Introduction
Serrated polyposis syndrome (SPS) is a heterogeneous disease arbitrarily defined according
to the following World Health Organization (WHO) criteria [1 ]: (i) at least five serrated lesions proximal to the sigmoid colon, with two or more
of them being ≥ 10 mm in diameter; (ii) at least one serrated lesion proximal to the
sigmoid colon in a patient with a first-degree relative with SPS; or (iii) > 20 serrated
lesions spread throughout the colon. SPS prevalence has been reported as between 0.34 %
and 0.66 % of the population in the context of screening programs based on fecal occult
blood testing (FOBT) [2 ]
[3 ]. In establishing a diagnosis of SPS, the number of polyps is cumulative, so it is
often established after successive procedures [1 ]. A study showed that up to 45 % of SPS patients are not diagnosed at first colonoscopy,
even if this is performed by an experienced endoscopist [4 ].
The presence of numerous or large serrated lesions ([Fig. 1 ]) is a common finding in a fecal immunochemical test (FIT)-based colorectal cancer
(CRC) screening program [5 ]. However, surveillance recommendations for patients with serrated lesions remain
controversial. The American Gastroenterology Association (AGA) recommends follow-up
intervals that range from 3 to 10 years, according to location, size, dysplastic component,
and histological subtype of any serrated lesions, but annually if one of the WHO criteria
of SPS is fulfilled [6 ]. The European Society of Gastrointestinal Endoscopy (ESGE) proposes a simple approach
that takes into account size and dysplastic component [7 ]. An expert panel has recommended a 3-year surveillance colonoscopy in patients with
at least one sessile serrated adenoma/polyp (SSA/P) or traditional serrated adenoma
(TSA) ≥ 10 mm, three or more SSA/Ps or TSAs of any size, or any number of SSA/Ps with
dysplasia [8 ]. However, the diagnostic yield of surveillance colonoscopy in these patients remains
poorly studied.
Fig. 1 Examples of sessile serrated adenomas/polyps (SSA/Ps) showing their typical flat
morphology, color that is similar to the surrounding mucosa, mucus cap, and subtle
borders.
We hypothesized that, in a FIT-based population screening program, a reassessment
colonoscopy in patients with proximal serrated lesions would detect missed SPS patients.
Accordingly, our aims were to assess the incremental rate of SPS diagnosis after a
reassessment colonoscopy in patients with proximal serrated lesions on their baseline
colonoscopy and, secondly, to identify factors predictive of a diagnosis of SPS.
Methods
Patients and study design
This was a retrospective study of prospectively collected data from the organized
Barcelona FIT-based CRC screening program. This program, which began in 2010, is based
on a biennial FIT (OC-Sensor; Eiken, Japan; cut-off ≥ 20 μg of hemoglobin/mg of feces)
in asymptomatic individuals aged 50 – 69 years. All colonoscopies and pathology reports
are reviewed weekly by a committee composed of expert gastroenterologists, endoscopists,
and nurses before follow-up recommendations are given. Until 2015, post-polypectomy
surveillance recommendations were based on the guidelines of the Spanish Association
of Gastroenterology [9 ] and AGA [6 ]: 3-year interval for patients with “high risk adenoma” (≥ 3 adenomas or any adenoma
≥ 10 mm in size, villous histology, or high grade dysplasia); and 5-year interval
for those with “low-risk adenoma” (1 – 2 tubular adenomas < 10 mm with low grade dysplasia).
Given the lack of surveillance recommendations for serrated lesions, patients with
a significant burden of serrated lesions on their baseline colonoscopy were scheduled
for a reassessment colonoscopy with the aim of potentially detecting previously unnoticed
serrated lesions. The decision to perform the reassessment colonoscopy was not standardized
and was based on the presence of large or proximal serrated polyps, the presence of
dysplasia, or SSA/P histology. In order to avoid selection bias, we included in the
study all participants in the screening program who underwent a colonoscopy from January
2010 to July 2013, focusing the analysis on those who had presented at least one serrated
lesion that was proximal to the sigmoid colon and larger than 5 mm.
When several baseline colonoscopies were needed, for example for inadequate bowel
preparation, high burden of polyps, or complex polypectomy, the baseline colonoscopy
was based on the date of the last colonoscopy that completely scrutinized the entire
colon and/or achieved a clear colon. For analysis purposes, the findings of any repeated
colonoscopies were compiled into one. Individuals who underwent baseline colonoscopy
in other centers or who had an incomplete procedure (i. e. without cecal intubation)
were excluded.
Data was obtained from the screening program database and from Hospital Clinic’s digital
medical records.
This study was approved by the Ethics and Clinical Investigation Committee from Hospital
Clinic of Barcelona.
Procedures and endoscopic equipment
Baseline colonoscopies were performed following quality standards [10 ] by 12 experienced endoscopists, each having performed more than 400 colonoscopies
per year and with a high adenoma detection rate (i. e. 29.8 % in primary colonoscopy
screening and 47.1 % in FIT-based screening) [11 ]
[12 ]
[13 ]. Reassessment colonoscopies were performed by a subgroup of five of these endoscopists.
The endoscopists who performed the reassessment colonoscopies had a similar adenoma
detection rate to those who performed only baseline colonoscopies (48.7 % vs. 46.2 %;
P = 0.67).
Baseline colonoscopies were performed with standard definition white-light endoscopes
(CF-Q160 L/CF-Q165 L in combination with an EVIS EXERA II processor; Olympus, Tokyo,
Japan). According to availability, reassessment colonoscopies were performed with
standard definition or high definition technology (CF-H180AL/CF-HQ190 L combined with
EVIS EXERA III processor; Olympus) with or without the addition of chromoendoscopy,
either conventional (indigo carmine 0.4 % spraying during continuous extubation) or
electronic (narrow-band imaging [NBI]).
All patients were encouraged to follow a low-fiber/low-fat diet for 3 days before
the procedure. Bowel cleansing was carried out with 4 L of polyethylene glycol and
electrolyte lavage solution (Solución Evacuante BOHM; Laboratorios Bohm S.A., Fuenlabrada,
Madrid, Spain) in split doses. Bowel cleansing was considered adequate (excellent
or good) if the Boston score was ≥ 6 points (≥ 2 per colonic segment).
Procedures were performed with the patients breathing spontaneously under deep sedation
(propofol and remifentanil infusion) that was administrated by trained nurses supervised
by anesthesiologists. Colonoscopies were scheduled in time slots of 40 minutes.
Polyp location was divided into four colonic segments: right colon (cecum, ascending
colon, and hepatic flexure); transverse colon (including splenic flexure); descending
colon; and sigmoid colon and rectum.
Histopathology
Polyp histology was evaluated by four expert pathologists dedicated to gastrointestinal
oncology following the European guidelines for quality assurance in CRC screening
and diagnosis [14 ]. The number, size, and histology of all lesions were registered. Serrated lesions
included SSA/Ps (with or without dysplasia), hyperplastic polyps, and TSAs. Advanced
adenomas were those with a villous component, size ≥ 10 mm, or high grade dysplasia
(including intramucosal carcinoma). The surgical specimen was used to provide the
final pathological diagnosis in patients who were treated by surgery. All lesions
detected at reassessment colonoscopy were considered to have been missed at baseline
colonoscopy.
Outcome measures
The primary outcome was to evaluate the rate of SPS diagnosis on baseline and reassessment
colonoscopies. The rate of SPS was defined as the proportion of SPS cases diagnosed
compared with the total number of patients in the screening cohort. The diagnosis
of SPS on reassessment colonoscopy was made according to the cumulative number of
serrated lesions detected in both colonoscopies. Secondary outcomes were to identify
clinical, histopathological, and endoscopic factors that were predictive of SPS on
reassessment colonoscopy using a univariable and multivariable approach.
Statistical analysis
Quantitative variables were summarized using mean (standard deviation [SD]) and median
(interquartile range [IQR]) values for skewed data. Frequencies (%) were used to summarize
categorical variables. Student’s t test was used to compare continuous variables with a normal distribution and Mann – Whitney
U test (unpaired) for those with skewed distribution. The chi-squared test was used
to test associations among categorical variables. All statistical tests were two-sided,
and P values < 0.05 were considered statistically significant.
Multiple logistic regression was used to identify independent predictors of a diagnosis
of SPS using backward stepwise variable selection. Candidate variables for inclusion
in the model were those achieving a P value ≤ 0.1 in the univariable analysis. Odds ratios (ORs) and associated 95 % confidence
intervals (CIs) were used to quantify the level of association.
SPSS statistics software version 20.0 (SPSS Inc., Chicago, Illinois, USA) was used
to analyze the data.
Results
Patients included in the study
From a total of 3444 patients who underwent a colonoscopy after a positive FIT, 201
individuals (5.8 %) had one or more serrated lesions ≥ 5 mm proximal to the sigmoid
colon (see [Fig. 2 ]). Five individuals who underwent colonoscopy in other centers (n = 4) or with incomplete
colonoscopy (n = 1) were excluded.
Fig. 2 Study flow chart. FIT, fecal immunochemical test; SPS, serrated polyposis syndrome.
Eleven patients (73 % men; age 57 ± 3 years) fulfilled SPS criteria on their baseline
colonoscopy. Among the remaining 185 patients, 114 followed the standard surveillance
protocol based on adenoma burden, while 71 patients underwent a reassessment colonoscopy
at 11.9 ± 1.7 months. As shown in [Table 1 ], the demographic characteristics of both groups at baseline colonoscopy were comparable.
As expected, patients who underwent a reassessment colonoscopy had a higher burden
of polyps than patients scheduled for standard surveillance.
Table 1
Demographic characteristics and main baseline findings in patients who underwent reassessment
colonoscopy and those scheduled for standard surveillance.
Reassessment colonoscopy
Standard surveillance (n = 114)
P value (95 %CI)
Patient demographics
Mean age ± standard deviation, years
59.4 ± 5.1
58.8 ± 1.9
0.63
Sex, male, n (%)
35 (49.3 %)
69 (60.5 %)
0.13
Baseline findings at screening colonoscopy
Prevalence of polyp subtype, n (%)
Hyperplastic polyps ≥ 10 mm
18 (25.4)
34 (29.8)
0.51
Proximal hyperplastic polyps ≥ 10 mm
10 (14.1)
10 (8.8)
0.26
SSA/Ps
43 (60.6)
27 (23.7)
< 0.001
SSA/Ps ≥ 5 mm
44 (62.0)
33 (28.9)
< 0.001
SSA/Ps ≥ 10 mm
21 (29.6)
17 (14.9)
0.02
Proximal[1 ] SSA/Ps
41 (57.7)
26 (22.8)
< 0.001
Proximal[1 ] SSA/Ps ≥ 10 mm
15 (21.1)
10 (8.8)
0.02
SSA/Ps with dysplasia
8 (11.2)
10 (8.8)
0.58
Adenomas
56 (78.9)
79 (69.3)
0.15
Advanced adenomas[2 ]
42 (59.2)
44 (38.6)
0.006
Number of polyps per patient, median (IQR)
Total serrated lesions
3 (2 – 6)
1 (1 – 2)
< 0.001
Adenomas
2 (1 – 5)
1 (0 – 2)
< 0.001
Advanced adenomas[2 ]
1 (0 – 2)
0 (0 – 1)
< 0.001
CI, confidence interval; SSA/P, sessile serrated adenoma/polyp; IQR, interquartile
range.
1 Proximal to sigmoid colon.
2 Advanced adenomas: ≥ 10 mm in size, with villous component or high grade dysplasia.
Rate of SPS diagnosis
As mentioned above, 11/3444 patients (0.32 %) were diagnosed with SPS on their baseline
colonoscopy. As is shown in the [Fig. 2 ], out of 71 patients who underwent reassessment colonoscopy, 20 new patients (45 %
men; age 58 ± 2 years) fulfilled SPS criteria (criterion 1 fulfilled [n = 9], criterion
3 fulfilled [n = 6], and criteria 1 and 3 both fulfilled [n = 5]). Therefore, after
reassessment colonoscopy, the rate of SPS increased to 0.90 % (31/3444 patients).
As expected, the patients diagnosed with SPS on their reassessment colonoscopy had
significantly more serrated lesions than the 51 patients who were not diagnosed with
SPS (median 15 [IQR 9 – 21] vs. 5 [2 – 9], respectively; P < 0.001). There were no significant differences in the numbers of adenomas.
Missed lesions detected on reassessment colonoscopy
The number of all missed lesions detected on reassessment colonoscopy was 5 [1 – 9],
with missed lesions being more common in the proximal colon than in the distal colon
to splenic flexure (5 [1 – 10] vs. 2 [1 – 7], respectively; P < 0.001). Serrated lesions were more often overlooked than adenomas (2 [0 – 6] vs.
1 [0 – 3], respectively; P = 0.008), with this difference also being evident when considering just the proximal
colon (1 [0 – 4] vs. 0 [0 – 2], respectively; P = 0.01).
Usefulness of endoscopic techniques for reassessment colonoscopy
Among the reassessment colonoscopies, 41/71 (58 %) were performed using chromoendoscopy,
37 of these being conventional (26 standard definition and 11 high definition) and
4 being electronic ([Fig. 3 ]). The remaining 30 colonoscopies (42 %) were performed using white light alone (26
standard definition and 4 high definition). The use of chromoendoscopy or high definition
endoscopes at reassessment colonoscopy was not related to polyp burden at baseline
colonoscopy ([Table 2 ]).
Fig. 3 Example of a large flat elevated (Paris classification 0-IIa) sessile serrated adenoma/polyp
visualized with different endoscopic techniques: a high definition white-light endoscopy; b high definition conventional chromoendoscopy (with indigo carmine 0.4 % dye); c electronic chromoendoscopy (narrow-band imaging [NBI]).
Table 2
Findings on baseline colonoscopy and effect of image-enhancement techniques and type
of endoscope used at reassessment colonoscopy.
Finding on baseline colonoscopy
Reassessment colonoscopies (n = 71)
Image-enhancement techniques
Type of endoscope
Chromo-endoscopy[1 ]
White-light endoscopy[2 ]
Odds ratio[3 ] (95 %CI)
P value
High definition
Standard definition[2 ] (n = 52)
Odds ratio[3 ] (95 %CI)
P value
1 – 2 serrated lesions < 10 mm
13
46 %
54 %
0.56
0.35
15 %
84 %
0.43
0.31
≥ 1 serrated lesion with dysplasia
8
50 %
50 %
0.70
0.71
13 %
87 %
0.35
0.67
3 – 4 serrated lesions < 10 mm
9
67 %
33 %
1.54
0.73
33 %
67 %
1.43
0.69
1 – 2 serrated lesions ≥ 10 mm
11
45 %
55 %
0.55
0.51
18 %
82 %
0.56
0.72
3 – 4 serrated lesions≥ 10 mm
34
59 %
41 %
1.08
0.86
23 %
77 %
0.72
0.56
≥ 5 proximal[4 ] serrated lesions
29
62 %
38 %
1.35
0.54
34 %
66 %
1.93
0.22
1 SSA/P
18
56 %
44 %
0.88
0.83
28 %
72 %
1.07
0.91
≥ 2 SSA/Ps
25
72 %
28 %
2.57
0.07
72 %
28 %
1.10
0.86
≥ 2 SSA/Ps ≥ 10 mm
11
73 %
27 %
2.18
0.34
18 %
82 %
0.56
0.72
CI, confidence interval; SSA/P, sessile serrated adenoma/polyp.
1 Chromoendosocopy: conventional (i. e. indigo carmine 0.4 % dye spraying) or electronic
(i. e. narrow-band imaging).
2 White-light endoscopy and use of a standard definition endoscope were the respective
reference groups.
3 Univariable analysis.
4 Proximal to the sigmoid colon.
The number of serrated lesions detected with chromoendoscopy was higher than with
white light alone (3 [1 – 9] vs. 1 [0 – 5], respectively; P = 0.046) regardless of the type of endoscope used. The number of serrated lesions detected
with high definition white light was higher than with standard definition white light
(6 [4 – 8] vs. 1 [0 – 4], respectively; P = 0.03). When analyzing the colonoscopies performed with standard definition endoscopes,
the number of serrated lesions detected with chromoendoscopy was higher than with
white light alone (3 [1 – 9] vs. 1 [0 – 4], respectively; P = 0.008). Therefore, as is shown in [Fig. 4 ], the use of chromoendoscopy and/or high definition endoscopes results in the detection
of significantly more serrated lesions and proximal serrated lesions. The endoscopic
technique did not affect the adenoma detection.
Fig. 4 Usefulness of advanced endoscopic techniques for the detection of different lesions
on reassessment colonoscopy. a Proximal to sigmoid colon.
Factors predictive of SPS being diagnosed on reassessment colonoscopy
We evaluated factors on the baseline colonoscopy that were predictive of SPS being
diagnosed in our cohort of individuals empirically scheduled for a reassessment colonoscopy
([Table 3 ]).
Table 3
Univariable and multivariable analysis of factors predictive of a diagnosis of serrated
polyposis syndrome (SPS) at reassessment colonoscopy.
Risk factors
Number of reassessment colonoscopies
SPS
Non-SPS[1 ] (n = 51)
Univariable analysis
Multivariable analysis
Odds ratio (95 %CI)
P value
Adjusted odds ratio (95 %CI)
P value
Sex, female
36
31 %
69 %
1.27
0.65
–
–
Age, 50 – 60 years old[2 ]
43
30 %
70 %
0.76
0.63
–
–
1 – 2 serrated lesions < 10 mm[3 ]
13
0 %
100 %
–
0.01
–
–
≥ 1 serrated lesions with dysplasia[3 ]
8
62 %
38 %
5.3
0.04
–
–
3 – 4 serrated lesions < 10 mm[3 ]
9
11 %
89 %
0.28
0.43
–
–
1 – 2 serrated lesions ≥ 10 mm[3 ]
11
18 %
82 %
0.51
0.72
–
–
3 – 4 serrated lesions ≥ 10 mm[3 ]
34
35 %
65 %
1.97
0.20
–
–
≥ 5 proximal[4 ] serrated lesions[3 ]
29
45 %
55 %
4.06
0.01
4.01
0.02
1 SSA/P[3 ]
18
33 %
67 %
1.39
0.57
–
–
≥ 2 SSA/Ps[3 ]
25
48 %
52 %
4.38
0.006
–
–
≥ 2 SSA/Ps ≥ 10 mm[3 ]
11
64 %
36 %
6.32
0.004
6.35
0.02
Chromoendoscopy[5 ] and/or high definition endoscopes at reassessment colonoscopy
41
37 %
63 %
2.88
0.07
4.99
0.04
CI, confidence interval; SSA/P, sessile serrated adenoma/polyp.
1 Non-SPS group as the reference group.
2 60 – 69 years as reference group.
3 On baseline colonoscopy.
4 Proximal to the sigmoid colon.
5 Chromoendoscopy: conventional (indigo carmine 0.4 % dye spraying) or electronic (narrow-band
imaging).
Univariable analysis showed that the presence of five or more proximal serrated lesions
(OR 4.06, 95 %CI 1.36 – 12.11; P = 0.01), two or more SSA/Ps (OR 4.38, 95 %CI 1.46 – 13.09; P = 0.006), and two or more SSA/Ps ≥ 10 mm (OR 6.32, 95 %CI 1.61 – 24.98; P = 0.004) were significantly associated with the diagnosis of SPS on reassessment colonoscopy.
Conversely, none of the SPS patients had just one or two serrated lesions < 10 mm
on baseline colonoscopy.
Multivariable analysis adjusted by age and sex showed that the presence of five or
more proximal serrated lesions (OR 4.01, 95 %CI 1.20 – 13.45; P = 0.02) or two or more SSA/Ps ≥ 10 mm (OR 6.35, 95 %CI 1.40 – 28.81; P = 0.02) were independent predictors of SPS being diagnosed on reassessment colonoscopy.
The use of chromoendoscopy and/or high definition white-light endoscopes at reassessment
colonoscopy was also an independent predictor of SPS being diagnosed (OR 4.99, 95 %CI
1.11 – 22.36; P = 0.04).
Discussion
This is the first study to assess a diagnostic strategy that substantially improves
the detection of SPS in patients. For patients with proximal serrated lesions on their
baseline colonoscopy, a reassessment colonoscopy within 1 year tripled the total number
of SPS diagnoses made in a FIT-based CRC screening program. Indeed, the rate of diagnosis
of SPS increased from 0.32 % (11 patients) after the baseline colonoscopy to 0.90 %
(20 additional patients) after the reassessment colonoscopy.
Despite different methodology and endpoints, our results are consistent with a recent
multicenter study from five European CRC screening programs (three FOBT-based cohorts,
to which our center contributed with a part of the Spanish cohort, and two primary
colonoscopy cohorts) [13 ]. This study reported a rate of SPS of 0 % – 0.5 % on baseline colonoscopy, with
an increase of 0.4 % – 0.8 % after follow-up. Moreover, a recent systematic review
from six screening populations showed a rate of SPS of 0 % – 0.66 % on baseline colonoscopy,
being higher in FOBT-based screening cohorts (0.34 % – 0.66 %) and lower in primary
colonoscopy cohorts (0 % – 0.09 %) [15 ].
This increase in SPS prevalence [2 ]
[3 ]
[13 ]
[15 ] is attributed to greater clinical and pathological awareness and better endoscopic
diagnostic accuracy [16 ]
[17 ]. The diagnosis of SPS depends directly on one’s ability to detect serrated lesions,
which are often easily overlooked because of their imperceptibility [4 ].
The considerable variability in the rates of serrated lesions in the average risk
population (from 1 % to 27 %) [13 ]
[18 ] and the FOBT-based preselected population (from 15 % to 19 %) [13 ] supports the idea that serrated lesions are more often missed than adenomas. Tandem
colonoscopy studies have shown a substantial adenoma miss rate of 20 % – 24 % [19 ]
[20 ]. Thus far, no study has specifically addressed the miss rate for serrated lesions.
Our study demonstrates that a reassessment colonoscopy performed within 1 year consistently
detects higher numbers of serrated lesions than adenomas (2 [0 – 6] vs. 1 [0 – 3],
respectively; P = 0.008). Although we cannot rule out that some of these polyps could be newly grown
polyps that have developed during the year, it is more likely that they were overlooked
at the time of baseline colonoscopy. Therefore, the serrated lesion miss rate is likely
to be much higher than that reported for adenomas.
The significance of serrated lesions has escalated in importance in recent years and
20 % – 30 % of all CRCs are thought to develop through the serrated neoplasia pathway.
It has been hypothesized that poor detection [18 ] and subtotal resection of serrated lesions [21 ] are responsible for the relative failure of colonoscopy to protect against CRC in
the proximal colon [8 ], which leads to an increase risk of interval CRC. Two recent studies [22 ]
[23 ], including the largest cohort of SPS patients so far reported, showed 5-year cumulative
incidences for CRC during surveillance of 1.9 % and 1.5 %. This CRC risk associated
with SPS is certainly much lower than previously reported. However, the prevalence
of CRC at the moment of SPS diagnosis was 29.3 % [22 ] and 15.8 % [23 ]. These data support the importance of a proper diagnostic approach in these patients
and of subsequent surveillance with highly proficient colonoscopies being performed
by specialist endoscopists.
The endoscopists’ meticulousness and optical training in the detection of serrated
lesions are key factors for SPS diagnosis: endoscopists with a high adenoma detection
rate may find 7 – to 18-fold more serrated lesions than are found by endoscopists
with lower detection rates [18 ]
[24 ]. In the present study, all colonoscopies were performed in the setting of an organized
CRC screening program with high standards of quality by expert endoscopists who were
aware of high risk conditions [2 ].
The reassessment colonoscopy was specifically directed to the detection of serrated
lesions; therefore high definition endoscopes and image enhancement techniques, such
as chromoendoscopy (conventional or electronic), were used in 63 % of patients. To
date, there are scarce data on the potential of advanced endoscopy to improve SPS
diagnostic yields. The use of high definition white-light endoscopy has been associated
with a higher prevalence of proximal serrated lesions in an average risk population
[16 ]. Conventional chromoendoscopy has never been formally assessed in this very specific
setting; however, it has been shown to increase polyp detection (especially hyperplastic
polyps) in an average risk population [25 ] and in high risk conditions, such as Lynch syndrome [26 ] and long-standing ulcerative colitis [27 ]. The usefulness of NBI is still controversial: in SPS patients, although a single
center tandem study showed that NBI was superior to high definition white light for
detecting serrated lesions [28 ], a multicenter tandem study showed no significant differences in the serrated lesion
miss rates for the two techniques [29 ].
In our series, the use of chromoendoscopy (either conventional or electronic) and
high definition endoscopes at reassessment colonoscopy was associated with higher
detection specifically of serrated lesions, but not of adenomas, and was an independent
factor for the diagnosis of SPS on reassessment colonoscopy. Therefore, our results
provide a rationale for recommending the use of chromoendoscopy and/or high definition
endoscopes to increase the diagnostic yield in the detection of serrated lesions.
More studies are needed to assess the true clinical impact of this strategy.
Traditionally, surveillance guidelines have focused on conventional adenomas and have
not considered serrated lesions. In fact, only recent guidelines have included serrated
lesions in their algorithms, recommending: annual colonoscopies for patients who fulfil
at least one SPS criteria; surveillance colonoscopy at a 3-year interval for patients
with at least one TSA, serrated lesion, or SSA/P ≥ 10 mm or with a dysplastic component;
and surveillance colonoscopy at a 5-year interval for patients with at least one small
(< 10 mm) SSA/P without dysplasia [6 ]. However, these recommendations are based on the consensus opinion of experts without
solid evidence [8 ].
In our study, the presence of five or more proximal serrated lesions or two or more
SSA/Ps ≥ 10 mm on baseline colonoscopy increased the chances of having SPS by four-
and six-fold, respectively. Although these baseline factors may be biased by initial
patient selection, we consider that they may be a useful threshold to recommend a
1-year surveillance colonoscopy. Certainly, prospective studies are required to validate
these results.
The present study encompasses a large population and provides new and interesting
insights that are reflective of a real clinical setting. However, several limitations
should be acknowledged and, although data were prospectively collected and were not
reinterpreted, the retrospective design of the study certainly limits the generalization
of the results.
First, reassessment colonoscopy was indicated in an individualized and non-structured
way, which could imply a selection bias. In fact, a fraction of patients who also
had at least one large and/or proximal serrated lesion did not undergo reassessment
colonoscopy. However, decisions were taken based on the burden of serrated lesions
by a dedicated multidisciplinary team in the context of an organized population-based
screening program. Moreover, none of the patients who underwent standard surveillance
(28/114) has been diagnosed with SPS.
Second, the endoscopic techniques used during the study were heterogeneous. The higher
proportion of high definition endoscopes and advanced ancillary techniques (chromoendoscopy)
used during reassessment colonoscopy could have introduced a major advantage for the
detection of serrated lesions, thereby artificially enhancing the increase in diagnostic
accuracy. If all baseline colonoscopies had been performed with high definition white-light
endoscopes and/or chromoendoscopy, more than 11 SPS patients would probably have been
detected initially and, consequently, the yield of the reassessment colonoscopy might
have been lower. However, standard definition white-light endoscopy is still the most
widespread and routinely used technique in the West. To date, guidelines do not recommend
high definition endoscopes or chromoendoscopy as standard use for screening. Moreover,
in the present study, the choice of the technique was subject to instrumental availability
and was not related to the baseline characteristics of the patient.
On the other hand, reassessment colonoscopies were performed by a subgroup of five
endoscopists who were obviously more motivated to detect serrated lesions. This increased
awareness could have influenced the higher detection of serrated lesions at reassessment
colonoscopy. However, the similar adenoma detection rate of all of the endoscopists
performing baseline colonoscopies indicates that, without the reassessment colonoscopy,
most of these SPS patients would in any case have been missed.
Finally, the potential drawback of interobserver variability among pathologists for
differentiation between microvesicular hyperplastic polyps and SSA/Ps was minimized
by using as the main outcome a variable that compiled all of the serrated lesion subtypes
(SSA/P, hyperplastic polyp, and TSA) together. Moreover, histological interpretation
was performed following the updated WHO 2010 guidelines [8 ].
In summary, we have confirmed that SPS is an underdiagnosed condition, even in the
setting of an organized FIT-based CRC screening program with high quality colonoscopies.
A high index of suspicion and the proper training in detection of serrated lesions
are the keys to detecting these high risk patients. A feasible diagnostic strategy
of a 1-year reassessment colonoscopy in individuals with proximal serrated lesions
has shown a high yield, having tripled the rate of patients with SPS. The presence
of five or more proximal serrated lesions or two or more SSA/Ps ≥ 10 mm on baseline
colonoscopy could be considered thresholds to indicate the need for reassessment colonoscopy.
This colonoscopy should preferably be performed with the help of chromoendoscopy and
high definition endoscopes. Further prospective studies are required to validate these
results and adjust surveillance recommendations in patients with serrated lesions.
