321例大肠息肉的临床分析

本文报道３２１例大肠息肉并进行了临床分析，着重讨论了息肉与癌变的关系及术式处理，总癌变率为１４．６％，其中，绒毛状腺瘤５８．３％，混合性腺瘤５５％，管状腺瘤１２．４％。腺瘤不典型增生程度越重，癌变率越高，广基无蒂腺癌的癌变率占７０．８％（１７／２４），有蒡腺瘤的癌变率仅７．８％（１２／１５３）。本文对所报道病例的９５％（３０５／３２１）进行了随访。     

大肠腺瘤癌变的处理

报告４９例大肠腺瘤与癌变的关系及大肠腺瘤癌变的处理。男性２６例，女性２３例，平均年龄４３．７岁，其中癌变１４例，癌变率为２８．６％。腺瘤癌变与腺瘤的大小、部位、腺瘤的数目、组织学类型及病人年龄等因素有关。〈１ｃｍ腺瘤未发生癌变，≥２ｃｍ的癌变率为５５％，直肠及乙状结肠的腺瘤易恶变。管状腺瘤、绒毛状腺瘤、管状绒毛状腺瘤的癌变率分别为２２．７％、４１．２％、２０％，绒毛状腺瘤最易癌变。癌变腺瘤的术式选     

大肠息肉1884例患者的临床观察及恶变特征分析

目的：了解大肠息肉的临床表现，探讨息肉的恶变特征。方法：对6144例有下消化道症状患者进行结肠镜检查，记录大肠息肉患者的临床表现以及年龄、性别等资料，对大肠息肉的发生率、内镜下表现、病理类型进行分析。结果：发现结肠息肉患者1884例，检出率30．66％。男性占61．68％，女性占38．32％。年龄〉60岁者占64．12％。临床症状中便血占56．26％。息肉直径0．2～3．8 cm不等，恶变和重度不典型增生息肉直径〉2cm者占79．73％。息肉发生于左半结肠者占67．41％。癌变和重度不典型增生息肉发生于左半结肠占85．42％（375／439）。病理类型：腺瘤性息肉42．00％，炎性息肉38．30％，错构瘤性息肉5．92％，增生性息肉6．45％，幼年性息肉7．40％。炎性息肉2例（2枚）癌变。腺瘤伴轻至中度不典型增生460枚占15．98％，重度不典型增生106枚占5．56％，癌变279枚占9．69％。腺瘤性息肉中管状腺瘤占37．46％（1078／2878），绒毛状腺瘤31．51％（907／2878），混合性腺瘤31．03％（893／2878）。重度不典型增生和癌变率在上述三种腺瘤中分别为6．68％（72／1078）、24．15％（219／907）和16．57％（148／893）。结论：肠息肉临床症状以便血最多。多见于〉60岁的男性。息肉分布于左半结肠者多见，癌变息肉和重度不典型增生息肉也易发生于左半结肠，癌变和重度不典型增生多发生于腺瘤性息肉。管状腺瘤发生重度不典型增生和癌变率最低，绒毛状腺瘤最高。     

大肠腺瘤癌变的处理

报告49例大肠腺瘤与癌变的关系及大肠腺瘤癌变的处理。男性26例，女性23例，平均年龄43．7岁，其中癌变14例，癌变率为28．6％。脉瘤癌变与腺癌的大小、部位、腺癌的数目、组织学类型及病人年龄等因素有关。＜1cm腺癌未发生癌变，≤2cm的癌变率为55％，直肠及乙状结肠的腺癌易恶变。管状腺瘤、绒毛状腺癌、管状绒毛状腺癌的癌变率分别为22．7％、41．2％、20％，绒毛状腺癌最易癌变。癌变腺癌的术式选择应根据癌变浸润深度、病理组织分类、癌细胞分化程度、切缘是否有癌残留以及淋巴管和静脉是否有癌浸润等决定。     

122例大肠腺瘤、腺瘤癌变的粘液组化观察

大肠腺瘤是一类癌前病变,文献报道管状腺瘤、绒毛状腺瘤的癌变率分别为5％、29～70％) 本文通过对1(?)例大肠腺瘤、腺瘤癌变的粘液组化观察,探讨其在病理外检诊断中的意义,现将结果报道如下。     

大肠小扁平腺瘤内镜和组织学特征及p53、p21表达研究

[目的]探讨大肠小扁平腺瘤的形态学特征及p53、p21表达的生物学意义。[方法]①用电子结肠镜及光学显微镜观察50例大肠小扁平腺瘤形态学特征。②用免疫组化二步法检测50例小扁平腺瘤及对照组26例大肠癌、15例正常人大肠黏膜中p53、p21表达率。[结果]①小扁平腺瘤发生于大肠任何部位．其发病率依次以横结肠、乙状结肠、直肠为多见；肠镜下见病灶呈圆形或椭圆形，扁平状，基底宽，体积〈1cm。②光镜下小扁平腺瘤呈管状腺瘤样图像，上皮具有不同程度的异型增生。⑧小扁平腺瘤中p53、p21的表达率分别为58％（29／50）、56％（28／50）。随着小扁平腺瘤异型增生程度的增高．p53、p21的表达率也逐渐升高（P〈0．05）。p53、p21在正常肠黏膜、小扁平腺瘤及大肠癌组中阳性表达率均逐渐升高，三组问差异有显著性（P〈0．05）。[结论]大肠小扁平腺瘤有其独特的形态学特征，p53、p21的表达与大肠小扁平腺瘤的癌变发生发展有密切关系。     

大肠腺瘤及其癌变的临床病理分析

目的探讨大肠腺瘤及腺瘤癌变与临床病理特征的关系。方法回顾性分析大肠腺瘤及癌变病例与腺瘤大小、解剖部位、外形、病理类型的关系。结果776例大肠腺瘤患者发生癌变者为42例,癌变率为5.4%,绒毛状腺瘤癌变率最高,管状腺瘤癌变率较低;直肠腺瘤癌变率均高于右半结肠(P<0.05);大肠腺瘤癌变率随着腺瘤的增大而升高,并且广基形腺瘤比长蒂形腺瘤更易癌变。大肠腺瘤的癌变率随异型增生程度的增高而增高(P<0.05)。结论大肠腺瘤癌变与腺瘤大小、解剖部位、外形、病理类型及腺瘤异型增生程度等因素有关。     

53例大肠息肉癌变分析

本组大肠息肉５４８例，８１５枚，５３例（枚）癌变，癌变率９．７％．以乳头状腺癌、混合腺瘤癌变率较高，二者间无差异（Ｐ＞０．０５），管状腺瘤较低，与前二者差异明显（Ｐ＜０．０１），且发现１例炎性息肉癌变．直径＞２．ｏｃｍ，息肉癌变率明显高于２．０ｃｍ以下者（Ｐ＜０．０１）．广基息肉癌变率高于带蒂者（０．０５＞Ｐ＞０．０１）．癌变息肉表面色泽均有改变．在儿童期未检出癌变息肉；中年期息肉癌变率高于青年期（Ｐ＜０．０５），而与老年期无差异（Ｐ＞０．０５）．各大肠段息肉癌变率无差异（Ｐ＞０．０５）．内镜检查并取材活检明显提高了息肉及其癌变的检出率，内镜下治疗息肉可降低大肠癌的发病率．     

大肠癌PKC-α、CyclinD1和Cdk4的表达与临床病理学特征的关系

目的：探讨大肠癌PKC-α，CyclinD1和Cdk4的表达与临床病理学特征的关系。方法：应用免疫组织化学sP法对PKC-α，CyclinD1和Cdk4的表达进行检测。结果：PKC-α在大肠癌组织中阳性表达率31／47（66．0％）与大肠正常组织3／15（20．0％）及腺瘤10／21（47．6％）对比有显著性差异（P〈0．05），与大肠癌分化程度，Dukes分期，淋巴结转移及CEA水平明显相关（P〈0．05）。CyclinD1和Cdk4在大肠癌中阳性表达率分别为26／47（55．5％），28／47（59．6％），与正常组织中表达2／15（13．3％），1／15（6．70％）及腺瘤组织中表达8／21（38．1％），9／21（42．9％）相比呈递增趋势（P〈0．05）。大肠癌中CyclinD1阳性表达与肿瘤分化程度，Dukes分期，淋巴结转移呈正相关关系（P〈0．05），而与CEA水平关系不大（P〉0．05）；Cdk4阳性表达则与分化程度，Dukes分期有关（P〈0．05），与淋巴结转移及CEA水平关系不密切（P〉0．05）。结论：PKC-α，Cy-clinD1和Cdk4的高表达与大肠癌分化程度，Dukes分期呈明显相关，对判断大肠肿瘤恶性程度具有一定的临床意义。     

胃癌、大肠癌及癌前病变中MGcl单克隆抗体的表达及其意义

应用肠型胃癌单克隆抗体ＭＧｃｌ，ＰＡＰ免疫组化染色，对大肠癌、胃癌、大肠腺瘤等进行标记，发现胃癌ＭＧｃｌ阳性率为８５．７％；大肠癌、大肠腺瘤和炎性息肉阳性率分别为９０．７％、４５．８％和１３．０％，三组有显著差异（Ｐ＜０．０５）。绒毛状和绒毛管状腺癌明显阳性者高于管状腺瘤（Ｐ＜０．０５）。结果表明，ＭＧｃｌ免疫组化标记对于大肠癌和癌前病变的诊断和估计预后有意义。     

Cell culture of human colon adenomas and carcinomas

Cell lines were established from colon adenomas, including tubular and villous polyps, primary adenocarcinomas, and metastases arising in patients with colon adenocarcinomas. The protocol for cultivating these diverse tissues includes primary cultivation of tissue explants on a type I collagen gel followed by nonenzymatic subculture of the epithelial outgrowth. All early passages were accomplished using low subculture ratios. Cultured cells elaborate morphological structures which are similar to features present in the tissues from which they were cultivated. Specifically, all structural features of colon epithelial cells were identified, including junction formation, prominent microvilli, and mucin secretion, in several cell lines. Five cell lines cultured from colonic neoplasms at different stages of cancer progression were selected for detailed characterization. Cells grown from two tubular polyps had normal human karyotypes. Cells from a villous polyp and all adenocarcinomas were aneuploid with stable marker chromosomes. The established cell lines exhibit distinct phenotypes based on growth characteristics in vitro and in athymic mice; and it is suggested that these cell lines represent useful models for studying the evolution of colon cancer from a benign to an aggressive cell type.     

The DNA content in rectal adenomas

Flow cytometric DNA analysis was performed in 67 tubular, tubulovilous and villous rectal adenomas with different degree of dysplasia. One of the adenomas contained a focus of early invasive carcinoma. All but one of the 67 adenomas had near diploid DNA histograms; the exception was a tubular adenoma with severe dysplasia but without signs of early invasion. Flow cytometric DNA analyses of adenomas may in some cases provide valuable information. The low frequency of aneuploidy indicates, however, that routine DNA measurements are questionable. Rather, the analysis should be restricted to certain cases like those with high malignant potential, cases with suspected early invasive carcinoma, and adenomas not radically removed.     

CEA levels in patients with colorectal polyps.

Preoperative plasma CEA levels were measured in 93 selected patients with histologically defined colorectal adenomata removed at fibroptic colonoscopy in order to determine whether CEA levels are elevated in patients with colonic polyps, or vary with different histologic patterns. None of the patients had inflammatory bowel disease, previous history of carcinoma, or evidence of liver disease. Fifteen percent of the patients had elevated CEA levels (greater than or equal to 2.5 ng/ml; Hansen method), and two-thirds of these were between 2.5 and 4.0 ng/ml. Increased association of elevated CEA levels was noted with old age, villous adenomas (2- to 4-fold), and increased tumor size (greater than 2.3-cm diameter; 2-fold), but not with foci of dysplasia or carcinoma in situ as such. One-half (7/14) of the patients with elevated CEA levels showed the following: two patients had villous tumors with carcinoma in situ, one had a villous adenoma, two had mixed villous and tubular adenomas (with a high proportion of villous pattern), and two were subsequently shown to have carcinoma elsewhere in the colon. It is uncertain that the polyps were the source of the elevated circulating CEA levels; other factors including smoking and patient selection need to be considered. This preliminary study suggests that patients with colorectal adenomata and elevated circulating CEA may be at higher risk for the development of carcinoma. Further follow-up studies of the malignant potential of the polyp-bearing colon are essential.     

Expression of MUC2-mucin in colorectal adenomas and carcinomas of different histological types

The expression of mucin MUC2 was investigated in normal colonic tissue, in colonic adenomas and in carcinomas of the mucinous and non-mucinous type. The latter were subdivided into carcinomas originating from the adenoma-carcinoma sequence (ACS) and de novo (DN) carcinomas. The expression was assayed by immunohistochemistry with the monoclonal anti-MUC2 antibody CCP58 and by mRNA semiquantitation. MUC2 protein epitope CCP58 was strongly expressed in 21 % of normal colonic tissues, in 40% of villous and in 48% of tubular adenomas. Mucinous carcinomas exhibited strong expression in 72%, ACS carcinomas in 21 % and DN adenocarcinomas in none of the tumors investigated. Compared with the adjacent non malignant tissue (transitional mucosa), CCP58 epitope expression in the tumor was higher in 74% of mucinous carcinomas, but equal or lower in 69% of ACS carcinomas and in 100% of de novo carcinomas. The alterations of MUC2 expression detected by immunohistochemistry in adenocarcinomas were confirmed on mRNA level. These data indicate that the MUC2 expression pattern is different in the 3 carcinoma types investigated. MUC2 over-expression occurs in the adenomatous tissue. It is always maintained in mucinous carcinomas, but frequently decreased in non-mucinous ACS carcinomas. DN carcinomas are most frequently associated with decreased expression of MUC2. © 1994 Wiley-Liss, Inc.     

Tissue CEA detection by immunoperoxidase (PAP) test in colorectal polyps: correlations with the degree of dysplasia

We study the presence of Carcinoembryonic antigen (CEA) on 39 colorectal polyps by the immunoperoxidase technique. The histological examination demonstrated 15 tubular adenomas, one villous adenoma, two tubulo-villous adenomas, six tubular adenomas with slight dysplasia, one tubular adenoma with moderate dysplasia, four tubular adenomas with severe dysplasia, three tubulo-villous adenomas with severe dysplasia, five tubular adenomas with neoplastic degeneration, and two tubulo-villous adenomas with neoplastic degeneration. Twenty-eight of thirty-nine polyps (71.79%) showed a positive staining reaction for CEA. Regarding the intensity of the reaction (classified as absent or negative [-], slightly positive [+], and markedly positive [+ +]), 11/39 polyps presented a negative reaction (28.21%), 19/39 (48.71%) presented a slight reaction, and 10/39 polyps (25.64%) presented a marked reaction. Results demonstrated a higher intensity of the staining reaction in severely dysplastic polyps and in neoplastic degeneration. In conclusion, it is possible that the presence of CEA can be useful to show an initial cellular restlessness of certain polyps.     

Over-expression of p53 nuclear oncoprotein in colorectal adenomas.

p53 is a nuclear phosphoprotein which controls normal cell growth. Normal p53 protein is undetectable by standard immunohistochemical staining and the over-expression found in neoplastic cells correlates with the presence of point mutations of evolutionary conserved regions of the p53 gene. We examined the expression of p53 protein in a series of 36 colorectal adenomas (13 tubular, 17 tubulovillous, 6 villous) showing different degrees of dysplasia (11 mild, 19 moderate, 6 severe), 11 moderately differentiated adenocarcinomas (6 Duke's A, 4 Duke's B, 1 Duke's C) and 5 metaplastic polyps using the polyclonal antibody CM1 which recognises p53 protein in conventionally fixed and processed histological material. We found that 15 out of 36 colorectal adenomas showed p53 immunoreactivity, although in 4 positive cases (26%) the staining was very focal (less than 0.1% positive cells). More than 80% of severely dysplastic adenomas showed strong p53 immunoreactivity and this over-expression was correlated with increased cell proliferative rate as detected by the proliferating-cell-nuclear-antigen (PCNA) staining. p53 nuclear staining was also seen in 8 out of 11 (65%) colorectal adenocarcinomas as previously shown. Our data suggest that the p53 gene mutation, with the subsequent over-expression of the protein, occurs in colorectal adenomas and may therefore be a fundamental genetic event underlying the dysplasia and loss of proliferative control that are characteristic of adenomas with malignant potential.     

家族性胃肠道腺瘤病表面微细结构的研究

Fourty-one adenomas from 13 cases of familial gastrointestinal adenomatosis, with 6 samples of normal colonic mucosa, 4 well differentiated adenocarcinomas and 2 villous adenomas as control, were examined by scanning electron microscopy. The surface feature of the adenomas was classified into three types: tubular, branching and irregular, based mainly on the irregularity of the enlarged and distorted crypts. There is close relationship between surface architecture and inner histologic pattern, especially the degree of atypia. The more irregular the surface architecture, the higher the atypia in histology. Those of tubular type are mostly tubular adenomas with mild dysplasia, while the majority of branching type are villous or villous-tubular adenomas with moderate or severe dysplasia. Irregular type usually implies malignant transformation. The results suggest that the observation and evaluation of the surface structure of familial adenomatosis be of great value, as a supplementary procedure, in identifying premalignancy and early malignancy in adenoma-carcinoma sequence.     

Reliability in the classification of advanced colorectal adenomas.

In conjunction with a pooled analysis of risk factors for advanced adenomas [adenomas with severe dysplasia, carcinoma in situ (CIS), and intramucosal carcinoma], we undertook a reliability study on the pathological diagnosis of advanced adenomas. We assessed intraobserver agreement (using Kappa (kappa) as the measure of agreement) across two time periods 10 years apart with a single pathologist and interobserver agreement (using Kappa) between two pathologists rating the same slides concurrently. The study pathologists were blinded to the original case classification. We used the slides of 190 colorectal adenomatous polyp cases (104 originally diagnosed as advanced adenomas, 86 adenomas without advanced lesions) from a colonoscopy-based case-control study conducted in New York City between 1986 and 1988. We also assessed conditional agreement for 71 slides of advanced adenomas from four adenoma case-control studies conducted in different geographic regions of the United States in the 1990s. Intra- and interobserver agreement was only fair to moderate on the classification of both histological type (villous, tubulovillous, and tubular: intraobserver kappa = 0.28; 95% confidence interval (CI), 0.17-0.39; interobserver kappa = 0.48; 95% CI, 0.33-0.62) and degree of dysplasia (none/mild, moderate, severe, CIS, and intramucosal: intraobserver kappa = 0.20; 95% CI, 0.12-0.28; interobserver kappa = 0.42; 95% CI, 0.29-0.55). Using broader, rather than finer, classifications for degree of dysplasia substantially improved the reliability (interobserver agreement for high-grade dysplasia (including severe dysplasia, CIS, and intramucosal carcinoma) versus low-grade dysplasia: kappa = 0.69; 95% CI, 0.55-0.83). These findings suggest that future epidemiological studies of advanced adenomas should use broad categories, such as high-grade versus low-grade dysplasia, include central review of all slides, and take measurement error into account in sample size calculations.     

K-ras mutations in incident sporadic colorectal adenomas

BACKGROUND: Although K-ras is the most frequently mutated protooncogene in colorectal carcinoma, the specific role and timing of K-ras mutations in colorectal carcinogenesis remains controversial. In the current study, the authors investigated associations with K-ras mutation in incident sporadic colorectal adenomas that occurred during a chemoprevention trial of calcium supplementation. METHODS: K-ras genotyping was performed on 303 colorectal adenomas that were removed from 207 participants during the follow-up phase of the Calcium Polyp Prevention Study. Mutations in codons 12 or 13 of K-ras were detected by denaturing high-performance liquid chromatography and were confirmed by direct sequencing. RESULTS: The adenomas analyzed had a mean estimated size of 0.5 cm, and 3.0% were identified with mutations (95% confidence interval [95% CI], 1.3-4.4%). These mutations were more common in larger adenomas (risk ratio [RR], 12.7 for tumors that measured > 0.5 cm vs. < or = 0.5 cm; 95% CI, 2.7-59.7), in adenomas with more advanced histology (RR, 20.6 for tubulovillous/villous vs. tubular; 95% CI, 4.4-96.0), and in adenomas that were located in the rectum compared with the colon (RR, 8.4; 95% CI, 2.3-30.5). CONCLUSIONS: Compared with previous studies, the current analysis was novel, because it focused on incident adenomas that were diagnosed within a few years of a previous "clean" colonoscopy. The results provided evidence for a very low rate of K-ras mutation among these small, early adenomas and strong support for a role of K-ras mutations in adenoma progression.     

BRAF和EphB2在人结直肠锯齿状腺瘤中的表达及意义

目的:探讨鼠类肉瘤滤过性病毒致癌基因同源体B1(v-raf murine sarcoma viral oncogene homolog B1,BRAF)和生促红素人肝细胞蛋白(erythropoietin-producing hepatoma cell line B2,EphB2)在人结直肠锯齿状腺瘤中的表达及其意义。方法:收集滨州医学院附属医院1996年1月至2008年5月10例正常结直肠肠黏膜、21例增生性息肉、22例锯齿状腺瘤、55例腺瘤性息肉(18例管状腺瘤、16例管状绒毛状腺瘤、21例绒毛状腺瘤)石蜡标本。免疫组织化学法检测BRAF和EphB2蛋白的表达量,同时观察蛋白的表达部位。结果:增生性息肉中BRAF蛋白阳性细胞多位于隐窝中下区域,腺瘤性息肉的阳性细胞多表达位于隐窝上部区域,而锯齿状腺瘤阳性细胞多表达于隐窝全层。锯齿状腺瘤与腺瘤性息肉的BRAF蛋白表达量相近[(0.129±0.030)vs(0.130±0.026),P>0.05],但远高于增生性息肉[(0.129±0.030)vs(0.102±0.014),P<0.01];锯齿状腺瘤、管状腺瘤、管状绒毛状腺瘤、绒毛状腺瘤之间BRAF蛋白表达量差异无统计学意义[(0.129±0.030)vs(0.116±0.019),(0.119±0.037),(0.122±0.008),P>0.05]。增生性息肉中EphB2蛋白阳性细胞多位于隐窝中下区域细胞膜上,腺瘤性息肉EphB2蛋白阳性细胞位于隐窝上部,而锯齿状腺瘤EphB2蛋白阳性细胞表达于隐窝全层。锯齿状腺瘤与腺瘤性息肉的EphB2蛋白表达量相近[(0.138±0.024)vs(0.139±0.025),P>0.05],而远高于增生性息肉[(0.138±0.024)vs(0.169±0.018),P<0.01];锯齿状腺瘤与管状腺瘤、管状绒毛状腺瘤、绒毛状腺瘤间EphB2蛋白表达量无区别[(0.138±0.024)vs(0.143±0.027),(0.139±0.028),(0.133±0.021),P>0.05]。结论:BRAF和EphB2蛋白在增生性息肉、腺瘤性息肉中隐窝部分区域表达,而在锯齿状腺瘤中隐窝全层表达,提示锯齿状腺瘤是一类独立的不同于腺瘤性息肉的结直肠肿瘤。