香港中文大學(xué)威爾士親王醫(yī)院的Siew C. Ng博士及其同事報(bào)告稱，與中國健康成人的同胞相比，中國結(jié)直腸癌患者的無癥狀兄弟姐妹發(fā)生晚期結(jié)直腸腫瘤的風(fēng)險(xiǎn)增加2倍，發(fā)生任何結(jié)直腸腺瘤的風(fēng)險(xiǎn)增加1倍。這項(xiàng)研究發(fā)表在《胃腸病學(xué)》雜志3月刊上(doi:10.1053/j.gastro.2012.11.011)。

Ng博士表示，鑒于上述結(jié)果，對這一高危人群有必要進(jìn)行結(jié)直腸篩查，并切除篩查發(fā)現(xiàn)的任何癌前病變。

現(xiàn)行指南建議對結(jié)直腸癌患者的近親屬較早、較頻繁地進(jìn)行篩查，但以前并不清楚這樣的篩查可產(chǎn)生怎樣的成效。Ng博士及其同事對比了結(jié)直腸癌患者的同胞和結(jié)直腸篩查結(jié)果為陰性者的同胞的晚期腫瘤患病率。“選擇這樣的對照組可以避免家族史帶來的偏倚，并且消除后天或環(huán)境因素的影響。”

10年期間共有374名結(jié)直腸癌患者同胞(年齡40~70歲，平均53歲)參加該研究，對照組招募了374名年齡、性別匹配的健康人同胞。兩組受試者的腸道準(zhǔn)備質(zhì)量相似。所有篩查均采用常規(guī)白光結(jié)腸鏡，在靜脈內(nèi)注射咪達(dá)唑侖和哌替啶清醒麻醉的情況下實(shí)施檢查。3名參加研究的內(nèi)鏡醫(yī)生均有豐富經(jīng)驗(yàn)，且有可比的腺瘤檢出率。

主要結(jié)局為晚期腫瘤(定義為直徑≥10 mm、有高級別發(fā)育異?；蚪q毛狀/管狀組織學(xué)特性的癌癥或腺瘤)患病率。結(jié)果顯示，結(jié)直腸癌患者同胞的患病率(7.5%)接近健康對照者同胞(2.9%)的3倍，比值比(OR)為3.07。

有6名結(jié)直腸癌患者同胞被檢出腺癌，而對照者中無1例檢出腺癌。前者中包括Ⅰ期、Ⅱ期和Ⅲ期癌癥各2例。結(jié)直腸癌患者同胞的大腺瘤患病率(5.9%)也接近對照者(2.1%)的3倍。前者的小腺瘤患病率(31%)約為后者(18.2%)的2倍。

當(dāng)根據(jù)病變部位對數(shù)據(jù)進(jìn)行分析時(shí)，研究者發(fā)現(xiàn)結(jié)直腸癌患者同胞的各種腺瘤患病率均高于對照者：遠(yuǎn)端腺瘤(13.1% vs. 8.3%)、近端腺瘤(12.0% vs. 6.2%)、同時(shí)性腺瘤(5.9% vs. 2.7%)。兩組的增生性息肉患病率具有可比性(27.3% vs. 21.4%)。

當(dāng)根據(jù)受試者年齡進(jìn)行分析時(shí)，研究者發(fā)現(xiàn)各個(gè)年齡段的結(jié)直腸癌患者同胞，結(jié)直腸腺瘤的患病率均高于對照者：＜50歲(21.0% vs. 9.8%)、50~60歲(34.4% vs. 23.9%)或＞60歲(41.0% vs. 20.5%)。

在2項(xiàng)敏感性分析中，上述結(jié)果仍保持魯棒性。

研究者還注意到，假如結(jié)直腸癌患者的病灶位于遠(yuǎn)端結(jié)腸而非近端結(jié)腸，則其同胞被檢出晚期腺瘤的風(fēng)險(xiǎn)更高；假如結(jié)直腸癌患者為女性而非男性，則其同胞也有較高的晚期腺瘤風(fēng)險(xiǎn)。不過，由于這些亞組的受試者數(shù)量較小，因此對于上述結(jié)果需要謹(jǐn)慎解讀。

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.