Bye William A, Nguyen Tran M, Parker Claire E, Jairath Vipul, East James E
Department of Gastroenterology and Hepatology, St Vincent's Hospital, Sydney, Australia.
Cochrane Database Syst Rev. 2017 Sep 18;9(9):CD000279. doi: 10.1002/14651858.CD000279.pub4.
Patients with longstanding ulcerative colitis and colonic Crohn's disease have an increased risk of colorectal cancer (CRC) compared with the general population. This review assessed the evidence that endoscopic surveillance may prolong life by allowing earlier detection of CRC or its pre-cursor lesion, dysplasia, in patients with inflammatory bowel disease (IBD).
To assess the effectiveness of cancer surveillance programs for diagnosis of IBD-associated colorectal cancer and in reducing the mortality rate from colorectal cancer in patients with IBD.
We searched MEDLINE, EMBASE, CENTRAL and clinical clinicaltrials.gov from inception to 19 September 2016. We also searched conference abstracts and reference lists to identify additional studies.
Potentially relevant articles were reviewed independently and unblinded by two authors to determine eligibility. Randomised controlled trials (RCTs) or observational studies (cohort or case control) assessing any form of endoscopic surveillance aimed at early detection of CRC were considered for inclusion. Studies had to have a no surveillance comparison group to be eligible for inclusion.
Eligible studies were reviewed in duplicate and the results of the primary research trials were independently extracted by two authors. The primary outcome was detection of CRC. Secondary outcomes included death from CRC, time to cancer detection, time to death and adverse events. Deaths from CRC were derived from life tables, survival curves or where possible, by calculating life tables from the data provided. The presence of significant heterogeneity among studies was tested by the chi-square test. Because this is a relatively insensitive test, a P value of less than 0.1 was considered statistically significant. Provided statistical heterogeneity was not present, the fixed effects model was used for the pooling of data. The 2x2 tables were combined into a summary test statistic using the pooled odds ratio (OR) and 95% confidence intervals as described by Cochrane and Mantel and Haenszel. The methodological quality of the included studies was assessed using the Newcastle-Ottawa scale for non-randomised studies The overall quality of the evidence supporting the primary and selected secondary outcomes was assessed using the GRADE criteria.
No RCTs were identified. Five observational studies (N = 7199) met the inclusion criteria. The studies scored well on the Newcastle-Ottawa scale, but due to the nature of observational studies, a high risk of bias was assigned to all the studies. Three studies were pooled to assess the rate of cancer detected in the surveillance group compared to the non-surveillance group. The studies found a significantly higher rate of cancer detection in the non surveillance group compared to the surveillance group. CRC was detected in 1.83% (53/2895) of patients in the surveillance group compared to 3.17% (135/4256) of patients in the non-surveillance group (OR 0.58, 95% CI 0.42 to 0.80; P = 0.0009). Four studies were pooled to assess the death rate associated with CRC in patients who underwent surveillance compared to patients who did not undergo surveillance. There was a significantly lower death rate associated with CRC in the surveillance group compared to the non-surveillance group. Eight per cent (15/176) of patients in the surveillance group died from CRC compared to 22% (79/354) of patients in the non-surveillance group (OR 0.36, 95% CI 0.19 to 0.69, P=0.002). Data were pooled from two studies to examine the rate of early stage versus late stage colorectal cancer (Duke stages A & B compared to Duke stages C & D) in patients who underwent surveillance compared to patients who do not undergo surveillance. A significantly higher rate of early stage CRC (Duke A & B) was detected in the surveillance group compared to the non-surveillance group. Sixteen per cent (17/110) of patients in the surveillance group had early stage CRC compared to 8% (9/117) of patients in the non-surveillance group (OR 5.40, 95% CI 1.51 to 19.30; P = 0.009). A higher rate of late stage CRC (Duke C & D) was observed in the non-surveillance group compared to the surveillance group. Nine per cent (10/110) of patients in the surveillance group had late stage CRC compared to 16% (19/117) of patients in the non-surveillance group (OR 0.46, 95% CI 0.08 to 2.51; P = 0.37). A GRADE analysis indicated that the quality of the data was very low for all of these outcomes. The included studies did not report on the other pre-specified outcomes including time to cancer detection, time to death and adverse events.
AUTHORS' CONCLUSIONS: The current data suggest that colonoscopic surveillance in IBD may reduce the development of both CRC and the rate of CRC-associated death through early detection, although the quality of the evidence is very low. The detection of earlier stage CRC in the surveillance group may explain some of the survival benefit observed. RCTs assessing the efficacy of endoscopic surveillance in people with IBD are unlikely to be undertaken due to ethical considerations.
与普通人群相比,患有长期溃疡性结肠炎和结肠克罗恩病的患者患结直肠癌(CRC)的风险增加。本综述评估了内镜监测通过在炎症性肠病(IBD)患者中更早检测出CRC或其前驱病变发育异常从而延长生命的证据。
评估癌症监测计划对IBD相关结直肠癌的诊断效果以及降低IBD患者结直肠癌死亡率的效果。
我们检索了从数据库建立至2016年9月19日的MEDLINE、EMBASE、CENTRAL和ClinicalTrials.gov。我们还检索了会议摘要和参考文献列表以识别其他研究。
两位作者独立且不设盲地审查潜在相关文章以确定其是否符合纳入标准。纳入评估任何旨在早期检测CRC的内镜监测形式的随机对照试验(RCT)或观察性研究(队列或病例对照)。研究必须有一个非监测比较组才有资格纳入。
符合条件的研究由两人进行重复审查,主要研究试验的结果由两位作者独立提取。主要结局是CRC的检测。次要结局包括CRC导致的死亡、癌症检测时间(time to cancer detection)、死亡时间和不良事件。CRC导致的死亡来自生命表、生存曲线,或在可能的情况下,通过根据提供的数据计算生命表得出。通过卡方检验检测研究之间显著异质性的存在。由于这是一个相对不敏感的检验,P值小于0.1被认为具有统计学意义。如果不存在统计学异质性,则使用固定效应模型合并数据。按照Cochrane以及Mantel和Haenszel的描述,将2×2表格合并为一个汇总检验统计量,使用合并比值比(OR)和95%置信区间。使用纽卡斯尔-渥太华量表评估纳入研究的方法学质量,用于非随机研究。使用GRADE标准评估支持主要结局和选定次要结局的证据的总体质量。
未识别到RCT。五项观察性研究(N = 7199)符合纳入标准。这些研究在纽卡斯尔-渥太华量表上得分良好,但由于观察性研究的性质,所有研究均被赋予高偏倚风险。三项研究被合并以评估监测组与非监测组相比检测到癌症的比率。研究发现,与监测组相比,但非监测组中检测到癌症的比率显著更高。监测组中1.83%(53/2895)的患者检测到CRC,而非监测组中为3.17%(135/4256)的患者(OR 0.58,95% CI 0.42至0.80;P = 0.0009)。四项研究被合并以评估接受监测的患者与未接受监测的患者相比与CRC相关的死亡率。与非监测组相比,监测组中与CRC相关的死亡率显著更低。监测组中8%(15/176)的患者死于CRC,而非监测组中为22%(79/354)的患者(OR 0.36,95% CI 0.19至0.69,P = 0.002)。从两项研究中汇总数据,以检查接受监测的患者与未接受监测的患者相比早期与晚期结直肠癌(杜克分期A和B与杜克分期C和D)的比率。与非监测组相比,监测组中早期CRC(杜克A和B)的比率显著更高。监测组中16%(17/110)的患者患有早期CRC,而非监测组中为8%(9/117)的患者(OR 5.40,95% CI 1.51至19.30;P = 0.009)。与监测组相比,非监测组中观察到晚期CRC(杜克C和D)的比率更高。监测组中9%(10/110)的患者患有晚期CRC,而非监测组中为16%(19/117)的患者(OR 0.46,95% CI 0.08至2.51;P = 0.37)。GRADE分析表明,所有这些结局的数据质量都非常低。纳入研究未报告其他预先指定的结局,包括癌症检测时间、死亡时间和不良事件。
目前的数据表明,IBD中的结肠镜监测可能通过早期检测降低CRC的发生以及CRC相关的死亡率,尽管证据质量非常低。监测组中早期CRC的检测可能解释了观察到的一些生存获益。由于伦理考虑,不太可能进行评估内镜监测对IBD患者疗效的RCT。