Prevalence and predictive factors of colorectal sessile serrated lesions in younger individuals

Abstract

Background Sessile serrated lesions (SSLs) are obscured lesions predominantly in the right-sided colon and associated with interval colorectal cancer; however, their prevalence and risk factors among younger individuals remain unclear.

Methods This retrospective study enrolled individuals who underwent index colonoscopy. The primary outcome was the SSL prevalence in the younger (<50 years) and older (≥50 years) age groups, while the secondary outcomes included clinically significant serrated polyps (CSSPs). Multivariable logistic regression was employed to identify predictors.

Results Of the 9854 eligible individuals, 4712 (47.8%) were categorized into the younger age group. Individuals in the younger age group exhibited lower prevalences of adenomas (22.6% vs. 46.2%; P<0.001) and right-sided adenomas (11.2% vs. 27.2%; P<0.001) compared with their older counterparts. However, both groups exhibited a similar prevalence of SSLs (7.2% vs. 6.5%; P=0.16) and CSSPs (10.3% vs. 10.3%;P=0.96). Multivariable analysis revealed that age 40–49 years (odds ratio [OR] 1.81, 95%CI 1.01–3.23), longer withdrawal time (OR 1.17, 95%CI 1.14–1.20, per minute increment), and endoscopist performance (OR 3.35, 95%CI 2.44–4.58) were independent predictors of SSL detection in the younger age group. No significant correlation was observed between adenoma and SSL detection rates among endoscopists.

Conclusion SSLs are not uncommon among younger individuals. Moreover, diligent effort and expertise are of paramount importance in SSL detection. Future studies should explore the clinical significance of SSLs in individuals of younger age.

Introduction

Colorectal cancer (CRC) consistently ranks as a prominent malignancy in developed countries [1] [2] [3]. The majority of CRC cases originate from adenomatous polyps; however, nearly 10%–15% of CRC cases have a different origin, stemming from a distinct premalignant lesion known as a sessile serrated lesion (SSL) [4] [5]. Unlike conventional adenomas, SSLs tend to be located in the right-sided colon, exhibit a flat and obscure appearance, and are often covered by mucus ([Fig. 1]) [6] [7] [8]. These characteristics can pose challenges in their detection through the current screening tools, potentially leading to screening failure [9] [10] [11]. Moreover, under-detection of SSLs may be associated with the development of subsequent interval CRCs [12] [13].

Fig. 1 Endoscopic images of a large sessile serrated lesion at the hepatic flexure showing on: a white-light imaging, a thick fold covered by mucus; b narrow-band imaging, a cloudy surface pattern with lacy vessels; c chromoendoscopy with indigo carmine spray, the border of the whole lesion now clearly visualized.

The natural progression of SSLs is characterized by an indolent course, often taking more than 10–15 years to advance to cytologic dysplasia and ultimately malignant transformation [14] [15] [16]. Progressive promoter hypermethylation, a prerequisite for SSL carcinogenesis, becomes more pronounced with advanced age [17]. Interestingly, research has indicated that serrated CRCs are relatively rare in younger patients [18] [19]. Nevertheless, whether this rarity in younger age groups is attributable to the infrequency of SSLs in this population or is a consequence of the gradual and indolent nature of the carcinogenesis process remains an unresolved question.

A systematic review indicated that the combined overall prevalence of SSLs was 4.6%, with only a modest increase with advancing age compared with conventional adenomas [6]; however, this review did not include individuals aged under 50 owing to the lack of available data. Until recently, most CRC screening programs and databases have focused on the “average risk population,” typically aged ≥50 years. Therefore, it is imperative to determine the true prevalence of SSLs and the proportion of cases with cytologic dysplasia among younger individuals to gain a more comprehensive understanding of SSLs in early onset CRC.

At present, only a few studies have explored the prevalence of SSLs in this younger age group [20] [21]; however, in their results, SSLs were mixed with other types of lesions such as hyperplastic polyps (HPPs), and neither of the studies identified clinical risk factors in this population. Therefore, our study aimed to address this research gap by examining the prevalence of SSLs and identifying any potential clinical risk factors associated with SSLs in younger individuals. During 2018–2022, our institute achieved a noteworthy SSL detection rate of 7.1% through index colonoscopies, which is higher than that achieved in historically pooled data [6] and meets the conventionally stipulated detection benchmark [22]. The present study aimed to explore the prevalence of SSLs and determine the potential clinical risk factors for SSLs in younger individuals.

Methods

Study design

This retrospective single-center study analyzed colonoscopy records obtained from outpatient services and health check-up services at E-Da Dachang Hospital. The data were collected between June 2018 and June 2022. E-Da Dachang Hospital, established in 2016 in downtown Kaohsiung, served as the primary source of these records. The study protocol was approved by the institutional review board of our institute (No. EMRP111149).

The study included individuals aged ≥20 years who underwent a complete index colonoscopy. Individuals who visited outpatient services were mostly symptomatic, eligible for screening colonoscopy, or had had abnormal fecal/tumor marker test results. Additionally, asymptomatic individuals who underwent health check-ups at their own expense or who adhered to national labor law requirements were included. The exclusion criteria were as follows: (i) duplicated cases owing to prior colonoscopy examinations; (ii) inadequate bowel preparation; (iii) history of hospitalization or colonoscopy as part of an emergency room visit; (iv) unsuccessful cecal intubation or flexible sigmoidoscopy; (v) suspicion of or confirmed inflammatory bowel disease. Notably, individuals who had previously undergone colonoscopy at other hospitals, as confirmed by their electronic medical records or chart review, were also excluded.

Eligible individuals were subsequently classified into two groups: a younger age group (20–49 years) and an older age group (>50 years).

Colonoscopy procedures and histologic evaluation

All colonoscopies in this study were performed by experienced endoscopists who had conducted >500 colonoscopy procedures annually, with ≥300 diagnostic or therapeutic procedures. The EvisLucera CV-290 colonoscope (Olympus Medical Systems, Tokyo, Japan) was used. Patients received bowel preparation regimens that included split-dose sodium phosphate, sodium picosulfate/magnesium citrate, or same-day polyethylene glycol solution. During the examinations, the decision to perform a biopsy, snare polypectomy, or endoscopic mucosal resection for a colorectal neoplasm was made at the discretion of the endoscopist. In cases involving difficult-to-treat polyps, subsequent endoscopic or surgical resection was performed within 6 months following the index colonoscopy.

The final histologic diagnosis was based on the results from both the index colonoscopy and the subsequent analysis; however, polyps and lesions that were not removed within 6 months of the index colonoscopy were excluded from the analysis, regardless of the initial endoscopic diagnosis. A total of 10 pathologists involved in the histologic evaluation in the study period. All of the lesions included in this study were confirmed through histologic evaluation by the on-duty pathologist in our hospital.

Outcome assessment

The primary outcome of this study was SSL prevalence. The secondary outcomes were the prevalences of SSLs with cytologic dysplasia, clinically significant serrated polyps (CSSPs), and the detection rate of right-sided HPPs. CSSPs were defined as the combination of: (i) SSLs; (ii) traditional serrated adenomas; and (iii) any HPP ≥1 cm in the left-sided colon or ≥0.5 cm in the right-sided colon [22]. Additional auxiliary outcomes included the prevalences of adenomas, advanced adenomas, and CRC. Advanced adenomas were characterized by polyps meeting one of the following criteria: (i) high grade dysplasia, carcinoma in situ, or intramucosal carcinoma; (ii) a size of ≥1 cm; or (iii) containing >25% villous component. The right-sided colon refers to the cecum, ascending colon, and transverse colon.

Various baseline and endoscopic characteristics, including age, sex, use of intravenous anesthesia, withdrawal time, bowel preparation status, and any family history of CRC, were recorded for predictive factor analysis. Adequate bowel preparation was defined as excellent or good based on the Aronchick scale [23]. The definitions of metabolic disease including obesity, metabolic syndrome, hypertension, diabetes mellitus, and fatty liver disease were described according to our previous article [24] (Appendix 1s, see online-only Supplementary material).

Statistical analysis

In this study, continuous variables were compared using Student’s t test and are presented as mean (SD). Categorical variables were compared using the chi-squared test and are presented as frequency (percentage). P <0.05 indicated statistical significance. To compare the primary outcomes, odds ratios (ORs) and their corresponding 95%CIs were calculated. All statistical analyses were conducted using SPSS version 22.0 (IBM, Armonk, New York, USA).

To evaluate the predictors of SSLs in the younger age group, we considered several variables, including age, sex, any family history of CRC, presence of symptoms (abdominal pain, bowel habit changes, or hematochezia), the proportion of positive fecal immunochemical tests, the use of intravenous anesthesia, colonoscopy withdrawal time, and the presence of relevant neoplasms. Significant variables in the univariable analyses were included in the multivariable binary logistic regression model using the enter method. Subsequently, the significant variables were subjected to validation and sensitivity analysis using data from the older age group. To further examine the potential correlation between variables, we employed a two-sided partial correlation analysis using SPSS software.

Results

Study participants and baseline characteristics

In all, 14 181 records were initially retrieved from the database. A flowchart of the participant selection process is presented in [Fig. 2]. Following the application of the exclusion criteria, a final cohort of 9854 individuals (51.5% women) was eligible for the analysis. Within this cohort, 4712 and 5142 individuals belonged to the younger and older age groups, respectively.

Fig. 2 Flowchart of participant inclusion and exclusion in the study.

The baseline characteristics of each group are summarized in [Table 1]. The younger and older age groups had mean ages of 39.7 and 61.3 years, respectively. A larger proportion of individuals in the younger age group underwent colonoscopy as part of a health check-up compared with the older age group (47.6% vs. 24.3%; P < 0.001). Compared with those in the younger age group, a significantly higher proportion of individuals in the older age group had adenomas (46.2% vs. 22.6%; P <0.001), advanced adenomas (14.2% vs. 4.0%; P <0.001), and CRC (1.4% vs. 0.4%; P <0.001). A significantly longer mean (SD) withdrawal time (9.4 [5.3] vs. 7.5 [3.5] minutes; P <0.001) and mean (SD) number of adenomas (0.7 [1.0] vs. 0.3 [0.6]; P <0.001) were also found in the older age group. The detection rate of SSLs however was similar in the two groups (6.5% vs. 7.2%; P=0.16). Furthermore, the older age group exhibited a nearly twofold higher occurrence of cytologic dysplasia, although this difference did not reach statistical significance (5.1% vs. 2.6%; P=0.10). Similarly, the prevalence of CSSPs was comparable between the two groups (10.3% vs. 10.3%; P=0.96).

Table 1 Baseline demographic and endoscopic characteristics of the two age cohorts.

	Younger age group (<50 years)	Older age group (≥50 years)	P value
CRC, colorectal cancer; SSL, sessile serrated lesion; SSLD, SSL with dysplasia; HPP, hyperplastic polyp; CSSP, clinically significant serrated polyp.
Cases, n (%)	4712 (47.8)	5142 (52.1)	–
Cases from health check-up, n (%)	2242 (47.6)	1248 (24.3)	<0.001
Symptomatic cases, n (%)	1985 (42.1)	2763 (53.7)	<0.001
Age, mean (SD)	39.7 (6.4)	61.3 (8.0)	<0.001
Sex, female, n (%)	2425 (51.5)	2649 (51.5)	0.96
Family history of CRC, n (%)	318 (6.7)	164 (3.2)	<0.001
Intravenous anesthesia used, n (%)	3875 (82.2)	3579 (69.6)	<0.001
Withdrawal time, mean (SD), minutes	7.5 (3.5)	9.4 (5.3)	<0.001
Adenomas, n (%)	1063 (22.6)	2375 (46.2)	<0.001
Advanced adenomas, n (%)	188 (4.0)	728 (14.2)	<0.001
Right-sided adenomas, n (%)	526 (11.2)	1399 (27.2)	<0.001
Right-sided advanced adenoma, n (%)	63 (1.3)	336 (6.5)	<0.001
Adenoma numbers, mean (SD)	0.3 (0.6)	0.7 (1.0)	<0.001
CRCs, n (%)	19 (0.4)	72 (1.4)	<0.001
SSLs, n (%)	341 (7.2)	335 (6.5)	0.16
SSLDs, n (%)	9 (0.2)	17 (0.3)	0.18
SSLD among SSLs, n (%)	9 (2.6)	17 (5.1)	0.10
Right-sided HPPs, n (%)	181 (3.8)	243 (4.7)	0.03
Traditional serrated adenomas, n (%)	8 (0.2)	21 (0.4)	0.03
CSSPs, n (%)	485 (10.3)	531 (10.3)	0.96
CSSP numbers, mean (SD)	0.1 (0.4)	0.1 (0.4)	0.55

Clinical features of outpatient versus health check-up cases in the younger age group

Nearly half (47.6%) of the younger individuals underwent colonoscopy as part of a health check-up service, and their clinical characteristics are further detailed in [Table 2]. Compared with those who underwent health check-ups, younger individuals who visited the outpatient service were less likely to have had intravenous anesthesia used (69.0% vs. 96.8%; P < 0.001) and a positive fecal occult blood test (0.5% vs. 7.2%; P <0.001). No significant differences in age and sex were observed between the two subgroups.

Table 2 Baseline characteristics of younger individuals (aged <50 years) from outpatient services and younger individuals from health check-up services.

	Outpatient	Health check-up	P value
CRC, colorectal cancer; SSL, sessile serrated lesion; SSLD, SSL with dysplasia; HPP, hyperplastic polyp; CSSP, clinically significant serrated polyp.
Cases, n (%)	2470 (52.4)	2242 (47.6)	–
Age, mean (SD)	39.7 (6.6)	39.6 (6.1)	0.58
Sex, female, n (%)	1293 (52.3)	1132 (50.5)	0.20
Intravenous anesthesia used, n (%)	1704 (69.0)	2171 (96.8)	<0.001
Family history of CRC, n (%)	182 (7.4)	136 (6.1)	0.08
Positive fecal occult blood test, n (%)	179 (7.2)	11 (0.5)	<0.001
Withdrawal time, mean (SD), minutes	7.7 (3.8)	7.4 (3.0)	0.001
Adenomas, n (%)	511 (20.7)	552 (24.6)	0.001
Advanced adenomas, n (%)	116 (4.7)	80 (3.2)	0.009
Right-sided adenomas, n (%)	217 (8.8)	309 (13.8)	<0.001
Right-sided advanced adenoma, n (%)	30 (1.2)	33 (1.5)	0.44
Adenoma numbers, mean (SD)	0.2 (0.6)	0.3 (0.6)	0.014
CRCs, n (%)	16 (0.6)	3 (0.1)	0.005
SSLs, n (%)	133 (5.4)	208 (9.3)	<0.001
SSLDs, n (%)	5 (0.2)	4 (0.2)	0.85
SSLD among SSLs, n (%)	5 (3.8)	4 (1.9)	0.30
Right-sided HPPs, n (%)	69 (2.8)	112 (5.0)	<0.001
Traditional serrated adenomas, n (%)	3 (0.1)	5 (0.2)	0.40
CSSPs, n (%)	192 (7.8)	293 (13.1)	<0.001
CSSP numbers, mean (SD)	0.1 (0.3)	0.1 (0.4)	<0.001

Younger individuals who visited the outpatient service had lower risks of overall adenomas (20.7% vs. 24.6%; P = 0.001) and right-sided adenomas (8.8% vs. 13.8%; P <0.001), but greater risks of advanced adenomas (4.7% vs. 3.2%; P=0.009) and CRC (0.6% vs. 0.1%; P=0.005). The younger outpatients also had a lower rate of SSLs (5.4% vs. 9.3%; P < 0.001), right-sided HPPs (2.8% vs. 5.0%; P < 0.001), and CSSPs (7.8% vs. 13.1%; P <0.001), and a slightly longer mean (SD) withdrawal time (7.7 [3.8] vs. 7.4 [3.0] minutes; P < 0.001) compared with those who underwent health check-ups. The proportion of SSLs with cytologic dysplasia was similar in the two subgroups (3.8% vs. 1.9%; P=0.30).

Correlation between adenoma and SSL detection rates among endoscopists

This study involved seven endoscopists (endoscopists A–G). Their adenoma detection rates ranged from 17.1% to 43.8%, while their SSL detection rates ranged from 2.0% to 11.0%. The corresponding data are presented in Fig. 1s. Two endoscopists (endoscopists E and G) had the highest SSL detection rates (7.7% and 11.0%, respectively). These two endoscopists were responsible for conducting 90.7% of the health check-up colonoscopy examinations and 44.5% of outpatient colonoscopy examinations, which may explain the better performance observed in the health check-up subgroup. Interestingly, our analysis did not reveal a significant correlation between the prevalence of adenomas and SSL detection rate (P = 0.08).

Predictors of SSL detection in the younger age group

In our analysis, we investigated the associations with the presence of SSLs during colonoscopy among younger individuals. The results of the univariable analysis for predefined clinical factors are presented in [Table 3]. Younger individuals with SSLs tended be older (41.6 [SD 5.2] vs. 39.6 [SD 6.4] years; P <0.001), male (55.1% vs. 48.0%; P=0.003), and have longer mean (SD) withdrawal times (10.6 [4.3] vs. 7.3 [3.3] minutes; P <0.001). They were also more likely to be asymptomatic (72.7% vs. 56.7%; P <0.001) and have undergone colonoscopy during a health check-up (61.0% vs. 46.5%; P <0.001). Because the latter two variables seemed to be highly correlated, and the two higher performers were responsible for the majority of the health check-up examinations, we finally took age, sex, withdrawal time, and endoscopist performance into the multivariable analysis.

Table 3 Baseline characteristics of younger individuals with and without a sessile serrated lesion (SSL).

	With SSL (n=341)	Without SSL (n=4371)	P value
CRC, colorectal cancer; HPP, hyperplastic polyp.
Age, mean (SD), years	41.6 (5.2)	39.6 (6.4)	<0.001
20–29, n (%)	13 (3.8)	363 (8.3)
30–39, n (%)	87 (25.5)	1551 (35.5)
40–49, n (%)	241 (70.7)	2457 (56.2)
Sex, female, n (%)	153 (44.9)	2272 (52.0)	0.011
From outpatient service, n (%)	133 (39.0)	2337 (53.5)	<0.001
Symptomatic cases, n (%)	93 (27.3)	1892 (43.3)	<0.001
Family history of CRC, n (%)	26 (7.0)	294 (6.7)	0.83
Positive fecal occult blood test, n (%)	14 (4.1)	176 (4.0)	0.94
Intravenous anesthesia used, n (%)	278 (81.5)	3597 (82.3)	0.72
Withdrawal time, mean (SD), minutes	10.6 (4.3	7.3 (3.3	<0.001
Adenomas, n (%)	84 (24.6)	979 (22.4)	0.34
Advanced adenomas, n (%)	14 (4.1)	174 (4.0)	0.91
Right-sided adenomas, n (%)	49 (14.4)	477 (10.9)	0.05
Right-sided advanced adenoma, n (%)	4 (1.2)	59 (1.3)	0.78
CRCs, n (%)	1 (0.3)	18 (0.4)	0.74
Right-sided HPPs, n (%)	9 (2.6)	172 (3.9)	0.23
Traditional serrated adenomas, n (%)	0	8 (0.2)	0.43

In the multivariable analysis, we divided the individuals in the younger age group into three subgroups (20–29, 30–39, and 40–49 years) for finer grained results on age. The benchmark SSL detection rate was set at 7% to define high performers and average performers [22]. Consequently, binary logistic regression results ([Table 4]) revealed that increased age (40–49 years, OR 1.81, 95%CI 1.01–3.23; P=0.04), longer withdrawal time (OR 1.17, 95%CI 1.14–1.20, per minute increment; P <0.001), and endoscopist performance (high vs. average performers, OR 3.35, 95%CI 2.44–4.58, per minute increment; P <0.001) were independent predictors of SSLs among the younger individuals.

Table 4 Results of logistic regression analysis of predictive factors for the presence of sessile serrated lesions in the younger age group.

	Univariable analysis		Multivariable analysis
	Odds ratio (95%CI)	P value	Odds ratio (95%CI)	P value
SSLDR, sessile serrated lesion detection rate.
Age, vs. 20–29 years
30–39 years	1.56 (0.86–2.83)	0.14	1.22 (0.67–2.24)	0.51
40–49 years	2.73 (1.55–4.83)	0.001	1.81 (1.01–3.23)	0.04
Withdrawal time, per 1-minute increment	1.18 (1.15–1.21)	<0.001	1.17 (1.14–1.20)	<0.001
Sex, male	1.33 (1.06–1.66)	0.01	1.09 (0.87–1.38)	0.43
Endoscopist, vs. average performers (SSLDR <7%)
High performers (SSLDR ≥ 7%)	3.01 (2.24–4.05)	<0.001	3.35 (2.44–4.58)	<0.001

Sensitivity analysis and subgroup analysis

The effects of withdrawal time, endoscopist performance, and age were further examined using the data from the older age group. Longer withdrawal time (OR 1.07, 95%CI 1.05–1.09, per minute increment; P <0.001) and endoscopist performance (high performers, OR 2.41, 95%CI 1.89–3.07; P <0.001) remained significant predictive factors for SSL detection in this group. However, individuals aged 50–59 years exhibited SSL detection rates similar to those in the group aged 40–49 years (OR 0.91, 95%CI 0.75–1.11; P=0.91). All other older age subgroups exhibited lower SSL detection rates, implying a potential peak at the age range of 40–49 years in this cohort (Table 1s). Age-based analysis suggested that, although adenoma detection was strongly correlated with advanced age, the detection rates of SSLs, SSLs with cytologic dysplasia, and CSSPs exhibited flatter trends with age increment (Fig. 2s). Notably, significant correlation was observed between SSLs and cytologic dysplasia per 10-year age increment (partial correlation 0.19; P <0.001).

Finally, we analyzed the data of individuals who had their SSLs detected in a health check-up; we did so to identify additional predictors of SSLs at a younger age (Table 2s). In this subgroup, younger individuals with SSLs tended to have a slightly higher mean (SD) age (41.4 [5.2] vs. 39.5 [6.4] years; P <0.001). They were also more likely to be obese (24.5% vs. 17.7%; P=0.02), have metabolic syndrome (16.8% vs. 11.9%; P < 0.001), and have diabetes mellitus (7.2% vs. 2.8%; P <0.001). Additionally, current tobacco use (22.1% vs. 15.4%; P=0.01) was more prevalent among individuals with SSLs, and they had longer mean (SD) colonoscopy withdrawal times (9.7 [3.5] vs. 7.1 [2.8] minutes; P < 0.001); however, the multivariable logistic regression revealed that only colonoscopy withdrawal time was a significant factor (Table 3s).

Discussion

Currently, the recommended starting age for CRC screening is set at 45 years in response to the increasing incidence of early onset CRC, which occurs before the age of 50 [25] [26]. Although SSLs are less likely to be associated with early onset CRC, effective screening for SSLs may lead to further cancer prevention given their long indwelling time.

This study explored SSL prevalence among younger adults using a cohort with a high detection rate. The findings highlight that SSL prevalence is not negligible among individuals aged <50 years. Moreover, by the age of 40, the prevalence becomes comparable with that observed in older individuals. The association between age and SSLs in younger people has been explored by only a few studies [20] [21].

Our findings were in line with the current literature, in that SSLs exhibit a steadier prevalence with age in comparison with adenomas. There are however several differences between the current and previous studies. The primary outcome in Kim et al. [21] was serrated lesions, which were predominantly HPPs, so the SSL prevalence was quite low (0.5%) in their cohort. In contrast, the design of the study of Lall et al. [20] is more similar to our study, and the non-differing SSL detection rates between the younger and older age groups was concordant with our study. They did not however exclude patients with prior colonoscopies; as it would be suggested that patients with prior lesions undergo follow-up, the detection rate might be cofounded by metachronous lesions, which could consequently affect the analysis of results. Moreover, some technical issues, such as withdrawal time and the variation in endoscopist expertise, were less explored in the previous study. Lastly, cytologic dysplasia, which is considered a critical step in SSL transformation, was not analyzed. While these two studies were important foundations for the current study, we also look forward to further validation studies regarding SSLs in younger people.

Because a substantial proportion of SSLs may develop in younger adults, effective detection and management of SSLs among younger individuals may be beneficial in preventing future serrated CRCs; however, detecting and completely resecting SSLs may be challenging owing to their obscured appearance and indistinct borders [8] [11] [27]. Although the SSL detection rate has been shown to be correlated with adenoma detection rates, endoscopists may differ considerably in their clinical performance [28] [29], as also demonstrated in the present study. In the present study, no significant correlation was noted between adenoma detection and SSL detection, which may be attributed to the relatively small number of endoscopists involved, leading to statistically underpowered results. Our findings did however reveal that longer withdrawal times were associated with higher SSL detection rates, which is consistent with the findings of prior studies [30] [31].

Endoscopist performance independent of withdrawal time was also highlighted in our study. Although the exact factors affecting detection performance remain to be investigated, expertise may be attributed to the recognition of lesion characteristics, examination technique, and the use of image-enhanced endoscopy. Inspiringly, detection ability may be improved by active training [32]. Furthermore, the assistance of attachment devices and artificial intelligence may also aid better detection of SSLs [33] [34]. Overall, detecting SSLs requires a considerable level of expertise and meticulous effort, and strategies to improve outcomes should be formulated.

This study is one of the few to have explored the prevalence of SSLs in younger adults and has several strengths, including a large cohort and a high detection rate. Additionally, we employed a strict definition of SSLs based on histologic diagnosis, and considered CSSPs and right-sided HPPs, which are highly correlated with SSLs in clinical practice. Moreover, the study population consisted mainly of relatively healthy individuals undergoing an index colonoscopy, which may reflect a scenario similar to ordinary screening practice. We also undertook meticulous analysis in order to reduce potential cofounding, such as discrepancy in endoscopist performance in subsets of the cohorts.

Nevertheless, this study has some limitations. First, although we tried our best to include only index examinations, individuals who underwent prior colonoscopies may not have been reported. That said, given the slow growth of SSLs, intervention bias may be extremely low for younger individuals, as indicated by the age-specific prevalence analysis. Second, some key factors, such as smoking, obesity, and diabetes mellitus, were only available for a subset of study participants, which may lead to underpowering for these factors. Diabetes mellitus has been reported to be a well-known risk factor of CRC by mechanisms that include enhanced DNA methylation, which is also an important carcinogenesis pathway for serrated CRCs [35]. Therefore, further analysis with a larger patient database in the future may provide more insights into these factors. Third, the withdrawal time in our study consisted of both observation and intervention; however, the association is even more prominent in cases that had a withdrawal time ≤9 minutes (OR 1.85, 95%CI 1.68–2.04), suggesting minimal intervention bias. Fourth, we did not report the prevalence of serrated polyposis syndrome among younger people. Finally, interobserver variation among pathologists may not be completely ruled out. Future large-scale studies with expert pathologists are warranted to investigate the role of SSLs in early and late onset CRC in the younger population.

In summary, our study demonstrated that SSLs are not uncommon in younger individuals, with a significant increase in prevalence starting at the age of 40. Longer withdrawal times during colonoscopy and endoscopist expertise appear to be associated with improved SSL detection. Further research is required to assess the clinical significance of SSLs in younger people and their potential implications for future screening practices.

Conflict of Interest

The authors declare that they have no conflict of interest.

Acknowledgement

The authors appreciate the assistance of Ms. Tzu-Shan Chen for advice on statistical analysis, and Ms. Pin-Yu Haung for clinical data collection. We also thank the Division of Medical Statistics and Bioinformatics, Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University for help provided. This manuscript was edited by Wallace Academic Editing.

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Publication History

Received: 15 October 2023

Accepted after revision: 16 February 2024

Accepted Manuscript online:
20 February 2024

Article published online:
04 April 2024