.1%)
12.8 (1.24, 132)
0.03
Adjusted 1†
–
–
14.7 (1.41, 153)
0.02
Adjusted 2‡
–
–
12.0 (1.08, 134)
0.04
HD scope
Unadjusted
5/199 (2.5%)
8/132 (6.1%)
2.50 (0.80, 7.82)
0.12
Adjusted 1§
–
–
2.26 (0.63, 8.09)
0.21
Adjusted 2¶
–
–
2.34 (0.66, 8.38)
0.19
Unadjusted multilevel logistic regression suggests that HD-WLE found more adenomatous
neoplasia (6.1%) than SD (2.5%) (OR 2.50, 95% CI 0.80–7.82, P =0.12), but it was not
significant when adjusting for confounders including year of procedure, age at IBD
and PSC
diagnosis, and quality of bowel preparation (OR 2.26, 95% CI 0.65–8.09, P =0.21),
and use of dye spray (OR 2.34, 95% CI 0.66–8.38, P =0.19).
Logistic regression of endoscopic technique and neoplasia detection according to IBD
subtype
Ulcerative colitis
Unadjusted multilevel logistic regression identified that CE detected more neoplasia
(16%) than WLE (3%) (OR 8.10, 95% CI 1.72–38.2, P =0.008). When year of procedure
and age of IBD diagnosis were factored into the analysis, the association remained
(OR10.7, 95% CI 1.44–79.4, P =0.02), as well as when further adjustment was made
for the previous variables and use of an HD scope (OR 8.86, 95% CI 1.33–59.2, P =
0.02) (Supplementary Table 1 ).
Unadjusted multilevel logistic regression showed that HD-WLE detected more neoplasia
(15%) than SD (8%) although it was not significant (OR 2.14, 95% 0.92–4.94,
P =0.08).
Crohn’s disease
Unadjusted multilevel logistic regression showed that CE identified less neoplasia
(4.4%)
than WLE (5.1%) (OR 0.82, 95% CI 0.06–11.2, P =0.88) although it was not significant
(Supplementary Table 2 ). It was not possible to fit use of HD scopes into the
regression because no cases of neoplasia were detected when HD scopes were not used.
This
also impacted the analysis of the association between use of HD scopes and detection
of
neoplasia. However, using Fisher’s exact test, the association was not statistically
significant (P =0.07).
Discussion
This study demonstrated a higher frequency of colorectal neoplasia detection in patients
with PSC-IBD using chromoendoscopy compared with WLE, even when adjusting for use
of HD
colonoscopes. Use of chromoendoscopy increased detection of both SSLs and adenomatous
polyps, although only adenomatous lesions remained significant once adjusted for
confounders.
We found that adoption of both CE and HD colonoscopes in PSC-IBD was slow over the
10 years
and was not universal by 2020. Similarly, rates of adoption for CE in IBD surveillance
have
been poor. Even in expert centers, rates of CE use only reached 76%, equivalent to
our
results [26 ]. Slow implementation and
lack of systematic guidance for training in CE are factors that need consideration.
Despite
the British Society of Gastroenterology recommendation since 2010 [22 ], CE was less used than SD-WLE among
our cohort until 2013 and from 2015 onward, it was used in about 60% of colonoscopies
in
these patients ([Fig. 2 ]). Furthermore, training
endoscopists in use of CE takes time, more so given increased detection of lesions
and need
to determine whether to act on the findings. This gap was resolved only recently when
the
European Society of Gastrointestinal Endoscopy (ESGE) released guidance on competence
standards for optical diagnosis of diminutive colorectal polyps [27 ].
Fig. 2 Uptake of colonoscopies (percentage) using standard-definition colonoscopes and
chromoendoscopy (CE), high-definition colonoscopes only (HD), a combination of CE
and
high-definition colonoscopes (CE + HD), and standard-definition colonoscopes only
(SD)
throughout the study duration.
There has been considerable debate about the additional value of chromoendoscopy in
the HD
era. In a network meta-analysis in patients with IBD alone, dye-based CE was not superior
to
HD-WLE alone to detect polyps [28 ].
The combined introduction of HD-WLE and CE may explain why in our cohort the median
year of
first procedure in the “never” chromoendoscopy category was later than the “sometimes”
category. A cohort study using virtual and dye-based CE compared to HD-WLE in patients
with
IBD detected roughly twice more serrated lesions with CE compared with HD-WLE, 17%
vs 8%
[29 ]. Another cohort study
identified that CE use increased the likelihood of detection of serrated neoplasia
(Adjusted
OR 1.99, 95% CI 1.13–3.51) [30 ]. The
increased detection of serrated neoplasia, usually subtle and non-polypoid, may have
similarly made CE more effective in our series. Furthermore, “invisible” dysplasia
is more
frequently reported in PSC-IBD cohorts than IBD-only cohorts, 66% vs 21% in one large
study,
which might also be revealed by CE for targeted biopsy [14 ]. The rate of progression from
low-grade dysplasia to high-grade dysplasia and finally CRC has not been elucidated
in
patients with PSC-IBD [9 ].
In our PSC-IBD cohort, both SSL and adenomatous polyps were detected at surveillance
colonoscopy, with higher numbers of serrated than adenomatous lesions. This may be
due to an
underappreciated understanding that PSC-related colonic lesion progress via the serrated
pathway, or those techniques used heighted SSL detection. A possible role for the
serrated
carcinogenesis pathway in contributing to the increased risk of colon cancer in PSC
is not
well understood, but warrants further investigation, especially following the high
frequency
of serrated lesions detected here. PSC cancers and serrated lesions both have a strong
predilection for the right side of the colon [31 ], and serrated nonconventional dysplasia was associated with higher
CRC progression risk in IBD [14 ]
, . Moreover, serrated polyps with dysplasia are associated
with advanced neoplasia risk in IBD patients [32 ]. Given that PSC is characterized by low-grade, right-sided
inflammation, dysbiosis and possible immune dysregulation, it is possible that the
serrated
carcinogenesis pathway predominates and contributes to the disproportionate cancer
risk in
this condition. Further research will be required to establish this.
The differences in colonic neoplasia between PSC-UC and PSC-CD were evident in our
cohort
and confirm previous reports of increased chance of neoplasia in those with PSC-UC
[11 ]
[12 ]. This subgroup had the majority of
lesions identified in this cohort, including the only case of CRC among our patients.
They
also had 90% of all sessile serrated polyps identified, further supporting the argument
that
PSC-UC patients might have an increased risk of nonconventional neoplasia compared
to PSC-CD
and IBD-only populations.
There are some limitations in our study. As a retrospective cohort, there is possible
historical bias. Our service is a national reference center for the management of
IBD and
PSC, hence our cohort of patients may not be representative of the overall population
with
PSC-IBD. The pathology reporting for this study follows the Vienna criteria and included
serrated lesions; however recent publications have highlighted the role of nonconventional
dysplasia which were mainly published after the study period and are not reported
here [33 ]. We did not consider the use of
virtual chromoendoscopy (e.g., NBI) as the ESGE guidelines that proposed this were
only
published in 2019 [21 ]. Finally, the
sample size of this study is relatively small, which may underpower the subgroup analyses,
and the findings ideally should be replicated in larger randomized controlled trials.
However, it is unlikely that resources would be devoted to a major trial in this niche
area.
Dye-based CE enhanced detection of all neoplastic lesions (adenomatous and serrated)
at
surveillance colonoscopy in PSC-IBD, with results suggesting that it detected more
neoplasia
than WLE even when adjusting for confounding factors, including use of HD endoscopes.
These
results highlight that implementing recommendations and recognizing their results
takes
time. It has been almost a decade since the first SCENIC guidelines on use of
chromoendoscopy for CRC surveillance in IBD, and we are finally identifying the impact
of
the technique in real-life patient care. Furthermore, these results support recommendations
by international societies, including the most recent SCENIC update from 2021 [34 ], that CE positively impacts
neoplasia screening in patients with IBD. They also suggest a benefit of this technique
to
this high-risk group with PSC-IBD.
The role of virtual chromoendoscopy in identifying neoplasia in PSC-IBD patients has
yet to
be clarified, and guideline recommendations to consider its use in general IBD surveillance
as equivalent to dye-based CE post-date our cohort [34 ]
[35 ]
[36 ]. Artificial intelligence-based
neoplasia detection (computer-aided detection [CADe]) for IBD neoplasia is being developed
(IBD-CADe) [37 ]; however, it is
unclear if CADe algorithms developed on non-PSC-IBD datasets will be generalizable
to
PSC-IBD surveillance [38 ].
Conclusions
In conclusion we found that dye-based chromoendoscopy increased neoplasia detection
even
when HD colonoscopes were used in a PSC-IBD cohort over a 10-year period. The majority
of
neoplasia was detected in the PSC-UC subgroup.
Bibliographical Record
