结直肠癌常用筛查方法综述_英文_

· In terna tiona l Comm un ica tion· 　　【编者按 】　《中国全科医学 》杂志目前已被国内、外各大数据库收录 , 并成为 Medline的扩展期刊 , 随着杂志 影响力的逐步提升 , 陆续收到一些国外医疗机构或个人的英文投稿 , 同时 , 国内丰富的医疗经验也日益受到国外密切 关注。本栏目的开辟旨在开放国际间医疗技术的交流窗口 , 搭建国际和国内全科医学临床工作者相互沟通和交流的平 台。 Rev iew Colorecta l Cancer Screen ing: Current Ava ilable M ethods J ianm ing Song, MD, MSc, DABFM; Gaylen Kelton, MD , FAAFP, CCFP; J iajiW ang, M Med 　　Author address: Dunes Fam ily Health Care and Lower Umpqua Hosp i2 tal, O regon Health & Science University (J ianm ing Song, A ttending Physi2 cian, MD, MSc, DABFM ) ; Department of Fam ily Medicine, Indiana - Purdue University School of Medicine, and IU /Methodist Fam ily Practice Center ( Gaylen Kelton, A ssociate Professor, MD, FAAFP, CCFP ) ; School of Public Health and General Practice, Guangzhou Medical College (J iajiW ang p rofessor, MMed) 作者单位 : 97403美国俄勒冈健康科学大学 , Dunes家庭保健中 心与 Lower Umqua医院 ( J ianm ing Song, 主治医师 , 医学博士 , 理学 硕士 , 美国家庭医学委员会注册医师 ) ; 印第安纳波里普渡大学医学 院家庭医学系 , IU /Methodist家庭医疗中心 ( Gaylen Kelton, 临床家庭 医学副教授 , 医学博士 , 美国家庭医师学会会员 , 加拿大家庭医师学 院文凭 ) ; 广州医学院公共卫生与全科医学学院 (王家骥 , 教授 , 医 学硕士 ) 　　【Abstract】　Colorectal cancer (CRC) is one of the most frequent cancers in North America. The identification of indi2 viduals at risk and the early diagnosis of CRC are of critical importance since a large p roportion can be p revented or cured by sur2 gical removal before metastasis has occurred. The strategies used for screening have been based p rimarily on fecal occult blood tests, barium enema, flexible sigmoidoscopy, and colonoscopy. The best method for population screening still remains uncer2 tain, molecular screening or other new techniques will hopefully soon comp lement these methods and may result in a reduction of morbidity and mortality from CRC. This review discusses the current various CRC screening methods and other potential screening tests, and finally outlines the future CRC screening p rogram development. 　　【Key word】　Colorectal cancer; Screening; Methods 　　【JEL cla ssif ica tion】R 73513　【W r iting mark】A　【Paper num ber】1007 - 9572 ( 2008) 06B - 1115 - 06 结直肠癌常用筛查方法综述 　　【摘要】　结直肠癌是北美地区最常见的恶性肿瘤之一。由于大部分未发生转移的结直肠癌都可以通过手术切除 的方式实施预防或治疗 , 因此结直肠癌高危个体的识别和早期诊断显得尤其重要。常用的筛查措施主要包括粪便隐血 试验、钡灌肠检查、纤维乙状结肠镜与结肠镜检查等。目前适用于人群筛查的最佳方法尚不确定 , 分子筛查及其他新 的技术有望应用于人群结直肠癌筛查 , 将有助于减少结直肠癌的发病率和病死率。本文讨论了几种结直肠癌的筛查方 法以及其他潜在的筛查试验。并概述了结直肠癌筛查项目的发展趋势。 　　【关键词 】　结直肠癌 ; 筛查 ; 方法 In troduction Colorectal cancer ( CRC) is a common malignancy, ranking third to lung cancer and p rostate cancer as a cause of cancer mortal2 ity among males and third to lung cancer and breast cancer among females in the United States and Canada[ 1 - 2 ] . It is recognized that most CRC arises from benign adenomatous polyp s, removal of these p recursor lesions is feasible[ 3 ] . It has been shown that the interval between appearance of polyp s and transformation to cancer is usually long, normally over a 5 - to 15 - year period[ 4 ] , if polyp s can be detected and removed during this period, cancer can be p revented. A s well the CRC survival rates are closely related to the stage of cancer at the time of diagno2 sis[ 5 ] , this strong relation between tumor stage and survival p ro2 vides a rationale for intervention at an early pathological or p rema2 lignant stage. Efforts to p revent CRC or detect it at a potentially curable stage would seem the best way to decrease morbidity and mortality. To date the classic app roach to CRC screening has involved testing for blood in the stool or direct imaging of the bowel either by diagnostic radiological techniques or by endoscopy. The strategies used for screening have been based p rimarily on fecal occult blood tests, barium enema, flexible sigmoidoscopy, and colonoscopy. However, the bestmethod for population screening still remains un2 certain. The purpose of this article is to take a critical look at the available diagnostic tools that allow detecting CRC in a p recursor or localized, curable form, to compare these screening tests, and to identify future areas of CRC screening study and development. Feca l O ccult Blood Tests Traditional fecal occult blood tests ( FOBT) detect the peroxi2 dase - like activity of hemoglobin in the stool and depend on the tendency of CRC to bleed. Three major FOBT test technologies have been developed: [ 6 ] ( i) . guaiac tests, which detect haem ei2 ther free or as part of the hemoglobin molecule; ( ii) . immuno2 chem ical tests, which are directed at the immuno - reactivity of in2 tact or near - intact hemoglobin and are highly sensitive for colorec2 tal bleeding; ( iii) . haem - porphyrin assays, which are directed at the haem - derived porphyrins, but requires laboratory based flu2 orescent spectrometry, this test is not readily available. The test most widely used for detecting blood in the stool is the ·5111· guaiac - based test. Guaiac tests include Hemoccult, Hemoccult II, and Hemoccult II SENSA. Guaiac tests are the simp lest and least expensive of the FOBT. Unfortunately, the test sensitivity and specificity is lim ited because not all cancers or polyp s bleed and not all lower gastrointestinal bleeding are due to cancer. Sensitivity of single guaiac tests to detect CRC is usually in the region of 30% ～50% [ 7 ] , sensitivity is much lower for adenomas, because most adenomas do not bleed. Rehydrating the test cards with a drop of water before testing can increase sensitivity. Rehydration of the test slides imp roves sensitivity at the expense of decreased specificity, reduced specificity imp lies a large number of testswill be false posi2 tive, and more individuals who do not have CRC will require com2 p lex and expensive follow - up studies[ 8 ] . Specificity for guaiac test is also low and depends on whether patients avoid dietary sources of hemoglobin and myoglobin, this may lower the accep tability of the tests[ 9 ] . There is also clear evidence that dietary restrictions can modify positive rate and considered as a factor in comp liance with FOBT screening. Guaiac tests may also be falsely positive due to consump tion of red meats, some vegetables and fruits containing peroxidase or antioxidants such as vitam in C. Nonetheless, screening using Guaiac - based FOBT test is be2 ginning to demonstrate its utility in reducing mortality from CRC. Three comp leted random ized controlled trials using the guaiac tests have demonstrated a relative reduction in mortality in the screened group of between 15% and 33% , mortality is reduced because more cancer are discovered at an earlier stage in patients who are screened compared with patients who are not screened[ 10 - 12 ] . Re2 cently finding from the 18 year follow - up of the M innesota trial suggest that the use of either annual or biennial fecal occult - blood testing significantly reduces the incidence of CRC[ 13 ] . Persons with positive FOBT tests should be offered for comp lete colonic evalua2 tion to determ ine whether CRC is p resent, ideally using colonosco2 py. False - positive results dramatically increase the cost of screen2 ing, since personswith positive tests should be referred for colonos2 copy. False - negative results of FOBT occur as well, potentially delaying the diagnosis of cancer. W ith the introduction of immune - based tests that may enhance the sensitivity and specificity of FOBT, the costs of screening may also be imp roved. Immune - based testing for FOBT detects only intact human hemoglobin by using specific antibodies, it elim inates false positive from dietary causes and makes the test much more specific for lower gastrointestinal bleeding, as hemoglobin from more p roximal bleed2 ing is rap idly degraded in the stomach and small intestine and un2 likely to remain intact. HemeSelect, FlexsureOBT and InSureTM are one of such tests. Robinson et al[ 14 ] found that the addition of HemeSelect to a mass - screening p rogram imp roved the detection of cancers, although the test by itself was less specific. A llison et al studied the combination of HemeSelectwith the guaiac - based mod2 ified version, Hemoccult II Sensa in asymp tomatic subjects, and found that the combination was significantly better than either test a2 lone[ 15 ] . In SureTM - a new immunochem ical FOBT, which was ap2 p roved for use by the Food and D rug Adm inistration ( FDA ) in Jan2 uary 2001, had been tested in a group of 240 peop le considered at high risk of develop ing colorectal cancer based on their personal or fam ily history of colorectal cancer and adenomas, and also sched2 uled for colonoscopy. Two samp les per patient were gathered. In this study, the test had a sensitivity for cancer of 87% ( 20 /23 ) and a sensitivity for adenomas > 10 mm of 4714% ( 9 /19). In a separate, normal population aged 40 and over thatwas evaluated for test specificity, specificity was 9719% ( 88 /90) , and in a popu2 lation under age 30, specificity was 9718% ( 92 /94 ). Test re2 sults were verified by colonoscopy[ 16 ] . Increased sensitivity without a corresponding loss of specificity m ight substantially imp rove the performance of FOBT and eventually result in relatively cost effective screening[ 17 ] . The major difficulty with the immune - based test is that it may require analysis in a la2 boratory, making it potentially less convenient and more labor in2 tensive and, as a result, somewhat more expensive. Desp ite its lim itations, FOBT is part of p ractical screening strategy currently available for the detection of CRC at an early stage. It is an inexpensive, affordable investigation and causes the patients little discomfort. Among all of the current screening tests, strong, direct evidence that screening (with app rop riate diagnostic follow - up and treatment) reduces mortality from CRC exists only for FOBT. Important issues regarding when FOBT screening is clearly worthwhile and when it is not and how it can be imp roved need further investigation. Flex ible S igm o idoscopy Flexible sigmoidoscopy ( FS) offers three important advantages over testing by FOBT, it allows to visualize the distal bowel direct2 ly; lesions can be biop sied; although the sensitivity of sigmoidos2 copy is lim ited by its reach, for cancers and polyp s in the part of its reach, sensitivity and specificity are both high. The 60 - cm flexi2 ble scope, can reach up to or beyond the p roximal end of the sig2 moid colon in 80% of exam ination and detect about 40% ～60% of adenomatous polyp s and CRC[ 18 ] , and because adenomas and canc2 er are directly visualized, a positive finding is almost always a true positive. Results from three case - control studies suggest that screening sigmoidoscopy can substantially reduce mortality from cancers of the rectum and distal colon[ 19 - 21 ] . These case - control studies show that screening sigmoidoscopy and polypectomy reduces CRC inci2 dence and mortality were due to diagnosis and remove polyp s and entering individuals in app rop riate surveillance p rogram s. These re2 sults appear imp ressive, however, case - control studies have man2 y inherent methodological inadequacies, and well - designed ran2 dom ized controlled trials are necessary to confirm the efficacy of sig2 moidoscopy in p revention of CRC. There are no comp leted large. Random ized controlled trials of FS for CRC screening until now. There is only the Telemark Polyp Study, a small random ized trial, demonstrated that one - time flexible sigmoidoscopy screening could reduce colorectal cancer incidence. However, no reduction in colorectal cancer mortality was observed in the screened group[ 22 ] . There are theoretical reasons for combining FOBT with FS. FS can detect polyp s as well as cancers in the distal colon, which could lead to cancer p revention. In addition, sigmoidoscopy is more accurate than FOBT for detecting adenomatous polyp s. Com2 bining FS and FOBT overcomes some of the disadvantages of each method and has long been recommended by the American Cancer Society[ 23 ] . Only one controlled study has evaluated the benefit of combination screening, the major finding was that patients screened with both rigid sigmoidoscopy and FOBT had better long - term sur2 vival after detection of cancer compared with rigid sigmoidoscopy a2 lone[ 24 ] . Modeling of colon screening p rogram s also suggests that there may significant added benefit of more cancer p revention when sigmoidoscopy is added to FOBT[ 8 ] . Compared with colonoscopy, FS is less costly, is safer, and may have a higher degree of comp liance. Bowel p reparation for colonoscopy requires 24 hours of severe dietary restriction whereas satisfactory p reparation for FS can be achieved with a single phos2 phate enema around 1 hour before exam ination[ 25 ] . Sedation is rou2 tinely adm inistered during colonoscopy while no medication is gen2 erally used during FS. W aye et al have reviewed the rates of com2 p lication reported in the literature from both p rocedures and found that the incidence rates for diagnostic colonoscopy of perforation and hemorrhage are higher than FS[ 26 ] . The major disadvantage of FS is that it does not perm it exam i2 nation of the p roximal colon where about 40% of adenomas and cancers are located. If an adenomatous polyp is found on sigmoid2 oscopy, there is an increased p robability that others are p resent elsewhere in the bowel, when adenomatous polyp s are found in the ·6111· rectosigmoid, patients have about a one in three chance of having additional adenomas more p roximally in the colon[ 27 ] . It is common p ractice to follow up an abnormal screening sigmoidoscopy with full colonoscopy, not only to excise the lesions already found, but also to look for more p roximal lesions. Future studies need to adjust whether the identification of isolated adenomatous polyp s at FS should be evaluated by a full colonoscopy to rule out synchronous polyp s in the colon at increased risk of CRC. Normally, full colonoscopy should be performed if a cancer, any adenomas > 1cm in diameter ormultip le adenomas is found on sigmoidoscopy. In ad2 dition, based on Read et al study, if a patient has small polyp s found on sigmoidoscopy, biop sies should be obtained - and if ade2 nomatous, full colonoscopy is recommended[ 28 ] . D ouble Con tra st Bar ium Enema Double contrast barium enema (DCBE) is a radiological study of the entire colon. Preparation involves a low residue or liquid diet for the 24 hours before the p rocedure, p lus laxatives and enema to clean the bowel. The exam ination takes 20～30 m inuteswith no re2 covery time required. Some patients experience temporary constipa2 tion or discomfort. DCBE is still widely used in the investigation of FOBT - posi2 tive individuals. Desp ite its reduced accuracy compared to colonos2 copy, it often offers advantages in term s of cost and accessibility. Results from its role to detect lesions which are the targets of other screening interventions suggest that the overall sensitivity for polyp s was 70% , increasing to 81% for polyp s ≥ 10 mm[ 29 - 30 ] . DCBE is less sensitive than colonoscopy, particular for adenomas less than 1 cm in diameter and in areas where a single lumen is not readily i2 dentifiable ( eg. sigmoid colon, rectosigmoid, sp lenic and hepatic flexures) [ 31 ] . False positive findings are mainly caused by adherent stool and non - neop lastic mucocal irregularities, with rates ranging from < 1% for cancer, 5% ～10% for large polyp s[ 30, 32 ] , and about 50% for small polyp s[ 30 ] . Traditionally, patients have undergone sigmoidoscopy before barium enema because barium enema was considered an inaccurate exam ination of the sigmoid colon and rectum[ 33 ] . In the Swedish random ized controlled trial, DCBE alone m issed 25% of cancers and a sim ilar p roportion of polyp s > 1cm in the rectosigmoid, the FS performed better than DCBE in this region[ 34 ] . The combination of FS and DCBE had a sensitivity of 98% for carcinomas and 99% for adenomas. A lthough DCBE has been suggested as a screening instrument for CRC[ 7 ] , it has not been evaluated in clinical trials for this purpose. Most published studies have focused almost exclu2 sively on its role in follow - up of other test - positive or symp tomat2 ic individuals. Indirect evidence of the effectiveness of DCBE in screening only comes from the fact that detecting polyp s and early cancers by other screening tests reduces the incidence and mortality from CRC and that DCBE detects many of these lesions. L ittle is known about its accep tability in population screening, there are al2 so clinical reasons for variation in performance such as skills of the exam iner and differences in patient′s anatomy. In addition, DCBE may have high rate of equivocal or falsely positive results, which will require full colonoscopy for evaluation. Current data do not support the use of DCBE for p rimary screening. Colonoscopy There have been interests in colonoscopy as a screening tool because FOBT detects only those polyp s and cancers that bleed; sigmoidoscopy allows inspection of only the distal half of the large bowel; and DCBE, although it can image the entire large bowel, does not allow biop sy or polypectomy. Colonoscopy is the only tech2 nique currently available that offers the potential to both finding and removing p remalignant lesions throughout the colon and rectum. There are no published RCT studies that directly exam ine the effectiveness of colonoscopy as a screening test for CRC in term s of CRC deaths. However, indirect evidence from several uncontrolled studies suggests that colonoscopy is almost certainly a highly effec2 tive screening test[ 35 ] . Colonoscopy is currently used for the evalua2 tion of other positive screening tests and contributes to their effec2 tiveness or as an initial screening test for certain high - risk group s. Potential benefits and efficacy of colonoscopy as a screening op tion include the following: ( i) . Colonoscopy is the most sensitive and specific method currently available for identifying adenomatous pol2 yp s and carcinomas of the colon[ 36 ] . It is likely that nearly all pa2 tients with significant colon pathology, either malignant or p re - malignant, could be identified with colonoscopy; ( ii) . Polyp s could be removed at the time of the initial colonoscopy, thus saving the cost, inconvenience and discomfort of a second p rocedure. The possibility of removing adenomas during colonoscopy has led to in2 terest in its use as a CRC p revention strategy. There is evidence from the National Polyp Study that colonoscopy with polypectomy a2 chieved a 76% ～90% reduction in CRC incidence[ 37 ] . A model of CRC screening developed by L ieberman has suggested that of all tests used for screening, only one - time colonoscopy has the grea2 test impact on CRC mortality, largely because of the assump tion that cancer would be p revented in most patients who undergo polypectomy[ 8 ] . ( iii) . The demographics of CRC suggest that only 10% of cancers arises before age 55 years[ 38 ] , therefore, if screen2 ing with colonoscopy occurred at age 55～60 years, itwould p roba2 bly p recede the development of cancer in most cases, resulting in significant cancer p revention if polyp s were detected and removed. ( iv). Current evidence suggests that the p rogression of neop lasia from normal mucosa to cancer may require more than 10 years[ 39 ] , if patients have no polyp s or a single small ( < 1cm) tubular adeno2 ma, the risk of develop ing cancer during the following 10 years is small and no follow - up may be needed[ 40 ] . Therefore it is possible that a one - time screening with colonoscopy could be more effective because efficacy would not depend on the need to repeat screening tests. Desp ite the efficacy of colonoscopy, comp liance in populations could be low because the p rocedure is so invasive. There is little literature on the accep tability of colonoscopy as a p rimary screening tool. W hen physicians and nurses and their spouse