3.7 Risk factors for ADR in individuals based on the cutoff age of 40 years
In the subgroup analysis based on age, no parameter was associated with ADR in patients 40 years and below. The multivariable analysis showed that age (OR = 1.038, 95%CI 1.020–1.056; P < .001), a personal history of adenoma (OR = 2.568, 95%CI 1.061–6.212; P = .036), diabetes mellitus (OR = 2.280, 95%CI 1.104–4.707; P = .026), insertion time (OR = 0.999, 95%CI 0.998–1.000; P = .006), and withdrawal time (OR = 1.009, 95%CI 1.007–1.011; p < .001) were risk factors for ADR in individuals above 40 years old.
3.8 Risk factors for ADR based on gender
In the subgroup analysis based on gender, the multivariable analysis showed that age (OR = 1.025, 95%CI 1.008–1.042; P = .003), diabetes mellitus (OR = 3.065, 95%CI 1.448–6.488; P = .003), and withdrawal time (OR = 1.007, 95%CI 1.005–1.010; P < .001) were risk factors for ADR in males. In females, age (OR = 1.064, 95%CI 1.042–1.087; P < .001) and withdrawal time (OR = 1.012, 95%CI 1.008–1.015; P < .001) were risk factors for ADR.
Adenoma detection is the key task of screening colonoscopy. Through standardized bowel preparation and colonoscopy parameters (e.g., withdrawal time), the ADR has reached the level suggested by the ASGE guidelines in this study. The overall PDR and ADR were 36.96% and 24.67%, respectively, significantly higher than previously reported in China and close to the requirement of the Chinese guidelines.
4.1 Risk factors for colon polyps and PDR
Previous studies have indicated that gender, smoking, alcohol, BMI, diet, physical activity, medication, and/or hormone replacement therapy are risk factors associated with colorectal polyps.[13,14] In contrast, factors such as use of non-steroidal anti-inflammatory drugs or aspirin, high intake of folate, calcium, and fiber were found to significantly decrease the risk of polyp. In a recent large multicenter chemoprevention study, evidence was provided that calcium and vitamin D supplementation increases the risk of SSA/Ps.
As for operator factors, studies of colonoscopists within the same gastroenterology groups consistently demonstrate an ADR variation of 3–6 fold between the best and worst performers.[16–18] When detection is expressed as adenomas per colonoscopy (APC), the differences between the top and bottom performers can even exceed 10 fold.
According to the above results, the PDR was 36.96% and related to age (P < .001), BMI (P = .001), procedure time (including withdrawal [P < .001] and insertion [P = .004] times), gender (P < .001), sedation (P = .023), a personal history of adenoma (P = .004) and diabetes mellitus (P < .001), tobacco (P = .001) and alcohol use (P = .003), and calcium and vitamin D use (P = .013). These findings corroborated reports by Western studies. Nevertheless, no significant associations were found between the PDR and family history of adenoma/colon cancer, coronary artery disease, use of aspirin, NSAIDS, folate and hormone replacement therapy, bowel preparation and operator experience, which may due to the limited samples size, for example, the numbers of patients with coronary artery disease (n = 18), acetylsalicylic acid use (n = 67), folate use (n = 35), and hormone replacement therapy (n = 29) were relatively low. There was no significant correlation between BMI and ADR in our study, which may be related to the narrow range of BMI of the study subjects. Because some patients with cardiovascular and cerebrovascular diseases used antiplatelet and anticoagulant drugs such as aspirin or clopidogrel, biopsy could not be performed. In addition, some patients refused polyp biopsy for economic and conceptual reasons. Furthermore, the rate of colonoscopy in China is low, especially in the previous decades, with deficient CRC screening. Therefore, data regarding family history of CRC or adenoma may not be accurate, which could also lead to discrepant statistical results.
4.2 Risk factors for colorectal adenoma
Multiple studies have assessed the risk factors of colorectal adenoma. It is generally acknowledged that the main risk factors include age, male gender, smoking, drinking, obesity, metabolic syndrome, and family history. It is estimated that 30–50% of the CRC risk is attributable to lifestyle factors such as smoking, high consumption of red and processed meat, obesity, diabetes, and excessive consumption of alcohol. Studies have reported an increased risk associated with long-term cigarette smoking, which may be responsible for 20% of CRC cases. Age as a risk factor is equally relevant in women and men. More than 50% of CRC cases are diagnosed after the age of 70, with only 10% being detected before age 55. Nevertheless, the risk of men developing advanced adenoma or cancer is roughly double that of women.[14,22] A recent study demonstrated that the male gender increases the risk to a similar extent as a positive family history of CRC.
In a Portuguese prospective study, the metabolic syndrome (MS) was shown to be associated with increased prevalence rates of adenoma (43% vs. 25%, P = .004) and CRC (13% vs. 5%, P = .027), compared to patients without MS. A recent meta-analysis of 29 eligible studies confirmed these estimates, indicating an increased risk of CRC in type 2 diabetes (RR = 1.29 for men and 1.34 for women).
Based on the high-quality colonoscopy data from the present prospective study, the multivariable analysis demonstrated that age (P < .001), gender (P = .016), a personal history of adenoma (P = .009), diabetes mellitus (P = .016) are predictors of adenoma incidence. With regard to alcohol use, a family history of adenoma, and a family history of colon cancer, our data failed to show significant differences in adenoma incidence rates, probably due to the limited sample size and the likely inaccuracy of family history mentioned above. In addition, most previous studies were performed in Western countries, and racial and genetic differences may explain the discrepancies described here.
On the other hand, protective factors for adenomas have been reported. Evidence suggests an association of regular aspirin use with reduced risk of adenomatous polyp and CRC. In a Health Technology Assessment report, pooled analysis of two studies evaluating 300 to 1200 mg/day of aspirin indicated a 26% reduction in CRC incidence over a 23-year follow-up period. Furthermore, a meta-analysis suggested that metformin therapy may be associated with a decreased risk of colorectal adenoma and CRC in type 2 diabetes mellitus patients. Another systematic review of four randomized, placebo-controlled trials including 2998 participants indicated a modest chemopreventive effect of calcium supplement against colorectal adenoma (approximately 10%–15% risk reduction; high-quality evidence).
Nevertheless, we found no significant association of these factors with adenoma, including use of acetylsalicylic acid, NSAIDS, folate, metformin, calcium/vitamin D, and hormone replacement therapy. These discrepancies are likely related to racial and genetic differences and the limited number of samples, especially for medication users. Therefore, more studies are needed for confirmation.
4.3 Withdrawal time and age have effects on the ADR
This study showed that the ADR was associated with age, gender, insertion time, withdrawal time, a personal history of adenoma, and diabetes mellitus. With withdrawal time <6 min, the ADR was significantly reduced (P < .001). Our results show that both the junior and the senior physicians have significantly improved ADR when the withdrawal time is >6 min, regardless of the operator's certification. Nevertheless, since the number of junior physicians involved in this study was only 12.8%, this conclusion needs further confirmation. According to the multivariable analysis, age, withdrawal time, a personal history of adenoma, and diabetes mellitus may be independent predictors of the ADR. In subgroup analysis based on age and gender, patients ≤40 years of age showed no parameter was associated with ADR except for withdrawal time, while patients above 40 years old showed similar risk factors with all subjects, and diabetes mellitus showed higher correlation with ADR in male. On the other hand, BMI, anesthesia, a family history of colon cancer, a family history of adenoma, coronary heart disease, tobacco use, drug use (acetylsalicylic acid, NSAIDS, folate calcium, vitamin D, and hormone replacement therapy), and bowel preparation were not directly associated with ADR.
Factors impacting the ADR have been widely studied. Indeed, bowel preparation and colonoscopy time, inspection time, and operator factors are known factors of ADR. The associations of some of these factors have been confirmed with ADR, with their inclusion in the guidelines for colonoscopy as control elements.[18,29–36] The ASGE has listed ADR factors in details in their 2015 edition of CRC screening and monitoring guidelines, and has made corresponding quality control requirements. For example, when colonoscopy is performed, withdrawal time should be >6 min. Operator factors also significantly affect the ADR, for example, observation skills (detection behind the intestinal content and dilated colon), and their predictive potential for the ADR may even exceed the effects of age and gender, through appropriate training that can significantly improve the ADR.[17,38–40]
Good bowel preparation is the basis for ensuring quality colonoscopy. Under poor bowel preparation, “micro adenomas” with diameters <5 mm are easily missed. Such patients need to shorten the screening period to avoid the occurrence of interphase CRC. In this study, due to the limited number of patients with inadequate bowel preparation, we found no significant association of bowel preparation with ADR.
The ADR directly correlates with the incidence and mortality of post-colonoscopy (or interval) CRC. Patients with a history of CRC or a family history of CRC have significantly higher rates of adenoma. As shown above, however, a family history of CRC seemed to have no significant correlation with the ADR, which may be due to the exclusion of cases with giant colonic neoplasms and polyposis in this study.
4.4 Men over 40 may need colonoscopic screening
With the increased incidence of sporadic CRC in young adults, several behavioral and environmental factors affecting CRC have been proposed. The current data showed that about 28.87% of men and 10.45% of women in their 40s have adenomas detected through colonoscopic screening. The NCCN published in 2013 a guideline about CRC screening, mention that people with unknown family history should begin screening for CRC at the age of 40. Since CRC screening in China has been very poor in previous decades, family history is often inaccurate and can be considered an unknown family history. Therefore, a cutoff age of 40 years was selected in this study. The ASGE stipulates that Caucasians at average risk should begin to undergo CRC colonoscopic screening at 50 years of age, requiring that ADR values for the population should reach 25% in men and 15% in women. These values were determined from domestic CRC epidemiology and ADR-related studies in the United States. No such data have been previously reported in China, which makes it very difficult for China to determine the age at which CRC screening should be performed. This study showed that the ADR in males increased gradually after the age of 40. Nevertheless, due to the limited sample size, we failed to analyze age subgroups at 5 year intervals, to provide information about the PDR and ADR in the region. Previous studies showed that the incidence of advanced adenoma in the average risk population in China is lower than that in Europe or America, but higher than the rates in other Asian countries. Accordingly, the screening age could be at 55 years, between 50 years in the USA and 60 years in South Korea. Differently, this study showed that in individuals over 40 years old, the ADR was higher than described by the ASGE, suggesting that CRC screening may occur earlier in China than in the United States, which is quite different from a previous similar study in China. However, an accurate answer to the problem of screening age cutoff requires larger sample size studies and more detailed analysis. Finally, we also found significant differences between ADR values in males and females of the same age groups, suggesting that screening strategies should take gender into consideration.
Several limitations should be mentioned of this study. First, this was a single center study, and the Han nationality in China is large; thus, all the study patients were Han Chinese. Therefore, the current data cannot reflect ethnic differences and the findings may not be generalizable. Second, the sample size was relatively limited. Third, during the procedure, patients with massive CRC were excluded, which may lead to selection bias. Fourth, since social responsibility is a major cultural concern for many Chinese, the rate of adequate preparation was quite high, preventing to observe an effect of bowel preparation on the ADR. Fifth, in the subgroup analysis based on age, no parameter was associated with ADR in patients 40 years and below, but this lack of association can be due to the small number of adenoma-positive patients among those <40 years of age. Sixth, because the examination procedures were carried out in the examination room in the study, the endoscopic physicians could not be blinded. Finally, in China, it is necessary to complete blood routine, coagulation function, pre-transfusion measurements, electrocardiogram, and other preoperative examinations before polypectomy. Therefore, when polyps are found and biopsied, they have to be removed during a second colonoscopy. This difference with Western practice could affect the generalizability of the results.
In conclusion, these findings add to several evidences for CRC screening in the Chinese population. ADR increases with age, withdrawal time, a personal history of adenoma, and diabetes mellitus. Age, insertion time, withdrawal time, a personal history of adenoma may be independent predictors of colorectal adenoma detection. This study, combined with European and American guidelines,[3,11] found that 40 years old may be a suitable age for beginning CRC screening in the general population in China. The relevance of the results to routine clinical practice is mainly the determination of the key factors that could suggest the need for CRC screening: male, >40 years of age, history of polyp, diabetes, etc. In addition, this study analyzed the factors related to the colonoscopy itself, in order to improve the detection rate of polyps/adenoma. Those factors include the time for entering and withdrawal of the endoscope, which can help clinicians to improve their ADR performance.
Data curation: Han Wang, Xiaogang Liu, Guangre Xu.
Formal analysis: Han Wang, Pu Wang, Xiaogang Liu, Guangre Xu.
Investigation: Han Wang, Liangping Li, Mengtian Tu.
Methodology: Han Wang, Pu Wang, Liangping Li, Xun Xiao, Di Zhang, Mengtian Tu.
Project administration: Xiaogang Liu, Di Zhang, Yi Li, Guangre Xu, Mengtian Tu, Yan Song.
Resources: Pu Wang, Xun Xiao, Di Zhang, Yi Li, Yan Song.
Software: Peixi Liu, Yi Li, Yan Song.
Supervision: Xun Xiao.
Validation: Peixi Liu.
Visualization: Peixi Liu.
Writing – Original Draft: Han Wang.
Writing – Review & Editing: Pu Wang, Xiaogang Liu, Liangping Li, Xun Xiao, Peixi Liu, Di Zhang, Yi Li, Guangre Xu, Mengtian Tu, Yan Song.
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Keywords:Copyright © 2019 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.
colorectal adenoma; detection; prospective study; risk factor