The rates of recurrent metachronous adenoma and advanced adenoma after polypectomy for colon polyps with HGD were 58% and 20%, respectively. Age, gender, stool occult blood, size of polyp, morphology, pathology, and site of polyp did not differ between patients with recurrent adenoma and those without.
The odds ratios of developing metachronous adenoma and advanced adenoma were 4.32 (2.06-9.04 95% CI) and 2.55(1.11-5.89 95% CI), respectively, upon comparing subjects with polyps ≥ 3 and ≤ 2 in number at index colonoscopy.
No metachronous adenocarcinoma was observed during the analysis period. The incidence rate of adenoma was 35.9 % among those who underwent screening colonoscopy. This rate is higher than similar patient population in Western countries, which have been cited as low as 20% . This rate is also higher than Taiwanese (8.13%) and other ethnically Chinese groups (16.5%) [15-17]. It should be noted that cases included in our study were mostly department referrals on complaint of stool occult blood or gastrointestinal symptoms.
Polypectomy is 50-80% successful in avoiding colon cancer, and interval cancers are located mainly in the right colon [18-20]. Interval carcinoma occurs more frequently in the right colon due to incomplete colonoscopy, often resulting from poor endoscopic technique , incomplete removal of polyps , difficulty in visualization of smaller adenomas in the right colon [23-24], or sessile serrated adenoma in the proximal colon.
At screening colonoscopy, the prevalence of polyps with HGD was 2.2% (258/11565) in our data set, which is slightly lower than 3.5% in the general ethnically Chinese population . There was no interval cancer seen during the follow up period in our study given that we performed the second look colonoscopy 6 to 12 months after piecemeal resection for advanced polyps or suspected incomplete resection to ensure complete resection of polyps and to decrease the rate of undetected adenomas at time of index colonoscopy. This protocol has been suggested by some endoscopists when using the piecemeal method [25-26]. Recurrent adenomas after polypectomy are reported to occur about 36 to 64 % within 2 to 6 years [12, 27-30]. In our study, the overall recurrence rate of metachronous adenomatous polyps was 58%, which is similar to that of 64% in Toll's study . The rate of recurrent advanced adenomas was 20% in our study, which is lower than the 40 % from Toll’s report.
HGD in adenoma is in line with the adenoma-adenocarcinoma sequence, and is a precursor of adenocarcinoma . However, the risk of future advanced adenomas in relation to HGD at index colonoscopy was reported to be small and variable.
In a meta-analysis study by Saini , patients with HGD in polyps experience a 1.84-fold risk of developing advanced adenoma (95% CI 1.06-3.19) compared to those without HGD. Some other studies, including a randomized controlled trial, revealed no association of HGD with subsequent advanced adenomas during surveillance colonoscopy [33-36].
Two meta-analyses [37-38] have shown that the presence of HGD is slightly associated with future advanced adenoma. Upon multivariate analysis, the presence of HGD was not found to confer recurrence of metachronous adenoma. Most advanced adenomas are ≥ 1 cm in size . The risk for metachronous recurrence may dependent on the number of colon polyps and gender, as shown in our study. Moreover, this rationale is also applicable to the association of villous histology in resected adenoma with the risk of recurrent advanced adenoma. Another cohort study found that the presence of villous adenoma at baseline colonoscopy carried a 1.8-fold risk of future adenoma . Two other studies, including one meta-analysis and a pooled analysis, found no association between villous histology and future adenoma development [32, 14]. Such results are in line with the findings of our study. The size of colonic adenoma has been shown to be closely related to HGD and cancer-like histological features . HGD and/or prominent villous components are seen in 87.5% of large polyps (≥ 1 cm) [95% CI = 86–89.4]) . Moreover, the risk of recurrent advanced adenoma was found to correspond with the size of polyps at index colonoscopy. Martinez  found that adenoma size ranges 1.0-1.9 cm and ≥ 2.0 cm at baseline colonoscopy carried a relative risk of 2.3 and 3.0 respectively for developing recurrent advanced adenoma compared to a size of 0.5 cm. Additionally, 4 other studies found increased risk of advanced adenoma in colonic adenomas greater than 1 cm at baseline [22, 32, 34-36]. The relative risk of polyps with HGD at baseline was 6.87 (95% CI 2.61–18.07) for interval advanced neoplasia in a study by Lieberman, in which 6 of 11 patients with recurrent cancer or high-grade dysplasia had lesions locallized to the resection site . In our study, size of adenomas greater than 1 cm did not increase the risk of advanced adenoma at surveillance colonoscopy, which is in line with Saini’s meta-analysis . Incomplete removal or overlooked adenoma [21-22] may account for these contradictory observations.
Adenoma number ≥ 3 has been shown to increase the risk of recurrent advanced adenoma. Relative risk for this parameter is between 1.5 and 5.0 [22, 32, 34-36], using a single adenoma as reference. Our findings agree with previous studies in terms of an odds ratios of 2.45 (1.22-4.93) upon univariate analysis and 2.11(1.00-4.43) on multivariate analysis, respectively, when comparing adenoma number ≥3 to adenoma number ≤ 2. Male gender is also associated with advanced adenoma recurrence in his study, with an odds ratio of 3.09. This is consistent with Zhang’s study .
The natural history of colonic adenoma is still elusive. Two longitudinal follow-up studies on small polyps (6-9 mm) using computed tomography found a tumor progress rates of 22%  and 35%  during follow-up periods of 8 and 3 years, respectively. Advanced disease was seen in 47% of progressive polyps , which is similar to the rate of 40% in our patient group with baseline adenoma number ≥ 3. The high incidence rate of recurrent and advanced adenoma in patients with multiple lesions is hard to explain solely based on incomplete resection. Multiple small polyps not detected at baseline colonoscopy might progress slowly to become detectable at surveillance colonoscopy. Multiplicity or polyclonicity in patients with adenoma number ≥ 3 is a reasonable explanation, but a longer observation period with other non-invasive study modalities such as computed tomography or capsule endoscopy to detect missed adenomas may be required to elucidate the natural history of recurrent adenomas. The surveillance period recommended by the United States Preventive Services Task Force (USPSTF) is 3 years after removal of advanced adenoma, traditional serrated adenoma, or advanced sessile serrate adenoma . The European guidelines  recommend a more aggressive surveillance at 1 year for high-risk polyps (≥ 20 mm). For treatment with piecemeal resection, Walsh et al. found a rate of 14% polyp recurrence after at least one negative examination, and the rate of CRC development was 17% among 65 patients with large, flat polyps . A second look examination for patients who undergo piecemeal resection or suspected incomplete resection may be warranted.
There were a few limitations associated with our study. We did not take into account the impact of diet or lifestyle change such as abstinence from smoking, alcohol, or reduction of body mass index after polypectomy. These changes may influence the recurrence of adenoma or advanced adenoma [47-48]. We also did not include low-risk patients as a control group, and the surveillance time of patients recruited was not uniform. These factors may influence the rate of adenoma recurrence.