New management of surveillance in patients with baseline serrated polyps: a large single-center retrospective cohort study in China

doi:10.21203/rs.3.rs-1997952/v1

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New management of surveillance in patients with baseline serrated polyps: a large single-center retrospective cohort study in China

https://doi.org/10.21203/rs.3.rs-1997952/v1

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Background: Serrated polyps (SP) is associated with an increased risk of colorectal cancer. Patients with SP history tend to have SP recurrence. However, the risk factors for metachronous polyps (MP) in those patients are not well established.

Methods: Data of colonoscopy were retrospectively reviewed from October 2012 to October 2021. The pathology database, electronic medical records and telephone follow-up data were also observed.

Results: A total of 906 patients were studied which consisted of 278 patients with MPs and 628 patients without. Multiplicity of polyps (OR 13.63;95% CI 8.80-21.75), older age (OR 5.71;95% CI 1.87-20.63), abdominal obesity (OR 2.46;95% CI 0.98-6.42), current smoker (OR 2.93;95% CI 1.15-7.83) and sedentary lifestyle (OR 1.41;95% CI 1.22-1.65) are significantly associated with the risk of MPs. Patients with baseline SP<10mm were more likely to develop higher or same risk-grade polyps (HSRGP) (P=0.0014). Patients with non-clinically significant SPs whether coexisted with adenoma or not developed HSRGPs while comparing to others (P<0.001).

Conclusions: Total number of polyps, older age, sedentary behavior, abdominal obesity and smoking status contributed to the risk of MPs at surveillance colonoscopy. Patients with grade 1 SPs might require closer surveillance. SPs coexisting with conventional adenoma did not increase the risk of MPs but may increase the risk of developing HSRGPs.

Adenoma

Serrated polyps

Risk factor

Colorectal cancer

Recurrence

Colorectal cancer(CRC)is the third most common cancer in males and females worldwide.¹ In addition to the adenoma-carcinoma pathway, colorectal carcinogenesis can occur via the serrated pathway through CpG island methylation, and mutation of BRAF, which can induce transcription silencing of a key mismatch repair gene(MLH1), resulting in microsatellite unstable polyps and progression to malignancy². Approximately 15–35% of sporadic CRCs arise via serrated precursor lesions^3,4. There are 3 distinct subcategories of serrated polyps (SP), most commonly classified as hyperplastic polyps (HP), sessile serrated lesions (SSL), and traditional serrated adenomas (TSA). SSLs and TSAs are considered precursor lesions for CRC⁵.

Since SP was gradually recognized, meta-analyses revealed statistically significant increased risks of SP associated with smoking, alcohol consumption, dietary fat, red meat, gender, physical activity, obesity, diabetes, and aspirin/NSAIDS use ⁶. Patients with SP history tend to have SP recurrence on follow-up colonoscopy, while the number of polyps, location, and baseline histology may be related to the different histological features of metachronous polyps at surveillance colonoscopy⁷. Guidelines suggest that individuals with HPs<10mm do not need surveillance colonoscopy and should be followed up akin to individuals with a normal colonoscopy⁸. Moreover, patients with HPs or with HPs <10mm were excluded from some cohorts study when analyzing the occurrence risk of metachronous/synchronous advanced neoplasia^7,9,10. However, patients with either proximal or distal HPs < 10 mm on index colonoscopy might have a higher chance of metachronous SSL development reported ¹¹. Besides those conflicting results, the risk factors for metachronous polyps in patients with baseline SPs are not well established. Therefore, we performed a study on individuals with baseline SPs to assess the risk factors of metachronous polyps and the effect of the coexistence of SP and conventional adenoma which may provide more convincing evidence for clinical practice.

Study Design

All colonoscopy and pathological reports at Shanghai Jiao-Tong University school of medicine Ren-Ji Hospital, China from October 2012 to October 2021 were retrospectively reviewed. The primary outcome is to analyze the risk factors of metachronous polyps in patients with baseline SPs. In addition, we also studied the characteristics of metachronous polyps and the relationship with baseline and surveillance colonoscopy findings.

Patients

Patients who had a baseline colonoscopy between October 2012 and October 2021, and were pathologically diagnosed with serrated lesions(n = 3677)were included in our study. Those with a history of colectomy, history of colorectal cancer, hereditary colorectal cancer syndrome (familial adenomatous polyposis, hereditary nonpolyposis colorectal carcinoma, and serrated polyposis syndrome), incomplete colonoscopy, and poor or inadequate bowel preparation were excluded.

Data collection

All colonoscopies and polypectomies were conducted by skilled endoscopists who had performed more than 3000 procedures and were done in the same endoscopy center by using standard colonoscopes (CF 240Lor 260L; Olympus Optical Co., Ltd.). Retrieved polypoid lesions were sent to the Department of Pathology, Shanghai Digestive disease institute for histologic evaluation and reviewed by two experienced pathologists and made the diagnosis based on WHO classification of tumors of the digestive system⁵.

Demographic factors including age, sex, height, weight, waist circumference, smoking status, drinking status, sedentary behavior, history of diabetes, hypertension, hyperlipidemia, and family history of CRC were obtained from the electronic medical records or telephone calls. Serum levels of triglycerides(TG), total cholesterol༈TC༉, total bile acids (TBA), and high-density lipoprotein cholesterol (H-DLC) between baseline and surveillance colonoscopies were also collected. Abdominal obesity (AO) was defined as waist circumference ≥ 85cm in men, and ≥ 80cm in women¹². Sedentary behavior was defined by the Sedentary Behavior Research Network as any waking behavior characterized by an energy expenditure ≤ 1.5 metabolic equivalents (METs) while in a sitting or reclining posture¹³, which commonly includes watching television, computer and computer game use, workplace sitting, resting, reading, and lying down¹⁴.

The histology, number, size, and location of the polyps were obtained from colonoscopy and pathology reports. Serrated polyps at baseline were defined as HPs, SSLs with or without dysplasia, and TSAs, according to the WHO 5th classification system⁵. Clinically significant (or clinically relevant) serrated polyp (CSSP) has been suggested as an SP detection indicator due to its ability to be CRC precursor ¹⁵ which is defined by combining histological features (serrated adenoma/polyp (SSA/P) or TSA) and size (HP ≥ 10mm)^15,16. The location of the polyps is defined as proximal (cecum to inclusive of the splenic flexure) or distal (descending colon to the rectum).

According to the ESGE recommendations¹⁷, results of colonoscopy could be divided into several risk grades as follows, grade 0: finding no polyps in colonoscopy; grade 1: finding 1–4 < 10mm adenomas with low grade dysplasia, irrespective of villous components, or any serrated polyps < 10mm without dysplasia; grade 2: finding at least 1 adenoma ≥ 10 mm or with high grade dysplasia, or ≥ 5 adenomas, or any serrated polyp ≥ 10 mm or with dysplasia, or traditional serrated adenomas, serrated polyps with dysplasia. Thus, when we compared the risk-grade of polyps at index and surveillance colonoscopy respectively, we arrived at three results which were patients who developed higher risk-grade polyps than index colonoscopy, remained the same risk-grade and became lower risk-grade.

Statistical analysis

Descriptive statistics of the demographic information, colonoscopy findings and clinical data are presented with percentages for categorical variables and mean and standard deviations or median and interquartile ranges for continuous variables. Analysis of ANOVA or the nonparametric Kruskal-Wallis test was used to assess differences in continuous variables, and the Pearson χ2 test was used for categorical factors. Kaplan-Meier curves and the log-rank test were used to evaluate the metachronous polyps or metachronous higher or same risk polyps free-cumulative probability, accounting for the difference in the time of follow-up. Follow-up time was calculated from baseline colonoscopy date until a surveillance endoscopy. A variable selection procedure for logistic regression was performed, which input all independent variables related and a multivariable logistic regression model was applied to identify factors associated with the metachronous polyps or higher risk-grade polyps in surveillance. All results in the logistic regression model were presented as odds ratios (ORs) and 95% confidence intervals (CIs). A P value < 0.05 was considered statistically significant. All analyses were performed by using R version 4.0.4 (The R Foundation for Statistical Computing, Vienna, Austria).

Selection of patients

From October 2012 through to October 2021, 3677 patients underwent a baseline colonoscopy in our endoscopy center and were simultaneously diagnosed with serrated polyps pathologically. 2771 patients who met the exclusion criteria, were lost in follow-up or lacked records of the surveillance colonoscopy were excluded. According to surveillance colonoscopy findings, 906 patients were divided into two groups based on the results of surveillance colonoscopy: 1) Group A with metachronous polyps, which included conventional adenoma and SP (n = 278, 30.68%); 2) Group B without metachronous polyps, which implied the completely normal result in the surveillance colonoscopy (n = 628, 69.32%). 93 patients in group A and 117 patients in group B received telephone follow-up and simultaneously offered laboratory data.

Baseline characteristics

There was no significant difference in surveillance interval between the two groups (21.52 ± 13.91 months, 21.49 ± 14.86 months, respectively) (Table 1). Different from the same trend that males have the priority of occurrence of metachronous polyps in both groups, patients older than 45 years were more common in group A (92.1% vs 82.2% P < 0.001). The categorization of the polyps was similar between two groups (HP 63.3% vs 69.1%; SSL 28.1% vs 21.5% and TSA 8.6% vs 9.4%). 38.1% of CSSP were found in group A and 33.4% in group B. 15 of 278 (5.4%) detected high-grade intraepithelial neoplasia in group A and 37 of 628 (5.9%) in group B. Most SPs at baseline appeared in the distal colon, but those growing in the proximal colon were more likely to have metachronous polyps (39.2% in group A and 36.9% in group B) and the majority of them were less than 10 mm with 84.9% in group A and 86.8% in group B. However, metachronous polyps preferred to appear if there were ≥ 3 polyps at index colonoscopy ( 39.2% in group A and 4.6% in group B, P < 0.001)(Table 1). The occurrence of synchronous colorectal adenoma is about 20.9% in group A and 15.4% in group B which was a slight difference(P = 0.057)(Table 1).

Table 1

Baseline demographic and histologic characteristics of patients with metachronous polyps or not
Characteristics	Group A (With metachronous polyps) N = 278	Group B (Without metachronous polyps) N = 628	P value
Gender
Male	189 (68.0)	388 (61.8)	0.086
Age (years)
≤ 45	22 (7.9)	112 (17.8)	< 0.001
> 45	256 (92.1)	516 (82.2)	< 0.001
Categorization
HP	176 (63.3)	434 (69.1)	0.1
SSL	78 (28.1)	135 (21.5)
TSA	24 (8.6)	59 (9.4)
CSSP	106 (38.1)	210 (33.4)	0.197
High-grade intraepithelial neoplasia	15 (5.4)	37 (5.9)	0.888
Location
Proximal	109 (39.2)	232 (36.9)	0.565
Distal	169 (60.8)	396 (63.1)	0.565
Total number of polyps
< 3	169 (60.8)	599 (95.4)	< 0.001
≥ 3	109 (39.2)	29 (4.6)	< 0.001
Mean Size of polyps
< 10mm	236 (84.9)	545 (86.8)	0.511
≥ 10mm	42 (15.1)	83 (13.2)	0.511
Synchronous colorectal adenoma	58 (20.9)	97 (15.4)	0.057
Surveillance interval (month) mean (SD)	21.52 (13.91)	21.49 (14.86)	0.976

Values presented as mean (SD) with ANOVA, median (IQR) with Kruskal test, n (%) with the Pearson χ2 test.

HP = hyperplastic polyp, SSL = sessile serrated lesion, TSA = traditional serrated adenoma, CSSP = clinically significant serrated polyps, defined as sessile serrated adenomas, traditional serrated adenomas, hyperplastic polyps ≥ 10mm.

The percentage of overweight patients (BMI > 24) is higher in group A(63.4%)than in group B (51.3%), especially with abdominal obesity (71.0% vs 49.6% P = 0.003) (Table 2). No statistical difference was observed in the history of HBP and diabetes. There was a tendency that patients with metabolic syndrome (MS) (41.5%) were more prone to metachronous polyps compared to patients without metachronous polyps (29.9%) but failed to reach a significant difference (Table 2). The reported smoking status differed among two groups with current smokers being more common in group A (44.7% vs 25.6% P = 0.014). Patients who had longer hours of sedentary lifestyle were more likely to be found with metachronous polyps with 4.39 hours in group A and 2.50 hours in group B (P<0.001) (Table 2). Unfortunately, family history of CRC and the history of any cancer both failed to reach a significant difference (Table 2).

Table 2

Baseline lifestyle and clinical characteristics of patients with metachronous polyps or not
Characteristics	Group A (With metachronous polyps) N = 93	Group B (Without metachronous polyps) N = 117	P value
	N (%)	N (%)
BMI > 24	59 (63.4)	60 (51.3)	0.104
Abdominal obesity	66 (71.0)	58 (49.6)	0.003
History of HBP	42 (45.2)	45 (38.5)	0.402
History of Diabetes	29 (31.2)	32 (27.4)	0.649
Level of TBA (median [IQR])	3.00 [1.80, 4.90]	3.50 [1.90, 5.70]	0.342
HTG	40 (43.0)	47 (40.2)	0.784
LHDL-C	30 (32.6)	40 (34.2)	0.926
MS	39 (41.5)	35 (29.9)	0.096
Smoking
Current	42 (44.7)	30 (25.6)	0.014
Ex-smoker	12 (12.8)	15 (12.8)
Never	40 (42.6)	72 (61.5)
Drinking
Current	10 (10.8)	17 (14.5)	0.423
Ex-drinker	21 (22.6)	19 (16.2)
Never	62 (66.7)	81 (69.2)
Family history
Colorectal cancer	17 (18.3)	28 (23.9)	0.411
Any cancer	34 (36.6)	39 (33.3)	0.733
Sedentary lifestyle (hours), mean (SD)	4.39 (2.22)	2.50 (2.26)	< 0.001

BMI = body mass index; HBP = high blood pressure; DM = diabetes mellitus; TBA = Total bile acid level; HTG = high triglycerides level, defined as TG level > 150mg/dL ; LHDL-C = low high-density lipoprotein cholesterol level, defined as HDL-C < 40mg/dL in male, HDL-C < 50mg/dL in female; MS = metabolic syndrome.

Survival analysis

The free-cumulative probability in patients with metachronous polyps and in patients who developed metachronous higher or same risk-grade polyps than index colonoscopy were shown by Kaplan-Meier plot and log-rank tests. Regarding the risk of metachronous polyps, our results showed that in patients with CSSP, older than 45 years old, multiplicity of polyps, SSL and TSA categories, SPs in proximal colon would decrease the metachronous polyp free rate (P < 0.05) (Fig. 1a-f). It can be seen that patients who had SPs < 10mm at index colonoscopy appear to have a higher occurrence of developing higher or same risk-grade polyps than those with ≥ 10mm SPs (P = 0.0014) (Fig. 1g).

Follow-up colonoscopy findings

After that, patients were divided into four groups based on the baseline pathologic characteristics, as patients with only non-CSSP and no synchronous adenoma (N-CSSP only), patients with non-CSSP and synchronous adenoma (N-CSSP + A), patients with only CSSP and no synchronous adenoma (CSSP only), patients with both CSSP and synchronous adenoma (CSSP + A). We observed a weak effect of the coexistence of non-CSSP and conventional adenoma on the development of ≥ 3 metachronous polyps (41.2% in N-CSSP + A while only 23.9% in N-CSSP, 20.7% in CSSP, 12.5% in CSSP + A P = 0.053). Furthermore, 138 patients with N-CSSP only (28.1%), and 34 patients in N-CSSP + A groups (34.3%) developed higher or same risk-grade polyps while comparing to 21 patients in CSSP (8.1%), and 6 patients in CSSP + A groups (10.1%) (P < 0.001) (Table 3).

Table 3

Follow-up colonoscopy findings
Metachronous polyps at surveillance coloscopy	Baseline colonoscopy N (%)				P value
	N-CSSP only N = 491	N-CSSP + A N = 99	CSSP only N = 260	CSSP + A N = 56	P value
Any polyps	138 (28.1)	34 (34.3)	82 (31.5)	24 (42.9)	0.105
SP	35 (25.4)	13 (38.2)	25 (30.5)	4 (16.7)	0.257
CRA	103 (74.6)	21 (61.8)	57 (69.5)	20 (83.3)	0.257
Coexistent SPs and adenomas	5 (3.6)	4 (11.8)	4 (4.9)	1 (4.2)	0.281
Location
Proximal	66 (47.8)	17 (50.0)	35 (42.7)	11 (45.8)	0.862
Size
≥ 10mm	24 (42.9)	1 (2.9)	8 (9.8)	2 (8.3)	0.651
High-grade intraepithelial neoplasia	11 (8.0)	1 (2.9)	5 (6.1)	2 (8.3)	0.742
Total number of polyps
≥ 3	33 (23.9)	14 (41.2)	17 (20.7)	3 (12.5)	0.053
High-risk adenoma	23 (22.3)	6 (28.6)	19 (33.3)	8 (40.0)	0.274
CSSP	8 (40.0)	2 (15.4)	10 (40.0)	2 (50.0)	0.270
Developing higher or same risk-grade in surveillance	138 (28.1)	34 (34.3)	21 (8.1)	6 (10.1)	<0.001

Values presented as n (%) with the Pearson χ2 test.

CSSP = clinically significant serrated polyps, SP = serrated polyps, CRA = colorectal adenoma, high-risk adenoma, defined as adenoma ≥ 10 mm and/or an adenoma with a villous component and/or high-grade dysplasia (HGD) and/or three or more adenomas. P-value < 0.05 considered statistically significant.

Multivariable analysis of the risk of metachronous polyps and developing higher or same risk-grade polyps at surveillance colonoscopy

A multivariable analysis was performed to identify the factors which may be associated with metachronous polyps. The risk of metachronous polyps was significantly associated with the total number of polyps at index colonoscopy (OR 13.63; 95% CI 8.80-21.75), older age(OR 5.71; 95% CI 1.87–20.63), abdominal obesity༈OR 2.46; 95% CI 0.98–6.42༉, current smoker༈OR 2.93; 95% CI 1.15–7.83༉, and sedentary lifestyle༈OR 1.41; 95% CI 1.22–1.65༉(Table 4 and Fig. 2).

According to the multivariable analysis, the risk of developing higher or same risk-grade polyps at surveillance colonoscopy was associated with ≥ 3 polyps at index colonoscopy (OR 7.76; 95% CI 5.07–12.04), sedentary lifestyle (OR 1.28; 95% CI 1.11–1.48). Being defined as CSSP at index colonoscopy was inversely correlated with the risk of developing higher or same risk-grade polyps at surveillance colonoscopy (OR 0.19; 95% CI 0.10–0.33). Details of the multivariable analysis are shown in Table 4 and Fig. 2.

Table 4

Baseline SPs characteristics associated with risk of metachronous polyps
Baseline SPs characteristics	Any metachronous polyps			Developing Higher or same risk-grade metachronous polyps
	OR	95% CI	P value	OR	95% CI			P value
Size, > 10mm	1.17	(0.67, 2.02)	0.58	0.76		(0.30, 1.80)	0.54
Defined as CSSP	1.23	(0.82, 1.83)	0.31	0.19		(0.10, 0.33)	< 0.001
Location at distal colon	0.93	(0.66,1.29)	0.65	0.84		(0.58, 1.22)	0.37
Total number of polyps ≥ 3	13.63	(8.80, 21.75)	< 0.001	7.76		(5.07,12.04)	< 0.001
HGD	0.65	(0.30, 1.34)	0.25	1.19		(0.45, 2.88)	0.72
With Synchronous adenoma	1.00	(0.65, 1.51)	1	0.97		(0.61, 1.50)	0.88

SP = serrated polyps; CSSP = clinically significant serrated polyps; HGD = high-grade dysplasia; OR = odds ratio; CI = confidence interval. P-value < 0.05 considered statistically significant.

In the present study, we found that the risk of developing metachronous polyps during surveillance colonoscopy in SPs patients may be influenced by the total number of polyps at baseline colonoscopy, older age (≥ 45 years), sedentary behavior, abdominal obesity and smoking status.

According to previous studies, the majority of guidelines put the age cut-off value at 50 or older^18,19. However, the incidence of early-onset colorectal cancer (EOCRC) has been on the rise over the past four decades²⁰ and is expected to increase by > 140% by 2030²¹. Chinese consensus on prevention of colorectal neoplasia suggests that risk assessment for CRC is recommended for individuals aged 40 years or elder, CRC screening is also recommended for high-risk individuals aged 40 years or elder²². In our study, metachronous polyps were more likely to be detected in individuals ≥ 45 years (OR 5.61, 95%CI 1.92–18.95) with an average surveillance interval of 21.5 months. While decreased immunity and genetic variations that occur with the advancing age ²³, the high young-onset rate is due to the adoption of a more “westernized” lifestyle and diet, particularly in the younger generation or due to intense environmental exposures with more susceptibility among the younger generations^24,25. Thus, our results support the start of screening for CRC earlier than 50 years old.

On the other hand, the surveillance interval after polypectomy was commonly about 3–5 years, which depended on histology, multiply and size of polyps, but whether the age of patient has play an important role in the post-polypectomy surveillance interval was unclarified^8,17, in other words, surveillance strategies for older and younger adults are similar. Nevertheless, associations between age and risk of adenoma recurrence have been proved previously^26,27 and we also found that polyps may recur in 2 years over the age of 45, while the cumulative free of metachronous polyp rate was higher in the younger group (< 45 years). Based on our study, age needs to be taken into consideration when scheduling different follow-up intervals, and individuals older than 45 may need shorter surveillance interval.

Whether or not 5 or more polyps is the cutoff point for surveillance intervals in most guidelines regarding the total number of polyps^17,28. And we found that multiplicity (total number of polyps ≥ 3) of polyps on index colonoscopy was a powerful indicator of metachronous polyps (OR 13.63, 95%CI 8.80-21.75). Multiply polyps were convinced to attribute to genetic imbalance of cell proliferation in some individuals, which could lead to accelerated carcinogenesis on normal mucosa^29,30. Another possibility is that missed diagnosis is likely to occur in the “multiplicity environment”³⁰, which means polyps missed at baseline colonoscopy are more likely to be seen as metachronous polyps at surveillance colonoscopy. Therefore, it is essential to ensure that proper surveillance time would be advised for these individuals and endoscopists should be more careful when performing colonoscopy in the “multiplicity environment”.

Our data support an association between sedentary behavior and metachronous polyps. Previous studies have shown the strong association between sedentary behavior and colorectal adenoma and cancer^31–33, some emphasized that the effect was more pronounced in males³². Numerous metabolic events are dysregulated as a result of sedentary behavior³⁴. Most of the available evidence supports the role of reduced energy expenditure along with weight gain and obesity over time. Obesity associated with both physical inactivity and sedentary behavior may facilitate colorectal carcinogenesis through several pathways, including insulin resistance, proinflammatory response, influence on metabolic hormones, altered secretions of adipokines³⁵ and low bioavailability of vitamin D³⁶. In addition, sedentary behavior might increase the risk of colorectal cancer by its effect on immune function, oxidative stress and DNA damage³⁷. Furthermore, Existing evidence supports an association between higher overall physical activity levels and reduced risk of CRC and colorectal adenomas^38,39. However, further study still needed to confirm whether sedentary behavior and physical activity differentially impact the initiation and progression events along the pathway from adenoma to carcinoma.

It is worth noting that in our study patients with AO are more than twice as likely to have metachronous polyps than patients without AO (OR 2.51). Abdominal fat distribution can be considered a marker of ectopic fat in many sites for non-abdominal obesity⁴⁰. A meta-analysis summarized that obesity can cause chronic inflammation, metabolic syndrome, insulin resistance and adipokine, subsequently resulting in inhibition of apoptosis, cell proliferation and angiogenesis which contribute to the development of polyps and further development of CRC⁴¹.

We also found that current smokers had two times increased odds for occurrence of metachronous polyps compared to never smokers (OR = 2.75). Strong evidence showed a correlation between smoking and microsatellite instability positive, CpG island methylator phenotype positive and/or BRAF-mutant tumors are thought to arise from SP, specifically SSA/P^42,43. Thus, either taking smoking status into account or advising smokers to quit is important when developing the follow-up strategies.

It is interesting to note that our survival analysis found patients with SPs < 10mm (grade 1) at baseline colonoscopy are more common to develope higher or same risk-grade polyps at surveillance colonoscopy. Guideline recommendations for surveillance colonoscopy after removal of grade 1 polyps vary considerably, ranging from recommendations for performance of surveillance in 5–10 years (USMSTF), no surveillance/return to routine screening in 10 years (EU/ESGE), follow-up without surveillance endoscopy (Chinese consensus on prevention of colorectal neoplasia)^8,17,22. Recent studies vary about the importance of grade 1 polyps. For example, Hamoudah et al.⁴⁴ demonstrated that patients with small and diminutive proximal HPs tend to harbor higher rates of synchronous advanced neoplasia compared with those without any serrated lesions detected on screening colonoscopy. This might be explained as the development of polyps is resulted from the accumulation of genetic mutations and epigenetic changes ⁴⁵. However, Vleugels et al. performed a systematic review which found that only 6% 1- to 9-mm adenomas progress to advanced adenomas within 2 to 3 years ⁴⁶. Based on our study, those grade 1 polyps might have the risk of developing a higher grade metachronous polyps which might require a close follow up. Future prospective studies involving larger cohorts are necessary to establish the more detailed surveillance strategies of those grade 1 polyps.

In our study, serrated polyps coexisting with conventional adenoma did not increase the risk of metachronous polyps or developing higher or same risk-grade polyps at surveillance colonoscopy. Different from the study of S. W. Hong et al.⁴⁷ which pointed out that the presence of synchronous SSL and adenoma did not increase the risk of metachronous high risk adenoma and advanced adenoma, but increased the risk of metachronous SSL. Another interesting finding in our study is although the coexistence of adenomas did not increase the developing metachronous serrated polyps or conventional adenoma at surveillance colonoscopy, the effect of coexistence of adenomas seemed to be different between N-CSSP patients(34.3%)and CSSP patients ༈10.1%༉. Pereyra et al⁹ used “serrated environment” to explain, which may predispose to CRC through both the adenoma-carcinoma pathway and the serrated pathway. We hypothesized that the adenoma-carcinoma pathway is the most common in the development of CRC, but when SP was identified as CSSP, the serrated pathway also came into dominant thus undermining the impact of adenoma-carcinoma pathway. These results emphasized different genetic and epigenetic pathways contribute to the development of CRC and may interact with each other. Further studies are needed.

Our study has several limitations. First, the number of cases was relatively small which may underestimate the effect of risk factors on occurrence of metachronous polyps. Second, potential biases related to the retrospective nature of the study were not avoidable. The average surveillance interval in our study was approximately 2 years, which is shorter than 3 years as most guidelines suggested. Since other studies found that the first year of follow up after colorectal adenoma polypectomy is most important and determined their follow-up period was similar to ours^48,49, we believe our results might represent the characteristics of the Asian population. Third, the updated WHO classification was publicated during our study, which turned (sessile serrated adenoma/polyp) SSA/P into SSL. However, the changes in diagnosis did not affect the classification and evaluation of serrated polyps in our study.

In conclusion, total number of polyps y, older age (≥ 45 years), sedentary behavior, abdominal obesity and smoking status contributed to the risk of developing metachronous polyps at surveillance colonoscopy in SPs patients. Moreover, patients with grade 1 SPs at baseline colonoscopy are more likely to develop higher or same risk-grade polyps which require a closer follow-up. Finally, serrated polyps coexisting with conventional adenoma did not increase the risk of metachronous polyps but increased the risk of developing higher or same risk-grade polyps, especially in the N-CSSP group. These findings might provide more convincing evidence for clinical practice and help to personalize surveillance recommendations.

Author contribution: All authors contributed to the study’s conception and design. Xiangxi Ye and Qinyan Gao wrote the main manuscript text, Xiangxi Ye, Peiyi Han and Chaofei Chen performed the data analysis and prepared figures, Xiangxi Ye, Peiyi Han, Qinyan Gao, Zhijie Wu and Yingxuan Chen prepared all tables. All authors read and approved the final manuscript.

Funding: Not Applicable

Conflict of interests: The authors declare no competing interests.

Acknowledgements:

Thanks are due to Jingyu Wu for assistance with the data filtering.

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No competing interests reported.

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New management of surveillance in patients with baseline serrated polyps: a large single-center retrospective cohort study in China

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Introduction

Methods

Study Design

Patients

Data collection

Statistical analysis

Results

Selection of patients

Baseline characteristics

Survival analysis

Follow-up colonoscopy findings

Discussion

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