结直肠癌筛查的选项。
Options for screening for colorectal cancer.
作者信息
Atkin W
机构信息
Colorectal Cancer Unit, Cancer Research UK, St Mark's Hospital, Northwick Park, Harrow, UK.
出版信息
Scand J Gastroenterol Suppl. 2003(237):13-6. doi: 10.1080/00855910310001421.
Unlike other types of cancer, there are several options for screening for colorectal cancer (CRC). The most extensively examined method, faecal occult blood testing (FOBT), has been shown, in three large randomized trials, to reduce mortality from CRC by up to 20% if offered biennally and possibly more if offered every year. Recently published data from the US trial suggest that CRC incidence rates are also reduced by up to 20%, but only after 18 years. In this study, the number of positive slides was associated with the positive predictive value both for CRC and adenomas larger than 1 cm, suggesting that the reduction in CRC incidence was caused by the identification and removal of large adenomas. In this respect, this study supports the concept that removing adenomas prevents CRC. More efficient methods of detecting adenomas include the use of colonoscopy or flexible sigmoidoscopy (FS). Considerable evidence exists from case-control and uncontrolled cohort studies to suggest that endoscopic screening by sigmoidoscopy reduces incidence of distal colorectal cancer. However, in the absence of evidence from a randomized trial, several countries have been reluctant to introduce endoscopic screening. Three trialsare currently in progress (in the UK, Italy and the US) to address this issue. Two of these trials are examining the hypothesis that a single FS screen at around age 55-64 might be a cost-effective and acceptable method for reducing CRC incidence rates. Recruitment and screening are now complete in both studies and the first analysis of results on incidence rates is expected in 2004. Colonoscopy screening at 10-year intervals has recently been endorsed in the US on the basis that the reductions in incidence observed with distal CRC screening can be extrapolated to the proximal colon. However, data are lacking and a pilot study for a trial of the acceptability and efficacy of colonoscopy screening is in progress in the US. It has also been suggested that FOBT testing should be used to detect proximal CRC missed by sigmoidoscopy screening, but the small amount of published data suggest that supplementing FS with FOBT offers very little advantage over FS alone. Other forms of CRC screening are under investigation and represent exciting options for the future. Extraction of DNA from stool is now feasible and a number of research groups have shown high sensitivity for CRC using a panel of DNA markers including mutations in k-ras, APC, p53 and BAT26. Data so far indicate that, with the exception of k-ras, these markers are highly specific and therefore represent a significant improvement over FOBT. Whether these tests will replace or supplement existing methods of screening has yet to be determined. It has been suggested that BAT26, which is a marker of microsatellite instability, a feature of proximal sporadic CRC, might be a useful adjunct to sigmoidoscopy screening. Others have suggested that a test for occult blood should be included with the DNA markers to further increase sensitivity. It is not yet known how sensitive these markers are for adenomas--it is only by detecting adenomas that CRC incidence rates can be reduced. A final exciting new option for screening is virtual colonoscopy (VC), which by screening out people without neoplasia allows colonoscopy to be reserved for patients requiring a therapeutic intervention. The sensitivity of VC for large adenomas and CRC appears to be high, although results vary by centre and there is a steep learning curve. Sensitivity for small adenomas is low, but perhaps it is less essential to find such lesions. Some groups have suggested that virtual colonoscopy might be a useful option for investigating patients who test positive with stool-based screening tests. Whichever CRC screening method is finally chosen (and there is no reason why several methods should not ultimately be available), high quality endoscopy resources will always be required to investigate and treat neoplastic lesions detected.
与其他类型的癌症不同,结直肠癌(CRC)有多种筛查方法。最广泛研究的方法是粪便潜血试验(FOBT),三项大型随机试验表明,如果每两年进行一次该检查,可将结直肠癌死亡率降低多达20%,如果每年进行一次,降低幅度可能更大。美国试验最近公布的数据表明,结直肠癌发病率也可降低多达20%,但这要在18年后才会显现。在这项研究中,阳性玻片数量与结直肠癌及直径大于1厘米腺瘤的阳性预测值相关,这表明结直肠癌发病率的降低是由于识别并切除了大腺瘤。在这方面,该研究支持切除腺瘤可预防结直肠癌这一概念。检测腺瘤的更有效方法包括使用结肠镜检查或乙状结肠镜检查(FS)。病例对照研究和非对照队列研究有大量证据表明,乙状结肠镜检查进行内镜筛查可降低远端结直肠癌的发病率。然而,由于缺乏随机试验的证据,一些国家一直不愿采用内镜筛查。目前有三项试验(分别在英国、意大利和美国)正在进行以解决这一问题。其中两项试验正在检验这样一个假设:在55 - 64岁左右进行一次乙状结肠镜检查可能是一种具有成本效益且可接受的降低结直肠癌发病率的方法。两项研究的招募和筛查工作现已完成,预计2004年将首次对发病率结果进行分析。基于远端结直肠癌筛查观察到的发病率降低情况可外推至近端结肠,美国最近批准了每10年进行一次结肠镜检查筛查。然而,目前缺乏相关数据,美国正在进行一项关于结肠镜检查筛查可接受性和有效性试验的试点研究。也有人建议使用FOBT检测来发现乙状结肠镜检查筛查遗漏的近端结直肠癌,但已发表的少量数据表明,FOBT与FS联合使用相比单独使用FS优势不大。其他形式的结直肠癌筛查正在研究中,是未来令人兴奋的选择。从粪便中提取DNA现在可行,一些研究小组使用包括k-ras、APC、p53和BAT26突变在内的一组DNA标记物对结直肠癌显示出高灵敏度。目前的数据表明,除k-ras外,这些标记物具有高度特异性,因此相对于FOBT有显著改进。这些检测是否会取代或补充现有的筛查方法尚待确定。有人提出,BAT26作为近端散发性结直肠癌特征性的微卫星不稳定性标记物,可能是乙状结肠镜检查筛查的有用辅助手段。其他人则建议DNA标记物检测应与潜血检测一起进行,以进一步提高灵敏度。目前尚不清楚这些标记物对腺瘤的灵敏度如何——只有通过检测腺瘤才能降低结直肠癌发病率。最后一个令人兴奋的新筛查选择是虚拟结肠镜检查(VC),它通过筛查出没有肿瘤的人,使结肠镜检查仅用于需要治疗干预的患者。VC对大腺瘤和结直肠癌的灵敏度似乎很高,尽管结果因中心而异且学习曲线较陡。对小腺瘤的灵敏度较低,但发现这类病变可能不那么重要。一些研究小组建议,虚拟结肠镜检查对于粪便检测呈阳性的患者可能是一种有用的检查选择。无论最终选择哪种结直肠癌筛查方法(而且最终没有理由不能同时采用几种方法),始终都需要高质量的内镜资源来检查和治疗检测到的肿瘤性病变。