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^2］。根据世界卫生组织在第5版消化系统肿瘤中的最新分类，锯齿状病变包括增生性息肉（hyperplastic，HP）、无蒂锯齿状病变（sessileserrated lesion，SSL）、无蒂锯齿状病变伴异型增生（sessileserrated lesion with dysplasia，SSL‑D）、传统锯齿状腺瘤（traditionalserrated adenoma，TSA）及未分类的锯齿状腺瘤（serratedadenoma‑unclassified）^3］。本文回顾锯齿状病变临床特征与组织学特点，并介绍新的锯齿状病变亚型及肠道微生物与锯齿状病变之间的关联。

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一、锯齿状病变的流行病学特征

^4］

二、锯齿状病变的分类

^7］8］。MVHP是大多数HP的亚型，常见于右侧结肠，锯齿状结构仅限于隐窝上2/3，隐窝内的细胞由数量不等的微泡细胞和杯状细胞组成，其中MVHP占主导地位，而GCHP常位于左侧结肠，锯齿状结构较少且隐窝内细胞具有丰富的杯状细胞^8］。白光内镜下，HP透明或苍白的颜色通常类似于周围黏膜，呈圆形或椭圆形，形态较平坦^9‑10］。窄带光成像（narrowband imaging，NBI）模式下，没有观察到腺体周围的毛细血管扩张，但通常存在Ⅱ型腺管开口^11］。

^13］。与以往WHO认为需要3个隐窝或2个连续隐窝才能诊断SSL要求不同，2019年WHO分类指出，仅需一个“特征性”隐窝即可诊断SSL^{［3］11，14］}。SSL表面常被黏液、粪便或胆汁盐覆盖，故内镜下很难看到病变边界，必须清洗黏液才能看清病变^9，12］。白光内镜下可见苍白、扁平或无蒂的形态，具有云雾状外观、不规则表面、黏液帽和边缘模糊的特征^［15］。在NBI模式下可观察到黏膜上有腺窝开口的黑色斑点^16］。

^15］。故有研究团队提出了一种包含上述四点的新方法可合理准确区分HP和SSL^［18］

^{19‑20］21］}。SSL‑D中一部分组织具有锯齿状息肉的特点，另一部分则具有异型增生的特点，其中异型增生区域可见以下现象：假复层的核，核分裂增加、染色质增多，隐窝拥挤、伸长、分支复杂性增加，有筛状结构和绒毛状结构，且异型增生区域往往具有更多的黏蛋白^8，11］。Murakami等^22］对于SSL‑D研究显示，无论有无异型增生或癌，几乎所有的SSL都存在黏液帽。高度可疑为SSL‑D的病变往往有以下特点：（半）带蒂形态、双隆起、中央凹陷和发红，存在至少一个特征对预测SSL‑D具有高度敏感度（91.7%）及特异度（85.3%）^22］。已有研究证实SSL病变内存在大小不一的结节或有部分突出的形态对预测SSL‑D的诊断准确率为93.3%（敏感度46.2%，特异度97.3%）^23］。

^22‑23］。据报道SSL‑D存在于高达32%的≥20mm的SSL中，但是也可存在于<5mm的SSL中^24‑25］。在266例SSL‑D患者中，病变平均大小12 mm，40%的病变<10mm^{［19］26］}

^7］27］。尽管TSA具有这些特征，还是常与管状绒毛状腺瘤相混淆^28］。在这些特征中，细胞学和锯齿状特征被认为是TSA决定因素，而异位隐窝不仅存在于TSA中，还见于管状绒毛状腺瘤、绒毛状腺瘤和锯齿状管状绒毛状腺瘤等病变中^29‑30］。因此，认为异位隐窝不是TSA独有特征，应避免单凭异位隐窝诊断TSA^{［8］13，31］}。NBI模式下病灶内也可见腺管开口的黑点，此特点与SSL相似，故在NBI模式下不能凭借这点来区分两者^16］。

^29］29］定义，诊断标准：（1）>25%的息肉含有绒毛成分；（2）>50%的息肉具有锯齿状形态；（3）<10%的息肉具有TSA型细胞学特征和裂缝状锯齿。组织学上，sTVA上皮呈锯齿状，有明显的分支和直角分支，呈“迷宫样”生长，有密集的卵圆形核、频繁的有丝分裂和嗜碱性细胞质，可见异位隐窝形成。免疫组化显示，sTVA有中至重度的β‑catenin表达，p53核表达相对于无异型增生的sTVA更常见于sTVA伴异型增生的病变中。Bettington等^29］发现与传统TVA相比，sTVA更大，更有可能位于近端，更易表现为KRAS突变和CpG岛甲基化，Ki67表达较低；与TSA相比，sTVA更可能位于近端，CpG岛甲基化较少，β‑catenin核表达较高，Ki67、CK7、CK20表达较低。因此，sTVA可能是KRAS突变、微卫星稳定的结直肠癌先兆。

^32‑33］。SuSA的大小为5~6mm，大多位于乙状结肠或直肠^34‑35］。SuSA表现为白色、无蒂或轻微隆起的病变，较大的病变表现为扁平或斑块样，边界清晰且不规则，有分叶状表面，均无黏液帽^35］。在组织学上，SuSA主要由垂直腺瘤性腺体组成，可见外层的浅表锯齿状与中下层无锯齿状腺体的转变，细胞呈柱状，细胞核基底部细长均匀^32］。免疫组化显示，CK20在SuSA上层表达，与正常黏膜相似；Ki‑67与MYC均表达于SuSA的中下层；SuSA不仅显示膜性β‑catenin表达，也显示中度核β‑catenin表达^32］。在分子水平上，KRAS突变和RSPO融合/过表达是SuSA最常见改变，这种现象在TSA中也常见^34，36］。SuSA的另一个特征是常与TSA共存，有研究证明在SuSA和相关的TSA成分中存在相同的KRAS突变和RSPO融合或过表达的成分，证实了它们之间的联系，但仅仅存在KRAS突变和RSPO融合或过度表达不足以促使SuSA发展为TSA，还需要其他未知因素^32，37］。故推测在生物学上SuSA可能与KRAS突变的TSA相关，且与sTVA一样，也可能是KRAS突变的微卫星稳定的结直肠癌的前驱病变。而SuSA大多是无蒂病变，缺乏TSA的有蒂或亚蒂形态及典型细胞学、异位隐窝形成和裂隙状锯齿状的特征，故很难确定孤立的SuSA和TSA之间的形态学联系，且只有30%的TSA存在KRAS突变和RSPO融合或过度表达，表明并不是所有TSA都起源于SuSA，而是一部分起源于SuSA^{［32，38］}

三、锯齿状病变的发生发展

^39］40］。且锯齿状病变与结直肠同步晚期肿瘤形成有关^{［41‑42］}，有研究表示近端、无蒂和（或）大（≥10mm）的锯齿状息肉是增加同步晚期肿瘤风险的独立危险因素^43‑44］，其中锯齿状息肉可将病变同步晚期肿瘤的风险增加2倍以上^45］。

^54］。近年来，片状冷圈套息肉切除术也显示出很高的疗效，具有避免热损伤的优势^［56］。

^58］。与EMR相比，传统的息肉切除方法例如热圈套器，似乎不可靠，尤其是对于大的SSL，它的不完全切除率很高（大约三分之一）^59］。

60］^61］

五、锯齿状息肉综合征（serratedpolyposis syndrome，SPS）

^3］，标准1：直肠近端至少有5个锯齿状息肉≥5mm，至少有2个≥10mm；标准2：整个肠道中分布超过20个任何大小的锯齿状息肉，且至少有5个位于直肠近端。SPS中发现的锯齿状息肉主要是SSL，常可见HP，偶见TSA，有研究表示超过50%的SPS位于直肠和乙状结肠^62］。一项在296名SPS患者中进行的多中心回顾性研究表明>2个近端SSL和≥1个SSL‑D是两个独立的结直肠癌预测因素，与没有危险因素的SPS患者相比，每增加一个危险因素，发生结直肠癌的概率就会增加两倍^62］。有研究表明SPS患者监测期间发生结直肠癌的5年累计发病率为1.5%^{［63］62，64］}。

六、锯齿状病变的监测

^65］。英国胃肠病学会（Britishsociety of gastroenterology，BSG）建议对≥20mm的锯齿状息肉进行EMR后，2~6个月内对切除部位进行检查^39］；对于SPS患者，建议每2年随访一次，且建议对SPS患者一级亲属进行结肠镜筛查，如果未发现息肉，则应每5年进行一次监测。

七、肠道微生物与锯齿状病变关系

^68］发现在管状腺瘤和SSL中显示相似的具核梭杆菌密度，但在结直肠癌组中更高，提示具核梭杆菌可能在锯齿状通路和腺瘤‑癌通路中均有作用。有研究证明仅在SSL中，具核梭杆菌的密度在乙状结肠至盲肠之间的路径显示逐渐增加的趋势，但在锯齿状病变各亚型之间，具核梭杆菌的阳性率差异无统计学意义，这一观察结果可通过SSL中的隐窝解剖结构来解释，其导致黏液产生过多，在内镜下被视为黏液帽，黏液帽可通过覆盖病变表面来帮助微生物生存，需要进一步调查证明具核梭杆菌与SSL中黏液帽之间的关系^69］。许多研究探索了具核梭杆菌与结直肠癌各亚型分子特征之间的关联，证明具核梭杆菌与BRAF突变、CpG岛甲基化、MLH1甲基化及MSI相关^70］。然而，关于具核梭杆菌状态是否与KRAS突变相关尚存在争议^71］。尽管这些结论提示具核梭杆菌与肠道病变的关联性，但未来需要更多研究来证明其在锯齿状病变通路中的作用。

八、结论

尽管结直肠锯齿状病变的诊断和命名一直存在争议，即使我们对于锯齿状病变的认识不断提高，但经锯齿状途径引起癌变的发病机制依然需要进一步研究，对于结直肠癌新途径的识别使科研人员和临床医生有机会通过优化筛查来应对这一挑战，从而进一步预防结直肠癌的发生及进展。未来应对结直肠锯齿状病变进行全面的分子分类，这将有助于患者的风险分层。

参考文献

[1]BrayF, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018:GLOBOCAN estimates of incidence and mortality worldwide for 36cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68(6):394‑424.DOI: 10.3322/caac.21492.

[2]GeramizadehB, Robertson S. Serrated polyps of colon and rectum: aclinicopathologic review[J]. J Gastrointest Cancer, 2017,48(4):291‑298. DOI: 10.1007/s12029‑017‑9977‑y.

[3]NagtegaalID, Odze RD, Klimstra D, et al. The 2019 WHO classification oftumours of the digestive system[J]. Histopathology, 2020,76(2):182‑188. DOI: 10.1111/his.13975.

[4]RashtakS, Rego R, Sweetser SR, et al. Sessile serrated polyps and coloncancer prevention[J]. Cancer Prev Res (Phila), 2017, 10(5):270‑278.DOI: 10.1158/1940‑6207.CAPR‑16‑0264.

[5]BailieL, Loughrey MB, Coleman HG. Lifestyle risk factors for serratedcolorectal polyps: a systematic review and Meta‑analysis[J].Gastroenterology, 2017, 152(1):92‑104. DOI:10.1053/j.gastro.2016.09.003.

[6]HeX, Wu K, Ogino S, et al. Association between risk factors forcolorectal cancer and risk of serrated polyps and conventionaladenomas[J]. Gastroenterology, 2018, 155(2):355‑373.e18. DOI:10.1053/j.gastro.2018.04.019.

[7]CrockettSD, Nagtegaal ID. Terminology, molecular features, epidemiology, andmanagement of serrated colorectal neoplasia[J]. Gastroenterology,2019, 157(4):949‑966.e4. DOI: 10.1053/j.gastro.2019.06.041.

[8]PaiRK, Bettington M, Srivastava A, et al. An update on the morphologyand molecular pathology of serrated colorectal polyps and associatedcarcinomas[J]. Mod Pathol, 2019, 32(10):1390‑1415. DOI:10.1038/s41379‑019‑0280‑2.

[9]VleugelsJL, IJspeert JE, Dekker E. Serrated lesions of the colon and rectum:the role of advanced endoscopic imaging[J]. Best Pract Res ClinGastroenterol, 2015, 29(4):675‑686. DOI:10.1016/j.bpg.2015.05.009.

[10]KahiCJ, Vemulapalli KC, Snover DC, et al. Findings in the distalcolorectum are not associated with proximal advanced serratedlesions[J]. Clin Gastroenterol Hepatol, 2015, 13(2):345‑351.DOI: 10.1016/j.cgh.2014.07.044.

[11]CasseseG, Amendola A, Maione F, et al. Serrated lesions of the colon‑rectum:a focus on new diagnostic tools and current management[J].Gastroenterol Res Pract, 2019, 2019:9179718. DOI:10.1155/2019/9179718.

[12]BettingtonM, Walker N, Clouston A, et al. The serrated pathway to colorectalcarcinoma: current concepts and challenges[J]. Histopathology, 2013,62(3):367‑386. DOI: 10.1111/his.12055.

[13]OkamotoK, Kitamura S, Kimura T, et al. Clinicopathological characteristicsof serrated polyps as precursors to colorectal cancer: Current statusand management[J]. J Gastroenterol Hepatol, 2017, 32(2):358‑367.DOI: 10.1111/jgh.13482.

[14]MaMX, Bourke MJ. Sessile Serrated Adenomas: How to Detect, Characterizeand Resect[J]. Gut Liver, 2017, 11(6):747‑760. DOI:10.5009/gnl16523.

[15]HazewinkelY, López‑Cerón M, East JE, et al. Endoscopic features ofsessile serrated adenomas: validation by international experts usinghigh‑resolution white‑light endoscopy and narrow‑bandimaging[J]. Gastrointest Endosc, 2013, 77(6):916‑924. DOI:10.1016/j.gie.2012.12.018.

[16]SaitoS, Tajiri H, Ikegami M. Serrated polyps of the colon and rectum:endoscopic features including image enhanced endoscopy[J]. World JGastrointest Endosc, 2015, 7(9):860‑871. DOI:10.4253/wjge.v7.i9.860.

[17]SinghR, Zorrón Cheng Tao Pu L, Koay D, et al. Sessile serratedadenoma/polyps: Where are we at in 2016?[J]. World J Gastroenterol,2016, 22(34):7754‑7759. DOI: 10.3748/wjg.v22.i34.7754.

[18]IJspeertJE, Bastiaansen BA, van Leerdam ME, et al. Development and validationof the WASP classification system for optical diagnosis of adenomas,hyperplastic polyps and sessile serrated adenomas/polyps[J]. Gut,2016, 65(6):963‑970. DOI: 10.1136/gutjnl‑2014‑308411.

[19]LiuC, Walker NI, Leggett BA, et al. Sessile serrated adenomas withdysplasia: morphological patterns and correlations with MLH1immunohistochemistry[J]. Mod Pathol, 2017, 30(12):1728‑1738.DOI: 10.1038/modpathol.2017.92.

[20]BettingtonM, Walker N, Rosty C, et al. Clinicopathological and molecularfeatures of sessile serrated adenomas with dysplasia or carcinoma[J].Gut, 2017, 66(1):97‑106. DOI: 10.1136/gutjnl‑2015‑310456.

[21]YangJF, Tang SJ, Lash RH, et al. Anatomic distribution of sessileserrated adenoma/polyp with and without cytologic dysplasia[J]. ArchPathol Lab Med, 2015, 139(3):388‑393. DOI:10.5858/arpa.2013‑0523‑OA.

[22]MurakamiT, Sakamoto N, Ritsuno H, et al. Distinct endoscopic characteristicsof sessile serrated adenoma/polyp with and withoutdysplasia/carcinoma[J]. Gastrointest Endosc, 2017, 85(3):590‑600.DOI: 10.1016/j.gie.2016.09.018.

[23]SanoW, Fujimori T, Ichikawa K, et al. Clinical and endoscopic evaluationsof sessile serrated adenoma/polyps with cytological dysplasia[J]. JGastroenterol Hepatol, 2018, 33(8):1454‑1460. DOI:10.1111/jgh.14099.

[24]YamadaM, Sakamoto T, Otake Y, et al. Investigating endoscopic features ofsessile serrated adenomas/polyps by using narrow‑band imagingwith optical magnification[J]. Gastrointest Endosc, 2015,82(1):108‑117. DOI: 10.1016/j.gie.2014.12.037.

[25]IwatateM, Sano Y, Hattori S, et al. The addition of high magnifyingendoscopy improves rates of high confidence optical diagnosis ofcolorectal polyps[J]. Endosc Int Open, 2015, 3(2):E140‑145.DOI: 10.1055/s‑0034‑1391362.

[26]BanS, Mitomi H, Horiguchi H, et al. Adenocarcinoma arising in smallsessile serrated adenoma/polyp (SSA/P) of the colon:clinicopathological study of eight lesions[J]. Pathol Int, 2014,64(3):123‑132. DOI: 10.1111/pin.12147.

[27]BettingtonML, Walker NI, Rosty C, et al. A clinicopathological and molecularanalysis of 200 traditional serrated adenomas[J]. Mod Pathol, 2015,28(3):414‑427. DOI: 10.1038/modpathol.2014.122.

[28]EastJE, Vieth M, Rex DK. Serrated lesions in colorectal cancer screening:detection, resection, pathology and surveillance[J]. Gut, 2015,64(6):991‑1000. DOI: 10.1136/gutjnl‑2014‑309041.

[29]BettingtonM, Walker N, Rosty C, et al. Serrated tubulovillous adenoma of thelarge intestine[J]. Histopathology, 2016, 68(4):578‑587. DOI:10.1111/his.12788.

[30]Hafezi‑BakhtiariS, Wang LM, Colling R, et al. Histological overlap between colorectalvillous/tubulovillous and traditional serrated adenomas[J].Histopathology, 2015, 66(2):308‑313. DOI: 10.1111/his.12555.

[31]NakaoY, Saito S, Ohya T, et al. Endoscopic features of colorectal serratedlesions using image‑enhanced endoscopy with pathologicalanalysis[J]. Eur J Gastroenterol Hepatol, 2013, 25(8):981‑988.DOI: 10.1097/MEG.0b013e3283614b2b.

[32]HashimotoT, Tanaka Y, Ogawa R, et al. Superficially serrated adenoma: aproposal for a novel subtype of colorectal serrated lesion[J]. ModPathol, 2018, 31(10):1588‑1598. DOI: 10.1038/s41379‑018‑0069‑8.

[33]MizuguchiY, Sakamoto T, Hashimoto T, et al. Identification of a novelPRR15L‑RSPO2 fusion transcript in a sigmoid colon cancerderived from superficially serrated adenoma[J]. Virchows Arch, 2019,475(5):659‑663. DOI: 10.1007/s00428‑019‑02604‑x.

[34]DePalma F, D"Argenio V, Pol J, et al. The molecular hallmarks of theserrated pathway in colorectal cancer[J]. Cancers (Basel), 2019,11(7). DOI: 10.3390/cancers11071017.

[35]MizuguchiY, Tanaka Y, Cho H, et al. Endoscopic features of isolated andtraditional serrated adenoma‑associated superficially serratedadenomas of the colorectum[J]. Dig Endosc, 2022, 34(1):153‑162.DOI: 10.1111/den.13992.

[36]SekineS, Yamashita S, Yamada M, et al. Clinicopathological and molecularcorrelations in traditional serrated adenoma[J]. J Gastroenterol,2020, 55(4):418‑427. DOI: 10.1007/s00535‑020‑01673‑z.

[37]McCarthyAJ, Serra S, Chetty R. Traditional serrated adenoma: an overview ofpathology and emphasis on molecular pathogenesis[J]. BMJ OpenGastroenterol, 2019, 6(1):e000317. DOI: 10.1136/bmjgast‑2019‑000317.

[38]TogashiK. Superficially serrated adenoma: Novel precursor in the serratedpathway[J]. Dig Endosc, 2022, 34(1):77‑78. DOI:10.1111/den.14074.

[39]EastJE, Atkin WS, Bateman AC, et al. British society of gastroenterologyposition statement on serrated polyps in the colon and rectum[J].Gut, 2017, 66(7):1181‑1196. DOI: 10.1136/gutjnl‑2017‑314005.

[40]OmoriK, Yoshida K, Tamiya S, et al. Endoscopic observation of the growthprocess of a right‑side sessile serrated adenoma/polyp withcytological dysplasia to an invasive submucosal adenocarcinoma[J].Case Rep Gastrointest Med, 2016, 2016:6576351. DOI:10.1155/2016/6576351.

[41]SymondsE, Anwar S, Young G, et al. Sessile serrated polyps with synchronousconventional adenomas increase risk of future advanced neoplasia[J].Dig Dis Sci, 2019, 64(6):1680‑1685. DOI:10.1007/s10620‑019‑5454‑8.

[42]AndersonJC, Butterly LF, Robinson CM, et al. Risk of metachronous high‑riskadenomas and large serrated polyps in individuals with serratedpolyps on index colonoscopy: data from the new hampshire colonoscopyregistry[J]. Gastroenterology, 2018, 154(1):117‑127.e2. DOI:10.1053/j.gastro.2017.09.011.

[43]NgSC, Ching JY, Chan VC, et al. Association between serrated polyps andthe risk of synchronous advanced colorectal neoplasia in average‑riskindividuals[J]. Aliment Pharmacol Ther, 2015, 41(1):108‑115.DOI: 10.1111/apt.13003.

[44]LiD, Liu L, Fevrier HB, et al. Increased risk of colorectal cancer inindividuals with a history of serrated polyps[J]. Gastroenterology,2020, 159(2):502‑511.e2. DOI: 10.1053/j.gastro.2020.04.004.

[45]GaoQ, Tsoi KK, Hirai HW, et al. Serrated polyps and the risk ofsynchronous colorectal advanced neoplasia: a systematic review andmeta‑analysis[J]. Am J Gastroenterol, 2015, 110(4):501‑509;quiz 510. DOI: 10.1038/ajg.2015.49.

[46]KimJH, Bae JM, Cho NY, et al. Distinct features between MLH1‑methylatedand unmethylated colorectal carcinomas with the CpG island methylatorphenotype: implications in the serrated neoplasia pathway[J].Oncotarget, 2016, 7(12):14095‑14111. DOI:10.18632/oncotarget.7374.

[47]TravaglinoA, D"Armiento FP, Cassese G, et al. Clinicopathological factorsassociated with BRAF‑V600E mutation in colorectal serratedadenomas[J]. Histopathology, 2019, 75(2):160‑173. DOI:10.1111/his.13846.

[48]HuaX, Newcomb PA, Chubak J, et al. Associations between molecularcharacteristics of colorectal serrated polyps and subsequent advancedcolorectal neoplasia[J]. Cancer Causes Control, 2020, 31(7):631‑640.DOI: 10.1007/s10552‑020‑01304‑1.

[49]FennellLJ, Jamieson S, McKeone D, et al. MLH1‑93 G/a polymorphism isassociated with MLH1 promoter methylation and protein loss indysplastic sessile serrated adenomas with BRAFV600E mutation[J]. BMCCancer, 2018, 18(1):35. DOI: 10.1186/s12885‑017‑3946‑5.

[50]TsikitisVL, Potter A, Mori M, et al. MicroRNA signatures of colonic polyps onscreening and histology[J]. Cancer Prev Res (Phila), 2016,9(12):942‑949. DOI: 10.1158/1940‑6207.CAPR‑16‑0086.

[51]AokiH, Nosho K, Igarashi H, et al. MicroRNA‑31 expression incolorectal serrated pathway progression[J]. World J Gastroenterol,2014, 20(34):12346‑12349. DOI: 10.3748/wjg.v20.i34.12346.

[52]TuomistoA, García‑Solano J, Sirniö P, et al. HIF‑1α expressionand high microvessel density are characteristic features in serratedcolorectal cancer[J]. Virchows Arch, 2016, 469(4):395‑404. DOI:10.1007/s00428‑016‑1988‑8.

[53]García‑SolanoJ, García‑Solano ME, Torres‑Moreno D, et al. Biomarkersfor the identification of precursor polyps of colorectal serratedadenocarcinomas[J]. Cell Oncol (Dordr), 2016, 39(3):243‑252.DOI: 10.1007/s13402‑016‑0269‑5.

[54]KimJS, Lee BI, Choi H, et al. Cold snare polypectomy versus cold forcepspolypectomy for diminutive and small colorectal polyps: a randomizedcontrolled trial[J]. Gastrointest Endosc, 2015, 81(3):741‑747.DOI: 10.1016/j.gie.2014.11.048.

[55]RaadD, Tripathi P, Cooper G, et al. Role of the cold biopsy technique indiminutive and small colonic polyp removal: a systematic review andmeta‑analysis[J]. Gastrointest Endosc, 2016, 83(3):508‑515.DOI: 10.1016/j.gie.2015.10.038.

[56]TutticciNJ, Hewett DG. Cold EMR of large sessile serrated polyps atcolonoscopy (with video)[J]. Gastrointest Endosc, 2018,87(3):837‑842. DOI: 10.1016/j.gie.2017.11.002.

[57]GuptaV, East JE. Optimal endoscopic treatment and surveillance of serratedpolyps[J]. Gut Liver, 2020, 14(4):423‑429. DOI:10.5009/gnl19202.

[58]RaoAK, Soetikno R, Raju GS, et al. Large sessile serrated polyps can besafely and effectively removed by endoscopic mucosal resection[J].Clin Gastroenterol Hepatol, 2016, 14(4):568‑574. DOI:10.1016/j.cgh.2015.10.013.

[59]KolbJM, Soetikno RM, Rao AK, et al. Detection, diagnosis, and resectionof sessile serrated adenomas and polyps[J]. Gastroenterology, 2017,153(3):646‑648. DOI: 10.1053/j.gastro.2017.05.060.

[60]KimKH, Kim KO, Jung Y, et al. Clinical and endoscopic characteristics ofsessile serrated adenomas/polyps with dysplasia/adenocarcinoma in aKorean population: a Korean association for the study of intestinaldiseases (KASID) multicenter study[J]. Sci Rep, 2019, 9(1):3946. DOI:10.1038/s41598‑019‑40559‑w.

[61]PelliseM, Burgess NG, Tutticci N, et al. Endoscopic mucosal resection forlarge serrated lesions in comparison with adenomas: a prospectivemulticentre study of 2000 lesions[J]. Gut, 2017, 66(4):644‑653.DOI: 10.1136/gutjnl‑2015‑310249.

[62]CarballalS, Rodríguez‑Alcalde D, Moreira L, et al. Colorectal cancerrisk factors in patients with serrated polyposis syndrome: a largemulticentre study[J]. Gut, 2016, 65(11):1829‑1837. DOI:10.1136/gutjnl‑2015‑309647.

[63]IJspeertJE, Rana SA, Atkinson NS, et al. Clinical risk factors of colorectalcancer in patients with serrated polyposis syndrome: a multicentrecohort analysis[J]. Gut, 2017, 66(2):278‑284. DOI:10.1136/gutjnl‑2015‑310630.

[64]EgoavilC, Juárez M, Guarinos C, et al. Increased risk of colorectal cancerin patients with multiple serrated polyps and their first‑degreerelatives[J]. Gastroenterology, 2017, 153(1):106‑112.e2. DOI:10.1053/j.gastro.2017.04.003.

[65]CrockettSD, Snover DC, Ahnen DJ, et al. Sessile serrated adenomas: anevidence‑based guide to management[J]. Clin GastroenterolHepatol, 2015, 13(1):11‑26.e1. DOI: 10.1016/j.cgh.2013.10.035.

[66]ShangFM, Liu HL. Fusobacterium nucleatum and colorectal cancer: areview[J]. World J Gastrointest Oncol, 2018, 10(3):71‑81. DOI:10.4251/wjgo.v10.i3.71.

[67]LeeDW, Han SW, Kang JK, et al. Association between fusobacteriumnucleatum, pathway mutation, and patient prognosis in colorectalcancer[J]. Ann Surg Oncol, 2018, 25(11):3389‑3395. DOI:10.1245/s10434‑018‑6681‑5.

[68]ParkCH, Han DS, Oh YH, et al. Role of Fusobacteria in the serratedpathway of colorectal carcinogenesis[J]. Sci Rep, 2016, 6:25271. DOI:10.1038/srep25271.

[69]ItoM, Kanno S, Nosho K, et al. Association of Fusobacterium nucleatumwith clinical and molecular features in colorectal serratedpathway[J]. Int J Cancer, 2015, 137(6):1258‑1268. DOI:10.1002/ijc.29488.

[70]deCarvalho AC, de Mattos Pereira L, Datorre JG, et al. Microbiotaprofile and impact of Fusobacterium nucleatum in colorectal cancerpatients of barretos cancer hospital[J]. Front Oncol, 2019, 9:813.DOI: 10.3389/fonc.2019.00813.

[71]ProençaMA, Biselli JM, Succi M, et al. Relationship between Fusobacteriumnucleatum, inflammatory mediators and microRNAs in colorectalcarcinogenesis[J]. World J Gastroenterol, 2018, 24(47):5351‑5365.DOI: 10.3748/wjg.v24.i47.5351.

来源：中华消化内镜杂志编辑：周昊校对：钱程 审核：唐涌进