结肠镜检查阴性者癌症风险低

圣迭戈(EGMN)——消化疾病周(DDW)上公布的一项分析证实了结肠镜筛查在预防结直肠癌偶发病例方面的作用。

苏格兰阿伯丁大学胃肠病专家Paul Lochhead博士及其同事采用了美国两项大型前瞻性观察研究的数据：护士健康研究和医务人员随访研究。Lochhead博士及其同事从护士健康研究获得随访24年(1984~2008年)的内镜筛查数据，并从卫生专业人员随访研究获得随访20年(1988~2008年)的内镜筛查数据。这两项研究的随访时间超过200万人·年，在随访期间，2,198例受试者新发结直肠癌。大部分受试者(随访时间为140万人·年)在研究期间未接受内镜筛查。乙状结肠镜筛查后随访424,000人·年，结肠镜筛查后随访300,000人·年，息肉切除术后随访65,000人·年。

该分析排除以下受试者：在索引内镜检查前曾进行结肠镜检查、在索引内镜检查前患有息肉或除了非黑色素瘤皮肤癌以外的任何癌症、患炎性肠病。研究者在校正年龄、体重指数、吸烟、结直肠癌家族史、定期阿司匹林使用情况、体力活动、饮食和复合维生素使用情况后，使用多变量Cox比例风险模型对随访数据进行分析。

多变量模型分析显示，与未接受内镜检查的受试者相比，结肠镜检查结果阴性者的结直肠癌发生率显著降低51%，乙状结肠镜检查阴性受试者和息肉切除术受试者的癌发生率均显著降低37%。

根据癌症部位(近端或远端)分层，与未接受内镜检查的受试者相比，结直肠镜检查阴性者的偶发近端癌发生率显著降低(26%)。在远端癌方面，与未接受内镜检查的受试者相比，结直肠镜检查阴性者的远端癌发生率显著降低71%，乙状结肠镜检查阴性受试者和息肉切除术受试者的远端癌发生率均显著降低53%。

在保护作用的持久性(即检查结果阴性的受试者处于低癌风险的时间)方面，与未接受内镜检查的受试者相比，结直肠镜检查阴性受试者的新发结直肠癌发生率显著降低34%，甚至在索引结肠镜检查后7年以上也是如此。然而，根据癌症部位进行分析发现，结肠镜检查提供的显著保护作用仅持续3年：与未接受筛查的受试者相比，结肠镜检查阴性受试者在检查后3年内发生癌症的风险显著降低41%，但3年以上的风险降幅则不显著。相比之下，结肠镜检查对远端癌的保护作用持续7年以上：与未接受筛查的受试者相比，结肠镜检查阴性受试者在检查后7年以上发生癌症的风险显著降低42%。

分析还显示，息肉切除术对所有部位癌的显著保护作用也仅持续3年，其对远端癌的显著保护作用持续5年，但对近端癌无显著保护作用，即使在术后3年内也是如此。

进一步的多变量分析显示，多次结肠镜检查具有累积保护作用。单次结肠镜筛查可使偶发癌症(近端和远端)的发生率显著降低47%，而2次结肠镜检查可使发生率降低59%，3次或3次以上结肠镜检查可使发生率降低64%。

总体而言，该研究结果支持目前对公众提出的结直肠癌筛查建议，即年龄50~75岁的成人每10年应进行1次结肠镜筛查。

Lochhead博士声明无经济利益冲突。

BY MITCHEL L. ZOLER
Elsevier Global Medical News
Breaking News 

SAN DIEGO (EGMN) – Screening colonoscopy showed its efficacy for preventing incident cases of colorectal cancer in prospectively collected data during follow-up of up to 24 years in about 170,000 average-risk Americans.

 The finding adds prospectively collected data from a large database of average-risk Americans to the evidence supporting routine colonoscopy screening for colorectal cancer. In contrast, data from the influential National Polyp Study assessed screening colonoscopy in high-risk patients who first underwent polypectomy (N. Engl. J. Med. 2012;366:687-96), Dr. Paul Lochhead said at the annual Digestive Disease Week.

 In general, the new findings support current public health recommendations for screening colonoscopy every 10 years in adults aged 50-75 years, but with a few caveats.

 The new results showed that screening colonoscopy can significantly cut the risk for new-onset colorectal cancer by 51%, that the benefit from a single colonoscopy screen extended beyond 7 years, and that colonoscopy worked better than screening sigmoidoscopy. The findings also highlighted that colonoscopy was much better at preventing new distal cancers compared with its efficacy for stopping incident proximal tumors, and that when people had two, three, or more screening colonoscopies over time their risk of incident colorectal cancer fell further than after a single screening, said Dr. Lochhead, a gastroenterologist at the University of Aberdeen (Scotland).

 “Although a single negative colonoscopy is associated with risk reduction, continued screening may be associated with greater benefit,” undercutting the notion that average-risk middle-aged adults should undergo just a single screening colonoscopy with no follow-up screening if the first proves negative, he said.

 In addition, “efforts to improve prevention [resulting from] proximal screening are warranted,” he added.

“For distal cancers, we saw benefit beyond 10 years, but for proximal cancers we’re less certain about the duration of benefit. It appears there was a pattern of additional risk reduction with multiple screens regardless of whether the cancers were proximal or distal. That is something to bear in mind before we say that once is enough,” he said in an interview. 

The study used data from two large, prospective, U.S. observational studies: the Nurses’ Health Study, which began in 1976 and initially included 121,700 U.S. women, and the Health Professionals Follow-Up Study, which began in 1986 and included 51,529 men. 

In the Nurses’ Health Study, data became available on screening endoscopy starting in 1984, so the data that Dr. Lochhead and his associates used through 2008 included up to 24 years of follow-up. The Health Professionals Follow-Up Study started tracking screening endoscopy in 1988, which gave as many as 20 years of follow-up data through 2008. 

For this analysis, the researchers excluded participants in the two studies who had a lower endoscopy prior to the index procedures included in the two databases, those who had prior polyps or any cancer other than nonmelanoma skin cancer before they had their index endoscopy, and participants with inflammatory bowel disease. They calculated multivariate Cox proportional hazard models on the follow-up data that controlled for age, body mass index, smoking, family history of colorectal cancer, regular aspirin use, physical activity, diet, and multivitamin use. 

The database included more than 2 million person-years of follow-up from both studies, and during follow-up 2,198 participants developed new-onset colorectal cancer. The majority of participants, constituting nearly 1.4 million person-years of follow-up, underwent no screening endoscopy during the years studied. About 424,000 person years of follow-up came after screening sigmoidoscopy, nearly 300,000 person years of follow-up came following screening colonoscopy, and over 65,000 person-years of follow-up came after polypectomy. 

In the multivariate model, compared with no endoscopy, a negative colonoscopy result cut the rate of colorectal cancer by a statistically significant 51%, while negative sigmoidoscopy and polypectomy each cut the subsequent cancer rates by a statistically significant 37%, Dr. Lochhead reported. 

When broken down by cancer site – proximal or distal – a negative colonoscopy was the only procedure to cut the risk for incident proximal cancers significantly, reducing the rate by 26% compared with no endoscopy. For distal cancers, colonoscopy cut the rate by 71%, compared with no screening, while sigmoidoscopy and polypectomy each cut the rate by 53%; all these risk reductions for distal cancers were statistically significant. 

In the analysis that assessed the durability of protection, screening colonoscopy cut the risk for new colorectal cancers by a statistically significant 34%, compared with no screening, even when incident cancers were tallied more than 7 years following the index colonoscopy procedure. When cancers were divided by location, however, colonoscopy only provided significant protection for the first 3 years, with a risk reduction of 41% compared with no screening. Beyond that, colonoscopy did not produce a statistically significant reduction in incident cancers compared with no screening. 

In contrast, for distal cancers the protective benefit of colonoscopy extended beyond 7 years: Screening colonoscopy provided a significant 42% cancer-rate reduction, compared with no screening, more than 7 years out. 

The analysis also showed that the statistically significant protective benefit from polypectomy lasted for just 3 years for all cancer locations, with a 52% protection rate compared with no screening. For distal cancers a significant protective effect lasted for 5 years, but for proximal cancers polypectomy did not provide significant protection, even during the first 3 years after the procedure. 

An additional multivariate analysis showed cumulative protection from multiple colonoscopies. A single screening colonoscopy cut the rate of incident cancers, both proximal and distal, by a statistically significant 47%, but two colonoscopies cut the risk by 59% and three or more colonoscopies cut the risk by 64%. 

Dr. Lochhead said that he had no disclosures.