修回日期: 2012-10-16
接受日期: 2012-11-07
在线出版日期: 2012-11-18
结直肠癌(colorectal cancer, CRC)是全球范围内最常见的恶性肿瘤之一, 其大多数由腺瘤等癌前病变进展而来. 因此, 及早发现并切除肠道腺瘤是预防其癌变的关键. 目前, 结肠镜检查被公认为是诊断和治疗肠道病变的金标准, 但常规肠镜检查对病灶有一定漏诊率. Rex等研究表明腺瘤≥1 cm时漏诊率为6%, 6-9 mm时为13%, ≤5 mm时为27%; 并且右半结肠腺瘤的漏诊率要高于左半结肠. 肠镜下漏诊腺瘤或恶性肿瘤势必会增加外科手术率和患者死亡率. 因此, 为了提高肠镜下腺瘤的检出率, 国内外的一些学者作了大量的研究工作, 并取得了一定的成果. 本文就提高内镜下肠道腺瘤检出率的一些技术和方法作一简要综述.
引文著录: 许吉成, 刘冰熔. 内镜技术在提高肠道腺瘤检出率中的应用. 世界华人消化杂志 2012; 20(32): 3118-3123
Revised: October 16, 2012
Accepted: November 7, 2012
Published online: November 18, 2012
Colorectal cancer (CRC) is one of the most common malignant neoplasms worldwide and develops mostly from precancerous lesions such as colorectal adenomas. Therefore, early detection and resection of colorectal adenomas is key to preventing CRC. At present, colonoscopy is acknowledged as the gold standard for the diagnosis and treatment of colorectal lesions; however, conventional colonoscopy is still associated with a certain rate of missed lesions. It is reported that the missed detection rate is 6% when adenomas are more than 1 cm, 13% for adenomas 6-9 mm, and 27% for adenomas less than 5 mm. The missed detection rate for right colonic adenomas is higher than that for left colonic adenomas. The missed diagnosis of colorectal adenomas or malignant tumors invariably increases surgical rate and mortality. Currently, great efforts have been made to improve the detection rate of colorectal adenomas. This paper will briefly review recent advances in endoscopic techniques for improving the detection rate of colorectal adenomas.
- Citation: Xu JC, Liu BR. Endoscopic techniques for improving colorectal adenoma detection: Recent progress. Shijie Huaren Xiaohua Zazhi 2012; 20(32): 3118-3123
- URL: https://www.wjgnet.com/1009-3079/full/v20/i32/3118.htm
- DOI: https://dx.doi.org/10.11569/wcjd.v20.i32.3118
肠镜的应用减少了结直肠癌(colorectal cancer, CRC)的发病率和死亡率, 这不仅仅是发现早期癌的缘故, 更是由于将检出的腺瘤作为癌前病变及时切除的结果. 因此, 腺瘤的检出率已经成为衡量肠镜质量的指标之一. 但是大量文献报道, 即使有经验的内镜医师再细心操作也会对较小的腺瘤有一定的漏诊率[1]. 原因就在于结肠的解剖结构中如袋状皱襞、直肠瓣、回盲瓣和转弯处易隐藏腺瘤而很难被发现. 因此, 为了提高肠镜下的腺瘤检出率, 国内外的一些学者作了大量的研究工作, 并取得了一定的成果. 本文就提高内镜下肠道腺瘤检出率的一些技术和方法作一简要综述.
放大内镜(high-definition colonoscopy, HDC)是一种具有高像素和高分辨率的内镜, 可使肉眼直观所见到的黏膜组织被不同程度放大, 可达到与解剖显微镜近乎相同的观察水平, 有利于观察微细结构变化. 与普通肠镜相比, 在理论上有一定优势, 然而却与一些相关报道的结果不一致. Buchner等[2]和Tribonias等[3]分别在HDC能否提高肠道腺瘤检出率方面做了对照研究. 前者回顾性分析了2 430名患者分别使用HDC和普通白光肠镜组(standard white-light colonoscopy, SWLC)进行检测的结果, HDC组为170度广角内镜必要时联(narrow-band imaging, NBIF), SWLC组为SC(standard colonoscopy, SC), 不使用窄带成像技术(narrow-band imaging, NBI). 结果显示, HDC组较SWLC组有更高的腺瘤检出率(28.8% vs 24.3%, P = 0.012); 后者前瞻性的将390名患者随机分为两组, 即HDC组与SWLC组, 结果亦显示HDC组在肠道腺瘤检出率上有一定优势. 但有些学者对此却持相反意见. 较早的报道来自于East等[4]对130名受试者的随机对照研究, 结果显示与SC相比, HDC并未提高肠道的腺瘤检出率. 随后Pellisé等[5]和Burke等[6]亦通过实验证实了这一点. 最近, Subramanian等[7]做了一项关于HDC对肠道腺瘤检出率的Meta分析, 该分析共纳入了5个相关实验和4 422名受试者, 结果表明HDC未能提高肠道腺瘤的检出率. Erim等[8]回顾性分析了900名患者行肠道腺瘤检出率的对照研究, 该研究选取了3名内镜医师在HDC和SWLC下分别检查的150例患者, 结果经统计学分析表明与SWLC相比HDC并未提高肠道腺瘤的检出率. 尽管回顾性研究有一定局限性, 但是其最大的优点就是减少了操作者的偏倚, 保证了数据的准确性. 由此可见, 在肠道腺瘤检出率方面, HDC较普通内镜并没有明显的提高, 其优势可能会在与其他内镜技术联合中得到体现, 这需要进一步的研究.
色素内镜是指在内镜常规检查的基础上, 辅助使用色素制剂及染料, 以增加病变与正常组织对比度, 使病灶的形态、范围更为清晰. 目前较为常用的有靛胭脂染色和亚甲蓝染色. 研究表明与SC相比, 全结肠色素内镜可以提高肠道腺瘤的检出率[9,10]. 国内俞力等[11]将常规内镜、窄带内镜、全结肠色素内镜及全结肠醋酸喷洒在结肠病变发现率上做了一项对比研究. 该实验共纳入240名患者随机化分为4组: 常规内镜组61例、窄带内镜组63例、全结肠色素内镜组54例、醋酸染色组62例. 观察其病变的发现率, 结果显示全结肠色素内镜及全结肠醋酸喷洒科提高结肠病变的检出率, 前者可提高扁平病变的发现率, 后者可提高隆起性病变的发现率. Matsumoto等[12]对13名家族性腺瘤性息肉病患者同时行SC、色素内镜、NBI和自发荧光内镜(autofluorescence imaging, AFI)检查, 比较其腺瘤检出率. 结果表明色素内镜(43.3±38.5)较SC(12.2±13.9, P = 0. 005), AFI(21.4±27.5, P = 0.0006)和NBI(20.1±21.5, P = 0.003)的腺瘤检出率要高. 与之相反, Hashimoto等[13]为了验证全结肠色素内镜能否提高肠道内腺瘤的检出率, 设计了以"背靠背"为检查方法的相关研究. 即在对受试者第1次行肠镜检查时, 将发现的腺瘤切除或将较难切除的病变用钛夹标记, 然后将所有第1次行肠镜检查的受试者随机分为色素肠镜组和SC组, 结果显示与SC比色素内镜并未提高肠道腺瘤的检出率(26.9% vs 32.7%, P = 0.47). 研究者甚至认为色素肠镜的退镜检查病变时间要比SC长得多, 如果二者时间相同, 色素肠镜的腺瘤检出率可能相对要低些. 近年来许多学者尝试着将色素内镜与HDC相结合, 结果显著提高了肠道腺瘤的检出率[14,15]. 综上所述, 色素内镜在提高肠道腺瘤检出率方面有着较好的应用前景, 并且其所需设备少、染料易得、不增加患者痛苦. 但其退镜时间几乎为常规内镜的2倍, 操作相对繁琐、成本较高等也是需要注意的问题.
NBI是将内镜广谱的光学滤器改成窄谱滤器, 使通过光学滤器的光谱发生改变, 由于不同的光谱所穿透的黏膜深度不同, 所以NBI下黏膜的形态与毛细血管的图像更清晰, 进而发现在SWLC下难以被发现的病变, 然而在提高腺瘤检出率方面, NBI技术的优越性仍存在争议. 早在2004年Cono等[16]便通过实验证实NBI较SWLC在观察结直肠微小病变上有优势. 随后, 诸多文献亦报道[17-20], 与SWLC相比, NBI有提高肠道腺瘤检出率的潜力, 尤其对于微小且扁平的病变. Inoue等[21]对243名受试者行前瞻性随机可控实验的研究, 将其分为SWLC组和NBI组, 结果显示与SWLC相比, NBI可以提高肠道腺瘤的检出率, 并且研究者认为可以将NBI作为检测小型腺瘤的常规检查. 而不同的是近年来国外学者通过大量实验证实与SWLC相比, NBI并不能提高肠道腺瘤的检出率[22-28]. 近日, Pasha等[29]和Nagorni等[30]的最新报道也分别证实了这一点. 二者都采用了收集关于NBI能否提高肠道腺瘤检出率的多个研究行Meta分析. 前者共纳入了9项研究, 后者共纳入了8项研究, 3 673名受试者. 通过分析, 二者均认为NBI不能提高肠道腺瘤的检出率. 由此可见, 与SC相比, NBI在提高肠道腺瘤检出率方面并没有明显优势. 此外, 在NBI结肠镜检查中大大延长了退镜时间, 而且其检查时肠液呈红色, 与血液相似等, 这些都很大程度上影响该技术的发挥.
AFI是一种新型的内镜检查技术, 其原理基于激光激发组织产生荧光, 主要以蓝紫光作为激发光, 组织激发出的荧光被赋予红色或绿色, 不同组合的红绿色分光图像再经处理产生AFI特定图像. 通过这种伪彩色图像来诊断消化道隆起性病变[31]. 在AFI结肠镜下, 息肉或腺瘤等隆起性病变呈红色荧光, 而正常组织呈绿色荧光[32]. 目前, 关于AFI对肠道腺瘤的检出率的报道甚少, 且结论不一. Matsuda等[33]研究认为AFI对肠道腺瘤的漏诊率为30%, 显著低于常规肠镜49%的漏诊率; 但van den Broek等[34]的研究表明, AFI结肠镜和常规肠镜对腺瘤的漏诊率分别为20%和29%, 差异无统计学意义. McCallum等[35]利用LIFE系统(加拿大xillix公司出品的自发荧光系统)在107例受试者中进行了比较研究, 结果AFI检出了全部75个腺瘤, 而常规肠镜仅漏诊3个, 其检出率差异无统计学意义. 国内姜智敏等[36]对516名受试者行AFI和标准白光内镜(white light, WL)在腺瘤观察率方面的对照研究. 结果显示AFI模式下的腺瘤漏诊率为15.9%(20/126), 显著低于WL模式下的腺瘤漏诊率26.4%(28/106, P = 0.041). 研究者认为AFI能够提高肠道腺瘤的检出率. 不过对于AFI值得注意的是, 他需由经验丰富的内镜医生操作, 若肠道准备欠佳, 粪便和残渣不仅会影响观察, 而且其在AFI模式下同样表现为红色, 与病变相似, 这将给经验不足的医生带来困难, 甚至导致判断失误, 故良好的肠道准备是AFI模式下观察的前提.
透明帽辅助肠镜检查法(cap-assisted colonoscopy, CAC)是一项简单的技术, 即在肠镜前段安装一塑料透明帽. 透明帽长约4 mm, 在压平肠道皱襞的同时, 使肠黏膜和肠镜顶端的镜头间保持一定距离, 这样可以防止视野的丢失并便于观察隐藏于黏膜褶皱处的病变. 近年来诸多研究结果表明[37-41], 与SC相比, CAC可以显著提高肠道腺瘤的检出率. 尤其是来自美国的学者Hewett等[42]的实验研究表明了CAC减少了所有腺瘤, 特别是小腺瘤的漏诊率. 该实验对100个受试者行序贯形式的肠镜检查: 52名受试者先行CAC检查, 再行SC检查; 48名患者则正相反. 结果显示先行CAC检查组有较低的漏诊率(21% vs 33%, P = 0.039). 而Harada等[43]则通过对比研究认为CAC在肠道腺瘤检出率方面没有优势. 甚至一篇来自香港的报道认为与SC相比, CAC有更低的腺瘤检出率(30.5% vs 37.5%, P = 0.018), 研究者认为这可能与CAC组的退镜时间较短和肠道准备不充分有关. 最近, Rastogi等[44]将420名受试者随机分为均等的SC组和CAC组, 结果表明, 检出患有腺瘤的受试者CAC组要高于SC组(69% vs 56%, P = 0.009), 并且CAC对于每个受试者的平均腺瘤检出率也要高于SC(2.3 vs 1.4, P<0.001), CAC的检查时间也较短(3.29 min vs 3.98 min, P<0.001). 由此可见, 与SC相比, CAC在提高肠道腺瘤检出率上有绝对优势, 是一种安全、有效并且实用的方法.
广角结肠镜是一个可旋转170度视野(标准内镜为140度, 超出其观察范围30%)的内镜, 可以提高隐藏于肠道皱襞后腺瘤的检出率. 较早的一篇报道[45]显示肠镜下腺瘤漏诊率在广角结肠镜和SC中是相似的, 研究者认为广角结肠镜在腺瘤检出率方面并无明显优势. 同样, 西班牙学者Pellisé等[5]也将之与SC相比, 结果显示广角结肠镜并未提高肠道的腺瘤检出率. 近日, Adler等[46]应用最新一代的广角高分辨率内镜行病例对照观察实验. 广角结肠镜组有1 256名受试者, SC组有1 400名受试者. 在受试者的基本信息和退镜时间无明显差别的情况下, 在广角结肠镜的腺瘤检出率明显高于SC(0.33 vs 0.27, P = 0.01). 可见, 目前广角结肠镜在提高肠道腺瘤检出率上并未得到全面认可. 但随着内镜技术的不断发展和新设备的研发, 广角结肠镜必定有其较好的应用前景.
三只眼逆行性内镜(the third eye retroscopy, TER)是个1次性装置, 当肠镜到达回盲部后, TER便可通过活检孔道到达肠镜的顶端, 然后自动翻转180度形成一J字型, 这样便会在退镜阶段和观察褶皱近端时形成一个肠镜的逆向图像, 并且正向图像和逆向图像会同时出现在显示器上, 起到相互补充的作用. 国外有些文献报道显示TER与SC相比能够增加肠道腺瘤的检出率. 为了验证这一点, Triadafilopoulos等[47]制作出了3个长有模拟腺瘤的肠道模型. 其中每个模型分布有腺瘤40个, 长于普通肠黏膜处13个, 近褶皱隐藏处27个. 由6名有经验的内镜医师分别行方法A(SC检查法)和方法B(利用同一肠镜的TER检查法), 进行比较和分析. 结果显示: 在共计78处"易观察"的腺瘤中, 两种方法发的检出率相似, 而在162处分布于褶皱隐藏部位的腺瘤中, 方法B的腺瘤检出率要显著高于方法A(12% vs 81%, P<0.01). 随后, Triadafilopoulos等[48]便进行了一项对24个受试者行TER检查的实验性研究, 结果发现TER较SC在病变检出率方面增加了11.8%, 这些病变大多位于褶皱的隐蔽处. Thangaratinam等[49]通过一项由249名受试者参与的多中心实验证实, 与单纯结肠镜相比辅助以TER检查增加了11.0%的腺瘤检出率. 最新的1篇关于TER对肠道腺瘤检出率作用的报道来自于英国学者Leufkens等[50], 他们通过对448名受试者(有99名由于一些原因被排除)行一前瞻性的多中心随机可控实验研究, 结果表明与SC相比TER能够显著提高肠道腺瘤的检出率. 该研究分为两组, A组173名受试者先行SC检查, 再行TER检查. 结果又发现腺瘤49个, 腺瘤检出增加率为45.8%. B组176名受试者先行TER检查, 再行SC检查. 结果又发现腺瘤26个, 腺瘤检出增加率为22.6%. 将A组与B组行比较分析得知, 净腺瘤检出增长率为23.2%. 因此, TER对于提高腺瘤的检出率是行之有效的. 但是TER的缺点在于一旦发现息肉, 其为了行息肉切除术必须被撤出, 然后重新插入继续观察, 操作过程相对复杂, 并在退镜时间上要延长很多, 而且该装置要有专业的设备, 必须具备两个内镜系统, 这在大多数基层医院是不能普及应用的.
随着消化内镜诊疗技术的不断发展及相应器械的研发, 提高肠道腺瘤检出率的方法将越来越多, 效果也正逐渐突显, 使肠道腺瘤等癌前病变的早期诊断及治疗成为可能, 减少了漏诊率, 降低了CRC的发病率. 尤其是CAC的应用, 简单、安全且有效, 适合在临床工作中广泛开展.
一直以来, 由在肠镜检查中漏诊的腺瘤等癌前病变进展为结直肠癌(CRC)的较多, 因此提高肠道腺瘤检出率就显得尤为重要. 随着内镜技术的不断发展及相关器械的研发, 加之国内外学者的大量相关研究工作, 近年来提高肠道腺瘤检出率的方法也逐渐增多, 且有些效果较为显著, 使肠道腺瘤等癌前病变的早期诊断及治疗成为可能, 减少了漏诊率, 降低了CRC的发病率.
张国梁, 主任医师, 天津市第一中心医院消化内科
由于CRC的死亡率较高, 所以控制其癌前病变成为首要任务, 解决的根本途径就在于早期发现, 早期治疗. 为提高肠道腺瘤的检出率, 国内外学者作了大量的研究和研发工作. 如自发荧光内镜和三只眼逆行性内镜在肠道腺瘤检查中的应用, 还有关于透明帽辅助肠镜检查法(CAC)的对比和Meta分析, 都在逐步解决肠道腺瘤漏诊率高的问题.
HDC、色素内镜、窄带成像技术、广角内镜等在提高肠道腺瘤检出率方面结果不相一致, 而关于CAC和三只眼逆行性内镜的报道普遍认为有助于提高肠道腺瘤的检出率, 值得临床推广和应用.
本文介绍了当前比较新的各种内镜技术和方法, 通过对其了解, 有利于在临床工作中减少肠道腺瘤的漏诊率, 进而减少CRC的发病率, 提高患者的生活质量.
本文详细地阐述了提高肠道腺瘤检出率的研究进展, 基本涵盖了目前比较新的各种内镜技术, 对内镜医师有一定的指导作用.
编辑:翟欢欢 电编:闫晋利
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