Investigation On Risk Factors Associated With Missed Diagnosis And Detection Of Colorectal Flat Adenoma During Colonoscopy

Background and AimsColorectal cancer (CRC) is one of the common malignant tumors in China. At present, CRC is the second-third most common cancer in the western country. In China, the incidence of CRC has increased significantly in recent years and is currently the third-forth most common cancer in the country. CRC mainly originates from colorectal adenomas.Colonoscopy has been considered as the "golden standard" in detection of colorectal adenomas and plays an important role in CRC prevention.Colonoscopic polypectomy with follow-up monitoring has been proven to decrease the incidence of colorectal cancer by 80%, mainly in the left colon.So many countries carried out colonoscopy screening programmes and decreased the incidence of colorectal cancer.However, the difference of colonoscopy quality is very significant. Adenoma detection rates(ADR) of colonoscopy are 20%-46.5% in different units. ADR of different colonoscopists was difference by 4-10 times.These indicate that missed diagnosis and detection of colorectal adenoma exists and decreases protection of colonoscopy, for example, protection of the right colon after colonoscopy role is very limited, significantly lower than the left colon.According to the morphology, Kudo et al. classified colorectal adenomas into protruding adenoma and flat adenoma.Studies found not only in western countries but Oriental countries, asymptomatic or symptomatic crowds, incidences of flat adenomas are very high, which are a common form of adenoma.Compared with protruding adenomas, flat adenomas have different clinical pathological features.Flat colorectal adenomas have a greater tendency to develop into severe dysplasia and carcinoma than protruding adenomas.Other researches also think severe dysplasia has nothing to do with the morphology of adenoma.Thus, whether flat adenomas are closely related to severe dysplasia is not clear. And We need clarify the influence factors of flat adenomas developing into severe dysplasia.However, because of their flat morphology and low awareness among colonoscopists, many flat adenomas are missed during colonoscopy although they are often visible. Therefore, flat adenomas are not only difficult to detect, but also easy to miss. Specifically, the miss rates of flat adenomas during colonoscopy range from 35%-60%, which are much higher than those (4%-19%) seen in the protruding type of adenomas. It is believed that those undetected or missed adenomas may play an important role in the incidence of interval cancers.One study demonstrated that Colorectal cancer in the right colonic cancer are mainly composed of interval cancer, whose incidence was significantly higher than non-interval carcinoma. Flat adenomas are frequently localized at the right part of the colon, and it has been suggested that the high miss rate for flat adenomas at the right colon contributes to the high incidence of cancer at the right colon after colonoscopy.Therefore,it is extremely important and essential to recognize and identify these flat neoplastic lesions at an early stage.The application of new techniques such as chromoendoscopy or magnifying narrow-band imaging during colonoscopy in recent years appears to significantly improve the detection of colorectal flat adenoma during colonoscopy; however, controversy exists. What is more, there are only few studies evaluating the miss rates of flat adenomas. Moreover, the risk factors influencing the miss rate for flat adenomas have not been explored and thus are not understood. Flat adenoma detection rate (FADR) on colonoscopy is very different by 4-13.2%.FADR in symptomatic patients with total colonic chromoendoscopy is 34.1%.Nicolas-Perez etc studied the risk factors flat adenomas on colonoscopy for the first time in 2013 and found age older than 50 years, protruding adenomas, follow-up colonoscopy forpolyps or cancer and specifically trained endoscopist were associated independently with flat adenoma detection.Studies have showed that many factors including patient-related, adenoma-related, and procedure-related elements influenced ADR on colonoscopy and related to colonoscopy quality.However, this study has some limitations that it doesn’t discuss the main factors affecting the quality of colonoscopy.ADR is "golden standard" to evaluate the quality of colonoscopy.Because flat adenoma is the main type of missed diagnosis on colonoscopy and its miss rates were higher than protruding adenoma’s, improving ADR on colonoscopy may is the key to the detection of flat adenomas.There may be a certain relationship between FADR and ADR.In addition.as the flat adenomas are mainly in the right colon, FADR could help to assess the quality of colonoscopy on the right colon.Analyzing the relationship between FADR and ADR can clarify whether FADR can become another colonoscopy supplementary measure of quality.Therefore, this multicenter study aimed to discuss clinicalpathological features of flat adenomas and determine the miss rates and adenoma detection rates of colorectal flat adenomas during colonoscopy and their risk factors. We also study the relationship between the miss rates and adenoma detection rates of flat adenomas and total adenomas.Patients and MethodsThis was a multicenter, retrospective study in which patients carried out colonoscopy between September 2009 and September 2011 from four Chinese hospitals were pooled out from the database established in the computerized system for colonoscopy. These hospitals included Guangzhou Nanfang Hospital affiliated to Nanfang Medical University, Guangdong, Wuxi People’s Hospital affiliated to Nanjing Medical University, Jiangsu, Mianyang Central Hospital, Sichuan and Shenzhen Longgang Central Hospital, Guangdong. The study proposal was approved by the Ethics Committees of these four institutions. All patients gave written informed consent at the first and second colonoscopy to allow their colonoscopy data to be used for this research purpose.1、Study of clinicalpathological features of colorectal flat adenomasPatients with colorectal adenoma received repeat colonoscopy within 90 days after adenoma had been detected and removed on the second colonoscopy. The findings of two colonoscopies had been reviewed and analyzed retrospectively. The features of adenoma (including size,location,shape,numbers and pathology) and clinical characteristics of patients (including age, sex, symptoms, diverticular disease, history of adenomas, history of abdominal or pelvic surgery, bowel preparation and colonoscopy under sedation) were recorded. The clinicalpathological features of flat adenoma were analyzed. The multivariate logistic regression analysis was used to determine the independent risk factors of severe dysplasia of adenoma/flat adenoma.2、Study of missed rate and risk factors of colorectal flat adenoma on colonoscopyPatients with colorectal adenoma received repeat colonoscopy within 90 days after adenoma had been detected and removed on the second 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, symptoms, diverticular disease, history of adenomas, history of abdominal or pelvic surgery, bowel preparation and colonoscopy under sedation) and endoscopists (proficiency and specialty of colonoscopists, mode of colonoscopy and withdrawal time) were recorded. We determined the miss rate in detection of colorectal flat adenomas during colonoscopy and multivariate logistic regression analyzed the risk factors that influence the miss rate. And we investigated the relationship of miss rates between flat adenomas and total adenomas by spearman correlation analysis.3、Study of detection rate and risk factors of colorectal flat adenoma on colonoscopyPatients who meet the standards received from sep 2009 to sep 2011. The clinical characteristics of patients (including age, sex, diverticular disease, history of adenomas, bowel preparation and colonoscopy under sedation) and the features of adenoma (including size, shape, location, number and pathology)and endoscopists (proficiency and specialty of colonoscopists, mode of colonoscopy and withdrawal time) were recorded, we determined the detection rate of colorectal flat adenomas during colonoscopy and multivariate logistic regression analyzed the risk factors that influence the detection rates.And we investigated the relationship of detection rate between flat adenomas and total adenomas.RESULT1、In 2093 patients,4632 adenomas were detected. There were 916 flat adenomas (19.8%) and 3716 protruding adenomas (80.2%). Compared with the protruding colorectal adenomas, the flat adenomas were mainly localized in the proximal colon (410/916; 44.8%);Size of flat adenomas is larger than that of protruding adenomas (8.55±08.55mm vs 8.04±4.28mm, P=0.01),but flat adenomas whose sizes were more than 10 mm were less than protruding adenomas (18.8%vs29.0%). Pathologically, the majority of flat adenomas (81.3%) were tubular adenomas, followed by tubulovillous or villous adenoma (16.3%) and serrated adenomas (2.2%). The proportions of a villous structure and serrated adenomas in patients with flat adenomas were more than that in protruding adenoma (16.5% vs. 13.9%, P=0.041; 2.2%vs1.0%, P=0.003).262 adenomas developed into severe dysplasia among 4632 adenomas.Compared with the protruding adenomas, the flat adenomas were more associated with high grade dysplasia adenoma (7.5% vs.5.2%, P=0.006). Not only diameter<10 mm but>10 mm of flat adenomas more easily developed into severe dysplasia than protruding adenomas(0.5% vs 0.1%,37.8% vs 17.8%, P<0.01). Flat adenomas which were localized in the proximal colon or contain villi structures had larger proportion of severe dysplasia(7.8% vs 4.7%, P=0.019,43.0% vs 33.4%, P=0.029).Risk factors of adenomas developing into severe dysplasia were related to characteristics of adenomas by multivariate logistic regression analysis.Adenomas whose sizes were more than 10 mm(OR:24.104,95%CI:9.323-62.316, P<0.001) or which contained villous structure(OR:16.486,95%CI:10.295-26.402, P< 0.001)were easier to develop into severe dysplasia than adenomas whose sizes were less than 10 mm or tubular and serrated adenomas.Also, flat adenomas was easier to develop into severe dysplasia than protruding adenomas (OR:0.582,95%CI: 0.379-0.894, P=0.013). Risk factors of flat adenomas developing into severe dysplasia were related to sizes and Pathology of adenomas. Flat adenomas whose sizes were more than 10 mm or which contained villous structure were prone to develop into severe dysplasia.2^ Among the 2093 patients, "missed" adenomas were observed in 560, and thus the overall "per-patient" adenoma miss rate (AMR) was 26.8%. Accordingly, the "per-patient" AMR were 43.3%(299/691) in patients with flat adenomas. The "per-patient" AMR was 18.6%(261/1402) for those with only protruding adenomas, which was significantly lower than that in those with flat adenomas (χ2= 143.566, P <0.001).Among the 4632 adenomas,967 were missed at the first colonoscopy, and thus the overall "per-adenoma" AMR was 20.9%.Accordingly, the "per-adenoma" AMRs were 44.3%(406/916) and 15.1%(561/3716), respectively, for flat and protruding adenomas (x2=380.002, P<0.001).The "per-patient" and "per-adenoma" AMRs for advanced flat adenomas were 11.0% and 11.7%, respectively.In univariate analysis, older age, presence of concomitant protruding adenomas, poor bowel preparation, smaller size of adenoma, location at the right colon, tubular type, non-advanced adenoma, insufficient experience of the colonoscopist, double operative mode and withdrawal time<6 min were associated with an increased "per-adenoma" AMR for flat adenomas. In the multivariate analysis, all above factors, except for pathological type of adenomas, status of advanced adenoma, non-gastroenterology specialty and double operative mode were identified to be independently associated with an increased "per-adenoma" AMR for flat adenomasThe median "per-adenoma" AMRs for overall and flat adenomas obtained by different colonoscopists were 22.3%(interquartile range,18.37-26.35%) and 45.65% (interquartile range,34.48-60.83%). There was a moderate correlation between the miss rates in adenoma and in flat adenoma. The correlation coefficient was 0.516 (P <0.0001).3、Among the 16951 patients, adenomas were observed in 2938 patients. ADR was 17.3%(2938/16951).Flat adenomas were observed in 796 and FADR was 4.7%(796/16951). Among the 5052 adenomas, there were 1000 flat adenomas (19.8%) and 4052 protruding adenomas (80.2%). Laterally spreading tumor(LST) among flat adenomas was 17.5%(175/1000).In univariate analysis, patients’characteristics including age, history of adenomas, bowel preparation influenced detection rates of flat adenomas. FADR of patients over 60 years was 9.2%; FADR of patients with alarm symptoms was 5.4%; FADR of patients with history of adenomas was 13.1%; FADR of patients with good bowel preparation was 5.5%. Above-mentioned FADR was higher than control groups.There was similar FADR between male and female. FADR of proficient doctor who do colonoscopy> 1000 cases was 5.7%. FADR of one-person technique was 5.0%. FADR of withdrawal time≥6 min was 6.4%. Above-mentioned FADR was also higher than control groups. There was similar FADR between gastroenterologist and non-gastroenterologist.In the multivariate analysis, patient characteristics (including age, alarm symptoms,history of adenomas, bowel preparation) and endoscopists’characteristics (including proficiency, mode of colonoscopy and withdrawal time) was independent influence factors. Patients with over 60 years, alarm symptoms, history of adenomas or good bowel preparation and endoscopists who is proficient,do colonoscopy by one-person technique and withdraw colonoscopy over 6 min would help to detect flat adenomas which was significant.There was a moderate correlation between the total adenoma dectection rates and the flat adenoma dectection rates. The correlation coefficient was 0.666 (P< 0.001).Conclusions1、Flat adenoma is a major form of colorectal adenomas, which is located in the proximal colon. The percentage of villi structure and serrated adenoma in flat adenomas are higher. Flat adenomas were easier to develope into severe dysplasia,especially more than 10mm diameter and tissue containing villi structure.2、The miss rate for flat adenomas during colonoscopy is high. Patient’s age, concomitant protruding adenomas, bowel preparation, size and location of adenomas, proficiency of the colonoscopist, and withdrawal time are factors affecting the "per-adenoma" AMR for flat adenomas. There was a moderate correlation between the miss rates in adenoma and in flat adenoma.3、FADR on colonoscopy was 4.7%. Patients with over 60 years, alarm symptoms, history of adenomas or good bowel preparation and endoscopists who is proficient and withdraw colonoscopy over 6 min would help to detect flat adenomas. There was a moderate correlation between the total adenoma dectection rates and the flat adenoma dectection rates.