影響結(jié)直腸腺瘤檢出率相關(guān)因素的研究進(jìn)展

0 引言

結(jié)直腸癌是我國最常見的惡性腫瘤之一,其發(fā)病率及死亡率分別位居我國惡性腫瘤的第3位及第5位

.Ⅰ期結(jié)直腸癌的5年相對生存率為90%,而發(fā)生遠(yuǎn)處轉(zhuǎn)移的Ⅳ期結(jié)直腸癌的5年相對生存率僅為14%

.通常,結(jié)直腸癌是由腺瘤進(jìn)展而來,早期發(fā)現(xiàn)并切除腺瘤有利于預(yù)防結(jié)直腸癌的發(fā)生與發(fā)展.因此,提高結(jié)腸鏡檢查中的腺瘤檢出率(adenoma detection rate,ADR)至關(guān)重要.ADR指接受結(jié)腸鏡檢查者中發(fā)現(xiàn)腺瘤者占總檢查人數(shù)的比例.目前,多數(shù)指南提出結(jié)腸鏡檢查中ADR至少應(yīng)達(dá)到15%-20%

.本文就影響結(jié)腸鏡檢查ADR的術(shù)前、術(shù)中相關(guān)因素、醫(yī)生相關(guān)因素和設(shè)備相關(guān)因素加以概述,以期加強(qiáng)內(nèi)窺鏡醫(yī)生對ADR的認(rèn)識(shí).

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1 術(shù)前、術(shù)中相關(guān)因素

1.1 腸道準(zhǔn)備質(zhì)量 腸道準(zhǔn)備質(zhì)量與ADR相關(guān).腸道準(zhǔn)備質(zhì)量越高,結(jié)腸黏膜的可視程度越高,更有利于內(nèi)窺鏡醫(yī)生發(fā)現(xiàn)腺瘤.一項(xiàng)橫斷面研究將結(jié)腸分為右半結(jié)腸、橫結(jié)腸和左半結(jié)腸,分別探討了各結(jié)腸段ADR與腸道準(zhǔn)備質(zhì)量關(guān)系,結(jié)果發(fā)現(xiàn),在各結(jié)腸段中隨著腸道準(zhǔn)備質(zhì)量越高,ADR越高

.總的來說,低質(zhì)量腸道準(zhǔn)備會(huì)顯著降低ADR

,是由于腸道準(zhǔn)備質(zhì)量差時(shí),腸腔內(nèi)會(huì)殘留大量糞便及食物殘?jiān)?它們覆蓋于腸黏膜表面,掩蓋病變部位,進(jìn)而降低了ADR.然而,中-高質(zhì)量腸道準(zhǔn)備對ADR的影響尚無定論.有研究發(fā)現(xiàn),中等質(zhì)量和高質(zhì)量腸道準(zhǔn)備患者之間的ADR無顯著差別

,甚至中等質(zhì)量腸道準(zhǔn)備的ADR更高

.這可能是因?yàn)橹械荣|(zhì)量腸道準(zhǔn)備患者中,殘留的大便可能附著在鋸齒狀息肉的粘液帽上,從而提高可視化效果,同時(shí),內(nèi)窺鏡醫(yī)生對殘留物的沖洗,也會(huì)提高內(nèi)窺鏡醫(yī)生的注意力.相比之下,高質(zhì)量腸道準(zhǔn)備可能會(huì)降低醫(yī)生的警惕性,從而使ADR降低(圖1).

1.2 退鏡時(shí)間 延長退鏡時(shí)間可顯著提高ADR

.一項(xiàng)納入5073例行結(jié)腸鏡檢查患者的前瞻性隊(duì)列研究發(fā)現(xiàn),延長退鏡時(shí)間是ADR的獨(dú)立危險(xiǎn)因素(OR=1.04,95%CI=1.02-1.06,

<0.001)

.一項(xiàng)前瞻性觀察性研究將腸道分為右側(cè)結(jié)腸段(盲腸、升結(jié)腸和肝曲)、近端結(jié)腸段(盲腸、升結(jié)腸、肝曲和橫結(jié)腸)和左側(cè)結(jié)腸段(脾曲、降結(jié)腸、乙狀結(jié)腸和直腸),并根據(jù)各結(jié)腸段平均退鏡時(shí)間分為兩組,探討了各結(jié)腸段退鏡時(shí)間與ADR之間的關(guān)系,結(jié)果顯示,當(dāng)右側(cè)結(jié)腸段退鏡時(shí)間≥2 min(33.2%

13.7%,

<0.001)、近端結(jié)腸段≥4 min(47.4%

18.5%,

<0.001)、左側(cè)結(jié)腸段≥3 min(32.9%

14.6%,

<0.001)時(shí),ADR顯著提高

.綜上,延長退鏡時(shí)間可以顯著提高整體和各節(jié)段結(jié)腸ADR.然而,對于最佳的退鏡時(shí)間,目前尚無定論.Patel等

發(fā)現(xiàn),結(jié)腸鏡檢查的退鏡時(shí)間應(yīng)該達(dá)到11 min.Lee等

發(fā)現(xiàn),最佳的退鏡時(shí)間應(yīng)該為6 min-10 min,10 min以上的退鏡時(shí)間與ADR升高無關(guān).歐美國家指南建議,未行活檢和息肉切除等內(nèi)鏡操作的結(jié)腸鏡檢查的退鏡時(shí)間應(yīng)大于6 min

.

服務(wù)社區(qū)成員是時(shí)代賦予高校的光榮使命，是高校創(chuàng)新辦學(xué)模式的有效途徑，是高校改善辦學(xué)條件和辦學(xué)環(huán)境的重要前提。社區(qū)學(xué)院應(yīng)把為社區(qū)成員的個(gè)人發(fā)展服務(wù)放在首位，通過社區(qū)成員個(gè)人發(fā)展服務(wù)進(jìn)而為地區(qū)經(jīng)濟(jì)和文化教育發(fā)展服務(wù)。各高校應(yīng)高度重視社區(qū)教育在社會(huì)發(fā)展中的價(jià)值，支持社區(qū)教育事業(yè)的發(fā)展，使社區(qū)教育成為學(xué)校服務(wù)經(jīng)濟(jì)轉(zhuǎn)型、服務(wù)社會(huì)發(fā)展、服務(wù)公益事業(yè)的重要窗口。

1.5 雙人觀察模式 近期多項(xiàng)研究探討了在結(jié)腸鏡檢查過程中不同人群參與觀察對ADR的影響,發(fā)現(xiàn)同事(44.8%

37.1%,

=0.02)

、護(hù)士(30.4%

23.0%,

=0.034)

及實(shí)習(xí)生(63%

51%,

<0.001)

參與觀察均會(huì)顯著提高ADR.一項(xiàng)納入23項(xiàng)研究的薈萃分析同樣發(fā)現(xiàn),無論在隨機(jī)對照研究中(33.9%

29.5%,

=0.004)還是在隊(duì)列研究中(38.2%

28.5%,

<0.01),雙人觀察的ADR均高于單人觀察

.兩名觀察者互相查缺補(bǔ)漏,更易發(fā)現(xiàn)微小病變,可以更有效地對腸道進(jìn)行觀察,也可以降低內(nèi)窺鏡醫(yī)生因注意力不集中而遺漏腺瘤的幾率,從而提高ADR.綜上,雙人觀察會(huì)提高ADR,在有條件的醫(yī)院可以應(yīng)用這種檢查模式.

2.1 內(nèi)窺鏡醫(yī)生的經(jīng)驗(yàn) 內(nèi)窺鏡醫(yī)生的經(jīng)驗(yàn)對ADR的影響尚有爭論.既往多數(shù)研究認(rèn)為行結(jié)腸鏡檢查例數(shù)大于500例為經(jīng)驗(yàn)豐富的結(jié)腸鏡檢查醫(yī)師,且他們有著更高的ADR

.然而,Yousaf等

卻發(fā)現(xiàn)行結(jié)腸鏡檢查例數(shù)小于500例的內(nèi)窺鏡醫(yī)生反而有更高的ADR.這種差異可能由以下原因造成:(1)有經(jīng)驗(yàn)的內(nèi)窺鏡醫(yī)生需要檢查更多的患者,且需要更迅速的完成檢查任務(wù),這可能會(huì)導(dǎo)致他們更加疲勞,從而遺漏病變;(2)經(jīng)驗(yàn)較少的內(nèi)窺鏡醫(yī)生在結(jié)腸鏡檢查過程中會(huì)進(jìn)行更加仔細(xì)且廣泛的檢查,因此,他們意外發(fā)現(xiàn)腺瘤的幾率更高.

3.2 高清結(jié)腸鏡 與標(biāo)準(zhǔn)結(jié)腸鏡相比,高清結(jié)腸鏡使用了更加先進(jìn)的鏡頭、連接硬件和顯示器,可以呈現(xiàn)出更高分辨率的圖像,有利于內(nèi)窺鏡醫(yī)生對腸道進(jìn)行更加細(xì)致的觀察

.一項(xiàng)納入2468例患者的觀察性研究結(jié)果表明,高清結(jié)腸鏡檢查的ADR顯著高于標(biāo)準(zhǔn)結(jié)腸鏡檢查(30.4%

22.2%,

=0.02)

.此外,一項(xiàng)納入了6項(xiàng)隨機(jī)對照試驗(yàn)的薈萃分析發(fā)現(xiàn),與標(biāo)準(zhǔn)結(jié)腸鏡相比,高清結(jié)腸鏡不但可以提高總體ADR(40%

35%,

=0.001),而且可以顯著提高進(jìn)展期ADR(9.37%

6.69%,

=0.03)和無蒂鋸齒狀A(yù)DR(5.06%

3.39%,

=0.03)

.圖3.

1.3 進(jìn)鏡時(shí)間 目前,僅有少數(shù)研究探討了進(jìn)鏡時(shí)間對ADR的影響,各研究之間結(jié)果也存在差異.兩項(xiàng)研究根據(jù)進(jìn)鏡時(shí)間的四分位數(shù)將患者分為四組,探討了進(jìn)鏡時(shí)間對ADR的影響.Yang等

發(fā)現(xiàn)ADR隨進(jìn)鏡時(shí)間的延長而逐漸降低(36.8%

33.4%

32.7%

31.0%,

<0.01).von Renteln等

發(fā)現(xiàn)盡管總ADR與進(jìn)鏡時(shí)間無關(guān),但進(jìn)展期ADR隨著進(jìn)鏡時(shí)間的延長而逐漸降低(12.9%

10.9%

6.0%

5.0%,

<0.01).較長的進(jìn)鏡時(shí)間可能會(huì)導(dǎo)致內(nèi)窺鏡醫(yī)生的疲勞,從而降低ADR.然而,Fritz等

分析了1303例患者的結(jié)腸鏡檢查結(jié)果,發(fā)現(xiàn)進(jìn)鏡時(shí)間與退鏡時(shí)間的比值>1時(shí),腺瘤及進(jìn)展期腺瘤的檢出數(shù)量明顯降低,但當(dāng)退鏡時(shí)間足夠長時(shí),較長的進(jìn)鏡時(shí)間并不會(huì)降低ADR.

3.1 計(jì)算機(jī)輔助結(jié)腸鏡 計(jì)算機(jī)輔助結(jié)腸鏡是一種安裝了新型計(jì)算機(jī)輔助系統(tǒng)的結(jié)腸鏡.當(dāng)發(fā)現(xiàn)息肉時(shí),此系統(tǒng)會(huì)通過屏幕上的數(shù)字標(biāo)識(shí)或者聲音提示內(nèi)窺鏡醫(yī)生息肉的存在,實(shí)現(xiàn)息肉的自動(dòng)檢測

.一項(xiàng)隨機(jī)對照試驗(yàn)將1058例患者分為標(biāo)準(zhǔn)結(jié)腸鏡檢查組(

=536)和計(jì)算機(jī)輔助診斷組(

=522),比較了兩組的ADR;結(jié)果表明,計(jì)算機(jī)輔助診斷組的ADR顯著高于標(biāo)準(zhǔn)腸鏡檢查組(29.1%

20.3%,

<0.001)

.同樣,一項(xiàng)納入5項(xiàng)隨機(jī)對照試驗(yàn)的薈萃分析也發(fā)現(xiàn),與標(biāo)準(zhǔn)結(jié)腸鏡相比,計(jì)算機(jī)輔助結(jié)腸鏡ADR更高(36.6%

25.2%,

<0.01),且不受腺瘤大小、形態(tài)和位置的影響

.圖2.

2 醫(yī)生相關(guān)因素

1.4 體位改變 在結(jié)腸鏡檢查過程中,患者通常保持一個(gè)體位(左側(cè)臥位).近年來,有研究者提出退鏡過程改變體位可以提高ADR

.一項(xiàng)納入1072例進(jìn)行結(jié)腸鏡篩查患者的隨機(jī)對照試驗(yàn),將患者分為體位改變組(

=536)和單一體位組(

=536),探討了體位改變對ADR的影響,結(jié)果顯示,體位改變組的ADR顯著高于單一體位組(42.4%

33.0%,

=0.002)

.此外,一項(xiàng)納入了6項(xiàng)研究的薈萃分析結(jié)果也表明,與單一體位患者相比,體位改變患者的ADR更高(OR=1.36,95%CI=1.15-1.61,

<0.01)

.體位變化可以使內(nèi)窺鏡醫(yī)生觀察到單一體位檢查時(shí)容易忽略的腸道角落,并且有利于氣體撐開腸道,增加腸道黏膜的可視性,從而提高ADR.

第一，創(chuàng)建一個(gè)VI，在前面板上放置圖形顯示控件中的波形圖和Express XY圖，默認(rèn)的橫縱坐標(biāo)就可以，并將他們分別再復(fù)制兩個(gè)以作為顯示波形和頻譜。

2.2 醫(yī)生的專業(yè) 內(nèi)科醫(yī)生與外科醫(yī)生結(jié)腸鏡檢查的ADR不同,多項(xiàng)研究結(jié)果表明內(nèi)科醫(yī)生要比外科醫(yī)生更容易發(fā)現(xiàn)結(jié)直腸腺瘤

.Muthukuru等

分析了84名醫(yī)生進(jìn)行的4151例結(jié)腸鏡檢查結(jié)果,比較了消化內(nèi)科醫(yī)生、結(jié)直腸外科醫(yī)生和普通外科醫(yī)生的ADR,發(fā)現(xiàn)消化內(nèi)科醫(yī)生ADR最高(28.6%±1.2%),其次是結(jié)直腸外科醫(yī)生(24.3%±1.5%)和普通外科醫(yī)生(18.4%±2.3%).內(nèi)外科醫(yī)生ADR的差異可能是由于兩者內(nèi)窺鏡技術(shù)培訓(xùn)時(shí)長、完成結(jié)腸鏡檢查數(shù)量、性格特點(diǎn)及疲勞程度不同所致

.

3.3 Endocuff輔助結(jié)腸鏡 Endocuff輔助結(jié)腸鏡(endocuffassisted colonoscopy,EAC)是一種安裝在結(jié)腸鏡遠(yuǎn)端的輔助裝置,由一個(gè)軟塑料袖帶和側(cè)面的八個(gè)指狀突起組成;退鏡時(shí),Endocuff側(cè)面的突起會(huì)向后拉伸結(jié)腸黏膜皺襞,使黏膜皺襞充分展開,有助于內(nèi)窺鏡醫(yī)生發(fā)現(xiàn)在常規(guī)結(jié)腸鏡檢查中容易忽視的微小病變

.最近,一項(xiàng)納入2058例患者的隨機(jī)對照試驗(yàn)比較了標(biāo)準(zhǔn)結(jié)腸鏡檢查與EAC檢查的ADR,結(jié)果表明,接受EAC檢查患者的ADR要高于接受標(biāo)準(zhǔn)腸鏡檢查患者(39.2%

29.4%,

<0.001)

.既往一項(xiàng)納入了12項(xiàng)隨機(jī)對照試驗(yàn)的薈萃分析也發(fā)現(xiàn),與標(biāo)準(zhǔn)結(jié)腸鏡相比,EAC組的ADR更高(41.3%

34.2%,

=0.003)(圖4),且使用EAC不影響操作時(shí)間和回盲部到達(dá)率,總體操作也較為安全,值得在臨床應(yīng)用

.

在高等教育中，線性代數(shù)是最重要的基礎(chǔ)必修課程之一。選用的同濟(jì)大學(xué)第六版教材，可以滿足工科類本科數(shù)學(xué)基礎(chǔ)課程教學(xué)基本要求，卻被學(xué)生認(rèn)為是一門難度極大的課程。線性代數(shù)的學(xué)習(xí)難度，一方面來自于課程本身的高度抽象性；另一方面，課程要求學(xué)習(xí)者在較短的時(shí)間內(nèi)(一個(gè)學(xué)期)認(rèn)識(shí)了解一個(gè)新的研究對象以及相關(guān)的一套新的運(yùn)算規(guī)則。這些都與學(xué)生之前接觸的初等數(shù)學(xué)和高等數(shù)學(xué)規(guī)律有較大的差異，接受程度較低。

2.4 醫(yī)生的教育培訓(xùn) 部分內(nèi)窺鏡醫(yī)生的ADR較低可能是由于其對結(jié)腸鏡相關(guān)的知識(shí)和技術(shù)等方面掌握不足造成的.因此,對內(nèi)窺鏡醫(yī)生進(jìn)行相應(yīng)的教育培訓(xùn)可能會(huì)提高ADR.教育培訓(xùn)方式主要為組織內(nèi)窺鏡醫(yī)生觀看教學(xué)視頻和參加教育講座.兩項(xiàng)隨機(jī)對照試驗(yàn)發(fā)現(xiàn),內(nèi)窺鏡醫(yī)生接受教育培訓(xùn)后,ADR顯著提高

.然而,另一項(xiàng)隨機(jī)對照試驗(yàn)發(fā)現(xiàn),雖然接受教育培訓(xùn)的內(nèi)窺鏡醫(yī)生ADR由31%提高至42%,但是未接受教育培訓(xùn)的內(nèi)窺鏡醫(yī)生ADR也由36%提高至39%,且兩組間無統(tǒng)計(jì)學(xué)差異,因此無法確定教育培訓(xùn)是否可以提高ADR

.最近,針對這三項(xiàng)研究的薈萃分析證實(shí),培訓(xùn)教育是ADR的獨(dú)立危險(xiǎn)因素(OR=1.16,95%CI=1.00-1.34,

<0.05)

.綜上所述,有必要對內(nèi)窺鏡醫(yī)生進(jìn)行相應(yīng)的教育培訓(xùn),從而提高ADR.

3 設(shè)備相關(guān)因素

1.6 右半結(jié)腸再次直視退鏡技術(shù)與結(jié)腸鏡反轉(zhuǎn)技術(shù) 與左半結(jié)腸相比,右半結(jié)腸腺瘤較平坦,在結(jié)腸鏡檢查更易被忽略,導(dǎo)致漏診率更高.再次直視退鏡技術(shù)與結(jié)腸鏡反轉(zhuǎn)技術(shù)是提高右半結(jié)腸ADR的兩種方式.右半結(jié)腸再次直視退鏡技術(shù)是指進(jìn)行常規(guī)結(jié)腸鏡檢查后,再次對右半結(jié)腸進(jìn)行直視退鏡觀察;右半結(jié)腸結(jié)腸鏡反轉(zhuǎn)技術(shù)是指常規(guī)結(jié)腸鏡檢查后,在回盲部等位置將鏡身反轉(zhuǎn),觀察直視退鏡時(shí)易被忽略的腸道皺襞.一項(xiàng)隨機(jī)對照試驗(yàn)將648例患者分為再次直視退鏡組(

=332)和內(nèi)鏡反轉(zhuǎn)組(

=316),再次直視退鏡組和內(nèi)鏡反轉(zhuǎn)組的右半結(jié)腸ADR比常規(guī)退鏡分別提高了12%與9%

.此外,一項(xiàng)納入了4項(xiàng)研究的薈萃分析也發(fā)現(xiàn),內(nèi)鏡反轉(zhuǎn)組(28.4%

22.7%,

<0.01)和再次直視退鏡組的右半結(jié)腸ADR比常規(guī)退鏡均更高(33.6%

26.7,

<0.01)

.

等他布下子，烏有先生嘴里的嘮叨卻停了下來，眼睛里忽然泛起驚奇的神光，那邊廂，子虛道人的眉頭，也緊緊地皺起來，七八道皺紋成列，好像疊起來的石片一樣。

2.3 醫(yī)生的性格特征 目前,僅有兩項(xiàng)研究探討了醫(yī)生性格特征對ADR的影響.強(qiáng)迫程度高、更加仔細(xì)的內(nèi)窺鏡醫(yī)生的ADR更高,這可能是因?yàn)閺?qiáng)迫程度高和更加仔細(xì)的內(nèi)窺鏡醫(yī)生在結(jié)腸鏡檢查中觀察更加細(xì)致,從而可以發(fā)現(xiàn)更多的微小息肉

.此外,自我調(diào)節(jié)能力越強(qiáng)的內(nèi)窺鏡醫(yī)生ADR更高.他們受各種環(huán)境因素的影響較小,能時(shí)刻保持情緒穩(wěn)定并且輕松應(yīng)對內(nèi)外界的各種壓力,在結(jié)腸鏡檢查過程中也能更加專注

.

3.4 G-EYE氣囊內(nèi)鏡 G-EYE氣囊內(nèi)鏡是在標(biāo)準(zhǔn)結(jié)腸鏡的遠(yuǎn)端安裝一個(gè)可重復(fù)使用的充氣球囊,它可以展平腸褶皺并減少腸滑脫.退鏡時(shí),充氣球囊也可以使光線集中,增強(qiáng)結(jié)腸黏膜的可視化

.一項(xiàng)隨機(jī)對照試驗(yàn)將803例患者分為氣囊內(nèi)鏡組(

=407)和標(biāo)準(zhǔn)結(jié)腸鏡組(

=396),探討了氣囊內(nèi)鏡對ADR的影響,結(jié)果表明,氣囊內(nèi)鏡組ADR明顯高于標(biāo)準(zhǔn)結(jié)腸鏡組(48.0%

37.5%,

=0.0027),并且氣囊內(nèi)鏡可以顯著增加進(jìn)展期腺瘤(109

67,

=0.033)、扁平腺瘤(85

35,

<0.0001)和無蒂鋸齒狀腺瘤或息肉(20

3,

=0.0026)的檢出數(shù)量

.此外,另一項(xiàng)納入126例患者的隨機(jī)對照試驗(yàn)發(fā)現(xiàn),雖然兩組間的ADR無顯著差異,但氣囊內(nèi)鏡組腺瘤漏檢率更低(7.5%

44.7%,

=0.0002)

.

3.5 透明帽輔助水交換結(jié)腸鏡 透明帽輔助結(jié)腸鏡是指在結(jié)腸鏡前端安裝一個(gè)透明的塑料帽,有利于退鏡時(shí)結(jié)腸黏膜的暴露,增加結(jié)腸黏膜的可視性

.水交換結(jié)腸鏡是指在結(jié)腸鏡檢查過程中向腸腔內(nèi)注入溫水替代空氣或二氧化碳,可以增加患者的舒適度

.既往研究已證明,兩種腸鏡均可提高ADR

.近期兩項(xiàng)隨機(jī)對照研究探討了兩種腸鏡聯(lián)合應(yīng)用對ADR的影響,結(jié)果發(fā)現(xiàn),與標(biāo)準(zhǔn)結(jié)腸鏡組相比,透明帽輔助水交換結(jié)腸鏡組有更短的進(jìn)鏡時(shí)間,更低的疼痛評分以及更高的ADR

.綜上,透明帽輔助水交換結(jié)腸鏡不僅可以使盲腸插鏡時(shí)間縮短,減輕患者痛苦,還可以提高ADR,臨床應(yīng)用價(jià)值很高.

3.6 其它技術(shù)及設(shè)備 增強(qiáng)成像技術(shù)(染色內(nèi)鏡、窄帶成像、智能分光比色技術(shù)、藍(lán)激光成像)以及增加視野的新型內(nèi)鏡(全譜內(nèi)鏡、超廣角內(nèi)鏡、共聚焦內(nèi)鏡)均可能影響ADR.一項(xiàng)納入了74項(xiàng)研究的薈萃分析發(fā)現(xiàn),與高清結(jié)腸鏡檢查組相比,增強(qiáng)成像技術(shù)結(jié)腸鏡檢查組ADR顯著更高(OR=1.21,95%CI=1.09-1.35,

<0.05),但增加視野的新型內(nèi)鏡(OR=0.98,95%CI=0.79-1.21,

>0.05)與提高ADR無關(guān)

.然而,一項(xiàng)研究回顧分析了3998例行結(jié)腸鏡檢查患者的數(shù)據(jù),發(fā)現(xiàn)增加視野的新型內(nèi)鏡檢查組ADR顯著高于普通結(jié)腸檢查組

.隨著科學(xué)技術(shù)的發(fā)展進(jìn)步,新型結(jié)腸鏡設(shè)備層出不窮,但是他們提高ADR的效果還有待進(jìn)一步的臨床驗(yàn)證.

4 其他因素

除上述因素外,其他因素也可能影響ADR,如麻醉輔助結(jié)腸鏡、年齡、性別、結(jié)直腸腺瘤家族史等.一項(xiàng)納入了24795例結(jié)腸鏡檢查的回顧性研究發(fā)現(xiàn),麻醉輔助結(jié)腸鏡是ADR獨(dú)立風(fēng)險(xiǎn)因素(OR=1.45,95%CI=1.00-2.10)

,但另一項(xiàng)納入了48838例結(jié)腸鏡檢查的回顧性研究卻發(fā)現(xiàn),麻醉輔助結(jié)腸鏡檢查的ADR與普通結(jié)腸鏡檢查之間并無差別(13.0%

12.44%,

=0.337)

.因此,麻醉輔助結(jié)腸鏡檢查能否提高ADR尚有爭議.目前研究發(fā)現(xiàn),50歲以上人群的ADR要顯著高于50歲以下人群

.這可能是因?yàn)槟挲g越大,暴露在各種危險(xiǎn)因素中(如吸煙,飲酒等)的時(shí)間越長,因此增加了結(jié)直腸腺瘤的發(fā)生幾率

.男性的ADR要顯著高于女性

,這是由于雌性激素作用于β雌激素受體可阻滯G1期細(xì)胞周期,從而抑制結(jié)腸癌細(xì)胞的增殖

.此外,有結(jié)直腸腺瘤家族史人群的ADR要顯著高于整體人群

.這可能與一些遺傳易感基因改變有關(guān),如染色體8 q 24區(qū)域rs6983267基因位點(diǎn)的變異會(huì)顯著增加結(jié)直腸腺瘤的發(fā)生風(fēng)險(xiǎn)

.綜上,與整體人群相比,年齡較大、男性、有結(jié)直腸腺瘤家族史的人群更應(yīng)該定期進(jìn)行結(jié)腸鏡檢查,從而降低結(jié)直腸癌的發(fā)病率及死亡率.

5 結(jié)論

隨著人們健康意識(shí)的提高以及消化道早癌篩查觀念的普及,主動(dòng)接受消化內(nèi)鏡檢查的居民數(shù)量顯著增加.然而,我國各地區(qū)的社會(huì)經(jīng)濟(jì)水平存在差異,醫(yī)療資源分布配置不平衡,制約了我國基礎(chǔ)醫(yī)療水平的提升,也使結(jié)腸鏡檢查質(zhì)量存在差異.ADR是衡量結(jié)腸鏡檢查質(zhì)量的關(guān)鍵指標(biāo)之一,因此充分認(rèn)識(shí)影響ADR的相關(guān)因素并且從這些方面著手提高ADR是非常必要的.保證充足的腸道質(zhì)量,適當(dāng)?shù)倪M(jìn)、退鏡時(shí)間,同時(shí)結(jié)合不同的退鏡方式和改變患者體位是提高ADR的有效手段.此外,有條件的醫(yī)院可以通過安排第二人參與觀察、加強(qiáng)對內(nèi)窺鏡醫(yī)生的教育培訓(xùn)和應(yīng)用新型的結(jié)腸鏡檢查設(shè)備等方式,提高結(jié)腸鏡檢查過程中的ADR(圖5),為結(jié)直腸癌防治工作做出更大的貢獻(xiàn).

1 鄭榮壽,孫可欣,張思維,曾紅梅,鄒小農(nóng),陳茹,顧秀瑛,魏文強(qiáng),赫捷.2015年中國惡性腫瘤流行情況分析.中華腫瘤雜志 2019;1:19-28 [DOI:10.3760/cma.j.issn.0253-3766.2019.01.005]

2 陳萬青,李霓,蘭平,陳宏達(dá),杜靈彬,孫鳳,黎國威,何曉生,王樂,李子一,朱陳,盧明,曹毛毛,孫殿欽,何思怡,李賀,楊卓煜.中國結(jié)直腸癌篩查與早診早治指南(2020,北京).中國腫瘤 2021;30:1-28[DOI:10.11735/j.issn.1004-0242.2021.01.A001]

3 Rees CJ,Thomas Gibson S,Rutter MD,Baragwanath P,Pullan R,Feeney M,Haslam N;British Society of Gastroenterology,the Joint Advisory Group on GI Endoscopy,the Association of Coloproctology of Great Britain and Ireland.UK key performance indicators and quality assurance standards for colonoscopy.

2016;65:1923-1929 [PMID:27531829 DOI:10.1136/gutjnl-2016-312044]

4 Rex DK,Schoenfeld PS,Cohen J,Pike IM,Adler DG,Fennerty MB,Lieb JG 2nd,Park WG,Rizk MK,Sawhney MS,Shaheen NJ,Wani S,Weinberg DS.Quality indicators for colonoscopy.

2015;110:72-90 [PMID:25448873 DOI:10.1038/ajg.2014.385]

5 Guo R,Wang YJ,Liu M,Ge J,Zhang LY,Ma L,Huang WY,Zhai HH.The effect of quality of segmental bowel preparation on adenoma detection rate.

2019;19:119 [PMID:31286888 DOI:10.1186/s12876-019-1019-8]

6 Lebwohl B,Kastrinos F,Glick M,Rosenbaum AJ,Wang T,Neugut AI.The impact of suboptimal bowel preparation on adenoma miss rates and the factors associated with early repeat colonoscopy.

2011;73:1207-1214 [PMID:21481857 DOI:10.1016/j.gie.2011.01.051]

7 Clark BT,Rustagi T,Laine L.What level of bowel prep quality requires early repeat colonoscopy:systematic review and metaanalysis of the impact of preparation quality on adenoma detection rate.

2014;109:1714-23;quiz 1724[PMID:25135006 DOI:10.1038/ajg.2014.232]

8 Tholey DM,Shelton CE,Francis G,Anantharaman A,Frankel RA,Shah P,Coan A,Hegarty SE,Leiby BE,Kastenberg DM.Adenoma detection in excellent versus good bowel preparation for colonoscopy.

2015;49:313-319 [PMID:25494362 DOI:10.1097/mcg.0000000000000270]

9 Choi JM,Seo JY,Lee J,Han YM,Jin EH,Bae JH,Lim JH.Longer Withdrawal Time Is More Important than Excellent Bowel Preparation in Colonoscopy of Adequate Bowel Preparation.

2021;66:1168-1174 [PMID:32419115 DOI:10.1007/s10620-020-06321-3]

10 Yousaf MS,Shafqat S,Gill RC,Khursheed AA,Parkash O.Adenoma detection rate as a quality indicator for colonoscopy:a descriptive cross-sectional study from a tertiary care hospital in Pakistan.

2020;8:E1707-E1712 [PMID:33140028 DOI:10.1055/a-1244-1646]

11 Calderwood AH,Thompson KD,Schroy PC 3rd,Lieberman DA,Jacobson BC.Good is better than excellent:bowel preparation quality and adenoma detection rates.

2015;81:691-699.e1 [PMID:25708756 DOI:10.1016/j.gie.2014.10.032]

12 Kashiwagi K,Inoue N,Yoshida T,Bessyo R,Yoneno K,Imaeda H,Ogata H,Kanai T,Sugino Y,Iwao Y.Polyp detection rate in transverse and sigmoid colon significantly increases with longer withdrawal time during screening colonoscopy.

2017;12:e0174155 [PMID:28328936 DOI:10.1371/journal.pone.0174155]

13 Jung Y,Joo YE,Kim HG,Jeon SR,Cha JM,Yang HJ,Kim JW,Lee J,Kim KO,Song HK,Hwangbo Y,Shin JE.Relationship between the endoscopic withdrawal time and adenoma/polyp detection rate in individual colonic segments:a KASID multicenter study.

2019;89:523-530 [PMID:30267654 DOI:10.1016/j.gie.2018.09.016]

14 Lee TJ,Blanks RG,Rees CJ,Wright KC,Nickerson C,Moss SM,Chilton A,Goddard AF,Patnick J,McNally RJ,Rutter MD.Longer mean colonoscopy withdrawal time is associated with increased adenoma detection:evidence from the Bowel Cancer Screening Programme in England.

2013;45:20-26 [PMID:23254403 DOI:10.1055/s-0032-1325803]

15 Patel VD,Thompson WK,Lapin BR,Goldstein JL,Yen EF.Screening Colonoscopy Withdrawal Time Threshold for Adequate Proximal Serrated Polyp Detection Rate.

2018;63:3084-3090 [PMID:29974376 DOI:10.1007/s10620-018-5187-0]

16 Yang MH,Cho J,Rampal S,Choi EK,Choi YH,Lee JH,Kim YH,Chang DK,Rhee PL,Kim JJ,Guallar E,Rhee JC,Son HJ.The association between cecal insertion time and colorectal neoplasm detection.

2013;13:124 [PMID:23915303 DOI:10.1186/1471-230x-13-124]

17 von Renteln D,Robertson DJ,Bensen S,Pohl H.Prolonged cecal insertion time is associated with decreased adenoma detection.

2017;85:574-580 [PMID:27590962 DOI:10.1016/j.gie.2016.08.021]

18 Fritz CDL,Smith ZL,Elsner J,Hollander T,Early D,Kushnir V.Prolonged Cecal Insertion Time Is Not Associated with Decreased Adenoma Detection When a Longer Withdrawal Time Is Achieved.

2018;63:3120-3125 [PMID:29721773 DOI:10.1007/s10620-018-5100-x]

19 Lee SW,Chang JH,Ji JS,Maeong IH,Cheung DY,Kim JS,Cho YS,Chung WJ,Lee BI,Kim SW,Kim BW,Choi H,Choi MG.Effect of Dynamic Position Changes on Adenoma Detection During Colonoscope Withdrawal:A Randomized Controlled Multicenter Trial.

2016;111:63-69 [PMID:26526085 DOI:10.1038/ajg.2015.354]

20 Nutalapati V,Desai M,Thoguluva-Chandrasekar VS,Olyaee M,Rastogi A.Effect of dynamic position changes on adenoma detection rate during colonoscope withdrawal:systematic review and meta-analysis.

2020;8:E1842-E1849 [PMID:33269319 DOI:10.1055/a-1265-6634]

21 Facciorusso A,Buccino VR,Tonti P,Licinio R,Del Prete V,Neve V,Di Maso M,Muscatiello N.Impact of fellow participation on colon adenoma detection rates:a multicenter randomized trial.

2020;92:1228-1235 [PMID:32433915 DOI:10.1016/j.gie.2020.05.015]

22 Wang W,Xu L,Bao Z,Sun L,Hu C,Zhou F,Xu L,Shi D.Differences with experienced nurse assistance during colonoscopy in detecting polyp and adenoma:a randomized clinical trial.

2018;33:561-566 [PMID:29541895 DOI:10.1007/s00384-018-3003-0]

23 Chalifoux SL,Rao DS,Wani SB,Sharma P,Bansal A,Gupta N,Rastogi A.Trainee participation and adenoma detection rates during screening colonoscopies.

2014;48:524-529 [PMID:24440932 DOI:10.1097/mcg.0000000000000022]

24 Aziz M,Weissman S,Khan Z,Fatima R,Lee-Smith W,Nawras A,Adler DG.Use of 2 Observers Increases Adenoma Detection Rate During Colonoscopy:Systematic Review and Meta-analysis.

2020;18:1240-1242.e3 [PMID:31589976 DOI:10.1016/j.cgh.2019.07.033]

25 Nú?ez Rodríguez MH,Díez Redondo P,Riu Pons F,Cimavilla M,Hernández L,Loza A,Pérez-Miranda M.Proximal retroflexion versus second forward view of the right colon during screening colonoscopy:A multicentre randomized controlled trial.

2020;8:725-735 [PMID:32379535 DOI:10.1177/2050640620924210]

26 Desai M,Bilal M,Hamade N,Gorrepati VS,Thoguluva Chandrasekar V,Jegadeesan R,Gupta N,Bhandari P,Repici A,Hassan C,Sharma P.Increasing adenoma detection rates in the right side of the colon comparing retroflexion with a second forward view:a systematic review.

2019;89:453-459.e3 [PMID:30222971 DOI:10.1016/j.gie.2018.09.006]

27 Jung Y,Cha JM,Lee NH,Joo YE,Lee YJ,Kim HG,Jeon SR,Shin JE,Yang HJ,Lee J,Kim KO,Kim JW,Na SY,Boo SJ,Kim JH,Han MJ,Hwangbo Y,Huh KC.Impact of Endoscopists’ Personality Traits on Adenoma and Polyp Detection Rates in Colonoscopy:A KASID Multicenter Study.

2020;65:2302-2310 [PMID:32157497 DOI:10.1007/s10620-020-06158-w]

28 Pace D,Borgaonkar M,Lougheed M,Marcoux C,Evans B,Hickey N,O’Leary M,Boone D,McGrath J.Effect of Colonoscopy Volume on Quality Indicators.

2016;2016:2580894 [PMID:27446831 DOI:10.1155/2016/2580894]

29 Zorron Cheng Tao Pu L,Lu K,Ovenden A,Rana K,Singh G,Krishnamurthi S,Edwards S,Wilson B,Nakamura M,Yamamura T,Ruszkiewicz A,Hirooka Y,Burt AD,Singh R.Effect of time of day and specialty on polyp detection rates in Australia.

2019;34:899-906 [PMID:30552716 DOI:10.1111/jgh.14566]

30 Muthukuru S,Alomari M,Bisen R,Parikh MP,Al Momani L,Talal Sarmini M,Lopez R,Muthukuru S,Thota PN,Sanaka MR.Quality of Colonoscopy:A Comparison Between Gastroenterologists and Nongastroenterologists.

2020;63:980-987 [PMID:32496332 DOI:10.1097/dcr.0000000000001659]

31 Ezaz G,Leffler DA,Beach S,Schoen RE,Crockett SD,Gourevitch RA,Rose S,Morris M,Carrell DS,Greer JB,Mehrotra A.Association Between Endoscopist Personality and Rate of Adenoma Detection.

2019;17:1571-1579.e7 [PMID:30326300 DOI:10.1016/j.cgh.2018.10.019]

32 Coe SG,Crook JE,Diehl NN,Wallace MB.An endoscopic quality improvement program improves detection of colorectal adenomas.

2013;108:219-26;quiz 227 [PMID:23295274 DOI:10.1038/ajg.2012.417]

33 Kaminski MF,Anderson J,Valori R,Kraszewska E,Rupinski M,Pachlewski J,Wronska E,Bretthauer M,Thomas-Gibson S,Kuipers EJ,Regula J.Leadership training to improve adenoma detection rate in screening colonoscopy:a randomised trial.

2016;65:616-624[PMID:25670810 DOI:10.1136/gutjnl-2014-307503]

34 Wallace MB,Crook JE,Thomas CS,Staggs E,Parker L,Rex DK.Effect of an endoscopic quality improvement program on adenoma detection rates:a multicenter cluster-randomized controlled trial in a clinical practice setting (EQUIP-3).

2017;85:538-545.e4 [PMID:27473182 DOI:10.1016/j.gie.2016.07.042]

35 Lim S,Hammond S,Park J,Hochman D,Lê ML,Rabbani R,Abou-Setta A,Zarychanski R.Training interventions to improve adenoma detection rates during colonoscopy:a systematic review and meta-analysis.

2020;34:3870-3882 [PMID:31595401 DOI:10.1007/s00464-019-07153-7]

36 Kudo SE,Mori Y,Misawa M,Takeda K,Kudo T,Itoh H,Oda M,Mori K.Artificial intelligence and colonoscopy:Current status and future perspectives.

2019;31:363-371 [PMID:30624835 DOI:10.1111/den.13340]

37 Wang P,Berzin TM,Glissen Brown JR,Bharadwaj S,Becq A,Xiao X,Liu P,Li L,Song Y,Zhang D,Li Y,Xu G,Tu M,Liu X.Realtime automatic detection system increases colonoscopic polyp and adenoma detection rates:a prospective randomised controlled study.

2019;68:1813-1819 [PMID:30814121 DOI:10.1136/gutjnl-2018-317500]

38 Hassan C,Spadaccini M,Iannone A,Maselli R,Jovani M,Chandrasekar VT,Antonelli G,Yu H,Areia M,Dinis-Ribeiro M,Bhandari P,Sharma P,Rex DK,R?sch T,Wallace M,Repici A.Performance of artificial intelligence in colonoscopy for adenoma and polyp detection:a systematic review and meta-analysis.

2021;93:77-85.e6 [PMID:32598963 DOI:10.1016/j.gie.2020.06.059]

39 Jrebi NY,Hefty M,Jalouta T,Ogilvie J,Davis AT,Asgeirsson T,Luchtefeld M.High-definition colonoscopy increases adenoma detection rate.

2017;31:78-84 [PMID:27287897 DOI:10.1007/s00464-016-4986-7]

40 Tziatzios G,Gkolfakis P,Lazaridis LD,Facciorusso A,Antonelli G,Hassan C,Repici A,Sharma P,Rex DK,Triantafyllou K.Highdefinition colonoscopy for improving adenoma detection:a systematic review and meta-analysis of randomized controlled studies.

2020;91:1027-1036.e9 [PMID:31954133 DOI:10.1016/j.gie.2019.12.052]

41 Rivero-Sánchez L,López Vicente J,Hernandez Villalba L,Puig I,Arnau-Collell C,Moreno L,Díaz M,Rodriguez de Miguel C,Oca?a T,Moreira L,Cuatrecasas M,Carballal S,Sánchez A,Ortiz O,Llach J,Balaguer F,Pellisé M;EndoCAR group from the Spanish Gastroenterology Association and the Spanish Society of Digestive Endoscopy.Endocuff-assisted colonoscopy for surveillance of serrated polyposis syndrome:a multicenter randomized controlled trial.

2019;51:637-645 [PMID:31174224 DOI:10.1055/a-0925-4956]

42 Karsenti D,Tharsis G,Perrot B,Cattan P,Tordjman G,Venezia F,Zrihen E,Gillot D,Gillet A,Hagege C,Samama J,Etienney I,Lab JP,Guigui B,Zago J,Benkessou B,Burtin P,Cavicchi M.Adenoma detection by Endocuff-assisted versus standard colonoscopy in routine practice:a cluster-randomised crossover trial.

2020;69:2159-2164 [PMID:32209605 DOI:10.1136/gutjnl-2019-319565]

43 Williet N,Tournier Q,Vernet C,Dumas O,Rinaldi L,Roblin X,Phelip JM,Pioche M.Effect of Endocuff-assisted colonoscopy on adenoma detection rate:meta-analysis of randomized controlled trials.

2018;50:846-860 [PMID:29698990 DOI:10.1055/a-0577-3500]

44 Halpern Z,Gross SA,Gralnek IM,Shpak B,Pochapin M,Hoffman A,Mizrahi M,Rochberger YS,Moshkowitz M,Santo E,Melhem A,Grinshpon R,Pfefer J,Kiesslich R.Comparison of adenoma detection and miss rates between a novel balloon colonoscope and standard colonoscopy:a randomized tandem study.

2015;47:238-244 [PMID:25704662 DOI:10.1055/s-0034-1391437]

45 Shirin H,Shpak B,Epshtein J,Karstensen JG,Hoffman A,de Ridder R,Testoni PA,Ishaq S,Reddy DN,Gross SA,Neumann H,Goetz M,Abramowich D,Moshkowitz M,Mizrahi M,Vilmann P,Rey JW,Sanduleanu-Dascalescu S,Viale E,Chaudhari H,Pochapin MB,Yair M,Shnell M,Yaari S,Hendel JW,Teubner D,Bogie RMM,Notaristefano C,Simantov R,Gluck N,Israeli E,Stigaard T,Matalon S,Vilkin A,Benson A,Sloth S,Maliar A,Waizbard A,Jacob H,Thielsen P,Shachar E,Rochberger S,Hershcovici T,Plougmann JI,Braverman M,Tsvang E,Abedi AA,Brachman Y,Siersema PD,Kiesslich R.G-EYE colonoscopy is superior to standard colonoscopy for increasing adenoma detection rate:an international randomized controlled trial (with videos).

2019;89:545-553 [PMID:30273591 DOI:10.1016/j.gie.2018.09.028]

46 李永強(qiáng),英崧嵩,馮志強(qiáng).透明帽輔助水交換結(jié)腸鏡技術(shù)在腸鏡篩查中的應(yīng)用.臨床醫(yī)學(xué)工程 2016;23:841-842 [DOI:10.3969/j.issn.1674-4659.2016.07.0841]

47 Facciorusso A,Triantafyllou K,Murad MH,Prokop LJ,Tziatzios G,Muscatiello N,Singh S.Compared Abilities of Endoscopic Techniques to Increase Colon Adenoma Detection Rates:A Network Meta-analysis.

2019;17:2439-2454.e25 [PMID:30529731 DOI:10.1016/j.cgh.2018.11.058]

48 張宗勝,陳明仁,韓燕燕,李衛(wèi)娜.透明帽輔助水交換結(jié)腸鏡技術(shù)在腸鏡檢查中的應(yīng)用.中國民間療法 2019;27:77-78 [DOI:10.19621/j.cnki.11-3555/r.2019.2340]

49 Nulsen B,Ungaro RC,Davis N,Turvall E,Deutsch L,Lewis B.Changes in Adenoma Detection Rate With Implementation of Fullspectrum Endoscopy:A Report of 3998 Screening Colonoscopies.

2018;52:885-890 [PMID:28787359 DOI:10.1097/mcg.0000000000000874]

50 Khan F,Hur C,Lebwohl B,Krigel A.Unsedated Colonoscopy:Impact on Quality Indicators.

2020;65:3116-3122[PMID:32696236 DOI:10.1007/s10620-020-06491-0]

51 Zhao S,Deng XL,Wang L,Ye JW,Liu ZY,Huang B,Kan Y,Liu BH,Zhang AP,Li CX,Li F,Tong WD.The impact of sedation on quality metrics of colonoscopy:a single-center experience of 48,838 procedures.

2020;35:1155-1161 [PMID:32300884 DOI:10.1007/s00384-020-03586-y]

52 Barret M,Boustiere C,Canard JM,Arpurt JP,Bernardini D,Bulois P,Chaussade S,Heresbach D,Joly I,Lapuelle J,Laugier R,Lesur G,Pienkowski P,Ponchon T,Pujol B,Richard-Molard B,Robaszkiewicz M,Systchenko R,Abbas F,Schott-Pethelaz AM,Cellier C;Société Fran?aise d’Endoscopie Digestive.Factors associated with adenoma detection rate and diagnosis of polyps and colorectal cancer during colonoscopy in France:results of a prospective,nationwide survey.

2013;8:e68947 [PMID:23874822 DOI:10.1371/journal.pone.0068947]

53 Hemmasi G,Sohrabi M,Zamani F,Ajdarkosh H,Rakhshani N,Khoonsari M,Ameli M,Hatami K.Prevalence of colorectal adenoma in an average-risk population aged 40-50 versus 50-60 years.

2015;24:386-390 [PMID:25380192 DOI:10.1097/cej.0000000000000097]

54 Murphy N,Strickler HD,Stanczyk FZ,Xue X,Wassertheil-Smoller S,Rohan TE,Ho GY,Anderson GL,Potter JD,Gunter MJ.A Prospective Evaluation of Endogenous Sex Hormone Levels and Colorectal Cancer Risk in Postmenopausal Women.

2015;107 [PMID:26232761 DOI:10.1093/jnci/djv210]

55 Wang H,Wang P,Liu X,Li L,Xiao X,Liu P,Zhang D,Li Y,Xu G,Tu M,Song Y.Factors predicting the colorectal adenoma detection rate in colonoscopic screening of a Chinese population:A prospective study.

2019;98:e15103 [PMID:30985664 DOI:10.1097/md.0000000000015103]

56 Montazeri Z,Theodoratou E,Nyiraneza C,Timofeeva M,Chen W,Svinti V,Sivakumaran S,Gresham G,Cubitt L,Carvajal-Carmona L,Bertagnolli MM,Zauber AG,Tomlinson I,Farrington SM,Dunlop MG,Campbell H,Little J.Systematic meta-analyses and field synopsis of genetic association studies in colorectal adenomas.

2016;45:186-205 [PMID:26451011 DOI:10.1093/ije/dyv185]