无蒂锯齿状腺瘤/息肉(SSA/P)的临床特点及其治疗研究进展

结直肠锯齿状息肉是一种具有锯齿状隐窝结构的息肉类型,根据WHO分类标准,分为增生性息肉(HP)、无蒂锯齿状腺瘤/息肉(SSA/P)和传统锯齿状腺瘤(TSA)三种亚型。目前认为,除了已知的致癌途径,包括腺瘤—癌、炎症—异型增生—癌变、de novo癌途径,锯齿状通路被认为是结直肠癌发病机制的新途径,而SSA/P被认为是锯齿状通路的早期前驱病变。因SSA/P具有独特的组织结构和临床意义,现对其特征、癌变途径以及治疗等方面作一综述。     

无蒂锯齿状腺瘤/息肉的研究进展

无蒂锯齿状腺瘤/息肉(SSA/P)是锯齿状病变的一种,具有高度恶变潜能,不同于传统腺瘤的癌变途径,SSA/P可通过锯齿状通路进行癌变,如SSA/P伴细胞异型增生,其进展到结直肠癌(CRC)的时间将会大大提前。但SSA/P在内镜下易被误诊为增生性息肉(HP),鉴于其误诊率及恶变潜能较高,本文对SSA/P的内镜特征、治疗及随访等方面作一综述。     

广基锯齿状病变临床诊断价值及其相关研究现状

结直肠锯齿状病变是一类腺窝上皮呈锯齿状的息肉,其中广基锯齿状病变具有恶变潜能。广基锯齿状病变和传统锯齿状腺瘤的癌变途径代表了15%~30%的结直肠癌发生途径。但广基锯齿状病变,尤其是伴有异型增生的广基锯齿状病变,在内镜检查、病理诊断中均存在相应的难点。本文就广基锯齿状病变的癌变机制、病理特征、流行病学特征、内镜特征等作一归纳和总结。     

结直肠无蒂锯齿状病变癌变的内镜及通路改变

结直肠癌是中国发病率居高的消化系统恶性肿瘤，15%~30%的散发结直肠癌来源于锯齿状病变癌变途径。锯齿状病变内镜下表现、分子信号通路改变、病理改变、自然病程等与经典“腺瘤-癌”途径不同，特别是无蒂锯齿状病变，由于内镜下发现率低，病灶边缘不清导致不完全切除，是间期癌的重要来源。因此，认识无蒂锯齿状病变非常重要。本文就无蒂锯齿状病变分类、内镜下pit pattern分型、分子改变特征作一综述。     

结直肠锯齿状癌变途径及β-catenin在其中的作用和调控机制

结直肠锯齿状癌变途径是近年来提出的大肠癌发生的一条新的癌变途径,包括增生性息肉、无蒂锯齿状腺瘤、传统锯齿状腺瘤、混合性腺瘤。与传统的腺瘤-癌途径不同,以β-catenin为核心的经典WNT信号通路在锯齿状癌变途径中可能不起主要作用。β-catenin在锯齿状癌变途径中主要起黏附作用。β-catenin粘附和转录功能的调控机制包括翻译后修饰(磷酸化)和构象变化(C端折叠)。     

结直肠无蒂锯齿状腺瘤的筛检及临床处理策略探讨

近年来提出的“锯齿状癌变途径”是一条受到广泛重视的结直肠癌（colorectal callcer,CRC）癌变通路[1]。锯齿状息肉主要包括增生性息肉（hyperplastic polyp,HP）、无蒂锯齿状腺瘤（sessile serrated adenoma,ssA）和传统锯齿状腺瘤（tra—ditional serrated adenoma,TSA）。SSA是新近发现的、具有高危恶变倾向的病变,与右半结肠CRC密切相关[2-3]。SSA的早期检出和正确处理是阻止其进展及癌变的重要途径,但目前尚缺乏统一的诊断标准及处理策略[3]。     

结直肠锯齿状息肉40例临床、内镜和病理学特征分析

背景:结直肠锯齿状息肉是一组具有恶性潜能的组织学异质性病变,包括增生性息肉(HP)、广基锯齿状腺瘤/息肉(SSA/P)和传统锯齿状腺瘤(TSA)。SSA/P是散发性结直肠癌的主要癌前病变之一。目的:分析结直肠锯齿状息肉的临床、内镜和病理学特点,提高临床和内镜医师对该病的认识水平。方法:复习江苏省南通和苏州地区三家医院2012年1月—2017年10月的结肠镜检查资料,筛选出内镜或外科手术切除且病理确诊的锯齿状息肉病例40例,进行回顾性分析。结果:结直肠锯齿状息肉占近5年结肠镜检查的0. 1%(40/39 607),男性患者多于女性,平均年龄(56. 5±13. 4)岁。对46枚有代表性的息肉进行分析(SSA/P 9枚,TSA 13枚,HP 24枚),不同类型锯齿状息肉的临床特征以及内镜下部位、形态和大小差异均无统计学意义(P 0. 05),SSA/P与TSA的异型增生检出率及其严重程度、癌变检出率差异亦无统计学意义(P 0. 05)。结论:结直肠锯齿状息肉临床上相对少见,不同类型病变的内镜和病理学表现有其自身特点。SSA/P和TSA有重度异型增生和癌变风险。     

锯齿状息肉的研究进展

结直肠癌是一种常见的消化道恶性肿瘤,其癌变途径主要为腺瘤途径(50%~70%)、de novo途径(3%~5%)、锯齿状息肉途径(30%~50%)。目前已有大量研究对锯齿状息肉进行了探讨,但对其癌变机制、内镜特点、治疗策略仍缺乏统一的认识。本文就锯齿状息肉的内镜特征、分子病理特征、治疗策略作一综述。     

结直肠无蒂锯齿状腺瘤的研究进展

结直肠癌(colorectal cancer,CRC)是世界上第3大常见的恶性肿瘤和第4大癌症死亡原因。根据世界卫生组织(WHO)对消化系统肿瘤的分类,锯齿状息肉（serrated polyposis,SPs）分为无蒂锯齿状腺瘤/息肉(sessile serrated adenoma/polyps,SSA/P)、增生性息肉（hyperplastic polyp,HP）和传统锯齿状腺瘤(traditional serrated adenoma,TSA)。除传统的腺瘤-癌序列途径,TSA和SSA均可通过锯齿状途径导致结CRC,又因TSA较为罕见,故SSA是该途径导致CRC的主要病变。本文总结了SSA/P的相关因素、组织学表现、分子生物学特征、内镜表现及内镜治疗的最新研究进展。     

锯齿状腺瘤研究进展

锯齿状腺瘤（serrated adenoma，SA）是同时具有增生性息肉（hyperplasic polyp，HP）的锯齿状结构和传统腺瘤异型性上皮特征的一种新腺瘤类型。具有锯齿状结构的病变包括HP、HP腺瘤混合性息肉（admixed hyperplasic polyp／adenoma，HP／AD）和SA。近年临床病理学和分子生物学方面的研究认为，HP可能是一种结、直肠癌发生新途径的早期阶段，即“HP—SA-癌”途径。SA组织学发生、形态结构、分子遗传学改变等具特殊性。有研究表明，SA可在2年内发展为进展期大肠癌。因此HP和SA作为一种新的癌前病变值得我们深入研究。     

结肠锯齿状病变临床病理分析

目的锯齿状病变代表一种异源性病变,其中一些具有恶性潜能。进一步明确锯齿状病变的临床病理特征,以期为临床治疗提供广阔思路。 方法对河北医科大学第四医院切除的788例结肠息肉病变进行形态学观察、免疫组化检测。按不同的检测方法确定每种锯齿状病变的临床病理特征,病变的比例通过χ²检验,P值<0.05为差异具有统计学意义。 结果增生性息肉（hyperplastic polyp,HP）占息肉总数比例较高（508,64.6%）,好发于远端结肠（381,75.1%）,多数伴有急性、慢性炎反应（330,64.9%;178,35.1%）;而在广基锯齿状腺瘤/息肉（sessile serrated adenoma,SSA）（伴或不伴不典型增生）、传统性锯齿状腺瘤（traditional serrated adenoma,TSA）具有较多以下特征如伴发急性炎反应,平滑肌束长入固有层。以及临床特征中传统锯齿状腺瘤、广基锯齿状腺瘤/息肉伴异型增生中BRAF检测阳性44（62.8%）、19（35.2%）;而且有肠病恶变的患者中（TSA）比例较高42例及随访健康的患者中（HP）比例较高490例,两组比较差异具有统计学意义（χ²=21.438,P<0.05） 结论锯齿状病变仍是一种在基因水平认识不足的综合征,而且与结肠腺癌的患病风险的相关性无从论证。因此,临床病理工作者对疾病的正确认识在需要每年检查结肠镜的患者中担任着非常重要的责任。     

Clinicopathological characteristics of serrated polyps as precursors to colorectal cancer: Current status and management

Serrated polyps have long been thought to lack malignant potential in the human colorectum. However, identification of the serrated pathway to colorectal cancer based on molecular biology has improved our understanding of the pathogenesis of colorectal cancers. Accordingly, serrated polyps such as traditional serrated adenoma and sessile serrated adenoma/polyps (SSA/P) are now considered to be precursor lesions of the serrated pathway. Recently, serrated polyps were classified into three subtypes, consisting of hyperplastic polyp, SSA/P, and traditional serrated adenoma, according to the World Health Organization classification. It has been suggested that SSA/P in the proximal colon are a precursor lesion of pathogenesis of colorectal cancer and are characterized by BRAF mutation and a CpG island methylator phenotype with or without microsatellite instability. However, SSA/P is more challenging to detect by colonoscopy and is likely to account for some interval cancers, particularly in the proximal colon because it presents flat or sessile, isochroous appearance, and occasionally has a mucous cap. Furthermore, the possibility has been raised that pathologists misclassify SSA/P as hyperplastic polyp. It is important for gastroenterologists to recognize the endoscopic features of serrated polyps to facilitate their detection and removal and also to establish postpolypectomy surveillance guidelines. In this review, we discuss the recent classification of serrated polyps; the molecular characteristics of the serrated pathway; appropriate diagnostic methods using endoscopy, including a new image‐enhanced endoscopic technique; and management of these lesions.     

Pathogenesis and Management of Serrated Polyps: Current Status and Future Directions

Hyperplastic or serrated polyps were once believed to have little to no clinical significance. A subset of these polyps are now considered to be precursors to colorectal cancers (CRC) in the serrated pathway that may account for at least 15% of all tumors. The serrated pathway is distinct from the two other CRC pathways and involves an epigenetic hypermethylation mechanism of CpG islands within promoter regions of tumor suppressor genes. This process results in the formation of CpG island methylator phenotype tumors. Serrated polyps are divided into hyperplastic polyps, sessile serrated adenomas/polyps (SSA/Ps), and traditional serrated adenomas (TSAs). The SSA/P and the TSA have the potential for dysplasia and subsequent malignant transformation. The SSA/Ps are more common and are more likely to be flat than TSAs. Their flat morphology may make them difficult to detect and thus explain the variation in detection rates among endoscopists. Challenges for endoscopists also include the difficulty in pathological interpretation as well surveillance of these lesions. Furthermore, serrated polyps may be inadequately resected by endoscopists. Thus, it is not surprising that the serrated pathway has been linked with interval cancers. This review will provide the physician or clinician with the knowledge to manage patients with serrated polyps.     

结直肠无蒂型锯齿状腺瘤的临床病理特征

无蒂型锯齿状腺瘤（SSA）属结直肠锯齿状病变之一,具有独特的形态学特点、生物学行为和分子基因学改变,其内镜形态和组织学特征有别于其他结直肠锯齿状病变,且与新近提出的结直肠癌变的锯齿状通路密切相关.近年研究发现SSA是微卫星不稳定性癌的前期病变,可直接发生癌变.但目前国内尚缺乏对这一病变的认识.本文就SSA的定义、形态学特征和病理组织学诊断标准作一综述,旨在提高临床医师对这一病变的认识.     

Serrated pathway in colorectal carcinogenesis

Serrated adenocarcinoma is a recently described subset of colorectal cancer(CRC),which account for about10%of all CRCs and follows an alternative pathway in which serrated polyps replace the traditional adenoma as the precursor lesion to CRC.Serrated polyps form a heterogeneous group of colorectal lesions that includes hyperplastic polyps(HPs),sessile serrated adenoma(SSA),traditional serrated adenoma(TSA)and mixed polyps.HPs are the most common serrated polyp followed by SSA and TSA.This distinct histogenesis is believed to have a major influence in prevention strategies,patient prognosis and therapeutic impact.Genetically,serrated polyps exhibited also a distinct pattern,with KRAS and BRAF having an important contribution to its development.Two other molecular changes that have been implicated in the serrated pathway include microsatellite instability and the CpG island methylator phenotype.In the present review we will address the current knowledge of serrated polyps,clinical pathological features and will update the most recent findings of its molecular pathways.The understanding of their biology and malignancy potential is imperative to implement a surveillance approach in order to prevent colorectal cancer development.     

Serrated polyposis syndrome: molecular, pathological and clinical aspects

Hyperplastic polyps have traditionally been considered not to have malignant potential. New pathological classification of serrated polyps and recent discoveries about the serrated pathway of carcinogenesis have revolutionized the concepts and revitalized the research in this area. Until recently, it has been thought that most colorectal cancers arise from conventional adenomas via the traditional tumor suppressor pathway initiated by a mutation of the APC gene, but it has been found that this pathway accounts for only approximately 70%-80% of colorectal cancer (CRC) cases. The majority of the remaining colorectal cancer cases follow an alternative pathway leading to CpG island methylator phenotype carcinoma with BRAF mutation and with or without microsatellite instability. The mechanism of carcinomas arising from this alternative pathway seems to begin with an activating mutation of the BRAF oncogene. Serrated polyposis syndrome is a relatively rare condition characterized by multiple and/or large serrated polyps of the colon. Clinical characteristics, etiology and relationship of serrated polyposis syndrome to CRC have not been clarified yet. Patients with this syndrome show a high risk of CRC and both sporadic and hereditary cases have been described. Clinical criteria have been used for diagnosis and frequent colonoscopy surveillance should be performed in order to prevent colorectal cancer. In this review, we try to gather new insights into the molecular pathogenesis of serrated polyps in order to understand their possible clinical implications and to make an approach to the management of this syndrome.     

Emerging concepts in colorectal serrated polyps

Colorectal serrated polyps are heterogeneous epithelial lesions characterized by a serrated architecture. They include the classical hyperplastic polyps and the much rarer serrated adenomas and mixed polyps. Whereas serrated adenomas are composed of an unequivocal adenomatous epithelium with architectural serrated, mixed polyps include two separate hyperplastic and adenomatous components. During the past few years, another type of serrated polyp with only very subtle proliferation abnormalities has been described. These atypical serrated polyps may occur either sporadically or in the context of colorectal polyposis. Despite their close resemblance to traditional hyperplastic polyps, some authors argued that they should be regarded as authentically neoplastic lesions and have proposed to call them "sessile serrated adenomas". Their malignant potential requires their removal when discovered during colonoscopy. This article reviews the histological features, the endoscopic appearance, the natural history and the molecular phenotype of the different categories of serrated polyps and introduces the concept of "serrated neoplastic pathway" in the development of colorectal cancer.     

结直肠锯齿状病变的微卫星状态研究

目的 比较结直肠锯齿状病变与传统腺瘤、腺癌的微卫星状态的差异,以期间接验证传统型锯齿状成瘤通路的存在.方法 收集北京军区总医院病理科保存的75例大肠息肉及肿瘤组织蜡块标本,其中锯齿状腺癌(Sca)15例,非锯齿状腺癌(N-Sca)20例,传统型锯齿状腺瘤(TSA)20例,普通腺瘤20例.抽提基因组DNA,采用荧光标记引物扩增BAT25、BAT26两个位点,随后使用DNA自动测序仪检测其微卫星状态,并对实验结果进行统计学分析.结果部分标本扩增失败,对于成功扩增的68例标本:18例TSA中6例为高度微卫星不稳定型(MSI-H),12例为低度微卫星不稳定型(MSI-L)/微卫星稳定型(MSS);18例普通腺瘤均为MSS;13例Sca中3例为MSI-H,10例为MSI-L/MSS;19例N-Sca中仅1例为MSI-H,18例为MSI-L/MSS.统计学分析表明,普通腺瘤组、N-Sca组MSI-H发生率明显低于TSA组和Sca组(P<0.05),而后两组间差异无统计学意义(P>0.05).结论 与普通腺瘤、N-Sca相比,MSI-H更多见于TSA、Sca,由此推断存在一条有别于传统"腺瘤-癌"发生模式的传统型锯齿状成瘤通路,但尚需大规模前瞻性研究确认.     

Serrated neoplasia of the colorectum

Serrated polyps of the colorectum form a group of related lesions which include aberrant crypt foci （ACF）, conventional hyperplastic polyps, mixed （admixed） polyps, serrated adenomas and sessile serrated adenomas. In recent years the molecular differences between these morphologically similar lesions have been highlighted, and their differing biological potential has been realised. In particular, the sessile serrated adenoma has become recognised as the precursor lesion to a group of sporadic colorectal carcinomas characterised by morphological and molecular features distinct from conventional adenomas. These recent findings have challenged the long held paradigm that all colorectal carcinomas arise via the traditional adenoma-carcinoma sequence. In addition, they present a major challenge for the early detection and management of colorectal cancer, which is no longer regarded as a homogeneous entity.