Rectal aberrant crypt foci identified using high-magnification-chromoscopic colonoscopy: biomarkers for flat and depressed neoplasia

BACKGROUND: Aberrant crypt foci may represent preneoplastic lesions in the human colon. The prevalence of aberrant crypt foci detected using magnification chromoscopic colonoscopy is known to follow a stepwise progression from normal subjects to those with exophytic adenomas and colon cancer. No studies have addressed the prevalence of rectal aberrant crypt foci in patients with flat and depressed colonic lesions that cluster within the right hemi-colon and may undergo de novo neoplastic transformation. METHODS: All patients underwent total colonoscopy by a single endoscopist using the Olympus CF240Z magnifying colonoscope. Flat and depressed lesions were diagnosed using targeted indigo carmine chromoscopy. Prior to extubation, pan high-magnification-chromoscopy using indigo carmine was applied to the rectum and the distal 10 cm of mucosa examined using forward and retroflexed views. Aberrant crypt foci were defined as two or more crypts with dilated or slit-like openings that were raised above the adjacent mucosa. Using high-magnification chromoscopic colonoscopy we assessed the prevalence and dysplastic features of aberrant crypt foci in three groups: endoscopically "normal" subjects, patients with flat/depressed adenoma, and flat/depressed cancer. RESULTS: Two thousand five hundred and fifty-nine patients underwent colonoscopy of which 1,000 were eligible for inclusion. The median number of aberrant crypt foci per patient in the endoscopically normal, adenoma, and cancer group was 1 (range: 0-5), 9 (range: 0-22), and 38 (range: 14-64), respectively. The estimated relative risk of dysplastic aberrant crypt foci when comparing the flat adenoma group with the endoscopically "normal" group was 4.68 (95% CI: 2.23-9.91) with the relative risk for flat cancer versus endoscopically normal group being 21.8 (95% CI: 10.9-23.8). Patients with >5 flat adenomas had higher crypt foci densities than those with <5 adenomas (r=0.53; p<0.001). CONCLUSIONS: The number of aberrant crypt foci in normal patients, patients with flat adenoma, and flat cancer follow a stepwise incremental change as previously observed for exophytic adenomas and cancer. Detection of aberrant crypt foci in the rectum may be a useful biomarker for proximal colonic flat neoplasia and could be used at index flexible sigmoidoscopic screening to stratify risk of proximal colonic neoplasia. Patients with dysplastic aberrant crypt foci of high density should receive total colonoscopy.     

Number of aberrant crypt foci in the rectum is a useful surrogate marker of colorectal adenoma recurrence

Aim: Endoscopic screening and removal of colorectal adenomas can reduce the incidence of colorectal cancer. However, given the possibility of adenoma recurrence, surveillance colonoscopy is currently recommended after the initial screening and removal of colorectal adenomas. Aberrant crypt foci (ACF) have been shown to serve as a reliable surrogate marker of colorectal carcinogenesis. In this study, the relationship between the number of ACF at the initial endoscopic polypectomy and the likelihood of colorectal adenoma recurrence after polypectomy were investigated. Methods: High‐magnification chromoscopic colonoscopy was performed in 82 subjects who underwent endoscopic polypectomy to identify ACF in the lower rectum. Surveillance colonoscopy was then performed 3 years after the baseline polypectomy at Yokohama City University Hospital. Results: The number of ACF was greater in patients who showed adenoma recurrence (7.88 ± 6.35) than in those who did not (2.19 ± 2.95) (P < 0.001). Receiver–operating curve analysis showed that the number of ACF was a highly specific predictor of the risk of adenoma recurrence. Conclusions: This is the first study conducted to investigate the relationship between the number of ACF after endoscopic polypectomy and the likelihood of recurrence of colorectal adenomas. These results suggest that the number of ACF is a useful predictor of the likelihood of colorectal adenoma recurrence.     

直肠异常隐窝病灶对结肠肿瘤的预警作用

目的 评判内镜下直肠异常隐窝病灶(ACF)与结肠病变及高癌变潜能肿瘤(AN)的关系.方法 接受全结肠镜检查的正常、息肉、腺瘤及癌的患者212例,在退镜时用0.4%靛胭脂对直肠进行染色,根据直肠ACF的数目对患者分级,无ACF者为0级,ACF数目为1～4,5～9,≥10者分别为Ⅰ、Ⅱ、Ⅲ级,统计分析ACF级别与结肠病变(息肉、腺瘤和癌),高癌变潜能肿瘤(≥1 cm,绒毛状、管状绒毛状,高度异型增生或浸润癌)的关系.结果 212例患者中,72例直肠ACF为0级,48例为Ⅰ级,41例为Ⅱ级,51例为Ⅲ级.直肠有ACF(包括Ⅰ、Ⅱ、Ⅲ级)的患者发生结肠病变及结肠高癌变潜能肿瘤的概率较无ACF者明显升高,其OR值(95%CI)分别为22.352(6.716～74.395),7.982(1.838～34.672).结论 直肠ACF对结肠病变及高癌变潜能肿瘤有预示作用.     

Chemopreventive effect of aspirin on growth of aberrant crypt foci in rats

Nonsteroidal anti-inflammatory drugs display a chemopreventive effect on polyps and cancer of the large bowel. This study evaluated the inhibitory effect of aspirin on the distribution and growth of aberrant crypt foci (ACF), the earliest putative preneoplastic and early neoplastic lesions in a rat model. For initiation of ACF, Sprague Dawley rats were injected with azoxymethane (30 mg/kg), a well-established rat carcinogen. After the second injection the rats were allocated to three groups, which received 0.2% or 0.6% aspirin or the solvent only (control group). After 6 weeks the animals were killed, and their colons removed, fixed in formalin, and screened for distribution and size of ACF, separately for middle and distal parts of the large intestine. The rats injected with azoxymethane showed a 100% incidence of ACF. Administration of 0.2% and 0.6% aspirin resulted in 55% and 54% reduction, respectively, in overall frequency of ACF. Aspirin significantly reduced the frequency of medium-sized (four to six crypts per focus) and large (three to six crypts per focus) but not the small (one to three crypts per focus) ACF. In the control group the ACF of the same multiplicity were larger than those in the aspirin-treated rats. No statistically significant difference in ACF-inhibiting effect was noted between 0.6% and 0.2% aspirin solution. Aspirin given at a concentration of either 0.2% of 0.6% thus has a chemopreventive effect on ACF, acting on postinitiation stage of azoxymethane-induced colonic carcinogenesis model in rats. Accepted: 20 July 1998     

Risk factors associated with missed colorectal flat adenoma: A multicenter retrospective tandem colonoscopy study

AIM: To determine the miss rate for colorectal flat adenomas during colonoscopy and the risk factors. METHODS: Flat adenomas are frequently missed during colonoscopy. However, the risk factors that influence their miss rates are unclear. This was a multicenter, retrospective study in which patients diagnosed with colorectal adenomas at a diagnostic colonoscopy and followed within 3 mo by a second therapeutic colonoscopy were pooled out from the established database. The “per-patient” and “per-adenoma” adenoma miss rates (AMR) for overall adenomas and flat adenomas, and patient-, adenoma-, and procedure-related risk factors potentially associated with the “per-adenoma” AMR for flat adenomas were determined. RESULTS: Chromoscopy and high-definition colonoscopy were not taken under consideration in the study. Among 2093 patients with colorectal adenomas, 691 (33.0%) were diagnosed with flat adenomas, 514 with concomitant protruding adenomas and 177 without. The “per-patient” AMR for flat adenomas was 43.3% (299/691); the rates were 54.3% and 11.3%, respectively, for those with protruding adenomas and those without (OR = 9.320, 95%CI: 5.672-15.314, χ² = 99.084, P < 0.001). The “per-adenoma” AMR for flat adenomas was 44.3% (406/916). In multivariate analysis, older age, presence of concomitant protruding adenomas, poor bowel preparation, smaller adenoma size, location at the right colon, insufficient experience of the colonoscopist, and withdrawal time < 6 min were associated with an increased “per-adenoma” AMR for flat adenomas. The AMR for flat adenomas was moderately correlated with that for overall adenomas (r = 0.516, P < 0.0001). The AMR for flat adenomas during colonoscopy was high. CONCLUSION: Patient’s age, concomitant protruding adenomas, bowel preparation, size and location of adenomas, proficiency of the colonoscopist, and withdrawal time are factors affecting the “per-adenoma” AMR for flat adenomas.     

窄带内镜、染色内镜与常规内镜对远端大肠ACF发现率的对比研究

目的比较常规内镜与窄带内镜（NBI）、染色内镜对远端大肠异常隐窝灶（aberrant cryptfoci,ACF）的发现率。方法选择2011年8月至12月就诊于江西省萍乡市人民医院准备接受结肠镜检查的患者670例,用随机数字表法将患者分为3组：其中常规内镜组228例、NBI组220例、染色内镜组222例。比较三种方法对远端大肠ACF检出率及各组间所用操作时间。结果在三组中,共发现155例ACF病例数。常规内镜、NBI组及染色内镜组发现ACF病例数分别为5例（2.19%）、25例（11.36%）,125例（56.31%）,三组组间比较有显著性统计学差异（P〈0.01）。但是与常规内镜相比,NBI组、染色内镜组操作时间有所延长。结论染色内镜能大幅提高远端大肠ACF发现率。NBI内镜较常规白光内镜能提高远端结肠ACF发现率,但比染色内镜低。常规白光内镜对远端结肠ACF发现率低。     

结肠癌患者直肠异型隐窝灶中脂肪酸合成酶的表达及其意义

背景：异型隐窝灶（ACF）是结直肠上皮性肿瘤最早期的形态学改变,可经腺瘤进展至结直肠癌。脂肪酸合成酶（FAS）在多数人恶性肿瘤组织中呈高表达。目的：检测结肠癌患者直肠ACF中的FAS表达情况,探讨ACF中FAS表达异常在结直肠癌形成中的意义。方法：30例确诊的散发性结肠癌患者纳入研究。以0.2%亚甲蓝溶液行直肠黏膜染色,通过放大结肠镜寻找、识别ACF,选取隐窝数目超过30个的较大的ACF为研究对象。以免疫组化染色检测直肠ACF以及配对结肠癌组织和正常结肠组织中的FAS表达。结果：30例结肠癌患者共确定116个目标ACF,不伴异型增生91个,伴异型增生25个。结肠癌组织中的FAS阳性表达率显著高于ACF和正常结肠组织（76.7%对32.8%和10.0%,P〈0.05）,ACF与正常结肠组织间差异亦有统计学意义（P〈0.05）。伴异型增生的ACF FAS阳性表达率与不伴异型增生者无明显差异（36.0%对31.9%,P〉0.05）。结论：F.AS在结直肠癌腺瘤-癌发生序列的最早期即已出现表达异常,在结直肠癌的形成中发挥重要作用。以FAS抑制剂抑制ACF进展可能成为结直肠癌化学预防的手段之一。     

Sequential Changes in Aberrant Crypt Foci and Lectin Expression in the Early and Late Stages of DMH-Induced Colon Carcinogenesis in Rats

Background/Aims

The purpose of this study was to investigate the malignant potential of aberrant crypt foci (ACF) by measuring the multiplicity of crypts and lectin expression in the early and late stages of 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis.

Methods

Six-week-old Wistar rats were injected subcutaneously with DMH for 27 weeks. We classified ACF according to the number of crypts per ACF as a few crypts (≤3 crypts, FC ACF) or numerous crypts (≥4 crypts, NC ACF). Immunohistochemistry was used to evaluate lectin expression.

Results

In the early stage, FC ACF (590/1,902, 31.0%) occurred more frequently than NC ACF (35/449, 7.8%); whereas in the late stage, NC ACF (176/449, 39.2%) occurred more frequently than FC ACF (324/1,902, 17.0%). The number of ACF peaked at 15 to 20 weeks. The ratio of NC/FC ACF increased gradually during carcinogenesis. The expression of both UEA1 and PNA was higher in NC ACF than FC ACF. Lectin expression increased in the late stage compared with the early stage.

Conclusions

The expression of lectin was higher in NC ACF and ACF in the late stage. Therefore, ACF with higher multiplicities in the late stage may have more malignant potential in DMH-induced colon carcinogenesis.     

Analysis of K-ras, APC, and beta-catenin in aberrant crypt foci in sporadic adenoma, cancer, and familial adenomatous polyposis

BACKGROUND & AIMS: We have previously shown that aberrant crypt foci (ACF) are the putative precursor lesions of colorectal adenomas and subsequent cancer in humans using magnifying endoscopy. The present study was designed to investigate these genetic alterations in ACF biopsy specimens from normal subjects, familial adenomatous polyposis (FAP) or sporadic patients. METHODS: The non-FAP cases included 34 normal subjects, 35 colorectal adenoma patients, and 19 colorectal cancer patients; there were 4 FAP patients. Biopsies were performed on ACF by magnifying endoscopy. K-ras mutations were analyzed by 2-step polymerase chain reaction and restriction fragment length polymorphism, APC mutations by in vitro-synthesized protein assay, and beta-catenin mutations by direct sequencing. Full-length APC and beta-catenin were detected by immunofluorescence. RESULTS: In non-FAP cases, K-ras mutations were detected in 82% (89/106) of nondysplastic ACF and 63% (17/27) of dysplastic ACF. APC mutation and beta-catenin accumulation were not detected in non-FAP ACF, whereas in adenoma of these patients, positivity of APC mutation and beta-catenin accumulation were 78% (24/31), and that of K-ras mutation was 65% (20/31). FAP patients showed K-ras mutations in only 13% (1/8) of dysplastic ACF, which is the predominant form of ACF found in FAP. In FAP patients, somatic APC mutations were found in 100% of dysplastic ACF, as they are in adenoma. The frequency of K-ras mutations was 73% (8 of 11) in FAP adenoma. CONCLUSIONS: The data suggest that in sporadic colorectal carcinogenesis, assuming the biological implication of ACF as a precursor of adenomas, there is a route where K-ras mutation mainly occurs during the formation of ACF, which then become adenomas wherein APC mutation occurs. In FAP, however, somatic mutation of APC predominantly occurs during ACF formation, followed by K-ras mutation.     

Relationship of aging and tobacco use with the development of aberrant crypt foci in a predominantly African-American population.

BACKGROUND AND AIMS: In clinical studies, diminished folate availability appears to increase the risk for colorectal neoplasms. Additionally, alcohol and tobacco use are associated with an increased risk for colon cancer, but the early pathologic events by which these agents promote neoplastic transformation are not well understood. Aberrant crypt foci (ACF) are potential precursors of adenoma and cancer, and can be visualized by magnification endoscopy. We hypothesized that folate depletion is linked to ACF formation and therefore studied the association between tissue folate, dietary habits, and ACF number in patients undergoing screening colonoscopy. METHODS: Eighty-three patients, undergoing screening colonoscopy at an urban Veterans Affairs and university hospital, completed a questionnaire concerning alcohol, nonsteroidal anti-inflammatory drug (NSAID), and tobacco use. Folate intake was calculated from food frequency questionnaires. Rectal ACFs were scored using magnification chromoendoscopy (magnification, 35 x) by methylene blue staining. Folate concentrations in rectal biopsy specimens were determined by microtiter bioassay. RESULTS: ACF number increased with age and with increasing tobacco intake. Decreased colonic folate level was associated with increased homocysteine levels and lower dietary folate intake but did not correlate with ACF number. CONCLUSIONS: Increasing age and tobacco use were linked independently to the presence of colonic ACF in this predominantly African-American population. Folate, alcohol, and acetylsalicylic acid (ASA) use did not influence the prevalence of these lesions.     

Identification and quantification of aberrant crypt foci in the colon of Min mice--a murine model of familial adenomatous polyposis

Min mice are heterozygous for a nonsense mutation in the murine adenomatous polyposis coli (APC) gene and spontaneously develop multiple intestinal neoplasms similar to the familial adenomatous polyposis (FAP) syndrome in humans. Aberrant crypt foci (ACF) are assumed to be preneoplastic lesions in both murine and human colon carcinogenesis and have been observed in FAP patients. Light microscopic examination of the colonic mucosa of 42 Min mice did not show even a single 'classical' ACF on the basis of previously defined criteria, specifying that they are elevated above the surrounding mucosa. However, in Min mice we discovered aberrant crypt foci of a different type, which we denoted ACF(Min). In contrast to the classical type, ACF(Min) were not elevated above the surrounding mucosa, their detection was totally dependent on methylene blue staining and transillumination, and they could not be identified with scanning electron microscopy. Histopathologic examination of ACF(Min) showed dysplastic crypts, similar to those found in larger lesions--that is, microadenomas in the Min mouse. The number of ACF(Min) increased up to the age of 6 weeks and then seemed to remain at a constant level of approximately four per colon. In conclusion, by transillumination of whole-mount preparations stained with methylene blue, we have identified and quantified small microscopic lesions that may be precursors of colonic adenomas in Min mice.     

结肠镜检查中大肠腺瘤的漏诊率及漏诊相关危险因素

目的 明确结肠镜检查中大肠腺瘤的漏诊率及漏诊腺瘤特征,探讨腺瘤漏诊的相关危险因素.方法 患者在初次结肠镜检查发现并切除腺瘤后120 d内进行结肠镜复查,分析2次结肠镜检查结果.记录2次结肠镜检查所见腺瘤的特征(包括大小、部位、形态、数目及病理)、患者临床特征(包括年龄、性别、结肠镜检查原因、腹部及盆腔手术史、大肠憩室病史及是否行无痛结肠镜检查)及不同的内镜操作医师.分析不同类型腺瘤在结肠镜检查中的漏诊率以及腺瘤特征、患者临床特征和内镜医师的操作水平对腺瘤漏诊的影响.结果 809例患者中271例发生腺瘤漏诊,2次结肠镜检查共检出腺瘤2134颗,漏诊腺瘤425颗,腺瘤总漏诊率为20%(425/2134);平均患者腺瘤漏诊率为33%(271/809).腺瘤体积大者,漏诊率低(P<0.01);乙状结肠、肝曲、盲肠和升结肠部位的腺瘤以及平坦型腺瘤容易漏诊(P<0.05);患者腺瘤数越多在结肠镜检查中腺瘤漏诊率越高(P<0.01);初级内镜医师与有经验内镜医师相比,其漏诊率明显增加(P<0.01).结论 结肠镜检查中存在部分腺瘤漏诊,腺瘤漏诊与腺瘤大小、形态、部位、数目以及结肠镜检查操作医师密切相关.     

Adenoma incidence decreases under the effect of polypectomy

AIM:To investigate whether,under the influence of pol-ypectomy,the incidence of adenoma decreases with age.METHODS:Consecutive patients with colonic adenomas identified at index colonoscopy were retrospectively selected if they had undergone three or more complete colonoscopies,at least 24 mo apart.Patients who had any first-degree relative with colorectal cancer were excluded.Data regarding number of adenomas at each colonoscopy,their location,size and histological classification were recorded.The monthly incidence density of adenomas after the index examination was estimated for the study population,by using the person-years method.Baseline adenomas were excluded from incidence calculations but their characteristics were correlated with recurrence at follow-up,using the χ 2 test.RESULTS:One hundred and fifty-six patients were included(109 male,mean age at index colonoscopy 56.8 ± 10.3 years),with follow-up that ranged from 48 to 232 mo.No significant correlations were observed between the number,the presence of villous component,or the size of adenomas at index colonoscopy and the presence of adenomas at subsequent colonoscopies(P = 0.49,0.12 and 0.78,respectively).The incidence of colonic adenomas was observed to decay from 1.4% person-months at the beginning of the study to values close to 0%,at 12 years after index colonoscopy.CONCLUSION:Our results suggest the sporadic formation of adenomas occurs within a discrete period and that,when these adenomas are removed,all neoplasia-prone clones may be extinguished.     

结肠镜检查中大肠腺瘤的漏诊率及漏诊相关危险因素

目的 明确结肠镜检查中大肠腺瘤的漏诊率及漏诊腺瘤特征,探讨腺瘤漏诊的相关危险因素.方法 患者在初次结肠镜检查发现并切除腺瘤后120 d内进行结肠镜复查,分析2次结肠镜检查结果.记录2次结肠镜检查所见腺瘤的特征(包括大小、部位、形态、数目及病理)、患者临床特征(包括年龄、性别、结肠镜检查原因、腹部及盆腔手术史、大肠憩室病史及是否行无痛结肠镜检查)及不同的内镜操作医师.分析不同类型腺瘤在结肠镜检查中的漏诊率以及腺瘤特征、患者临床特征和内镜医师的操作水平对腺瘤漏诊的影响.结果 809例患者中271例发生腺瘤漏诊,2次结肠镜检查共检出腺瘤2134颗,漏诊腺瘤425颗,腺瘤总漏诊率为20%(425/2134);平均患者腺瘤漏诊率为33%(271/809).腺瘤体积大者,漏诊率低(P<0.01);乙状结肠、肝曲、盲肠和升结肠部位的腺瘤以及平坦型腺瘤容易漏诊(P<0.05);患者腺瘤数越多在结肠镜检查中腺瘤漏诊率越高(P<0.01);初级内镜医师与有经验内镜医师相比,其漏诊率明显增加(P<0.01).结论 结肠镜检查中存在部分腺瘤漏诊,腺瘤漏诊与腺瘤大小、形态、部位、数目以及结肠镜检查操作医师密切相关.     

Histogenesis of human colorectal adenomas and hyperplastic polyps: the role of cell proliferation and crypt fission.

BACKGROUND: The histogenesis of human colorectal hyperplastic polyps and colorectal adenomas is poorly understood even now. METHOD: Human colorectal adenomas, hyperplastic polyps, and normal colorectal mucosae (patients with familial adenomatous polyposis and hereditary non-polyposis colorectal carcinoma were excluded) were obtained during colonoscopy and microdissected into individual crypts. Morphology, cell proliferation characteristics, and fission indices of crypts isolated from these lesions were then studied. RESULTS: Crypts isolated from colorectal adenomas and colorectal hyperplastic polyps were significantly larger (p<0.001) than crypts from normal colorectal mucosae. Crypt fission was an uncommon event in normal colonic mucosae but common in crypts isolated from adenomas and hyperplastic polyps (p<0.001). Analysis of the distribution of mitoses suggested an upward expansion of the proliferation compartment in adenomas to the surface of the crypt with no reversal of proliferating cell distribution, as has previously been described. CONCLUSIONS: Sporadic human colorectal adenomas and hyperplastic polyps grow by the process of crypt fission. Expansion of the proliferative compartment was demonstrated in crypts from adenomas, consistent with deregulation of cell cycle control.     

结肠镜检查中大肠腺瘤的漏诊率及漏诊相关危险因素

目的 明确结肠镜检查中大肠腺瘤的漏诊率及漏诊腺瘤特征,探讨腺瘤漏诊的相关危险因素.方法 患者在初次结肠镜检查发现并切除腺瘤后120 d内进行结肠镜复查,分析2次结肠镜检查结果.记录2次结肠镜检查所见腺瘤的特征（包括大小、部位、形态、数目及病理）、患者临床特征（包括年龄、性别、结肠镜检查原因、腹部及盆腔手术史、大肠憩室病史及是否行无痛结肠镜检查）及不同的内镜操作医师.分析不同类型腺瘤在结肠镜检查中的漏诊率以及腺瘤特征、患者临床特征和内镜医师的操作水平对腺瘤漏诊的影响.结果 809例患者中271例发生腺瘤漏诊,2次结肠镜检查共检出腺瘤2134颗,漏诊腺瘤425颗,腺瘤总漏诊率为20%（425/2134）;平均患者腺瘤漏诊率为33%（271/809）.腺瘤体积大者,漏诊率低（P〈0.01）;乙状结肠、肝曲、盲肠和升结肠部位的腺瘤以及平坦型腺瘤容易漏诊（P〈0.05）;患者腺瘤数越多在结肠镜检查中腺瘤漏诊率越高（P〈0.01）;初级内镜医师与有经验内镜医师相比,其漏诊率明显增加（P〈0.01）.结论 结肠镜检查中存在部分腺瘤漏诊,腺瘤漏诊与腺瘤大小、形态、部位、数目以及结肠镜检查操作医师密切相关.     

放大色素结肠镜观察FAS、Ki-67在直肠异常隐窝病灶中的表达

目的:观察FAS、Ki-67在结肠腺瘤、异常隐窝病灶(aberrant crypt foci,ACF)中的表达,探讨脂肪酸合成酶(fatty acid synthase,FAS)、增殖细胞核抗原(Ki-67)的异常表达在结直肠癌癌前病变形成中的意义.方法:对34例结肠镜确诊为腺瘤性息肉患者,常规内镜检查结束时,用0.2%的亚甲蓝溶液染色直肠黏膜,然后使用放大结肠镜观察直肠寻找ACF.对结肠腺瘤性息肉、ACF及正常黏膜活检标本进行免疫组织化学分析其FAS和Ki-67的表达.结果:34例结肠腺瘤性息肉患者,其中31例直肠发现ACF,共发现并活检ACF166处(其中伴异型增生14处,不伴异型增生152处).FAS、K i-67在结肠腺瘤、A C F中呈异常高表达(P<0.01).伴异型增生ACF中FAS、Ki-67表达较不伴异型增生ACF无明显上调.结论:FAS、Ki-67在结直肠癌的癌前病变(腺瘤、ACF)呈异常高表达.结直肠癌的癌前病变存在细胞能量代谢异常及异常增殖,在ACF阶段就已经异常增殖明显,抑制FAS有望成为结直肠癌预防、治疗的靶点.     

Role of aberrant crypt foci detected using high-magnification-chromoscopic colonoscopy in human colorectal carcinogenesis

Abstract Liaison between gastrointestinal endoscopists and histopathologists is essential to provide the highest standards of diagnostic accuracy and patient management. The histopathologist needs to be aware of the endoscopic findings when interpreting endoscopic biopsies. High-magnification-chromoscopic-colonoscopy (HMCC) is a new technology that provides the endoscopists with much greater resolution and functional staining of the gastrointestinal tract. Using HMCC, the endoscopist is now able to identify subtle changes in the colorectal luminal openings or crypts. Changes in crypt appearances now allow detection of aberrant crypt foci (ACF) in the colon, which might themselves be precancerous lesions but additionally might serve as a valid biomarker of subsequent adenoma and colorectal cancer formation. This article describes the role of the aberrant crypt focus in colorectal carcinogenesis and discusses the clinical impact of HMCC techniques as applicable to ACF.     

直肠异常隐窝病灶对大肠癌和进展型腺瘤的预警作用及其危险因素分析

目的 探讨直肠异常隐窝病灶（ACF）对大肠癌及进展型腺瘤的预警作用,并分析其危险因素.方法 应用独立样本t检验、单向方差分析及卡方检验分析比较直肠ACF的均数及发病率,应用Logistic回归分析直肠ACF与大肠癌及进展型腺瘤的关系,观察是否有预警作用,并筛选对ACF有显著意义的危险因素.结果 5个以上ACF显著增加大肠癌及进展型腺瘤的风险（P＜0.05）;高龄和吸烟为ACF的危险因素,而阿司匹林的应用为其保护因素.结论 5个以上ACF对大肠癌及进展型腺瘤有显著预警作用.在大肠癌的早期预防中,我们应该重视对ACF的形成有意义的影响因素.     

Daily soluble aspirin and prevention of colorectal adenoma recurrence: one-year results of the APACC trial

BACKGROUND & AIMS: Epidemiologic and experimental studies have suggested that aspirin intake reduces the risk for colorectal carcinogenesis. However, the available data are not sufficient to serve as the basis for firm recommendations. METHODS: We randomly assigned 272 patients with a history of colorectal adenomas (at least one more than 5 mm in diameter, or more than 3) to daily lysine acetylsalicylate (160 or 300 mg/day) or placebo for 4 years. The primary end points were adenoma recurrence after 1 and 4 years. These results are those of the year 1 colonoscopy. RESULTS: Among the 238 patients who completed the year 1 colonoscopy, at least one adenoma was observed in 38 patients of the 126 (30%) in the aspirin group and in 46 of the 112 (41%) in the placebo group; relative risk was 0.73 (95% confidence interval [CI]: 0.52-1.04; P = 0.08). At least one adenoma of more than 5 mm diameter was observed in 13 patients (10%) in the aspirin group and 26 (23%) in the placebo group (P = 0.01). The corresponding numbers for adenomas more than 10 mm in diameter were one (1%) and 7 (6%) (P = 0.05). Stepwise regression showed that independent factors associated with lower adenoma recurrence are aspirin treatment (adenoma >5 mm, P = 0.01), absence of personal history of adenoma before the entry colonoscopy (P = 0.01), and initial adenomatous polyp burden less than 10 mm (P = 0.001). CONCLUSIONS: Daily soluble aspirin is associated with a reduction in the risk for recurrent adenomas found at colonoscopy 1 year after starting treatment.