Abstract
Abstract
Objectives
Serrated polyps (SPs) with synchronous advanced adenoma (AA) may increase the incidence of colorectal cancer. However, current studies do not address this combination of SPs and AAs in detail with regard to their clinical characteristics in different age groups. The aim was to assess clinical characteristics and risk factors for SPs with synchronous AA in different age groups.
Design
Retrospective cohort study.
Setting
Electronic medical record data from January 2011 to January 2022 at three grade III class A hospitals were enrolled in the study.
Participants
A total of 1605 patients with SPs with synchronous AA, including 484 patients in the elderly group and 1121 patients in the non-elderly group, were studied.
Main exposure measure
The elderly group and the non-elderly group.
Main outcome measure
Sex, smoking history, drinking history, body mass index (BMI), SP location, size, morphology and pathology.
Results
The incidence of hyperplastic polyps (HPs) with synchronous AA in the elderly group was higher than that in the non-elderly group, while the incidence of sessile serrated adenomas/polyps (SSAs/Ps) with synchronous AA in the non-elderly group was higher than that in the elderly group. Male sex, drinking history and HP size (≤20 mm) were independent risk factors for HPs with synchronous AA in the non-elderly group, while drinking history and HP size (≤15 mm) were independent risk factors in the elderly group. For SSAs/Ps with synchronous AA, male sex, smoking history, drinking history, and SSA size (≥16 mm) were independent risk factors in the non-elderly group; high BMI was an independent risk factor in the elderly group.
Conclusions
SPs with synchronous AA showed different clinical characteristics and risk factors in different age groups.
Keywords: Risk Factors, GASTROENTEROLOGY, Adult gastroenterology, GERIATRIC MEDICINE
STRENGTHS AND LIMITATIONS OF THIS STUDY.
The cohort consisted of a large electronic medical record data of patients from January 2011 to January 2022 at three grade III class A hospitals and sufficient precision for subgroup analyses.
The study analyses the baseline data of patients with serrated polyps (SPs) in the non-elderly group and elderly group.
The study analyses the clinical characteristics of SPs with synchronous advanced adenoma (AA) between the non-elderly group and elderly group.
Multiple logistic regression analysis was used in the patients who had SPs with synchronous AA.
The exclusion criteria omitted some high-risk patients, such as those with inflammatory bowel disease or hereditary polyposis syndromes, which may limit the applicability of the findings to these populations.
Introduction
Colorectal cancer (CRC), which is the third most common global malignancy, is a common malignant tumour threatening human health, and the annual incidence of CRC is approximately 1.2 million. The case fatality rate of CRC is ranked fourth, resulting in approximately 608 000 deaths per year.1 The development and progression of CRC is a multistep, multistage and polygenic process. In recent years, with the rapid development of the economic level in China and the change in dietary habits, the incidence of CRC has increased year by year, with new cases and deaths each year accounting for 30% of the same period CRC cases worldwide.2 Meanwhile, when found mostly in advanced stages, the prognosis is poor and the case fatality rate is high.3,5 Most CRCs develop from mutations in the APC gene in the common ‘adenoma-adenocarcinoma’ pathway; however, it has been shown that, in addition to adenomas, serrated polyps (SPs) also have a propensity to undergo carcinogenesis and approximately 20%–35% of CRCs develop through the ‘hyperplastic polyp-serrated adenoma-serrated adenocarcinoma’ pathway.6 It was reported that only 10%–15% of CRCs were derived from serrated adenomas in 2007, while by 2011, a study in America proposed that 35% of CRCs were derived from serrated adenomas.7 Previous studies on precancerous lesions have mainly focused on traditional adenomatous polyps and the ‘adenoma-adenocarcinoma pathway’, but recent studies on SPs have increased significantly. Increased awareness of SPs is important to prevent CRC.
SPs are a group of lesions in which the crypt epithelium exists with a serrated morphology and is heterogeneous, including hyperplastic polyps (HPs), sessile serrated adenomas/polyps (SSAs/Ps) and traditional serrated adenomas (TSAs).8 SPs are precancerous lesions that have been studied in recent years for their discovery of extreme malignant potential. According to the Consensus of China,9 advanced adenoma (AA) was defined as finding three or more adenomas or one of these adenomas measuring 10 mm or more in diameter, with one-third villous architecture or more, or with higher grade intraepithelial neoplasia in a colonoscopy. Multiple international guidelines and consensus agree that AAs have a higher risk of colorectal tumourigenesis and increased risk of metachronous advanced neoplasia.10 11
It is thought provoking that we found a significant number of patients presenting with both SPs and AAs synchronously. Then, some questions were asked: what are the clinical features of SPs with synchronous AA in people of different ages? Do SPs with synchronous AA significantly increase the risk of CRC and what is its pathogenesis? Although there are still relatively few studies on SPs with synchronous AA, their value is significant in the clinic. A detailed understanding of the clinical characteristics and carcinogenesis mechanism of SPs with synchronous AA can effectively block their progression and carcinogenesis risk, which plays a very important role in the prevention of CRC. To address the first question, we retrospectively analysed the clinical characteristics of SPs with synchronous AA in two cohorts of elderly and non-elderly individuals to provide a prospective basis for studies on the cooccurrence of SPs and AA.
Materials and methods
Study subjects
A total of 4345 patients diagnosed with colorectal SPs according to the 2010 WHO pathological criteria of tumours of the digestive system after endoscopic biopsy, forceps or high-frequency electrical resection from January 2011 to January 2022 at three grade III class A hospitals were enrolled in the study. The patients were grouped according to age, with 1241 patients in the elderly group (age ≥65 years old) and 3104 patients in the non-elderly group (age <65 years old). A total of 1605 patients with SPs with synchronous AA among the 4345 patients with colorectal SPs were included, including 484 patients in the elderly group and 1121 patients in the non-elderly group.
Inclusion criteria
(1) Study data were sex, age, smoking history, drinking history, body mass index (BMI) and polyp clinical characteristics; (2) colonoscope was successfully inserted into the ileocecal valve and (3) study subjects were informed and consented to participate in this study.
Exclusion criteria
(1) History of inflammatory bowel disease, (2) hereditary polyposis (such as familial adenomatous polyposis or Peutz-Jeghers syndrome), (3) postoperative patients with CRC, (4) pathology suggestive of a cancerous colorectal polyp after polypectomy, (5) colonoscope insertion did not reach the ileocecal valve, (6) poor bowel preparation or (7) patients with incomplete clinical data.
All included patients signed informed consent forms, and this study was reviewed and approved by the Medical Ethics Committee of Xuanwu Hospital, Capital Medical University. In this study, SPs were classified into three categories: HP, SSA/P and TSA. According to the Consensus of China,9 AAs were defined as those with ≥3 adenomas or 1 of them ≥10 mm in diameter, with more than one-third of villous architecture or with high-grade intraepithelial neoplasia.
Research methods
The indication for colonoscopy
Indications for colonoscopy include (1) patients with altered bowel habits; (2) patients with bloody or purulent stool; (3) patients with lower abdominal discomfort; (4) patients with suspected colonic morphological changes or intestinal wall thickening by barium enema or abdominal CT or B-ultrasound; (5) patients requiring long-term follow-up, such as ulcerative colitis, Crohn’s disease, colonic polyps and postoperative follow-up of colon cancer; (6) patients over 40 years old with a family history of intestinal tumours and (7) patients with lower gastrointestinal polyps or benign tumours requiring colonoscopy.
The procedure of colonoscopy and data collecting
The patient was placed in the left lateral decubitus position, and the colonoscope was advanced through the anal circulation to the ileocaecal valve. The colorectal mucosa was observed carefully. The colour and smoothness of the colorectal mucosa, the peristalsis of the intestinal tube and the presence or absence of stenosis were repeatedly observed with a review scope, and the number, distribution position, diameter size and gross morphology of polyps were recorded in detail. After endoscopic polyp biopsy or resection using biopsy forceps or snares, the macroscopic observation of polyp disappearance and flattening of the surrounding tissue mucosa was used as the standard. All biopsied or resected polyps were sent for pathological examination after examination. The diagnosis of HP, SSA/P and TSA was based on endoscopic findings and pathological tissue examination referring to the 2010 WHO classification of tumours of the digestive system. The pathological results were published by the two pathologists after consensus. Both endoscopists and pathologists were skilled and experienced.
Next, a registry of clinical characteristics of patients with SPs was made. In the registry form, the sex, age, smoking history, drinking history, BMI, SP site, SP size, SP morphology, SP histological type, SP degree of dysplasia and the presence or absence of synchronous AA of patients were recorded. All medical record data were independently entered into the computer by two persons. The database was established, and a consistency test was performed.
Outcome measures
Patients were recruited to compare differences in age, sex, BMI, smoking history and drinking history between the elderly and non-elderly groups. Age, sex, BMI, SP distribution location, SP size, SP gross morphology, SP degree of dysplasia and the presence or absence of synchronous AA were compared between the elderly and non-elderly groups. Meanwhile, the associated risk factors for SPs with synchronous AA in the two groups were analysed. SPs were classified into three subtypes by histological type: HP, SSA/P and TSA. Smoking history was defined as the patient currently smoking or having a history of smoking for >6 months, with no limit on daily smoking quantity. The drinking history was defined as the patient currently drinking or having a history of drinking for >6 months, with no limit on the type and amount of alcohol consumed per day. With reference to the Chinese guidelines for the prevention and control of overweight and obesity in adults,12 BMI was categorised into two groups: ≥24 kg/m2 (overweight or obese) and <24 kg/m2 (non-overweight or non-obese). SPs were classified by diameter as ≤5 mm, 6–9 mm, 10–15 mm, 16–20 mm and >20 mm. The distribution sites of polyps were the rectum, sigmoid colon, descending colon (containing the splenic flexure), transverse colon (containing the hepatic flexure), ascending colon and ileocecal region. The polyp gross morphology was classified into type Is, type Isp, type Ip, type IIa and type IIb. Polyp pathology was classified into two categories based on the presence or absence of high-grade intraepithelial neoplasia.
Statistical methods
SPSS V.22.0 for Windows (IBM) was used to analyse the data. In terms of statistical inference, measurement data were expressed as frequencies and percentages, and comparisons between groups were expressed by the Pearson χ2 test or Fisher’s exact probability method (test level α=0.05). For SPs with synchronous AA, univariate analysis and multivariate logistic regression model analysis were carried out. The difference was statistically significant at p<0.05.
Patient and public involvement
None.
Results
Baseline data of patients with SPs in the non-elderly group and elderly group
Among the non-elderly patients who had SPs with synchronous AA, the proportions of males (p<0.001), patients with a smoking history (p<0.001) and those with a drinking history (p<0.001) were higher than in those without synchronous AA, and the difference was statistically significant. Although the proportion of patients with BMI ≥24 kg/m2 in non-elderly patients with SPs was higher, there was no significant difference compared with those without synchronous AA. The proportion of male patients who had SPs with synchronous AA was slightly higher in the elderly group, but there was no significant difference. The proportion of patients with a smoking history (p=0.034), drinking history (p=0.001) and BMI≥24 kg/m2 (p=0.009) in elderly patients who had SPs with synchronous AA increased markedly compared with those without synchronous AA (table 1).
Table 1. Baseline data of patients with SPs in the non-elderly group and elderly group n (%).
| Variables | With AA | Without AA | Statistic | P value |
| Patients with SPs in the non-elderly group | ||||
| Sex | ||||
| Male | 768 (68.51) | 1219 (61.47) | 15.398 | <0.001 |
| Female | 353 (31.49) | 764 (38.53) | ||
| Smoking history | 12.666 | <0.001 | ||
| Yes | 438 (39.07) | 649 (32.73) | ||
| No | 683 (60.93) | 1334 (67.27) | ||
| Drinking history | 19.334 | <0.001 | ||
| Yes | 574 (51.20) | 853 (43.02) | ||
| No | 547 (48.80) | 1130 (56.98) | ||
| BMI (kg/m2) | 1.734 | |||
| ≥24 | 616 (54.95) | 1041 (52.50) | 0.188 | |
| <24 | 505 (45.05) | 942 (47.50) | ||
| Patients with SPs in the elderly group | ||||
| Sex | 3.637 | 0.057 | ||
| Male | 285 (58.88) | 404 (53.37) | ||
| Female | 199 (41.12) | 353 (46.63) | ||
| Smoking history | 4.515 | 0.034 | ||
| Yes | 203 (41.94) | 272 (35.93) | ||
| No | 281 (58.06) | 485 (64.07) | ||
| Drinking history | 11.650 | 0.001 | ||
| Yes | 259 (53.51) | 330 (43.59) | ||
| No | 225 (46.49) | 427 (56.41) | ||
| BMI (kg/m2) | 6.855 | 0.009 | ||
| ≥24 | 293 (60.54) | 401 (52.97) | ||
| <24 | 191 (39.46) | 356 (47.03) |
AAadvanced adenomaBMIbody mass indexSPsserrated polyps
Comparison of clinical characteristics of SPs with synchronous AA between the non-elderly group and elderly group
Comparison of proportion of SPs with synchronous AA in two groups
Although there was no significant difference in the proportion of overall SPs with synchronous AA in the elderly group (484, 39.00%) and non-elderly group (112,36.11%) (χ2 value=3.170, p=0.075), the proportion of HPs with synchronous AA in the elderly group (312, 35.06%) was higher than that in the non-elderly group (695, 30.56%), and the difference was statistically significant (χ2 value=5.952, p=0.015). However, the proportion of SSAs/Ps with synchronous AA in the non-elderly group (196, 56.16%) was higher than that in the elderly group (80, 44.20%), with a statistically significant difference (χ2 value=6.833, p=0.009). There was no obvious difference in the incidence of TSAs with synchronous AA between the elderly group (92, 54.12%) and the non-elderly group (230, 47.82%) (χ2 value=1.995, p=0.158) (figure 1).
Figure 1. Comparison of proportion of SPs with synchronous AA in two groups (%). There was no significant difference in the proportion of overall SPs with synchronous AA in the elderly group (484, 39.00%) and non-elderly group (112, 36.11%) (χ2 value=3.170, p=0.075), however, the proportion of HPs with synchronous AA in the elderly group (312, 35.06%) was higher than that in the non-elderly group (695, 30.56%), and the difference was statistically significant (χ2 value=5.952, p=0.015). The proportion of SSAs/Ps with synchronous AA in the non-elderly group (196, 56.16%) was higher than that in the elderly group (80, 44.20%), with a statistically significant difference (χ2 value=6.833, p=0.009). There was no obvious difference in the incidence of TSAs with synchronous AA between the elderly group (92, 54.12%) and the non-elderly group (230, 47.82%) (χ2 value=1.995, p=0.158). AA, advanced adenoma; HPs, hyperplastic polyps; SPs, serrated polyps; SSAs/Ps, sessile serrated adenomas/polyps; TSAs, traditional serrated adenomas.
Analysis of the clinical characteristics of different types of SPs with synchronous AA in the non-elderly group and the elderly group
Clinical characteristics of patients who had HPs with synchronous AA
Significant differences were found in HP location (p=0.001), HP size (p<0.001) and HP gross morphology (p<0.001) between patients who had HPs with synchronous AA and those without synchronous AA in the non-elderly group. Those with HPs occurring at the descending colon, transverse colon, ascending colon and ileocecal region; those with HP size between 6 mm and 20 mm; or those with HP morphology of type Isp, type Ip and type IIb were more likely to have synchronous AA (online supplemental table 1). Remarkable differences in both HP size (p<0.001) and HP morphology (p<0.001) were observed between patients who had HPs with synchronous AA and those without synchronous AA in the elderly group. Those in the elderly group with HPs larger than 6 mm or HP morphology of types Isp, Ip and IIb were more likely to have synchronous AA (online supplemental table 2 and figure 1).
Clinical characteristics of patients who have SSAs/Ps with synchronous AA
In the non-elderly group, significant differences in SSA/P location (p=0.044), SSA/P size (p<0.001) and SSA/P morphology (p=0.040) were revealed between patients who had SSAs/Ps with synchronous AA and those without synchronous AA. SSAs/Ps occurring in the rectum, ascending colon and ileocecal region; SSA/P larger than 10 mm; or SSA/P of types Ip and IIb were more likely to be combined with synchronous AA (online supplemental table 3). A significant difference in the size (p<0.001) of the SSA/P was observed between SSA/P patients who had SSAs/Ps with synchronous AA and those without synchronous AA in the elderly group. However, an SSA/P larger than 16 mm was more likely to coexist with AA (online supplemental table 4 aand figure 2).
Clinical characteristics of patients who had TSAs with synchronous AA
Significant differences in TSA location (p<0.001), TSA size (p<0.001) and TSA morphology (p=0.012) were reviewed between patients who had TSAs with synchronous AA and those without synchronous AA in the non-elderly group. TSAs occurred in the descending colon, transverse colon, ascending colon and ileocecal region, with TSA sizes ranging from 6 mm to 20 mm, and TSA morphologies of types Is, Isp and Ip were more likely to combine with synchronous AA (online supplemental table 5). Significant differences in both TSA size (p=0.011) and TSA morphology (p=0.005) were observed between patients who had TSAs with synchronous AA and those without synchronous AA in the elderly group. Synchronous AAs were more likely to be combined with TSAs larger than 6 mm or TSA morphology of types Is, Isp and Ip (online supplemental table 6 and figure 3).
In conclusion, the location, size and morphology of the three types of SPs were strongly associated with synchronous AA in both the non-elderly and elderly groups.
Multiple logistic regression analysis of patients who had SPs with synchronous AA
Multiple logistic regression analysis of HPs with synchronous AA in the non-elderly group and the elderly group
In the non-elderly HPs with synchronous AA group, AA-related variables were HP location, HP size (<5 mm as a reference) and HP morphological typing. Sex, smoking history, drinking history, BMI and the above variables were included in the multivariate logistic regression, and a backward stepwise regression was performed. Sex (male, p=0.028, OR=0.798, 95% CI 0.653 to 0.975), drinking history (p=0.000, OR=1.481, 95% CI 1.224 to 1.791) and HP size (HP≤20 mm, ORs range from 1.885 to 5.492, 95% CIs range between 1.513 to 2.347 and 3.046 to 9.902) were independent facilitating factors for synchronous AA. For HPs with synchronous AA in elderly group, HP size (<5 mm as a reference) and HP morphological typing were statistically different between those with synchronous AA and without AA in the univariate analysis. Sex, smoking history, drinking history, BMI and the above variables were also included in the multivariate logistic regression. Then drinking history (p=0.000, OR=1.910, 95% CI 1.436 to 2.540) and HP size (HP≤15 mm, ORs range from 1.845 to 1.964, 95% CIs range between 1.316 to 2.588 and 1.306 to 2.953) were statistically significant independent Facilitating factors for synchronous AA (table 2).
Table 2. Multiple logistic regression analysis of HPs with synchronous AA in the non-elderly group and the elderly group.
| Index | Regression coefficient | SE | Wald | P value | OR value | 95% CI |
| Non-elderly group | ||||||
| Sex | −0.225 | 0.102 | 4.854 | 0.028 | 0.798 | 0.653 to 0.975 |
| Smoking history | −0.056 | 0.131 | 0.181 | 0.671 | 0.946 | 0.731 to 1.223 |
| Drinking history | 0.393 | 0.097 | 16.323 | 0 | 1.481 | 1.224 to 1.791 |
| BMI | 0.073 | 0.107 | 0.467 | 0.494 | 1.076 | 0.873 to 1.326 |
| HP size (<5 mm as a reference) | ||||||
| 6–9 mm | 0.634 | 0.112 | 32.055 | 0 | 1.885 | 1.513 to 2.347 |
| 10–15 mm | 1.045 | 0.131 | 63.875 | 0 | 2.844 | 2.201 to 3.675 |
| 16–20 mm | 1.703 | 0.301 | 32.075 | 0 | 5.492 | 3.046 to 9.902 |
| >20 mm | −0.063 | 0.823 | 0.006 | 0.939 | 0.939 | 0.187 to 4.716 |
| Elderly group | ||||||
| Sex | −0.085 | 0.211 | 0.164 | 0.686 | 0.918 | 0.608 to 1.387 |
| Smoking history | −0.153 | 0.199 | 0.587 | 0.444 | 0.858 | 0.581 to 1.269 |
| Drinking history | 0.647 | 0.145 | 19.802 | 0 | 1.91 | 1.436 to 2.540 |
| BMI | 0.191 | 0.147 | 1.692 | 0.193 | 1.211 | 0.908 to 1.615 |
| HP size (<5 mm as a reference) | ||||||
| 6–9 mm | 0.613 | 0.173 | 12.608 | 0 | 1.845 | 1.316 to 2.588 |
| 10–15 mm | 0.675 | 0.208 | 10.517 | 0.001 | 1.964 | 1.306 to 2.953 |
| 16–20 mm | 0.399 | 0.408 | 0.958 | 0.328 | 1.491 | 0.670 to 3.318 |
| >20 mm | 1.234 | 0.78 | 2.506 | 0.113 | 3.435 | 0.745 to 15.833 |
AAadvanced adenomaBMIbody mass indexHPshyperplastic polyps
Multiple logistic regression analysis of SSAs/Ps with synchronous AA in the non-elderly group and the elderly group
Among SSAs/Ps patients with synchronous AA in the non-elderly group, SSA/P site, SSA/P size (<5 mm as the reference) and SSA/P morphological typing were variables associated with synchronous AA in the univariate analysis. Sex, smoking history, drinking history, BMI and the above variables were included in the multivariate logistic regression, and a backward stepwise regression was performed. The results showed that sex (male, p=0.002, OR=0.381, 95% CI 0.208 to 0.699), smoking history (p=0.012, OR=0.505, 95% CI 0.295 to 0.863), drinking history (p=0.013, OR=0.512, 95% CI 0.301 to 0.868) and SSA/P size (SSA/p≥16 mm, ORs range from 8.338 to 11.689, 95% CIs range between 1.057 to 65.743 and 1.680 to 81.328) were independent facilitating factors for SSAs/Ps with synchronous AA. For SSAs/Ps with synchronous AA in elderly group, SSA/P size (<5 mm as the reference) was the only variable associated with synchronous AA in the univariate analysis. Sex, smoking history, drinking history, BMI and SSA/P size were included in the multivariate logistic regression. High BMI (p=0.021, OR=2.230, 95% CI 1.127 to 4.411）was significant independent Facilitating factors for SSAs/Ps with synchronous AA in elderly group (table 3).
Table 3. Multiple logistic regression analysis of SSAs/Ps with synchronous AA in the non-elderly group and the elderly group.
| Index | Regression coefficient | SE | Wald | P value | OR value | 95% CI |
| Non-elderly group | ||||||
| Sex | −0.964 | 0.309 | 9.744 | 0.001 | 0.381 | 0.208 to 0.699 |
| Smoking history | −0.684 | 0.274 | 6.244 | 0.012 | 0.505 | 0.295 to 0.863 |
| Drinking history | −0.67 | 0.27 | 6.166 | 0.013 | 0.512 | 0.301 to 0.868 |
| BMI | 0.442 | 0.256 | 2.981 | 0.084 | 1.556 | 0.942 to 2.572 |
| SSA/P size (<5 mm as a reference) | ||||||
| 6–9 mm | 0.486 | 0.969 | 0.252 | 0.616 | 1.626 | 0.243 to 10.865 |
| 10–15 mm | 1.571 | 0.96 | 2.679 | 0.102 | 4.811 | 0.733 to 31.566 |
| 16–20 mm | 2.459 | 0.99 | 6.171 | 0.013 | 11.689 | 1.680 to 81.328 |
| >20 mm | 2.121 | 1.054 | 4.052 | 0.044 | 8.338 | 1.057 to 65.743 |
| Elderly group | ||||||
| Sex | 0.026 | 0.386 | 0.005 | 0.945 | 1.027 | 0.482 to 2.188 |
| Smoking history | 0.564 | 0.426 | 1.754 | 0.185 | 1.758 | 0.763 to 4.050 |
| Drinking history | −0.259 | 0.376 | 0.472 | 0.492 | 0.772 | 0.369 to 1.614 |
| BMI | 0.802 | 0.348 | 5.306 | 0.021 | 2.23 | 1.127 to 4.411 |
| SSA/P size (<5 mm as a reference) | ||||||
| 6–9 mm | −1.287 | 1.033 | 1.552 | 0.213 | 0.276 | 0.036 to 2.091 |
| 10–15 mm | 0 | 0.956 | 0 | 1 | 1 | 0.154 to 6.513 |
| 16–20 mm | 1.331 | 0.99 | 1.808 | 0.179 | 3.786 | 0.544 to 26.358 |
| >20 mm | 1.937 | 1.23 | 2.482 | 0.115 | 6.941 | 0.623 to 77.309 |
AAadvanced adenomaBMIbody mass indexSSAs/Pssessile serrated adenomas/polyps
Multiple logistic regression analysis of TSAs with synchronous AA in the non-elderly group and the elderly group
According to the univariate analysis, TSA site (the rectum as reference), TSA size (<5 mm as a reference) and TSA morphological typing were statistically different between TSAs patients with synchronous AA and those without AA in the non-elderly. Sex, smoking history, drinking history, BMI and the above variables were included in the multivariate logistic regression, and a backward stepwise regression was performed. Sex (male, p=0.000, OR=0.366, 95% CI 0.228 to 0.578), drinking history (p=0.003, OR=0.513, 95% CI 0.331 to 0.794), TSA in the transverse colon (p=0.002, OR=3.029, 95% CI 1.478 to 6.207), TSA in the ileocecal region (p=0.026, OR=2.743, 95% CI 1.129 to 6.666) and TSA size (10–15 mm, p=0.001, OR=2.618, 95% CI 1.506 to 4.551) were independent facilitating factors for synchronous AA. For TSAs with synchronous AA in the elderly group, TSA size (<5 mm as the reference) and TSA morphological typing (type IIa as the reference) were variables associated with synchronous AA in the univariate analysis. Sex, smoking history, drinking history, BMI and the above variables were included in the multivariate logistic regression. Smoking history (p=0.001, OR=3.417, 95% CI 1.601 to 7.293), type Isp of TSA (p=0.024, OR=4.691, 95% CI 1.232 to 17.866) and type Ip of TSA (p=0.022, OR=12.102, 95% CI 1.444 to 101.429) were statistically significant independent Facilitating factors for TSAs with synchronous AA (table 4).
Table 4. Multiple logistic regression analysis of TSAs with synchronous AA in the non-elderly group and the elderly group.
| Index | Regression coefficient | SE | Wald | P value | OR value | 95% CI |
| Non-elderly group | ||||||
| Sex | −1.006 | 0.242 | 17.336 | 0 | 0.366 | 0.228 to 0.587 |
| Smoking history | 0.059 | 0.232 | 0.065 | 0.798 | 1.061 | 0.673 to 1.673 |
| Drinking history | −0.668 | 0.223 | 8.96 | 0.003 | 0.513 | 0.331 to 0.794 |
| BMI | 0.024 | 0.213 | 0.012 | 0.911 | 1.024 | 0.674 to 1.555 |
| TSA site (the rectum as reference) | ||||||
| Sigmoid colon | −0.312 | 0.258 | 1.468 | 0.226 | 0.732 | 0.441 to 1.213 |
| Descending colon | 0.459 | 0.368 | 1.558 | 0.212 | 1.582 | 0.770 to 3.252 |
| Transverse colon | 1.108 | 0.366 | 9.164 | 0.002 | 3.029 | 1.478 to 6.207 |
| Ascending colon | 0.624 | 0.336 | 3.449 | 0.063 | 1.866 | 0.966 to 3.603 |
| Ileocolic region | 1.009 | 0.453 | 4.964 | 0.026 | 2.743 | 1.129 to 6.666 |
| TSA size (<5 mm as a reference) | ||||||
| 6–9 mm | 0.419 | 0.229 | 3.337 | 0.068 | 1.52 | 0.970 to 2.382 |
| 10–15 mm | 0.963 | 0.282 | 11.643 | 0.001 | 2.618 | 1.506 to 4.551 |
| 16–20 mm | 1.927 | 1.15 | 2.808 | 0.094 | 6.87 | 0.721 to 65.440 |
| >20 mm | −0.584 | 1.339 | 0.19 | 0.663 | 0.558 | 0.040 to 7.695 |
| Elderly group | ||||||
| Sex | 0.127 | 0.41 | 0.097 | 0.756 | 1.136 | 0.509 to 2.535 |
| Smoking history | 1.229 | 0.387 | 10.088 | 0.001 | 3.417 | 1.601 to 7.293 |
| Drinking history | −0.284 | 0.477 | 0.537 | 0.464 | 0.753 | 0.353 to 1.608 |
| BMI | 0.421 | 0.368 | 1.312 | 0.252 | 1.524 | 0.741 to 3.132 |
| TSA morphologic typing (type IIa as the reference) | ||||||
| Is | 0.798 | 0.474 | 2.838 | 0.092 | 2.222 | 0.878 to 5.625 |
| Isp | 1.546 | 0.682 | 5.131 | 0.024 | 4.691 | 1.232 to 17.866 |
| Ip | 2.493 | 1.085 | 5.284 | 0.022 | 12.102 | 1.444 to 101.429 |
AAadvanced adenomaBMIbody mass indexTSAstraditional serrated adenomas
Discussion
In addition to adenomatous polyps, which have traditionally been considered precursors of CRC, the serrated adenoma pathway has been explored in the development of colorectal carcinogenesis.13 Previous epidemiological studies of SPs showed that the prevalence of SPs in the average risk population was 20%–40%, and most of them were HPs. A study in China found that14 the detection rate of SPs in all polyps increased year by year, reaching 8.74% by 2019. Among all SPs, 69.84% of them were diagnosed as HPs, 22.04% as SSAs/Ps and 7.76% as TSAs. This result is consistent with the findings of this study. TSAs and SSAs/Ps are considered precursors of CRC; therefore, they have an increased risk of synchronous and metachronous advanced tumours. The serrated pathway is characterised by mutations in the BRAF protooncogene, mutations in RAS and RAF, disruptions to the Wnt and P53 signalling pathways, the existence of microsatellite instability (MSI) and microsatellite stability, and widespread methylation of CpG islands. Complex internal correlations exist among each pathway, but they also show differences. SPs and traditional AAs can occur simultaneously, although they originate from two different biological pathways. It should be noted that current guidelines do not address this combination of pathologies. People with simultaneous SPs and AAs have been proven to be a high-risk population for CRC. According to a study assessing the risk after SSAs/Ps with or without synchronous adenoma compared with that following a conventional adenoma, synchronous conventional adenomas may increase the malignant potential of SSA/P. This study revealed that high-risk adenoma (HRA) (HR=2.04, 95% CI 1.70 to 2.45) and SSA/P with synchronous adenoma (HR=3.20, 95% CI 1.31 to 7.82) were independent predictors of future advanced neoplasia compared with low-risk adenoma.15 Another study demonstrated that the cumulative incidence of 3-year isochronous advanced CRC in patients with both SPs and adenoma was 17.9% (95% CI 8.0% to 27.6%), which was significantly higher than 10.7% (95% CI 7.7% to 3.6%) in patients with simple adenoma.16 The coexistence of SPs and AAs significantly increased the risk of heterochrony advanced CRC, and these people may have different risk factor characteristics than patients with only SPs or AAs. This study, therefore, analysed the clinical characteristics of SPs with synchronous AA in elderly and non-elderly people in detail.
A prospective analysis revealed that independent predictors of developing CRC in patients who had SPs with AA were age ≥65 years old (OR=1.15, 95% CI 1.05 to 1.26) and male sex (OR=2.13, 95% CI 1.3 to 3.49),17 while our study led to the same conclusion that the proportion of SPs with synchronous AA was higher in elderly or male patients. In another prospective study,18 30.5% of patients with serrated polyposis syndrome (SPS) were diagnosed with synchronous AA/CRC. The findings suggested that older age and higher BMI were independent risk factors for SPS, which was consistent with the findings in our study that patients who had SPs with high BMI were prone to the development of comorbid AA in the elderly group. The age-related mechanism of SPs is complex,19,21 involving the following aspects: (1) Chronic inflammation of the gut: With ageing, the intestinal mucosa may be more susceptible to chronic inflammation, and prolonged inflammatory stimulation may lead to cell proliferation and polyp formation. Intestinal inflammation may lead to repeated cell damage and repair, increasing the incidence of these molecular events (BRAF mutation, KRAS mutation, CpG island methylation and MSI), which may promote the development and carcinogenesis of SPs. (2) Alterations in molecular biology: SPs is characterised by genetic and epigenetic alterations that may be more common in elder adults because of the increased likelihood of mutation accumulation due to the increased number of cell divisions that occur with age. (3) Immunosenescence: Patients with SPs experience immunosenescence and decreased immune surveillance function. The function of the immune system in the elderly gradually declines with age, a phenomenon known as immunosenescence. Immunosenescence can lead to the weakened ability of immune cells to monitor and clear tumours, which may increase the risk of SPs occurrence and malignant transformation.
Current smoking is a common high-risk factor for both SPs and AAs. Studies have found that current smoking increases the risk of SPs or HRAs by nearly threefold, and it increases the risk of SPs plus HRA by more than eightfold.22 A systematic review and meta-analysis found that alcohol intake (RR 1.33; 95% CI 1.17 to 1.52) and BMI (RR 1.40; 95% CI 1.22 to 1.61) were also risk factors significantly increasing SPs, in addition to smoking (RR 2.47; 95% CI 2.12 to 2.87), and SSA/P was directly associated with smoking and drinking compared with HP, except for BMI.23 Previous studies have also suggested risk factors for SSA/P, including Caucasian ethnicity, family history of CRC, smoking and drinking.24 These findings enhance our understanding of the mechanisms underlying the development of SPs and suggest that the risks of CRC from the serrated pathway could be reduced with lifestyle changes. When data from large prospective studies were analysed,25 researchers reported that smoking, BMI, drinking, family history of CRC and height were associated with a higher risk of SPs and conventional adenomas, respectively, and this association was stronger, especially in synchronous SPs and conventional adenomas. However, smoking, BMI and drinking were more closely associated with SPs than with conventional adenomas, and our study found that all three associated risk factors were also strongly associated with SPs with synchronous AA in both the non-elderly and elderly groups. These findings provide support for the aetiological heterogeneity of colorectal neoplasia. It has been shown26 that independent risk factors for TSA include age ≥50 years old, hypertension and current smoking, with 59.5% of patients with TSAs synchronously having AAs. AAs and HRAs can be more frequently observed in patients with TSAs than in patients with adenomas alone. Another study also showed27 that patients with one or more TSAs had a sevenfold higher risk of developing synchronous advanced CRC than those with one or more HPs. In our study, a higher proportion of TSAs with synchronous AA was found; however, it did not differ statistically between the elderly and non-elderly groups.
In general, we believe that all SPs are considered to be precursors of CRC, except HPs. HP is the most common type of SP, and its incidence is approximately 4.88%.28 An HP with a diameter ≤5 mm, which is mostly distributed in the distal colon and rectum,29 has the same distribution pattern as a TSA.30 Some previous studies have suggested that some HPs might be associated with an increased risk of CRC. Nevertheless, a prospective study on the risk of adenoma recurrence associated with HPs suggested that patients with coexistent HPs and adenomas were not found to have an increased risk of adenoma recurrence in the subsequent 3-year follow-up evaluation, regardless of HPs located in the proximal or distal colon.31 In our study, patients with HPs ≥6 mm and morphological types Isp, Ip and IIb were found to be more likely to have AAs both in the elderly and non-elderly groups. We also found that HPs in the non-elderly group were more likely to have synchronous AA when they occurred in the proximal colon. For patients who have HPs with synchronous AA, whether elderly or non-elderly, we should treat them carefully according to the principles of management and surveillance for AAs.
The incidence of SSA/P is lower than that of HP, approximately 1.11%, and is mainly located in the proximal colon. The incidence rate of TSA is approximately 0.66%, and TSA is mainly located in the distal colon.28 Colonoscopy showed that the prevalence of SSA/P and TSA was influenced by patients, endoscopic technique and pathological diagnosis. The prevalence of SSA/P was approximately dozens of times that of TSA, while the malignant potential of SSA/P and TSA was comparable.32 SSA/P, usually located in the proximal colon and with a diameter of >10 mm, is a sessile flat eminence with a pale surface that is similar to the colour of the mucosal background, which is difficult to find under ordinary endoscopy and can easily cause a missed diagnosis.33 In addition to being prone to occur in the proximal colon (ascending colon and ileocecal region), SSAs/Ps with synchronous AA in the non-elderly were also prone to occur in the rectum in this study. Studies suggest that a high-fat diet, red meat, obesity and smoking are high-risk factors for left colon and rectal lesions,34 and the incidence of SSA/P in the left colon and rectum is increasing as people’s living standards improve and dietary habits change. Age ≥65 years old is an independent predictor of the development of CRC from AAs or SSAs/Ps17; however, this study found that the proportion of SSAs/Ps with synchronous AA in the non-elderly group was significantly higher than that in the elderly group, suggesting that CRC should also be monitored in non-elderly patients with SSAs/Ps. Yang et al found35 that three features on white light endoscopy, including a mucinous cap, indistinct border and cumulus-like surface structure, were independent factors for predicting SSA/P. Tadepalli et al pointed out36 that a mucinous cap was the most common feature of SSA/P. In this study, the above characteristics were confirmed and are also an important basis for the diagnosis of SSA/P by colonoscopy. Some scholars demonstrated that SSAs/Ps were larger and more likely to be accompanied by synchronous and metachronous advanced CRC (6.79% and 6.08%, respectively) than HPs (2.14%). They found that large SPs (diameter ≥10 mm, OR: 2.52, 95% Cl 1.40 to 4.55) and SSAs/Ps with high-grade intraepithelial neoplasia (OR 13.85, 95% CI 3.28 to 58.56) were associated with an increased risk of synchronous advanced CRC.14 Traditionally, the larger the SSA/P volume is, the more likely it is to be accompanied by dysplasia or cancer. In this study, univariate analysis suggested that synchronous AA was closely associated with SSA/P diameter ≥10 mm in the non-elderly group, whereas it was easily associated with SSA/P diameter ≥16 mm in the elderly group. Those SSA/P with morphology types Ip and IIb were more likely to have synchronous AA. Multivariate analysis in this study also identified SSA/P diameter ≥16 mm as a risk factor for synchronous AAs in the non-elderly group. Thus, it is suggested that we should be alert to the risk of synchronous AA and metachronous advanced neoplasia, in addition to the risk of synchronous advanced neoplasia when finding a larger SSA/P of types Ip and IIb during colonoscopy. These patients with SSAs/Ps may be high risk for the development of CRC in the future and a population for focused follow-up surveillance.
Current resection criteria for SPs are not uniform. American researchers37 recommend that all serrated lesions in the proximal sigmoid colon and those serrated lesions >5 mm in diameter in the sigmoid colon and rectum be completely resected. Japanese scholars38 suggest that endoscopic resection for SSAs/Ps ≥10 mm and TSAs ≥5 mm be performed, and HPs ≥10 mm located in the proximal colon also be treated with endoscopic resection, which is difficult to distinguish from SSAs/Ps. However, how to define the resection standard of SPs needs further research and verification for SPs with synchronous AA.
This study also has some limitations. First, the current study is a retrospective study. Second, the current study was conducted in three tertiary endoscopy centre in one city, so selection bias cannot be ignored. Third, because most of the subjects in our study were symptomatic patients who underwent colonoscopy to clarify the cause and a small number were asymptomatic patients who underwent colonoscopy for health screening, there may be bias in colonoscopy data. We will conduct prospective studies to continuously observe the morbidity characteristics, treatment and clinical outcomes of SPs with synchronous AA. Fourth, AA criteria vary across countries, each criterion does not carry the same risk for CRC. Because our study is the analysis of clinical characteristics and risk factors on SPs with synchronous AA in the Chinese population. Therefore, we have applied the diagnostic criteria of AA in the Chinese consensus. In the future, we will expand the scope of our research, draw on the international guidelines and make our research more scientific and universal. Fifth, drinking history may not carry the same effect across different populations. In the future, our research will be more detailed and quantified. Drinking history will be precisely defined as daily alcohol consumption and daily drinking frequency. Additionally, the exclusion criteria omitted some high-risk patients, such as those with inflammatory bowel disease or hereditary polyposis syndromes, which may limit the applicability of the findings to these populations.
In conclusion, this study showed that the incidence of HPs with synchronous AA in the elderly group (312, 35.06%) was significantly higher than that in the non-elderly group (695, 30.56%), while the incidence of SSAs/Ps with synchronous AA in the non-elderly group (196, 56.16%) was remarkably higher than that in the elderly group (80, 44.20%). Multivariate analysis revealed that male sex (OR 0.798, 95% CI 0.653 to 0.975), drinking history (OR 1.481, 95% CI 1.224 to 1.791) and HP size (≤20 mm, ORs range from 1.885 to 5.492, 95%CIs range between 1.513 to 2.347 and 3.046 to 9.902) were independent facilitating factors for HPs with synchronous AA in the non-elderly group, while drinking history (OR 1.910, 95% CI 1.436 to 2.540) and HP size (≤15 mm, ORs range from 1.845 to 1.964, 95% CIs range between 1.316 to 2.588 and 1.306 to 2.953) were independent facilitating factors for HPs with synchronous AA in the elderly group. For SSAs/Ps with synchronous AA, male sex (OR 0.381, 95% CI 0.208 to 0.699), smoking history (OR 0.505, 95% CI 0.295 to 0.863), drinking history (OR 0.512, 95% CI 0.301 to 0.868) and SSA size (≥16 mm, ORs range from 8.338 to 11.689, 95% CIs range between 1.057 to 65.743 and 1.680 to 81.328) were independent facilitating factors in the non-elderly group; nevertheless, only higher BMI (OR 2.230, 95% CI 1.127 to 4.411) was an independent risk factor in the elderly group. This study has important significance for clarifying the clinical characteristics and risk factors for SPs with synchronous AA in different age groups. It also provides a theoretical basis for the development of a digestive endoscopy screening plan or follow-up period after colorectal polypectomy for different risk groups to improve the early detection and early endoscopic treatment of SPs and AAs.
supplementary material
Footnotes
Funding: This work has not been supported by any financial grant.
Prepublication history and additional supplemental material for this paper are available online. To view these files, please visit the journal online (https://doi.org/10.1136/bmjopen-2024-083930).
Provenance and peer review: Not commissioned; externally peer reviewed.
Patient consent for publication: Not applicable.
Ethics approval: The study protocol was done in accordance to the ethical guidelines of the 1975 Declaration of Helsinki. This study protocol was approved by the ethics committee of Xuanwu Hospital of Capital Medical University. Written informed consent was obtained from all the participants in the study, which was approved by the ethics committee at our hospital (XWKD-20220122). Participants were consented to their non-anonymised medical records being used after being contacted via phone and if the patients agreed to be enrolled, we arranged the community doctor to sign the informed consent form with the patients.
Patient and public involvement: Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Contributor Information
Tianyu Chi, Email: xiaoyu800524.student@sina.com.
Ying Liu, Email: lyj7299@163.com.
Cuicui Yang, Email: ycctmg@126.com.
Qing Jia, Email: jiaqing_hosp@163.com.
Quchuan Zhao, Email: linethree@sina.com.
Data availability statement
Data are available on reasonable request.
References
- 1.Vatandoost N, Ghanbari J, Mojaver M, et al. Early detection of colorectal cancer: from conventional methods to novel biomarkers. J Cancer Res Clin Oncol. 2016;142:341–51. doi: 10.1007/s00432-015-1928-z. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Guo TA, Xie L, Zhao J, et al. Trend analysis of morbidity and mortality of colorectal cancer in China from 1988 to 2009. Chin J Gastrointest Surg. 2018;21:33–40. [PubMed] [Google Scholar]
- 3.Feng R-M, Zong Y-N, Cao S-M, et al. Current cancer situation in China: good or bad news from the 2018 Global Cancer Statistics? Cancer Commun (Lond) 2019;39:22. doi: 10.1186/s40880-019-0368-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Zhang L, Cao F, Zhang G, et al. Trends in and Predictions of Colorectal Cancer Incidence and Mortality in China From 1990 to 2025. Front Oncol. 2019;9:98. doi: 10.3389/fonc.2019.00098. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.National Clinical Research Center for Digestive Diseases. National Alliance of Centers for Prevention and Treatment of Early Gastrointestinal Cancer. Digestive Endoscopy Society of Chinese Medical Association Chinese consensus of early colorectal cancer screening (2019, Shanghai) Chin J Intern Med. 2019;58:736–44. [Google Scholar]
- 6.Muto T, Bussey HJ, Morson BC. The evolution of cancer of the colon and rectum. Cancer. 1975;36:2251–70. doi: 10.1002/cncr.2820360944. [DOI] [PubMed] [Google Scholar]
- 7.Snover DC. Update on the serrated pathway to colorectal carcinoma. Hum Pathol. 2011;42:1–10. doi: 10.1016/j.humpath.2010.06.002. [DOI] [PubMed] [Google Scholar]
- 8.Rex DK, Ahnen DJ, Baron JA, et al. Serrated lesions of the colorectum: review and recommendations from an expert panel. Am J Gastroenterol. 1314;107 doi: 10.1038/ajg.2012.161. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Li P, Wang YJ, Chen GY, et al. Chinese consensus on screening, diagnosis and treatment of early colorectal cancer and precancerous lesions. Chin J Pract Intern Med. 2015;35:211–27. [Google Scholar]
- 10.Gupta S, Lieberman D, Anderson JC, et al. Recommendations for Follow-Up After Colonoscopy and Polypectomy: A Consensus Update by the US Multi-Society Task Force on Colorectal Cancer. Am J Gastroenterol. 2020;115:415–34. doi: 10.14309/ajg.0000000000000544. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Hassan C, Quintero E, Dumonceau J-M, et al. Post-polypectomy colonoscopy surveillance: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2013;45:842–51. doi: 10.1055/s-0033-1344548. [DOI] [PubMed] [Google Scholar]
- 12.Guidelines for prevention and Control of Overweight and Obesity in Chinese Adults (Excerpt) Ying Yang Xue Bao. 2004;26:1–4. [Google Scholar]
- 13.Sweetser S, Smyrk TC, Sinicrope FA. Serrated colon polyps as precursors to colorectal cancer. Clin Gastroenterol Hepatol. 2013;11:760–7.:S1542-3565(12)01504-2. doi: 10.1016/j.cgh.2012.12.004. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Tao E-W, Wang YF, Zou TH, et al. Relationship between serrated polyps and synchronous and metachronous advanced neoplasia: A retrospective study. J Dig Dis. 2020;21:558–65. doi: 10.1111/1751-2980.12928. [DOI] [PubMed] [Google Scholar]
- 15.Symonds E, Anwar S, Young G, et al. Sessile Serrated Polyps with Synchronous Conventional Adenomas Increase Risk of Future Advanced Neoplasia. Dig Dis Sci. 2019;64:1680–5. doi: 10.1007/s10620-019-5454-8. [DOI] [PubMed] [Google Scholar]
- 16.Park S-K, Kim H-S, Yang H-J, et al. Coexistent adenoma and serrated polyps on index colonoscopy and the risk of metachronous advanced colorectal neoplasia. Endosc Int Open. 2019;7:E1748–54. doi: 10.1055/a-1019-2976. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Adán Merino L, Mercedes A-M, Jose B-A, et al. Factors related to colorectal cancer in advanced adenomas and serrated polyps: a further step toward individualized surveillance. Eur J Gastroenterol Hepatol. 2018;30:1337–43. doi: 10.1097/MEG.0000000000001227. [DOI] [PubMed] [Google Scholar]
- 18.Toyoshima N, Sakamoto T, Makazu M, et al. Prevalence of serrated polyposis syndrome and its association with synchronous advanced adenoma and lifestyle. Mol Clin Oncol. 2015;3:69–72. doi: 10.3892/mco.2014.423. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Anderson JC, Levine JB. Age and CRC Risk in the Serrated Pathway. J Clin Gastroenterol. 2018;52:465–7. doi: 10.1097/MCG.0000000000001051. [DOI] [PubMed] [Google Scholar]
- 20.Sninsky JA, Shore BM, Lupu GV, et al. Risk Factors for Colorectal Polyps and Cancer. Gastrointest Endosc Clin N Am. 2022;32:195–213. doi: 10.1016/j.giec.2021.12.008. [DOI] [PubMed] [Google Scholar]
- 21.Andrea M, Jepsen RK, Klein MF, et al. Colorectal serrated lesions and polyps in the Danish population: A large nationwide register-based cohort study. Endosc Int Open. 2023;11:E1116–22. doi: 10.1055/a-2206-4486. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Anderson JC, Calderwood AH, Christensen BC, et al. Smoking and Other Risk Factors in Individuals With Synchronous Conventional High-Risk Adenomas and Clinically Significant Serrated Polyps. Am J Gastroenterol. 2018;113:1828–35. doi: 10.1038/s41395-018-0393-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Bailie L, Loughrey MB, Coleman HG. Lifestyle Risk Factors for Serrated Colorectal Polyps: A Systematic Review and Meta-analysis. Gastroenterology. 2017;152:92–104. doi: 10.1053/j.gastro.2016.09.003. [DOI] [PubMed] [Google Scholar]
- 24.Crockett SD, Nagtegaal ID. Terminology, Molecular Features, Epidemiology, and Management of Serrated Colorectal Neoplasia. Gastroenterology. 2019;157:949–66. doi: 10.1053/j.gastro.2019.06.041. [DOI] [PubMed] [Google Scholar]
- 25.He X, Wu K, Ogino S, et al. Association Between Risk Factors for Colorectal Cancer and Risk of Serrated Polyps and Conventional Adenomas. Gastroenterology. 2018;155:355–73. doi: 10.1053/j.gastro.2018.04.019. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Kim J, Lee JY, Hwang SW, et al. Risk factors of traditional serrated adenoma and clinicopathologic characteristics of synchronous conventional adenoma. Gastrointest Endosc. 2019;90:636–46. doi: 10.1016/j.gie.2019.04.241. [DOI] [PubMed] [Google Scholar]
- 27.Duh E, Sowa P, Roberts MB, et al. Traditional serrated adenomas (TSA) and the company they keep: TSA presence predicts advanced neoplasm states. Int J Colorectal Dis. 2020;35:1351–4. doi: 10.1007/s00384-020-03587-x. [DOI] [PubMed] [Google Scholar]
- 28.Mirzaie AZ, Khakpour H, Mireskandari M, et al. Investigating The Frequency of Serrated Polyps/Adenomas and Their Subtypes in Colonic Polyp Samples. Med Arch. 2016;70:198–202. doi: 10.5455/medarh.2016.70.198-202. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Fan C, Younis A, Bookhout CE, et al. Management of Serrated Polyps of the Colon. Curr Treat Options Gastroenterol. 2018;16:182–202. doi: 10.1007/s11938-018-0176-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Bettington ML, Walker NI, Rosty C, et al. A clinicopathological and molecular analysis of 200 traditional serrated adenomas. Mod Pathol. 2015;28:414–27. doi: 10.1038/modpathol.2014.122. [DOI] [PubMed] [Google Scholar]
- 31.Laiyemo AO, Murphy G, Sansbury LB, et al. Hyperplastic polyps and the risk of adenoma recurrence in the polyp prevention trial. Clin Gastroenterol Hepatol. 2009;7:192–7. doi: 10.1016/j.cgh.2008.08.031. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Kawasaki K, Kurahara K, Yanai S, et al. Colonoscopic features and malignant potential of sessile serrated adenomas: comparison with other serrated lesions and conventional adenomas. Colorectal Dis. 2016;18:795–802. doi: 10.1111/codi.13276. [DOI] [PubMed] [Google Scholar]
- 33.Chino A, Osumi H, Kishihara T, et al. Advantages of magnifying narrow-band imaging for diagnosing colorectal cancer coexisting with sessile serrated adenoma/polyp. Dig Endosc. 2016;28:53–9. doi: 10.1111/den.12631. [DOI] [PubMed] [Google Scholar]
- 34.Chen X, Cao HL, Wang SN, et al. Research Progress of the Mechanisms of High Fat Diet Induced Colorectal Cancer. Anti-Tumor Pharm. 2016;6:11–4. [Google Scholar]
- 35.Yang H-J, Lee JI, Park S-K, et al. External Validation of the Endoscopic Features of Sessile Serrated Adenomas in Expert and Trainee Colonoscopists. Clin Endosc. 2017;50:279–86. doi: 10.5946/ce.2016.107. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36.Tadepalli US, Feihel D, Miller KM, et al. A morphologic analysis of sessile serrated polyps observed during routine colonoscopy (with video) Gastrointest Endosc. 2011;74:1360–8. doi: 10.1016/j.gie.2011.08.008. [DOI] [PubMed] [Google Scholar]
- 37.Rex DK, Ahnen DJ, Baron JA, et al. Serrated lesions of the colorectum: review and recommendations from an expert panel. Am J Gastroenterol. 2012;107:1315–29. doi: 10.1038/ajg.2012.161. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 38.Tanaka S, Saitoh Y, Matsuda T, et al. Evidence-based clinical practice guidelines for management of colorectal polyps. J Gastroenterol. 2015;50:252–60. doi: 10.1007/s00535-014-1021-4. [DOI] [PubMed] [Google Scholar]