| Background and AimsColorectal cancer (CRC) is one of the common malignant tumors which are serious threats to human health. At present, CRC is the third most common cancer and the forth leading cause of death by cancer in the world. In China, the incidence of CRC has increased significantly in recent years and is currently the fourth most common cancer and the fifth leading cause of death by cancer in the country. Colorectal neoplasia screening and removal by colonoscopy is an effective strategy for reducing CRC incidence and mortality. Therefore, Colonoscopy is currently regarded as "gold standand" for detecting colorectal neoplasia. However, missed colorectal adenoma or cancers are detected during repeat colonoscopy in clinical practice. Despite current colonoscopic surveillance guidelines are recommended by few west counties, but the surveillance intervals in these guidelines are based on the natural history of adenoma, and the missed diagnosis of colorectal adenoma and cancer during colonoscopy is not refered in these guidelines. Missed colorectal adenoma can progress to malignant leision during surveillance interval, which leads to the loss of the chance of early diagnosis and treatment. A large proportion of endoscopists and patients consider that repeat colonoscopy should be performed after shorter interval because of the following causes:1. missed adenoma or cancer exist during colonoscopy; 2. many endoscopists do not undersand the natural history of adenoma and can not determine the concrete surveillance time of colonoscopy; 3. most of patients with adenoma worry about their risk of colorectal cancer. With the pervasion of colorectal cancer screening, particularly the dramatic increase in screening colonoscopy, a large number of patients with adenomas are being diagnosed. So, more and more patients received colonoscopic surveillance after initial colonoscopic examination, which not only contributes to the increase of patients' economic burden and the risk of complication, but also places a huge burden on medical resources applied to surveillance. Therefore, there is a need for increase efficiency of surveillance colonoscopy practices to decrease the cost, risk, and overutilization of resources for unnecessary examinations. Few west countries have recommended colonoscopic surveillance guideline based on the study results derived from colonoscopic surveillance study regarding domestic people. Their reports demonstrated that the surveillance time should be prolonged and recommended that surveillance time vary in different persons stratified by adenoma features and patients'characteristics.At the present time, there are no recommended colonoscopy surveillance guidelines for the Chinese population in our country. The incidence of colorectal adenoma and cancer vary in different race and different territory. Whether western surveillance guidelines and practices can be directly applied to the Chinese population needs to be studied. Therefore, in order to further enhance the quality of colonoscopy and develop reasonable guideline of colonoscopic surveillance for Chinese population, we design this program according to the following points:to analyze miss rate and features of different missed adenoma; and assesse the effect of adenoma features and patients characteristics and endoscopists on missed adenoma; and to evaluate the relationship between adenoma recurrence and surveillance time.Patients and Methods1. The rate and risk factors of missed diagnosis for colorectal adenoma during colonoscopyPatients with colorectal adenoma received repeat colonoscopy within 120 days after adenoma had been detected and removed on the initial colonoscopy. The findings of two colonoscopies had been reviewed and analyzed retrospectively. The features of adenoma (including size, shape, location, number and pathology) and clinical characteristics of patients (including age, sex, history of diverticular disease, history of abdominal or pelvic surgery and colonoscopy under sedation) and endoscopists were recorded. The miss rate and features of different missed adenoma were analyzed. And we assessed the effect of adenoma features, patients' characteristics and endoscopists on missed diagnosis of adenoma.2. The risk and causes of interval colorectal cancer after colonoscopic polypectomy.We retrospectively analyzed data (endoscopy, pathology, demography) of patients who received surveillance colonoscopy within five years after colonoscopic polypectomy and reviewed all colonoscopy and pathology reports and collected data regarding the number, size, location, shape and pathology of adenoma as well as patient age, sex, indications and time of colonoscopy. In addition, the cause and time of surveillance colonoscopy, the size, shape, location, and pathology stage of interval cancer were also recorded. Causes and risk of interval colorectal cancer were assessed.3. Recurrence of colorectal adenomas and colonoscopic surveillance after polypectomyData of patients undergoing endoscopic polypectomy and completing three or more colonoscopies between 1976 and 2007 were retrospectively analyzed. The database of colonoscopic surveillance was set up using the sofeware of Epidata. The data regarding features of adenoma (including size, shape, number, location and pathology), and the characteristics of patients with adenoma at baseline colonoscopy were collected and enter the database. The risk of recurrence of any adenoma and advanced adenoma were assessed based on size, presence of villous, numbers of baseline adenoma and patient age and sex by the Cox proportional hazard model in which hazard ratio (HR) and the 95% confidence intervals (CI) were computed.4. Five-year risk of colorectal neoplasia after normal baseline colonoscopy for subjects over 50 years of age.Data of patients who were 50 years of age or older and underwent colonoscopic examination between 1990 and 2004 years and were followed up with colonoscopy at the end of 5 years were analyzed retrospectively. Characteristics of all adenomas detected at baseline colonoscopy and repeat colonoscopy at the end of five years were recorded according to size, location, shape and number. Baseline colonoscopy and follow-up colonoscopy findings were categorized based on the most advanced lesion present:no adenoma, non-advanced adenoma and advanced adenoma. Five-year risk of colorectal neoplasia in these subjects were assessed according to the rates of adenoma and advanced adenoma at the end of five years.Results1. Of a total of 809 patients with adenoma,271 had missed adenomas on initial colonoscopy. Two thousand one hundred and thirty four adenomas were found on initial and repeat colonoscopy, and 425 adenomas were detected on repeat colonoscopy. A pooled miss rate for the first procedure was 20% (425/2134). A per patient miss rate was 33% (271/809). The diameter (1 mm increments) was independently associated with a decrease in the miss rate for adenoma [Odds Ratio, (OR),0.84,95% confidence interval (CI),0.80-0.87]. Conversely, sessile or flat shape (OR,2.21; 95% CI,1.64-2.97) and sigmoid (OR,2.02; 95% CI,1.43-2.87), hepatic flexure(OR,1.95; 95% CI,1.07-3.54), cecum and ascending colonic location (OR, 2.15; 95% CI,1.45-3.17)were significantly associated with a higher miss rate of adenoma, as were two adenomas (OR,1.87; 95% CI,1.24-2.82) or≥3 adenomas (OR, 4.20; 95% CI,2.84-6.21) detected at initial colonoscopy. A higher miss rate of adenoma often occurred in primary colonoscopists, as compared with experience colonoscopists (OR,2.77,95%CI,1.93-3.97). The mean size (X±SD) of missed advanced adenoma was smaller than that of advanced adenoma detected on initial colonoscopy (15.9±6.9mm vs 10.9±4.0mm, p=0.000).2. Among 1794 patients undergoing surveillance colonoscopy within five years after colonoscopic polypectomy,14 patients were diagnosed to suffer from interval colorectal cancer. The mean follow-up time was 2.67 years and incidence density of interval colorectal cancer was 2.9 cases per 1000 person-years. Fifty percent of interval colorectal cancers were found in patients who underwent an incomplete endoscopic resection, and 27% of interval colorectal cancer were missed cancer and 23% were new cancer. The risk of interval colorectal cancer was higher in patients with advanced adenoma on initial colonoscopy than in patients with non-advanced adenoma on initial colonoscopy (p=0.024). The age of patients with interval colorectal cancer were older than patients with no interval colorectal cancer (p=0.030).3. Among 6462 patients underwent endoscopic removal of colorectal adenomas between 1976 and 2007, a total of 1356 patients who included in colonoscopic surveillance program received colonoscopic surveillance examination. Seven hundred fourteen (52.7%) patients had non-advanced adenomas, and 642 (47.3%) patients had advanced adenomas. The Cumulative recurrence rates of advanced adenoma in patients with advanced adenoma at baseline were 3.8%,13.1%,34.7%and 52.0% during surveillance intervals of 1-3,3-5,5-10, and 10-20 years post-initial colonoscopy; for patients with non-advanced adenoma at baseline, the Cumulative recurrence rates were 0.9%,3.9%,5.8% and 29.2% during the same surveillance intervals, respectively. For patients with advanced adenoma at baseline, the Cumulative recurrence rates of any adenoma during four different surveillance intervals were 32.6%,58.1%,75.8% and 86.2%, as compared with those of 11.5%, 28.9%,45.3% and 62.5% for patients with non-advanced adenoma at baseline. For the cumulative hazard of both advanced adenoma and any adenoma recurrence at surveillance, a significant difference was found between the advanced adenoma and non-advanced adenoma at baseline (p=0.000).Male sex (HR,1.26; 95% CI,1.01-1.57), age of 50 to 60 years (HR,1.69; 95% CI, 1.30-2.19) or older than 60 years (HR,2.97; 95% CI,2.31-3.82) were associated significantly with the recurrence of any adenoma, as were the size of 10-19mm (HR, 1.40; 95% CI,1.05-1.87) or larger than 20mm in diameter (HR,1.49; 95% CI, 1.05-2.12), two adenomas (HR,1.55; 95% CI,1.18-2.05) or more than two adenomas (HR,1.90; 95% CI,1.49-2.43) detected on initial colonoscopy, the presence of villous (HR,1.38; 95% CI,1.03-1.85), high-grade dysplasia (HR,1.28; 95% CI,1.00-1.62). No significant differences emerged considering the location and the shape of baseline adenoma.Male sex (HR,2.11; 95% CI,1.27-3.53), age of 50-60 years (HR,1.81; 95% CI, 1.05-3.12) or older (HR,4.81; 95% CI,2.80-8.25), two adenomas (HR,1.92; 95% CI, 1.04-3.54) or more than two adenomas (HR,1.87; 95% CI,1.12-3.10) detected on initial colonoscopy, adenoma larger than 2cm (HR,2.35; 95% CI,1.09-5.06), tubulovillous and villous histology (HR,2.57; 95% CI,1.24-5.32), high-grade dysplasia (HR,1.61; 95% CI,1.07-2.42) at baseline were significant risk factors for developing advanced adenoma after polypectomy. The shape and location of baseline adenoma were not associated significantly with the recurrence of advanced adenoma.Based on the results of multivariate analysis for risk factors of advanced adenoma recurrence, patients were divided into two groups:a low risk group and a high risk group. In a low risk group, patient should be younger than 50 years old and had only one non-advanced adenoma at the baseline colonoscopy. In a high risk group, patients should have the following one or more characteristics:older than fifty years old, advanced adenoma at baseline colonoscopy, multiple adenomas.When the recurrence of advanced adenomas was found in 5% of patients, the estimate was 6.9 (95% CI, 6.3-12.2) years in the low risk group, and 3.0 (95% CI,2.7-3.2) years in the high risk group. The estimate for 10% quantile (the time when 10% of patients will develop advanced adenoma) was 12.6 (95% CI,8.5-14.5) years in the low risk group and 4.2 (95% CI,3.5-5.0) years in the high risk group. When the recurrence of advanced adenomas was found in 20% of patients, the estimate was 15.0 (95% CI,14.2-17.1) years in the low risk group, and 5.6 (95% CI,5.0-6.3) years in the high risk group.4. A total of 480 patients who were older than 50 years underwent follow-up colonoscopy at the end of five years. Among the 480 follow-up patients,147 (30.6%) were found to have non-advanced adenoma and 30 (6.3%) had advanced adenoma on the follow-up colonoscopy. Amoung 301 patients who had no baseline adenoma,77 (25.6%) patients had non-advanced adenoma and 5 (1.7%) had advanced adenomas. In patients with baseline non-advanced adenoma, non-advanced adenomas were found in 34 (37.8%) patients, and advanced adenomas were found in 4 (4.4%) patients. Of those who had baseline advanced adenomas, non-advanced adenoma and advanced adenoma were found in 36 (40.4%) and 21 (23.6%) patients, respectively, and one invasive cancer was found in one patient. No cancer was found in patients with no baseline adenoma and non-advanced adenoma.Any adenoma were found in 38 of 90 patients (42.2%) who had had non-advanced adenoma at baseline, as compared with 82 of 301 (27.3%) who had had no adenoma on baseline colonoscopy [Relative Risk (RR),1.79; 95% CI,1.04-3.10]. In subjects with baseline advanced adenoma, any adenoma was present in 57 of 89 (64.0%), as compared with 27.3% of subjects with normal baseline colonoscopic findings (RR, 4.48; 95% CI,2.55-7.86). Male sex, age and three or more adenoma at baseline were independent risk factors for any adenoma on five-year follow-up colonoscopy.Advanced adenomas were found in 21 of 89 patients (23.6%) who had had advanced adenoma at baseline, as compared with 5 of 301 (1.7%) who had had no adenoma on baseline colonoscopy (RR,14.11; 95% CI,4.51-44.12). Male sex, age and number of adenoma at baseline were also independent risk factors for advanced adenoma on five-year follow-up colonoscopy, whereas, non-advanced adenoma at baseline was no risk factor for advanced adenoma on five-year follow-up colonoscopy compared with no baseline adenoma (RR,1.85; 95% CI,0.43-7.89).Conclusions1. A significant miss rate of adenoma exists during colonoscopy. The missed diagnosos of adenoma is significantly associated with the size, shape, location and number of adenomas, and the operational level of endoscopists.2. Among patients undergoing surveillance colonoscopy within five years after colonoscopic polypectomy, the incidence density of interval colorectal cancer was 2.9 cases per 1000 person-years. A majority of interval colorectal cancers origin from incomplete resection of advanced adenoma and missed cancer, which can be prevented by improving endoscopic technique and selecting appropriate follow-up time interval. 3. Amoung our patient group, the recurrence of advanced adenoma after polypectomy was increased with the length of the surveillance interval. The size, number and histopathology of baseline adenoma were risk factors associated with the recurrence of any adenoma and advanced adenoma, as well as age and sex of patients. The 3-year and 6.9-year follow-up after polypectomy could be effective and safe in preventing the recurrence of advanced adenoma for high risk patients and low risk patients, respectively.4. The risk of advanced adenoma is also low 5 years after a normal baseline colonoscopy even in subjects over 50 years of age. Therefore, colonoscopic surveillance maybe safe for these subjects at least 5 years after initial colonoscopy.
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