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胃黏膜上皮内瘤变内镜切除术后病理与术前活检病理的差异比较及原因分析

2019-03-23 不详 消化科空间

胃黏膜上皮内瘤变是公认的癌前病变,2000版及2010版WHO消化系统肿瘤分类中指出上皮内瘤变是一种具有恶性潜能的非浸润性病变,可适用于所有浸润性癌的前驱病变,具有潜在的分子学异常。内镜下活检是获取胃黏膜病变病理组织学诊断最常用的技术。以往认为胃镜活检及病理检查是诊断胃癌及癌前病变的金标准,但是近年来有学者发现,部分病例内镜切除术后病理与术前活检病理比较有较大的差异,术后升级率较高,意味着术前活检

背景

黏膜上皮内瘤变是公认的癌前病变,2000版及2010版WHO消化系统肿瘤分类中指出上皮内瘤变是一种具有恶性潜能的非浸润性病变,可适用于所有浸润性癌的前驱病变,具有潜在的分子学异常。内镜下活检是获取黏膜病变病理组织学诊断最常用的技术。以往认为胃镜活检及病理检查是诊断胃癌及癌前病变的金标准,但是近年来有学者发现,部分病例内镜切除术后病理与术前活检病理比较有较大的差异,术后升级率较高,意味着术前活检存在一定的漏诊率,这也会影响患者治疗方案及随访监测方案的选择。因此一项旨在比较胃黏膜上皮内瘤变内镜切除前后病理的符合率,并探讨术后病理升级的相关危险因素的研究发表了相关结果。

研究如何进行?

研究收集2012年1月至2014年12月某医院消化内科接受内镜治疗的371例胃黏膜上皮内瘤变患者的资料。患者术前活检病理提示胃黏膜低级别上皮内瘤变(LGIN)或高级别上皮内瘤变(HGIN),且术前内镜超声和CT检查证实病变未侵犯固有肌层,无淋巴结转移。记录的资料包括:(1)患者一般情况:年龄、性别等;(2)病变相关因素:病变部位,大小,内镜下形态,表面有无发红、结节或溃疡等,术前与术后病理。病理切片由南京鼓楼医院经验丰富的病理科医师重新阅片确认。所有标本的组织病理学诊断分类参照WHO肿瘤新分类标准。

对活检诊断为上皮内瘤变的病变采用标准EMR或ESD治疗(图1)。术毕将病变黏膜回收并延展固定,标明其在体内的相对位置(如口侧、肛侧、前壁、后壁等)。内镜下肿瘤大体形态依据日本胃癌学会标准及巴黎分型标准,分为5种基本类型:隆起型(0-Ⅰ型)、浅表隆起型(0-Ⅱa)、浅表平坦型(0-Ⅱb)、浅表凹陷型(0-Ⅱc)和溃疡性(0-Ⅲ型)。参照Kim等研究,将表面充血定义为病灶黏膜较周围黏膜表面发红;黏膜溃疡定义为病灶表面存在黏膜缺损;表面结节样改变定义为病灶有不规则凸起。



研究得出了怎样的结果?

一、术前活检病理与术后病理结果比较

371例患者中,活检病理诊断LGIN 173例,HGIN 198例。LGIN组中术后病理与活检病理维持一致者占65.3%(113/173),升级为HGIN及早癌者分别为26.6%(46/173)、5.8%(10/173),总升级率32.4%(56/173),降级为慢性炎症者2.3%(4/173)。HGIN组术后病理与活检病理维持一致者为54.0%(107/198),升级为早癌者为39.4%(78/198),降级为LGIN者6.6%(13/198),详见表1。



二、单因素分析结果

将患者分为病理未升级组与升级组进行单因素分析,结果提示,病变直径大于2 cm、病变部位在近端胃、黏膜表面发红及表面凹陷或溃疡是胃黏膜上皮内瘤变内镜切除术后病理升级的危险因素,患者年龄、性别、病变形态均不是其危险因素(表2)。



三、多因素回归分析结果

对单因素分析中P<0.10的变量进行多因素回归分析,结果显示,病变直径大于2 cm、病变部位在近端胃、黏膜表面发红、表面凹陷或溃疡是胃黏膜上皮内瘤变内镜切除术后病理升级的独立危险因素。

讨论

胃黏膜上皮内瘤变是胃癌发生前的步骤,代表肿瘤性生长的起始阶段,其进展为胃癌的风险很高。我国一项纳入546例患者的前瞻性研究显示,在5年的随访周期内,轻度异型增生每年进展为胃癌的比例为0.6%,而重度异性增生为1.4%。西方的一项研究同样显示,轻到中度异型增生患者胃癌的年发生率是0.6%,重度异型增生患者胃癌的年发生率是6%,而且在随访一年内大约25%的重度异型增生患者被诊断为胃癌。

消化内镜及病理检查是筛选胃癌高危人群及识别早期胃癌最重要的方法,准确的术前诊断及分期决定了患者能否选择内镜治疗方案。2012年欧洲共识意见建议:对于内镜下未见明确病灶的LGIN患者,建议1年内随访;对于内镜下可见明确病灶的LGIN患者,应考虑内镜切除以获得更精确的组织病理学诊断;对于内镜下未见明确病灶的HGIN患者,建议再次大范围活检评估病变,并在6个月至1年内监测随访;对于内镜下可见明确病灶的HGIN患者,应考虑内镜切除或外科手术治疗。但是近年来很多学者发现术前胃镜活检诊断与术后病理诊断存在不同程度的差异。我们的研究发现,在173例术前诊断为LGIN的患者中,升级为HGIN者46例(26.6%),升级为癌者10例(5.8%),总升级率32.4%;198例术前诊断为HGIN的患者中,术后升级率为39.4%(78/198)。

进一步探讨术前术后病理不一致的可能因素,我们发现,病灶>2 cm、病变表面充血、表面凹陷或存在溃疡、病变部位位于近端胃是术后病理升级的独立危险因素,这和国内崔建芳等的研究结果一致。分析内镜切除术后病理升级的因素,我们考虑可能与以下几方面有关:

(1)病变大小及表面形态:有研究发现在低级别腺瘤的患者中,凹陷型病灶≥15 mm或表面隆起伴中央凹陷病灶≥20 mm,提示存在早期胃癌的可能性。国内姚佳等研究也发现病灶≥20 mm和病灶表面黏膜有溃疡是活检病理为胃黏膜HGIN易漏诊、癌变的独立危险因素。我们的研究也同样支持这一结论。

(2)胃镜操作者对病变的识别及准确活检取材能力:部分上皮内瘤变病灶内镜下表现无特异性,当操作者对病变认识不足或者视野清晰度不够,在活检时无法做到对最可疑病灶进行准确活检。一般活检的深度只包括黏膜层和黏膜固有层,而取材要求最好包括黏膜肌层,如果取材深度不够则只能得到表浅黏膜组织,影响对病变的准确判断。本研究发现近端胃贲门部病变术后病理升级的比率高于远端胃病变,考虑可能与近端胃贲门部内镜活检取材相对较困难,不易取到病变组织有关。

(3)病理诊断标准:我国的病理诊断标准多采用西方国家标准,认为明确的浸润是诊断癌的标准。然而,在临床实践中,因为活检取材深度的限制,有时做出明确浸润的诊断十分困难,我国病理医师普遍对结构异型性认识不足并且诊断较保守,临床与病理医师之间交流较少,也导致部分术前活检病理低判。

内镜技术的发展提高了临床医师对胃癌前病变及早期胃癌的识别能力。Yu等研究表明NBI结合放大内镜技术在早期胃癌的诊断上明显优于白光内镜。Maki等也证实在NBI放大内镜中采用VS分类系统鉴别早期胃癌的敏感度达95%。我们的研究中内镜切除术后病理升级的比例略低于国内一些研究机构的结果,原因可能在于当白光内镜发现可疑病变时,我们多结合染色内镜、NBI放大内镜、内镜超声等技术对病变再次观察,进一步判断病变的范围及浸润深度,如发现病变具有明显低分化或未分化癌特点且判断病变深度可能已浸润至黏膜下层以下时,即使术前病理诊断为上皮内瘤变也建议患者选择手术切除,而这部分病例未纳入本次研究的范围。相比单纯使用白光内镜检查,结合上述技术的靶向活检更准确。值得注意的是,既往多认为对于LGIN病灶可进行随访或内镜切除,我们的研究显示LGIN术后病理升级的比例高达32.4%,因此对于病变直径超过2 cm、且表面充血或表面有凹陷或溃疡的病例,其可能漏诊HGIN或早期胃癌的比例较高,应再次进行内镜精查或采取内镜切除获取大黏膜标本以明确诊断。

本研究对371例内镜切除前、后病理结果进行比较研究,与国内外相关报道相比,样本量较大,并采用多因素回归分析筛选术后病理升级的独立危险因素,提示在临床工作中需重视内镜下具有上述特点的病例,减少漏诊误诊的概率。

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    2019-05-17 baoya
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    2019-03-25 snowpeakxu

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