结肠镜检查中大肠肿瘤的漏诊、复发及结肠镜随访研究
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摘要
背景和目的
大肠癌是严重威胁人类健康的常见恶性肿瘤之一。在全球大肠癌发病率男女均居恶性肿瘤的第三位,死亡率居恶性肿瘤第四位。在中国,据不完全统计,大肠癌的发病率和死亡率分别居恶性肿瘤的第四位和第五位,且呈逐渐上升趋势。结肠镜对大肠肿瘤的筛查以及结肠镜下腺瘤的切除明显降低了大肠癌的发病率和死亡率,因而结肠镜检查也被公认为是检出大肠肿瘤的金标准。然而,在临床实践中却发现结肠镜检查中存在大肠息肉甚至是大肠癌的漏诊。尽管当前拟定了大肠息肉切除后结肠镜随访规范,但该规范是以大肠肿瘤自然生长史来确定随访时间,并没有考虑结肠镜检查中存在的大肠癌及其癌前病变即腺瘤的漏诊情况。而对于漏诊的腺瘤很可能在结肠镜随访间期发生恶变,导致在正常随访时间到来之前发展为浸润期癌,从而丧失了早诊早治的机会。而由于结肠镜检查中漏诊因素的存在以及内镜医师对结肠镜随访时间的不确定,同时患者又有恐癌心理的存在,因此多数患者及医生选择结肠镜检查后短时间再次结肠镜复查。此外,随着结直肠癌筛查的普及,特别是结肠镜筛查的迅猛增长,大量的腺瘤病人在筛查中被诊断。因此,随访的病人也越来越多。随访患者的增多及随访时间的缩短,一方面增加了患者的经济负担和检查并发症发生风险,另一方面对医疗资源也造成巨大浪费。如何对这些病人进行随访,如何能有效的提高结肠镜监测的效率,并且能降低投入、风险及不必要检查引发的资源过度利用是当前关于内镜下大肠腺瘤切除后结肠镜随访需解决的主要问题。当前少数西方国家根据自己国家人群的结肠镜随访研究结果提出了符合自己人群的结肠镜随访规范,其随访时间明显延长,并建议根据病变特征以及患者特征对患者进行危险分层,随访时间因人而异。在我国目前还没有自己的结肠镜随访指南。而因人种、地域等的差别,大肠腺瘤或癌的发生、发展存在很大差异,国外的规范是否适合中国人群,有待进一步研究。因此,针对我国目前患者众多而内镜资源及内镜医生相对短缺的结肠镜检查现状,本研究的目的在于通过了解结肠镜检查中肿瘤的漏诊率和漏诊相关的危险因素以及腺瘤复发与随访时间的关系等,为进一步提高结肠镜检查质量以及制定合理的结肠镜随访规范奠定基础。
基于以上目的,本研究从以下几个方面对结肠镜检查中大肠肿瘤的漏诊和复发进行研究。
病人与方法
1.结肠镜检查中大肠腺瘤的漏诊率及漏诊相关危险因素
患者在初次结肠镜检查发现并切除腺瘤后120天内进行了结肠镜复查,回顾性分析患者两次结肠镜检查结果。记录两次结肠镜检查所见腺瘤的特征(包括大小、部位、形态、数目及病理)、患者临床特征(包括年龄、性别、结肠镜检查原因、腹部及盆腔手术史、大肠憩室病史及是否行无痛结肠镜检查)及执行检查的内镜操作医师。分析不同类型腺瘤在结肠镜检查中的漏诊率以及腺瘤特征、患者临床特征和内镜医师的操作水平对腺瘤漏诊的影响。
2.结直肠腺瘤切除后结肠镜随访间期癌的发生风险及原因
回顾性分析结肠镜下腺瘤切除后5年内至少接受一次结肠镜随访患者的内镜、病理及人口学资料,记录初次结肠镜检查患者年龄、性别、结肠镜检查原因及检查时间,以及结肠镜检查中所发现腺瘤的大小、数目、部位、形态及病理。记录随访结肠镜检查时间、检查原因以及随访中发现间期癌的大小、形态、部位及肿瘤病理分期。评价腺瘤患者腺瘤切除术后5年内发生随访间期癌的风险及原因。
3.结直肠腺瘤切除术后复发与结肠镜随访
回顾性分析1976年到2007年期间行内镜下结直肠腺瘤切除术并至少经历两次以上结肠镜随访患者的结肠镜检查资料。用Epidata软件建立数据库,记录结直肠腺瘤的大小、形态、数目、部位和病理等特征以及腺瘤患者的临床特征并录入数据库,通过Cox风险比例模型计算腺瘤或高危腺瘤复发的风险比和95%可信区间来分析不同类型腺瘤切除后任意腺瘤及高危腺瘤在不同时间的复发风险；根据初次结肠镜检查发现腺瘤的特征分析不同类型腺瘤内镜下切除后再发高危腺瘤的结肠镜随访时间间隔。
4. 50岁以上的结肠镜检查正常者5年后发生结直肠肿瘤的风险
回顾性分析南方医院消化内镜中心1990-2004年期间行结肠镜检查5年后接受结肠镜随访的患者资料。记录初次结肠镜检查及随访结肠镜检查发现腺瘤的特征,包括腺瘤的大小、数目、部位、形态及组织病理学结果,以及患者年龄、性别等特征。根据初次结肠镜检查结果对患者进行分类,通过计算5年后高危腺瘤的发生率及logistic回归相对危险度分析初次结肠镜检查正常者在检查后5年发生腺瘤或高危腺瘤的风险。
结果
1. 809例患者中271例发生腺瘤漏诊,两次结肠镜检查共检出腺瘤2134颗,漏诊腺瘤425颗,腺瘤总漏诊率为20%(425/2134)；平均患者腺瘤漏诊率为33%(271/809)。小于5mm、5.10mm和大于10mm腺瘤的漏诊率分别是35%、17%和7%。高危腺瘤和非高危腺瘤漏诊率分别是7%和25%。有蒂隆起型、广基隆起型和平坦型腺瘤的漏诊率也存在差异,分别为11%、25%和35%。而结肠不同解剖部位腺瘤漏诊率按照直肠、乙状结肠、降结肠、脾区、横结肠、肝曲及升结肠和盲肠分别为12%、22%、16%、17%、18%、27%和26%。
随着腺瘤体积的增大(腺瘤直径每增加1mm),腺瘤的漏诊率降低[优势比,(Odds Ratio, OR):0.84;95%可信区间(Confidence Interval, CI):0.80-0.87];乙状结肠(OR：2.02；95% CI：1.43-2.87)、肝曲(OR：1.95；95% CI：1.07-3.54)、盲肠和升结肠(OR：2.15；95% CI：1.45-3.17)部位的腺瘤以及平坦型腺瘤(OR：2.21；95% CI：1.64-2.97)容易漏诊；患者腺瘤数越多在结肠镜检查中腺瘤漏诊率越高[腺瘤数2个(OR：1.87；95%CI：1.24-2.82)；腺瘤数≥3个(OR：4.20；95%CI:2.84-6,21)]；初级内镜医师与有经验内镜医师相比,其漏诊率明显增加(OR：2.77；95%CI：1.93.3.97)；与已发现高危腺瘤相比,漏诊高危腺瘤的体积小,平均大小分别为15.9±6.9mm和10.9±4.0mm(p=0.000),且平坦型腺瘤的比例明显高于已发现高危腺瘤(χ2=11.96,p=0.001)。
2.在1794例腺瘤切除患者中,14例发生间期大肠癌,平均随访时间2.67年,平均发病密度2.9例／1000人年(14例／4778人年)。随访间期癌发生原因主要包括初次结肠镜下腺瘤切除不完整(50%)、结肠镜检查中漏诊(27%)及新发生癌(23%)。初次结肠镜检查高危腺瘤患者发生随访间期癌的风险明显高于非高危腺瘤患者(p=0.024)。间期癌患者年龄(59.6±8.9岁)显著高于未发生间期癌患者年龄(52.4±12.4岁)(p=0.030)。
3.6462例腺瘤患者中行腺瘤切除并符合研究设计结肠镜随访方案的患者1356例。其中初次结肠镜检查为高危腺瘤的患者642例,非高危腺瘤714例。高危腺瘤患者在腺瘤切除后1-3年、3-5年、5.10年和10-20年四个时间段内高危腺瘤的累计复发率分别是3.8%、13.1%、34.7%和52.0%,总的腺瘤复发率分别是32.6%、58.1%、75.8%和86.2%。而非高危腺瘤患者,高危腺瘤的累计复发率分别是0.9%、3.9%、5.8%和29.2%,总的腺瘤复发率为11.5%、28.9%、45.3%和62.5%。两种腺瘤在不同随访时间段复发高危腺瘤或任意腺瘤的累计风险均存在很大差异(p=0.000)。
男性[风险比(Hazard Ratio,HR):1.26；5%CI:1.01-1.57],年龄50-60岁(HR：1.69；95% CI：1.30-2.19)和年龄大于60岁(HR：2.97；95% CI:2.31.3.82),腺瘤大小10-19mm(HR：1.40；95% CI：1.05-1.87),腺瘤≥20mm(HR：1.49；95% CI：1.05-2.12),两个(HR：1.55；95% CI：1.18-2.05)或两个以上腺瘤(HR：1.90；95%CI：1.49-2.43),绒毛和管状绒毛状腺瘤(HR：1.38；95% CI：1.03-1.85),高级别瘤变(HR：1.28；95% CI：1.00-1.62)与腺瘤的复发显著相关。
男性(HR：2.11；95% CI：1.27-3.53),年龄50-60岁(HR：1.81；95% CI：1.05-3.12),年龄在60岁以上(HR：4.81；95% CI：2.80-8.25),两个(HR：1.92；95% CI：1.04-3.54)或两个以上腺瘤(HR：1.87；95% CI：1.12-3.10),,直径大于2cm的腺瘤(HR：2.35；95% CI：1.09-5.06,),管状绒毛状和绒毛状腺瘤(HR：2.57；95% CI：1.24-5.32),高级别瘤变(HR：1.61；95% CI：1.07-2.42)与腺瘤切除后高危腺瘤复发显著相关。
当在5%的随访患者中出现高危腺瘤时,低风险组患者(初次结肠镜检查只有1个非高危腺瘤的年龄小于50岁患者)的随访时间大概是6.9(95% CI：6.3-12.2)年,而高风险组患者(初次结肠镜检查有下列一个特征或多个特征的患者：年龄大于50岁,高危腺瘤,多发腺瘤)的随访时间大概是3.0(95% CI：2.7-3.2)年。若10%的随访患者最终发展为高危腺瘤,低风险组患者随访时间约为12.6(95%CI：8.5-14.5)年,高风险组的随访时间约为4.2(95%CI：3.5-5.0)年。而当随访患者中高危腺瘤复发患者达到20%时,低风险组和高风险组的随访时问分别约为15.0(95%CI：14.2-17.1)年和5.6(95%CI：5.0-6.3)年。
4.在1990-2004年期间共有480位年龄大于50岁的结肠镜检查者在初次结肠镜检查5年后接受了结肠镜随访检查。在480例随访患者中,147例(30.6%)随访中发现非高危腺瘤,30例(6.3%)发现高危腺瘤。在初次结肠镜检查正常患者中,5年后发生非高危腺瘤者77例(25.6%),发生高危腺瘤者5例5(1.7%)。对于初次结肠镜检查为非高危腺瘤患者,5年后随访34例(37.8%)复发非高危腺瘤,4例(4.4%)发生高危腺瘤。而初次结肠镜检查为高危腺瘤的患者,5年后复发非高危腺瘤和高危腺瘤分别为36例(40.4%)和2l例(23.6%),1例患者发现浸润型癌。结肠镜检查正常者和非高危腺瘤患者随访中未发现癌。
90例初次结肠镜检查非高危腺瘤患者5年后随访38例(42.2%)复发腺瘤,与初次结肠镜检查正常者301例中82例(27.3%)复发腺瘤相比,腺瘤复发风险增加[相对危险度(Relative Risk, RR) 1.79; 95% CI:1.04-3.10]。初次结肠镜检查89例高危腺瘤患者中57例(64.0%)复发腺瘤,与结肠镜检查正常者相比,腺瘤复发风险明显增加(RR：4.48；95% CI：2.55-7.86)。男性、年龄以及三个或三个以上腺瘤是5年后随访中发生腺瘤的独立危险因素。
89例高危腺瘤患者中21例(23.%)在5年后的随访中发生高危腺瘤,与初次结肠镜检查正常者1.7%的发生率进行比较,复发高危腺瘤的风险明显增加(RR：14.11；95% CI：4.51-44.12)。男性、年龄以及腺瘤数目是5年后随访中发生高危腺瘤的独立危险因素。初次结肠镜检查非高危腺瘤并不是5年后复发高危腺瘤的危险因素(RR：1.85,95% CI：0.43-7.89)。
结论
1.结肠镜检查中存在部分腺瘤漏诊；腺瘤漏诊与腺瘤大小、形态、部位、数目以及结肠镜检查操作医师密切相关。
2.腺瘤患者在腺瘤切除术后5年内,随访间期大肠癌平均发病密度约2.9例/1000人年；大部分间期大肠癌来源于结肠镜检查漏诊或不完整切除,通过改善内镜检查治疗技术,以及有效的结肠镜随访等是可以避免的。
3.结直肠腺瘤切除术后腺瘤或高危腺瘤的累计复发率随随访时间的延长而增加；初次结肠镜检查腺瘤大小、数目和病理特征以及患者年龄、性别是腺瘤或高危腺瘤复发的危险因素；复发高危腺瘤的高风险患者和低风险患者可能至少分别在3年和6.9年进行结肠镜随访是安全的。
4. 50岁以上结肠镜检查正常者5年后发生结直肠肿瘤的风险很低,因此,对于该类人群可能至少在5年后随访是安全的。
Background and Aims
Colorectal 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 Methods
1. The rate and risk factors of missed diagnosis for colorectal adenoma during colonoscopy
Patients 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 polypectomy
Data 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.
Results
1. 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).
Conclusions
1. 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.
大肠癌是严重威胁人类健康的常见恶性肿瘤之一。在全球大肠癌发病率男女均居恶性肿瘤的第三位,死亡率居恶性肿瘤第四位。在中国,据不完全统计,大肠癌的发病率和死亡率分别居恶性肿瘤的第四位和第五位,且呈逐渐上升趋势。结肠镜对大肠肿瘤的筛查以及结肠镜下腺瘤的切除明显降低了大肠癌的发病率和死亡率,因而结肠镜检查也被公认为是检出大肠肿瘤的金标准。然而,在临床实践中却发现结肠镜检查中存在大肠息肉甚至是大肠癌的漏诊。尽管当前拟定了大肠息肉切除后结肠镜随访规范,但该规范是以大肠肿瘤自然生长史来确定随访时间,并没有考虑结肠镜检查中存在的大肠癌及其癌前病变即腺瘤的漏诊情况。而对于漏诊的腺瘤很可能在结肠镜随访间期发生恶变,导致在正常随访时间到来之前发展为浸润期癌,从而丧失了早诊早治的机会。而由于结肠镜检查中漏诊因素的存在以及内镜医师对结肠镜随访时间的不确定,同时患者又有恐癌心理的存在,因此多数患者及医生选择结肠镜检查后短时间再次结肠镜复查。此外,随着结直肠癌筛查的普及,特别是结肠镜筛查的迅猛增长,大量的腺瘤病人在筛查中被诊断。因此,随访的病人也越来越多。随访患者的增多及随访时间的缩短,一方面增加了患者的经济负担和检查并发症发生风险,另一方面对医疗资源也造成巨大浪费。如何对这些病人进行随访,如何能有效的提高结肠镜监测的效率,并且能降低投入、风险及不必要检查引发的资源过度利用是当前关于内镜下大肠腺瘤切除后结肠镜随访需解决的主要问题。当前少数西方国家根据自己国家人群的结肠镜随访研究结果提出了符合自己人群的结肠镜随访规范,其随访时间明显延长,并建议根据病变特征以及患者特征对患者进行危险分层,随访时间因人而异。在我国目前还没有自己的结肠镜随访指南。而因人种、地域等的差别,大肠腺瘤或癌的发生、发展存在很大差异,国外的规范是否适合中国人群,有待进一步研究。因此,针对我国目前患者众多而内镜资源及内镜医生相对短缺的结肠镜检查现状,本研究的目的在于通过了解结肠镜检查中肿瘤的漏诊率和漏诊相关的危险因素以及腺瘤复发与随访时间的关系等,为进一步提高结肠镜检查质量以及制定合理的结肠镜随访规范奠定基础。
基于以上目的,本研究从以下几个方面对结肠镜检查中大肠肿瘤的漏诊和复发进行研究。
病人与方法
1.结肠镜检查中大肠腺瘤的漏诊率及漏诊相关危险因素
患者在初次结肠镜检查发现并切除腺瘤后120天内进行了结肠镜复查,回顾性分析患者两次结肠镜检查结果。记录两次结肠镜检查所见腺瘤的特征(包括大小、部位、形态、数目及病理)、患者临床特征(包括年龄、性别、结肠镜检查原因、腹部及盆腔手术史、大肠憩室病史及是否行无痛结肠镜检查)及执行检查的内镜操作医师。分析不同类型腺瘤在结肠镜检查中的漏诊率以及腺瘤特征、患者临床特征和内镜医师的操作水平对腺瘤漏诊的影响。
2.结直肠腺瘤切除后结肠镜随访间期癌的发生风险及原因
回顾性分析结肠镜下腺瘤切除后5年内至少接受一次结肠镜随访患者的内镜、病理及人口学资料,记录初次结肠镜检查患者年龄、性别、结肠镜检查原因及检查时间,以及结肠镜检查中所发现腺瘤的大小、数目、部位、形态及病理。记录随访结肠镜检查时间、检查原因以及随访中发现间期癌的大小、形态、部位及肿瘤病理分期。评价腺瘤患者腺瘤切除术后5年内发生随访间期癌的风险及原因。
3.结直肠腺瘤切除术后复发与结肠镜随访
回顾性分析1976年到2007年期间行内镜下结直肠腺瘤切除术并至少经历两次以上结肠镜随访患者的结肠镜检查资料。用Epidata软件建立数据库,记录结直肠腺瘤的大小、形态、数目、部位和病理等特征以及腺瘤患者的临床特征并录入数据库,通过Cox风险比例模型计算腺瘤或高危腺瘤复发的风险比和95%可信区间来分析不同类型腺瘤切除后任意腺瘤及高危腺瘤在不同时间的复发风险；根据初次结肠镜检查发现腺瘤的特征分析不同类型腺瘤内镜下切除后再发高危腺瘤的结肠镜随访时间间隔。
4. 50岁以上的结肠镜检查正常者5年后发生结直肠肿瘤的风险
回顾性分析南方医院消化内镜中心1990-2004年期间行结肠镜检查5年后接受结肠镜随访的患者资料。记录初次结肠镜检查及随访结肠镜检查发现腺瘤的特征,包括腺瘤的大小、数目、部位、形态及组织病理学结果,以及患者年龄、性别等特征。根据初次结肠镜检查结果对患者进行分类,通过计算5年后高危腺瘤的发生率及logistic回归相对危险度分析初次结肠镜检查正常者在检查后5年发生腺瘤或高危腺瘤的风险。
结果
1. 809例患者中271例发生腺瘤漏诊,两次结肠镜检查共检出腺瘤2134颗,漏诊腺瘤425颗,腺瘤总漏诊率为20%(425/2134)；平均患者腺瘤漏诊率为33%(271/809)。小于5mm、5.10mm和大于10mm腺瘤的漏诊率分别是35%、17%和7%。高危腺瘤和非高危腺瘤漏诊率分别是7%和25%。有蒂隆起型、广基隆起型和平坦型腺瘤的漏诊率也存在差异,分别为11%、25%和35%。而结肠不同解剖部位腺瘤漏诊率按照直肠、乙状结肠、降结肠、脾区、横结肠、肝曲及升结肠和盲肠分别为12%、22%、16%、17%、18%、27%和26%。
随着腺瘤体积的增大(腺瘤直径每增加1mm),腺瘤的漏诊率降低[优势比,(Odds Ratio, OR):0.84;95%可信区间(Confidence Interval, CI):0.80-0.87];乙状结肠(OR：2.02；95% CI：1.43-2.87)、肝曲(OR：1.95；95% CI：1.07-3.54)、盲肠和升结肠(OR：2.15；95% CI：1.45-3.17)部位的腺瘤以及平坦型腺瘤(OR：2.21；95% CI：1.64-2.97)容易漏诊；患者腺瘤数越多在结肠镜检查中腺瘤漏诊率越高[腺瘤数2个(OR：1.87；95%CI：1.24-2.82)；腺瘤数≥3个(OR：4.20；95%CI:2.84-6,21)]；初级内镜医师与有经验内镜医师相比,其漏诊率明显增加(OR：2.77；95%CI：1.93.3.97)；与已发现高危腺瘤相比,漏诊高危腺瘤的体积小,平均大小分别为15.9±6.9mm和10.9±4.0mm(p=0.000),且平坦型腺瘤的比例明显高于已发现高危腺瘤(χ2=11.96,p=0.001)。
2.在1794例腺瘤切除患者中,14例发生间期大肠癌,平均随访时间2.67年,平均发病密度2.9例／1000人年(14例／4778人年)。随访间期癌发生原因主要包括初次结肠镜下腺瘤切除不完整(50%)、结肠镜检查中漏诊(27%)及新发生癌(23%)。初次结肠镜检查高危腺瘤患者发生随访间期癌的风险明显高于非高危腺瘤患者(p=0.024)。间期癌患者年龄(59.6±8.9岁)显著高于未发生间期癌患者年龄(52.4±12.4岁)(p=0.030)。
3.6462例腺瘤患者中行腺瘤切除并符合研究设计结肠镜随访方案的患者1356例。其中初次结肠镜检查为高危腺瘤的患者642例,非高危腺瘤714例。高危腺瘤患者在腺瘤切除后1-3年、3-5年、5.10年和10-20年四个时间段内高危腺瘤的累计复发率分别是3.8%、13.1%、34.7%和52.0%,总的腺瘤复发率分别是32.6%、58.1%、75.8%和86.2%。而非高危腺瘤患者,高危腺瘤的累计复发率分别是0.9%、3.9%、5.8%和29.2%,总的腺瘤复发率为11.5%、28.9%、45.3%和62.5%。两种腺瘤在不同随访时间段复发高危腺瘤或任意腺瘤的累计风险均存在很大差异(p=0.000)。
男性[风险比(Hazard Ratio,HR):1.26；5%CI:1.01-1.57],年龄50-60岁(HR：1.69；95% CI：1.30-2.19)和年龄大于60岁(HR：2.97；95% CI:2.31.3.82),腺瘤大小10-19mm(HR：1.40；95% CI：1.05-1.87),腺瘤≥20mm(HR：1.49；95% CI：1.05-2.12),两个(HR：1.55；95% CI：1.18-2.05)或两个以上腺瘤(HR：1.90；95%CI：1.49-2.43),绒毛和管状绒毛状腺瘤(HR：1.38；95% CI：1.03-1.85),高级别瘤变(HR：1.28；95% CI：1.00-1.62)与腺瘤的复发显著相关。
男性(HR：2.11；95% CI：1.27-3.53),年龄50-60岁(HR：1.81；95% CI：1.05-3.12),年龄在60岁以上(HR：4.81；95% CI：2.80-8.25),两个(HR：1.92；95% CI：1.04-3.54)或两个以上腺瘤(HR：1.87；95% CI：1.12-3.10),,直径大于2cm的腺瘤(HR：2.35；95% CI：1.09-5.06,),管状绒毛状和绒毛状腺瘤(HR：2.57；95% CI：1.24-5.32),高级别瘤变(HR：1.61；95% CI：1.07-2.42)与腺瘤切除后高危腺瘤复发显著相关。
当在5%的随访患者中出现高危腺瘤时,低风险组患者(初次结肠镜检查只有1个非高危腺瘤的年龄小于50岁患者)的随访时间大概是6.9(95% CI：6.3-12.2)年,而高风险组患者(初次结肠镜检查有下列一个特征或多个特征的患者：年龄大于50岁,高危腺瘤,多发腺瘤)的随访时间大概是3.0(95% CI：2.7-3.2)年。若10%的随访患者最终发展为高危腺瘤,低风险组患者随访时间约为12.6(95%CI：8.5-14.5)年,高风险组的随访时间约为4.2(95%CI：3.5-5.0)年。而当随访患者中高危腺瘤复发患者达到20%时,低风险组和高风险组的随访时问分别约为15.0(95%CI：14.2-17.1)年和5.6(95%CI：5.0-6.3)年。
4.在1990-2004年期间共有480位年龄大于50岁的结肠镜检查者在初次结肠镜检查5年后接受了结肠镜随访检查。在480例随访患者中,147例(30.6%)随访中发现非高危腺瘤,30例(6.3%)发现高危腺瘤。在初次结肠镜检查正常患者中,5年后发生非高危腺瘤者77例(25.6%),发生高危腺瘤者5例5(1.7%)。对于初次结肠镜检查为非高危腺瘤患者,5年后随访34例(37.8%)复发非高危腺瘤,4例(4.4%)发生高危腺瘤。而初次结肠镜检查为高危腺瘤的患者,5年后复发非高危腺瘤和高危腺瘤分别为36例(40.4%)和2l例(23.6%),1例患者发现浸润型癌。结肠镜检查正常者和非高危腺瘤患者随访中未发现癌。
90例初次结肠镜检查非高危腺瘤患者5年后随访38例(42.2%)复发腺瘤,与初次结肠镜检查正常者301例中82例(27.3%)复发腺瘤相比,腺瘤复发风险增加[相对危险度(Relative Risk, RR) 1.79; 95% CI:1.04-3.10]。初次结肠镜检查89例高危腺瘤患者中57例(64.0%)复发腺瘤,与结肠镜检查正常者相比,腺瘤复发风险明显增加(RR：4.48；95% CI：2.55-7.86)。男性、年龄以及三个或三个以上腺瘤是5年后随访中发生腺瘤的独立危险因素。
89例高危腺瘤患者中21例(23.%)在5年后的随访中发生高危腺瘤,与初次结肠镜检查正常者1.7%的发生率进行比较,复发高危腺瘤的风险明显增加(RR：14.11；95% CI：4.51-44.12)。男性、年龄以及腺瘤数目是5年后随访中发生高危腺瘤的独立危险因素。初次结肠镜检查非高危腺瘤并不是5年后复发高危腺瘤的危险因素(RR：1.85,95% CI：0.43-7.89)。
结论
1.结肠镜检查中存在部分腺瘤漏诊；腺瘤漏诊与腺瘤大小、形态、部位、数目以及结肠镜检查操作医师密切相关。
2.腺瘤患者在腺瘤切除术后5年内,随访间期大肠癌平均发病密度约2.9例/1000人年；大部分间期大肠癌来源于结肠镜检查漏诊或不完整切除,通过改善内镜检查治疗技术,以及有效的结肠镜随访等是可以避免的。
3.结直肠腺瘤切除术后腺瘤或高危腺瘤的累计复发率随随访时间的延长而增加；初次结肠镜检查腺瘤大小、数目和病理特征以及患者年龄、性别是腺瘤或高危腺瘤复发的危险因素；复发高危腺瘤的高风险患者和低风险患者可能至少分别在3年和6.9年进行结肠镜随访是安全的。
4. 50岁以上结肠镜检查正常者5年后发生结直肠肿瘤的风险很低,因此,对于该类人群可能至少在5年后随访是安全的。
Background and Aims
Colorectal 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 Methods
1. The rate and risk factors of missed diagnosis for colorectal adenoma during colonoscopy
Patients 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 polypectomy
Data 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.
Results
1. 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).
Conclusions
1. 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.
引文
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[20]Jarvinen HJ, Mecklin JP, Sistonen P. Screening reduces colorectal cancer rate in families with hereditary nonpolyposis colorectal cancer. Gastroenterology 1995;108:1405-11.
[21]Lanspa SJ, Jenkins JX, Cavalieri RJ, et al. Surveillance in Lynch syndrome: how aggressive? Am J Gastroenterol 1994;89:1978-80.
[22]Atkin WS, Morson BC, Cuzick J. Long-term risk of colorectal cancer after excision of rectosigmoid adenomas. N Engl J Med 1992;326:658-62.
[23]Leung K, Pinsky P, Laiyemo AO, et al. Ongoing colorectal cancer risk despite surveillance colonoscopy:the Polyp Prevention Trial Continued Follow-up Study. Gastrointest Endosc 2010;71:111-7.
[1]Zheng Shu, Cai S. Colorectal cancer epidemiology and prevention study in China. The Chinese-German Journal of Clinical Oncology 2003;2:72-75.
[2]Winawer SJ, Zauber AG, O'Brien MJ, et al. Randomized comparison of surveillance intervals after colonoscopic removal of newly diagnosed adenomatous polyps. The National Polyp Study Workgroup. N Engl J Med 1993;328:901-906.
[3]Winawer SJ, Zauber AG, Ho MN, et al. Prevention of colorectal cancer by colonoscopic polypectomy. The National Polyp Study Workgroup. N Engl J Med 1993;329:1977-1981.
[4]Winawer SJ, Zauber AG, Fletcher RH, et al. Guidelines for colonoscopy surveillance after polypectomy:a consensus update by the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society. CA Cancer J Clin 2006;56:143-159; quiz 184-145.
[5]Rex DK, Kahi CJ, Levin B, et al. Guidelines for colonoscopy surveillance after cancer resection:a consensus update by the American Cancer Society and the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology 2006;130:1865-1871.
[6]Martinez ME, Sampliner R, Marshall JR, et al. Adenoma characteristics as risk factors for recurrence of advanced adenomas. Gastroenterology 2001;120:1077-1083.
[7]Schatzkin A, Lanza E, Corle D, et al. Lack of effect of a low-fat, high-fiber diet on the recurrence of colorectal adenomas. Polyp Prevention Trial Study Group. N Engl J Med 2000;342:1149-1155.
[8]Baron JA, Cole BF, Sandler RS, et al. A randomized trial of aspirin to prevent colorectal adenomas. N Engl J Med 2003;348:891-899.
[9]Lieberman DA, Weiss DG, Harford WV, et al. Five-year colon surveillance after screening colonoscopy. Gastroenterology 2007;133:1077-1085.
[10]Pabby A, Schoen RE, Weissfeld JL, et al. Analysis of colorectal cancer occurrence during surveillance colonoscopy in the dietary Polyp Prevention Trial. Gastrointest Endosc 2005;61:385-391.
[11]Bressler B, Paszat LF, Chen Z, et al. Rates of new or missed colorectal cancers after colonoscopy and their risk factors:a population-based analysis. Gastroenterology 2007;132:96-102.
[12]Leung K, Pinsky P, Laiyemo AO, et al. Ongoing colorectal cancer risk despite surveillance colonoscopy:the Polyp Prevention Trial Continued Follow-up Study. Gastrointest Endosc 2010;71:111-117.
[13]Heresbach D, Barrioz T, Lapalus MG, et al. Miss rate for colorectal neoplastic polyps:a prospective multicenter study of back-to-back video colonoscopies. Endoscopy 2008;40:284-290.
[14]Rijn JC, Reitsma JB, Stoker J, et al. Polyp miss rate determined by tandem colonoscopy:a systematic review. Am J Gastroenterol 2006;101:343-350.
[15]Winawer SJ, Zauber AG. Colonoscopic polypectomy and the incidence of colorectal cancer. Gut 2001;48:753-754.
[16]Hamilton SR, Vogelstein B, Kudo S. Carcinoma of the colon and rectum. In: Hamilton SR, Altonen IA eds, Tumours of the digestive system WHO classification of tumors. Lyon:IARC Press; 2000:pp.113-114.
[17]Sauerbrei w. The use of resampling methods to simpify regression molels in medical statistics. Appl Stat 1999;48:313-329.
[18]Hsu CH, Long Q, Alberts DS. Estimation of colorectal adenoma recurrence with dependent censoring. BMC Med Res Methodol 2009;9:66.
[19]Leung WK, Lau JY, Suen BY, et al. Repeat-screening colonoscopy 5 years after normal baseline-screening colonoscopy in average-risk Chinese:a prospective study. Am J Gastroenterol 2009;104:2028-2034.
[20]Imperiale TF, Glowinski EA, Lin-Cooper C, et al. Five-year risk of colorectal neoplasia after negative screening colonoscopy. N Engl J Med 2008;359:1218-1224.
[21]Noshirwani KC, van Stolk RU, Rybicki LA, Beck GJ. Adenoma size and number are predictive of adenoma recurrence:implications for surveillance colonoscopy. Gastrointest Endosc 2000;51:433-437.
[22]Nusko G, Mansmann U, Kirchner T, Hahn EG. Risk related surveillance following colorectal polypectomy. Gut 2002;51:424-428.
[23]Bertario L, Russo A, Sala P, et al. Predictors of metachronous colorectal neoplasms in sporadic adenoma patients. Int J Cancer 2003;105:82-87.
[24]Laiyemo AO, Murphy G, Albert PS, et al. Postpolypectomy colonoscopy surveillance guidelines:predictive accuracy for advanced adenoma at 4 years. Ann Intern Med 2008;148:419-426.
[25]Loeve F, van Ballegooijen M, Boer R, Kuipers EJ, Habbema JD. Colorectal cancer risk in adenoma patients:a nation-wide study. Int J Cancer 2004;111:147-151.
[26]Martinez ME, Baron JA, Lieberman DA, et al. A pooled analysis of advanced colorectal neoplasia diagnoses after colonoscopic polypectomy. Gastroenterology 2009;136:832-841.
[27]Rex DK, Cutler CS, Lemmel GT, et al. Colonoscopic miss rates of adenomas determined by back-to-back colonoscopies. Gastroenterology 1997;112:24-28.
[28]Pinsky PF, Schoen RE, Weissfeld JL, et al. The yield of surveillance colonoscopy by adenoma history and time to examination. Clin Gastroenterol Hepatol 2009;7:86-92.
[29]Chlebowski RT, Wactawski-Wende J, Ritenbaugh C, et al. Estrogen plus progestin and colorectal cancer in postmenopausal women. N Engl J Med 2004;350:991-1004.
[30].Zisman AL, Nickolov A, Brand RE, Gorchow A, Roy HK. Associations between the age at diagnosis and location of colorectal cancer and the use of alcohol and tobacco:implications for screening. Arch Intern Med 2006;166:629-634.
[31]Paskett ED, Reeves KW, Pineau B, et al. The association between cigarette smoking and colorectal polyp recurrence (United States). Cancer Causes Control 2005;16:1021-1033.
[32]Reid ME, Marshall JR, Roe D, et al. Smoking exposure as a risk factor for prevalent and recurrent colorectal adenomas. Cancer Epidemiol Biomarkers Prev 2003;12:1006-1011.
[33]Fossi S, Bazzoli F, Ricciardiello L, et al. Incidence and recurrence rates of colorectal adenomas in first-degree asymptomatic relatives of patients with colon cancer. Am J Gastroenterol 2001;96:1601-1604.
[34]Wallace K, Baron JA, Karagas MR, et al. The association of physical activity and body mass index with the risk of large bowel polyps. Cancer Epidemiol Biomarkers Prev 2005;14:2082-2086.
[1]Winawer SJ, Zauber AG, Ho MN, et al. Prevention of colorectal cancer by colonoscopic polypectomy. The National Polyp Study Workgroup. N Engl J Med 1993;329:1977-1981.
[2]Newcomb PA, Storer BE, Morimoto LM, Templeton A, Potter JD. Long-term efficacy of sigmoidoscopy in the reduction of colorectal cancer incidence. J Natl Cancer Inst 2003;95:622-625.
[3]Muller AD, Sonnenberg A. Prevention of colorectal cancer by flexible endoscopy and polypectomy. A case-control study of 32,702 veterans. Ann Intern Med 1995;123:904-910.
[4]Farrar WD, Sawhney MS, Nelson DB, Lederle FA, Bond JH. Colorectal cancers found after a complete colonoscopy. Clin Gastroenterol Hepatol 2006;4:1259-1264.
[5]Lieberman DA, Weiss DG, Harford WV, et al. Five-year colon surveillance after screening colonoscopy. Gastroenterology 2007;133:1077-1085.
[6]Moss SM, Hardcastle JD, Coleman DA, Robinson MH, Rodrigues VC. Interval cancers in a randomized controlled trial of screening for colorectal cancer using a faecal occult blood test. Int J Epidemiol 1999;28:386-390.
[7]Pabby A, Schoen RE, Weissfeld JL, et al. Analysis of colorectal cancer occurrence during surveillance colonoscopy in the dietary Polyp Prevention Trial. Gastrointest Endosc 2005;61:385-391.
[8]Robertson DJ, Greenberg ER, Beach M, et al. Colorectal cancer in patients under close colonoscopic surveillance. Gastroenterology 2005;129:34-41.
[9]Leung K, Pinsky P, Laiyemo AO, et al. Ongoing colorectal cancer risk despite surveillance colonoscopy:the Polyp Prevention Trial Continued Follow-up Study. Gastrointest Endosc 2009.
[10]Winawer SJ, Zauber AG, Fletcher RH, et al. Guidelines for colonoscopy surveillance after polypectomy:a consensus update by the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society. CA Cancer J Clin 2006;56:143-159;quiz 184-145.
[11]Brenner H, Chang-Claude J, Seiler CM, Sturmer T, Hoffmeister M. Case-control study supports extension of surveillance interval after colonoscopic polypectomy to at least 5 yr. Am J Gastroenterol 2007; 102: 1739-1744.
[12]Laiyemo AO, Murphy G, Albert PS, et al. Postpolypectomy colonoscopy surveillance guidelines:predictive accuracy for advanced adenoma at 4 years. Ann Intern Med 2008;148:419-426.
[13]Atkin WS, Morson BC, Cuzick J. Long-term risk of colorectal cancer after excision of rectosigmoid adenomas. N Engl J Med 1992;326:658-662.
[14]Stolk RU, Beck GJ, Baron JA, Haile R, Summers R. Adenoma characteristics at first colonoscopy as predictors of adenoma recurrence and characteristics at follow-up. The Polyp Prevention Study Group. Gastroenterology 1998;115:13-18.
[15]Noshirwani KC, van Stolk RU, Rybicki LA, Beck GJ. Adenoma size and number are predictive of adenoma recurrence:implications for surveillance colonoscopy. Gastrointest Endosc 2000;51:433-437.
[16]Imperiale TF, Glowinski EA, Lin-Cooper C, et al. Five-year risk of colorectal neoplasia after negative screening colonoscopy. N Engl J Med 2008; 359:1218-1224.
[17]Leung WK, Lau JY, Suen BY, et al. Repeat-screening colonoscopy 5 years after normal baseline-screening colonoscopy in average-risk chinese:a prospective study. Am J Gastroenterol 2009;104:2028-2034.
[18]Winawer SJ, Zauber AG. Colonoscopic polypectomy and the incidence of colorectal cancer. Gut 2001;48:753-754.
[19]Brenner H, Chang-Claude J, Seiler CM, Sturmer T, Hoffmeister M. Does a negative screening colonoscopy ever need to be repeated? Gut 2006;55:1145-1150.
[20]Singh H, Turner D, Xue L, Targownik LE, Bernstein CN. Risk of developing colorectal cancer following a negative colonoscopy examination:evidence for a 10-year interval between colonoscopies. JAMA 2006;295:2366-2373.
[21]Schatzkin A, Lanza E, Corle D, et al. Lack of effect of a low-fat, high-fiber diet on the recurrence of colorectal adenomas. Polyp Prevention Trial Study Group. N Engl J Med 2000;342:1149-1155.
[22]Sansbury LB, Wanke K, Albert PS, et al. The effect of strict adherence to a high-fiber, high-fruit and -vegetable, and low-fat eating pattern on adenoma recurrence. Am J Epidemiol 2009;170:576-584.
[23]Regula J, Rupinski M, Kraszewska E, et al. Colonoscopy in colorectal-cancer screening for detection of advanced neoplasia. N Engl J Med 2006; 355:1863-1872.
[24]Martinez ME, Baron JA, Lieberman DA, et al. A pooled analysis of advanced colorectal neoplasia diagnoses after colonoscopic polypectomy. Gastroenterology 2009;136:832-841.
[25]Pinsky PF, Schoen RE, Weissfeld JL, et al. The yield of surveillance colonoscopy by adenoma history and time to examination. Clin Gastroenterol Hepatol 2009;7:86-92.
[26]Fossi S, Bazzoli F, Ricciardiello L, et al. Incidence and recurrence rates of colorectal adenomas in first-degree asymptomatic relatives of patients with colon cancer. Am J Gastroenterol 2001;96:1601-1604.
[27]Reid ME, Marshall JR, Roe D, et al. Smoking exposure as a risk factor for prevalent and recurrent colorectal adenomas. Cancer Epidemiol Biomarkers Prev 2003;12:1006-1011.
[28]Wallace K, Baron JA, Karagas MR, et al. The association of physical activity and body mass index with the risk of large bowel polyps. Cancer Epidemiol Biomarkers Prev 2005;14:2082-2086.
[2]Baron JA, Cole BF, Mott L, et al. Neoplastic and antineoplastic effects of beta-carotene on colorectal adenoma recurrence:results of a randomized trial. J Natl Cancer Inst 2003;95:717-722.
[3]Morson B. President's address. The polyp-cancer sequence in the large bowel. Proc R Soc Med 1974;67:451-457.
[4]Pignone M, Rich M, Teutsch SM, er al. Screening for colorectal cancer in adults at average risk:a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2002;137:132-141.
[5]Winawer SJ, Zauber AG, Fletcher RH, et al. Guidelines for colonoscopy surveillance after polypectomy:a consensus update by the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society. CA Cancer J Clin 2006;56:143-159; quiz 184-145.
[6]Winawer SJ, Zauber AG, Ho MN, et al. Prevention of colorectal cancer by colonoscopic polypectomy. The National Polyp Study Workgroup. N Engl J Med 1993;329:1977-1981.
[7]Pabby A, Schoen RE, Weissfeld JL, et al. Analysis of colorectal cancer occurrence during surveillance colonoscopy in the dietary Polyp Prevention Trial. Gastrointest Endosc 2005;61:385-391.
[8]Laiyemo AO, Murphy G, Albert PS, et al. Postpolypectomy colonoscopy surveillance guidelines:predictive accuracy for advanced adenoma at 4 years. Ann Intern Med 2008;148:419-426.
[9]Brenner H, Chang-Claude J, Seiler CM, Sturmer T, Hoffmeister M. Case-control study supports extension of surveillance interval after colonoscopic polypectomy to at least 5 yr. Am J Gastroenterol 2007; 102:1739-1744.
[10]Lieberman DA, Weiss DG, Harford WV, et al. Five-year colon surveillance after screening colonoscopy. Gastroenterology 2007;133:1077-1085.
[1]Morson B. President's address. The polyp-cancer sequence in the large bowel. Proc R Soc Med 1974;67:451-457.
[2]Pignone M, Rich M, Teutsch SM, et al. Screening for colorectal cancer in adults at average risk:a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2002;137:132-141.
[3]Winawer SJ, Zauber AG, Fletcher RH, et al. Guidelines for colonoscopy surveillance after polypectomy:a consensus update by the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society. Gastroenterology 2006; 130:1872-1885.
[4]Winawer SJ, Zauber AG. Colonoscopic polypectomy and the incidence of colorectal cancer. Gut 2001;48:753-754.
[5]Hamilton SR, Vogelstein B, Kudo S. Carcinoma of the colon and rectum. In: Hamilton SR, Altonen IA eds, Tumours of the digestive system WHO classification of tumors. Lyon:IARC Press; 2000:pp.113-114.
[6]Schlemper RJ, Riddell RH, Kato Y, et al. The Vienna classification of gastrointestinal epithelial neoplasia. Gut 2000;47:251-255.
[7]Dixon Mf. Gastrointestinal epithelial neoplasia: Vienna revisited. Gut 2002;51:130-131.
[8]Bensen S, Mott LA, Dain B, et al. The colonoscopic miss rate and true one-year recurrence of colorectal neoplastic polyps. Polyp Prevention Study Group. Am J Gastroenterol 1999;94:194-199.
[9]Kaltenbach T, Friedland S, Soetikno R. A randomised tandem colonoscopy trial of narrow band imaging versus white light examination to compare neoplasia miss rates. Gut 2008;57:1406-1412.
[10]Deenadayalu VP, Chadalawada V, Rex DK.170 degrees wide-angle colonoscope:effect on efficiency and miss rates. Am J Gastroenterol 2004;99:2138-2142.
[11]Harrison M, Singh N, Rex DK. Impact of proximal colon retroflexion on adenoma miss rates. Am J Gastroenterol 2004;99:519-522.
[12]Heresbach D, Barrioz T, Lapalus MG, et al. Miss rate for colorectal neoplastic polyps:a prospective multicenter study of back-to-back video colonoscopies. Endoscopy 2008;40:284-290.
[13]Lapalus MG, Helbert T, Napoleon B, et al. Does chromoendoscopy with structure enhancement improve the colonoscopic adenoma detection rate? Endoscopy 2006;38:444-448.
[14]Rex DK, Chadalawada V, Helper DJ. Wide angle colonoscopy with a prototype instrument:impact on miss rates and efficiency as determined by back-to-back colonoscopies. Am J Gastroenterol 2003;98:2000-2005.
[15]Stergiou N, Frenz MB, Menke D, Riphaus A, Wehrmann T. Reduction of miss rates of colonic adenomas by zoom chromoendoscopy. Int J Colorectal Dis 2006;21:560-565.
[16]Rijn JC, Reitsma JB, Stoker J, et al. Polyp miss rate determined by tandem colonoscopy: a systematic review. Am J Gastroenterol 2006; 101:343-350.
[17]Hofstad B, Vatn MH, Andersen SN, et al. Growth of colorectal polyps: redetection and evaluation of unresected polyps for a period of three years. Gut 1996;39:449-456.
[18]Rex DK, Cutler CS, Lemmel GT, et al. Colonoscopic miss rates of adenomas determined by back-to-back colonoscopies. Gastroenterology 1997; 112:24-28.
[19]Bressler B, Paszat LF, Chen Z, et al. Rates of new or missed colorectal cancers after colonoscopy and their risk factors:a population-based analysis. Gastroenterology 2007;132:96-102.
[20]Radaelli F, Meucci G, Sgroi G, Minoli G. Technical performance of colonoscopy: the key role of sedation/analgesia and other quality indicators. Am J Gastroenterol 2008;103:1122-1130.
[21]Huang Y, Liu S, Gong W, et al. Clinicopathologic features and endoscopic mucosal resection of laterally spreading tumors:experience from China. Int J Colorectal Dis 2009;24:1441-1450.
[22]姜泊,潘新颜,张亚历,等.内镜窄带成像与染色技术诊断大肠肿瘤的对比研究.中华消化内镜杂志2006；(23)：416—420.
[23]Kiesslich R, Neurath MF. Magnifying chromoendoscopy:Effective diagnostic tool for screening colonoscopy. Journal of Gastroenterology and Hepatology 2007;22:1700-1701.
[1]Mandel JS, Church TR, Bond JH, et al. The effect of fecal occult-blood screening on the incidence of colorectal cancer. N Engl J Med 2000;343:1603-7.
[2]Citarda F, Tomaselli G, Capocaccia R,et al. Efficacy in standard clinical practice of colonoscopic polypectomy in reducing colorectal cancer incidence. Gut 2001;48:812-5.
[3]Winawer SJ, Zauber AG, Ho MN, et al. Prevention of colorectal cancer by colonoscopic polypectomy. The National Polyp Study Workgroup. N Engl J Med 1993;329:1977-81.
[4]Martinez ME, Baron JA, Lieberman DA, et al. A pooled analysis of advanced colorectal neoplasia diagnoses after colonoscopic polypectomy. Gastroenterology 2009;136:832-41.
[5]Leung WK, Lau JY, Suen BY, et al. Repeat-screening colonoscopy 5 years after normal baseline-screening colonoscopy in average-risk Chinese:a prospective study. Am J Gastroenterol 2009;104:2028-34.
[6]Winawer SJ, Zauber AG. Colonoscopic polypectomy and the incidence of colorectal cancer. Gut 2001;48:753-4.
[7]Hamilton SR, Vogelstein B, Kudo S. Carcinoma of the colon and rectum. In: Hamilton SR, Altonen IA, eds. Tumours of the digestive system. WHO classification of tumors. Lyon:IARC Press,2000:pp.113-114.
[8]Pabby A, Schoen RE, Weissfeld JL, et al. Analysis of colorectal cancer occurrence during surveillance colonoscopy in the dietary Polyp Prevention Trial. Gastrointest Endosc 2005;61:385-91.
[9]Heresbach D, Barrioz T, Lapalus MG, et al. Miss rate for colorectal neoplastic polyps:a prospective multicenter study of back-to-back video colonoscopies. Endoscopy 2008;40:284-90.
[10]Huang Y, Liu S, Gong W, et al. Clinicopathologic features and endoscopic mucosal resection of laterally spreading tumors:experience from China. Int J Colorectal Dis 2009;24:1441-50.
[11]Robertson DJ, Greenberg ER, Beach M,et al. Colorectal cancer in patients under close colonoscopic surveillance. Gastroenterology 2005;129:34-41.
[12]Alberts DS, Martinez ME, Roe DJ, et al. Lack of effect of a high-fiber cereal supplement on the recurrence of colorectal adenomas. Phoenix Colon Cancer Prevention Physicians' Network. N Engl J Med 2000;342:11.56-62.
[13]Jorgensen OD, Kronborg 0, Fenger C. The Funen Adenoma Follow-up Study. Incidence and death from colorectal carcinoma in an adenoma surveillance program. Scand J Gastroenterol 1993;28:869-74.
[14]Winawer SJ, Zauber AG, O'Brien MJ, et al. Randomized comparison of surveillance intervals after colonoscopic removal of newly diagnosed adenomatous polyps. The National Polyp Study Workgroup. N Engl J Med 1993;328:901-6.
[15]Hotta K, Fujii T, Saito Y, Matsuda T. Local recurrence after endoscopic resection of colorectal tumors. Int J Colorectal Dis 2009;24:225-30.
[16]Bressler B, Paszat LF, Chen Z, et al. Rates of new or missed colorectal cancers after colonoscopy and their risk factors:a population-based analysis. Gastroenterology 2007;132:96-102.
[17]Rex DK. Still photography versus videotaping for documentation of cecal intubation:a prospective study. Gastrointest Endosc 2000;51:451-9.
[18]Marshall JB, Brown DN. Photodocumentation of total colonoscopy:how successful are endoscopists? Do reviewers agree? Gastrointest Endosc 1996;44:243-8.
[19]Winawer SJ, Fletcher RH, Miller L, et al. Colorectal cancer screening:clinical guidelines and rationale. Gastroenterology 1997;112:594-642.
[20]Jarvinen HJ, Mecklin JP, Sistonen P. Screening reduces colorectal cancer rate in families with hereditary nonpolyposis colorectal cancer. Gastroenterology 1995;108:1405-11.
[21]Lanspa SJ, Jenkins JX, Cavalieri RJ, et al. Surveillance in Lynch syndrome: how aggressive? Am J Gastroenterol 1994;89:1978-80.
[22]Atkin WS, Morson BC, Cuzick J. Long-term risk of colorectal cancer after excision of rectosigmoid adenomas. N Engl J Med 1992;326:658-62.
[23]Leung K, Pinsky P, Laiyemo AO, et al. Ongoing colorectal cancer risk despite surveillance colonoscopy:the Polyp Prevention Trial Continued Follow-up Study. Gastrointest Endosc 2010;71:111-7.
[1]Zheng Shu, Cai S. Colorectal cancer epidemiology and prevention study in China. The Chinese-German Journal of Clinical Oncology 2003;2:72-75.
[2]Winawer SJ, Zauber AG, O'Brien MJ, et al. Randomized comparison of surveillance intervals after colonoscopic removal of newly diagnosed adenomatous polyps. The National Polyp Study Workgroup. N Engl J Med 1993;328:901-906.
[3]Winawer SJ, Zauber AG, Ho MN, et al. Prevention of colorectal cancer by colonoscopic polypectomy. The National Polyp Study Workgroup. N Engl J Med 1993;329:1977-1981.
[4]Winawer SJ, Zauber AG, Fletcher RH, et al. Guidelines for colonoscopy surveillance after polypectomy:a consensus update by the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society. CA Cancer J Clin 2006;56:143-159; quiz 184-145.
[5]Rex DK, Kahi CJ, Levin B, et al. Guidelines for colonoscopy surveillance after cancer resection:a consensus update by the American Cancer Society and the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology 2006;130:1865-1871.
[6]Martinez ME, Sampliner R, Marshall JR, et al. Adenoma characteristics as risk factors for recurrence of advanced adenomas. Gastroenterology 2001;120:1077-1083.
[7]Schatzkin A, Lanza E, Corle D, et al. Lack of effect of a low-fat, high-fiber diet on the recurrence of colorectal adenomas. Polyp Prevention Trial Study Group. N Engl J Med 2000;342:1149-1155.
[8]Baron JA, Cole BF, Sandler RS, et al. A randomized trial of aspirin to prevent colorectal adenomas. N Engl J Med 2003;348:891-899.
[9]Lieberman DA, Weiss DG, Harford WV, et al. Five-year colon surveillance after screening colonoscopy. Gastroenterology 2007;133:1077-1085.
[10]Pabby A, Schoen RE, Weissfeld JL, et al. Analysis of colorectal cancer occurrence during surveillance colonoscopy in the dietary Polyp Prevention Trial. Gastrointest Endosc 2005;61:385-391.
[11]Bressler B, Paszat LF, Chen Z, et al. Rates of new or missed colorectal cancers after colonoscopy and their risk factors:a population-based analysis. Gastroenterology 2007;132:96-102.
[12]Leung K, Pinsky P, Laiyemo AO, et al. Ongoing colorectal cancer risk despite surveillance colonoscopy:the Polyp Prevention Trial Continued Follow-up Study. Gastrointest Endosc 2010;71:111-117.
[13]Heresbach D, Barrioz T, Lapalus MG, et al. Miss rate for colorectal neoplastic polyps:a prospective multicenter study of back-to-back video colonoscopies. Endoscopy 2008;40:284-290.
[14]Rijn JC, Reitsma JB, Stoker J, et al. Polyp miss rate determined by tandem colonoscopy:a systematic review. Am J Gastroenterol 2006;101:343-350.
[15]Winawer SJ, Zauber AG. Colonoscopic polypectomy and the incidence of colorectal cancer. Gut 2001;48:753-754.
[16]Hamilton SR, Vogelstein B, Kudo S. Carcinoma of the colon and rectum. In: Hamilton SR, Altonen IA eds, Tumours of the digestive system WHO classification of tumors. Lyon:IARC Press; 2000:pp.113-114.
[17]Sauerbrei w. The use of resampling methods to simpify regression molels in medical statistics. Appl Stat 1999;48:313-329.
[18]Hsu CH, Long Q, Alberts DS. Estimation of colorectal adenoma recurrence with dependent censoring. BMC Med Res Methodol 2009;9:66.
[19]Leung WK, Lau JY, Suen BY, et al. Repeat-screening colonoscopy 5 years after normal baseline-screening colonoscopy in average-risk Chinese:a prospective study. Am J Gastroenterol 2009;104:2028-2034.
[20]Imperiale TF, Glowinski EA, Lin-Cooper C, et al. Five-year risk of colorectal neoplasia after negative screening colonoscopy. N Engl J Med 2008;359:1218-1224.
[21]Noshirwani KC, van Stolk RU, Rybicki LA, Beck GJ. Adenoma size and number are predictive of adenoma recurrence:implications for surveillance colonoscopy. Gastrointest Endosc 2000;51:433-437.
[22]Nusko G, Mansmann U, Kirchner T, Hahn EG. Risk related surveillance following colorectal polypectomy. Gut 2002;51:424-428.
[23]Bertario L, Russo A, Sala P, et al. Predictors of metachronous colorectal neoplasms in sporadic adenoma patients. Int J Cancer 2003;105:82-87.
[24]Laiyemo AO, Murphy G, Albert PS, et al. Postpolypectomy colonoscopy surveillance guidelines:predictive accuracy for advanced adenoma at 4 years. Ann Intern Med 2008;148:419-426.
[25]Loeve F, van Ballegooijen M, Boer R, Kuipers EJ, Habbema JD. Colorectal cancer risk in adenoma patients:a nation-wide study. Int J Cancer 2004;111:147-151.
[26]Martinez ME, Baron JA, Lieberman DA, et al. A pooled analysis of advanced colorectal neoplasia diagnoses after colonoscopic polypectomy. Gastroenterology 2009;136:832-841.
[27]Rex DK, Cutler CS, Lemmel GT, et al. Colonoscopic miss rates of adenomas determined by back-to-back colonoscopies. Gastroenterology 1997;112:24-28.
[28]Pinsky PF, Schoen RE, Weissfeld JL, et al. The yield of surveillance colonoscopy by adenoma history and time to examination. Clin Gastroenterol Hepatol 2009;7:86-92.
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