结直肠癌患者的无症状同胞应接受筛查

香港中文大学威尔士亲王医院的Siew C. Ng博士及其同事报告称，与中国健康成人的同胞相比，中国结直肠癌患者的无症状兄弟姐妹发生晚期结直肠肿瘤的风险增加2倍，发生任何结直肠腺瘤的风险增加1倍。这项研究发表在《胃肠病学》杂志3月刊上(doi:10.1053/j.gastro.2012.11.011)。

Ng博士表示，鉴于上述结果，对这一高危人群有必要进行结直肠筛查，并切除筛查发现的任何癌前病变。

现行指南建议对结直肠癌患者的近亲属较早、较频繁地进行筛查，但以前并不清楚这样的筛查可产生怎样的成效。Ng博士及其同事对比了结直肠癌患者的同胞和结直肠筛查结果为阴性者的同胞的晚期肿瘤患病率。“选择这样的对照组可以避免家族史带来的偏倚，并且消除后天或环境因素的影响。”

10年期间共有374名结直肠癌患者同胞(年龄40~70岁，平均53岁)参加该研究，对照组招募了374名年龄、性别匹配的健康人同胞。两组受试者的肠道准备质量相似。所有筛查均采用常规白光结肠镜，在静脉内注射咪达唑仑和哌替啶清醒麻醉的情况下实施检查。3名参加研究的内镜医生均有丰富经验，且有可比的腺瘤检出率。

主要结局为晚期肿瘤(定义为直径≥10 mm、有高级别发育异常或绒毛状/管状组织学特性的癌症或腺瘤)患病率。结果显示，结直肠癌患者同胞的患病率(7.5%)接近健康对照者同胞(2.9%)的3倍，比值比(OR)为3.07。

有6名结直肠癌患者同胞被检出腺癌，而对照者中无1例检出腺癌。前者中包括Ⅰ期、Ⅱ期和Ⅲ期癌症各2例。结直肠癌患者同胞的大腺瘤患病率(5.9%)也接近对照者(2.1%)的3倍。前者的小腺瘤患病率(31%)约为后者(18.2%)的2倍。

当根据病变部位对数据进行分析时，研究者发现结直肠癌患者同胞的各种腺瘤患病率均高于对照者：远端腺瘤(13.1% vs. 8.3%)、近端腺瘤(12.0% vs. 6.2%)、同时性腺瘤(5.9% vs. 2.7%)。两组的增生性息肉患病率具有可比性(27.3% vs. 21.4%)。

当根据受试者年龄进行分析时，研究者发现各个年龄段的结直肠癌患者同胞，结直肠腺瘤的患病率均高于对照者：＜50岁(21.0% vs. 9.8%)、50~60岁(34.4% vs. 23.9%)或＞60岁(41.0% vs. 20.5%)。

在2项敏感性分析中，上述结果仍保持鲁棒性。

研究者还注意到，假如结直肠癌患者的病灶位于远端结肠而非近端结肠，则其同胞被检出晚期腺瘤的风险更高；假如结直肠癌患者为女性而非男性，则其同胞也有较高的晚期腺瘤风险。不过，由于这些亚组的受试者数量较小，因此对于上述结果需要谨慎解读。

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By: MARY ANN MOON, Internal Medicine News Digital Network

Asymptomatic siblings of Chinese colorectal cancer patients are at threefold higher risk for advanced colorectal neoplasms and at twofold higher risk for any colorectal adenoma, compared with siblings of healthy Chinese adults, Dr. Siew C. Ng and her colleagues reported in the March issue of Gastroenterology (doi:10.1053/j.gastro.2012.11.011).

Given these findings from a large prospective cross-sectional study, colorectal screening, with the removal of any premalignant lesions that are found, is warranted in this high-risk group, said Dr. Ng of the Prince of Wales Hospital and the Chinese University of Hong Kong and her associates.

Current guidelines recommend earlier and more frequent screening of close relatives of patients who have colorectal cancer, but what to expect on these screenings is unclear because "data from well-conducted prospective studies are lacking," they said.

Dr. Ng and her colleagues compared the prevalence of advanced neoplasms in such siblings against the prevalence in siblings of patients who underwent colorectal screening but had normal results. "The use of such a control group avoids a biased estimate of the association with family history, and removes the acquired or environmental component to this association," the investigators wrote.

All the screenings used a conventional white-light colonocope without high definition and were performed with patients under conscious sedation with intravenous midazolam and pethidine.

During a period of 10 years, 374 siblings (mean age, 53 years) of CRC patients aged 40-70 years participated in the study, as did 374 age- and sex-matched control subjects. The quality of bowel preparation was similar between the two groups.

All three study endoscopists were experienced, and they had comparable rates of adenoma detection.

The primary outcome was the prevalence of advanced neoplasms, defined as cancers or adenomas at least 10 mm in diameter that had high-grade dysplasia or villous/tubovillous histologic traits. This prevalence was approximately three times higher in the siblings of CRC patients (7.5%) as in the siblings of healthy controls (2.9%), with an odds ratio of 3.07.

Adenocarcinomas were detected in six siblings of CRC patients, but in none of the control subjects. These included two stage I cancers, two stage II cancers, and two stage III cancers.

Similarly, the prevalence of large adenomas was approximately three times as high in siblings of CRC patients (5.9%) as in controls (2.1%).

Siblings of CRC patients also had a higher prevalence of smaller adenomas (31%) than did control subjects (18.2%).

When the data were analyzed by lesion location, the siblings of CRC patients had a higher prevalence of every type: distal adenomas (13.1% vs. 8.3%), proximal adenomas (12.0% vs. 6.2%), and synchronous adenomas (5.9% vs. 2.7%).

The prevalence of hyperplastic polyps was comparable between the two groups (27.3% and 21.4%).

When the data were analyzed by subject age, siblings of CRC patients had a higher prevalence of all colorectal adenomas whether they were younger than 50 years (21.0% vs. 9.8%), 50-60 years old (34.4% vs. 23.9%), or older than 60 years (41.0% vs. 20.5%).

The study findings remained robust in two further sensitivity analyses.

Among the siblings of CRC patients, the risk of detecting an advanced adenoma was higher if the affected sibling’s cancer was located in the distal colon than if it was located in the proximal colon. This risk also was higher if the affected sibling was a woman than a man; however, this finding must be interpreted with caution because the number of subjects in these subgroups was small. 

These study results can be used to "provide a background against which screening strategies can be formulated." More important, the strong, significantly increased risk of advanced neoplasms means that siblings of CRC patients should be screened carefully, Dr. Ng and her associates said.