Assessment of Rectal Aberrant Crypt Foci by Standard Chromoscopy and its Predictive Value for Colonic Advanced Neoplasms

Seike, Kazuhiro; Koda, Keiji; Oda, Kazuhiro; Kosugi, Chihiro; Shimizu, Kimio; Nakagawa, Masaki; Shioiri, Masanobu; Takano, Shigetsugu; Ishikura, Hiroshi; Miyazaki, Masaru

doi:10.1111/j.1572-0241.2006.00578.x

Cited by 42 publications

(59 citation statements)

References 25 publications

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“…Indeed, it is possible to speculate that while the carcinogenic agents act along the entire bowel, eventually contributing to the appearance of the neoplastic tissue, they finally accumulate in the rectum, causing the increase in the number of ACF. This parallel, which is in agreement with the results reported by Seike et al [25], might mean that rectal ACF could be an indicator of a carcinoma elsewhere in the colon.…”

Section: Discussionsupporting

confidence: 83%

“…The option to study only rectal ACF, in accordance with studies that applied a similar methodology [19][20][21][22][23][24][25][26], deserves some justification. This decision was founded on investigations in surgical specimens [40,41] and endoscopic studies [23,42] that show that ACF are more frequently detected in the left colon and in the rectum.…”

Section: Discussionmentioning

confidence: 99%

“…The modulation of ACF by chemopreventive agents with proven activity in CRC is also described in animal studies [16][17][18]. With the emergence of magnification and chromoscopy, it is now possible to perform endoscopic in vivo human studies [19][20][21][22][23][24][25][26]. Although there are a number of arguments supporting the preneoplastic nature of ACF, such as an average number that increases with age [23], a higher prevalence in patients with neoplastic lesion of the colon [23], the identification of ACF with carcinoma in situ in a patient with sporadic colon cancer [27], the presence of ACF with dysplasia and APC mutations in patients with familial adenomatous polyposis [28,29], and the occurrence of microsatellite instability in ACF picked from patients with Lynch syndrome [30], the truth is that doubt still persists with regard the preneoplastic nature of ACF, which is unquestionable only in animal models of intestinal cancer.…”

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confidence: 99%

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Aberrant crypt foci: endoscopic assessment and cell kinetics characterization

Figueiredo

Donato

Urbano

et al. 2008

Int J Colorectal Dis

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Background and aims Aberrant crypt foci (ACF) are preneoplastic lesions in animal models of colorectal cancer. The aim of the study is to investigate if ACF are involved in human colorectal carcinogenic process and if they can be helpful in predicting the presence of a colorectal neoplasia. Methods The study included, between 2003 and 2005, 182 patients, 62 with adenoma, 55 with colorectal carcinoma, 53 without colorectal lesions, and 12 with nonneoplastic mucosal polyps. The number of rectal ACF was determined by colonoscopy. Proliferation and apoptosis indexes were evaluated by immunohistochemistry in rectal ACF, in normal rectal mucosa, and in carcinomatous tissue. Results The mean number of rectal ACF in patients with rectal neoplasia was 12.64, significantly higher than in patients with neoplastic lesions elsewhere in the colon (p= 0.01). The apoptosis index in ACF of patients with colorectal carcinoma or adenoma aged 50 years or older was significantly lower than in younger patients (1.3% vs 2.7%, p=0.01) and, in patients with carcinoma, lower than in normal mucosa (1.1% vs 2.1%, p=0.002). The proliferation index was significantly higher in ACF of patients with colorectal neoplasia aged less than 50 years than in normal mucosa (10.9% vs 7.7%, p=0.02). The apoptosis index in ACF foci of patients with carcinoma (1.1%) was significantly lower than in patients without lesions (2.2%) and than in normal mucosa (2%). The mean number of ACF is significantly higher in patients with polyps larger than 1 cm (11.28 vs 6.27, p=0.02). Conclusion Aberrant crypt foci probably precede the appearance of neoplasia and may be helpful in predicting the presence of a colorectal neoplastic lesion.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Aberrant crypt foci: endoscopic assessment and cell kinetics characterization

Figueiredo

Donato

Urbano

et al. 2008

Int J Colorectal Dis

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“…These studies have estimated the prevalence and/or histological grade of ACF in 'normal' subjects, and subjects with colonic polyps or colon cancer [8,[48][49][50][51][52][53][54][55][56][57][58][59], although the definition of 'normal' varies widely. None of these studies has been population-based, and very few have included patients with no apparent risk factors for CRC.…”

Section: Review Of Epidemiological Studiesmentioning

confidence: 99%

Epidemiology of colonic aberrant crypt foci: Review and analysis of existing studies

2007

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Since first described in a rodent model in 1987, aberrant crypt foci (ACF) in the colon have been shown to exhibit many of the molecular features of the more advanced colonic neoplasms including cancer. Therefore, they may be early lesions with potential for progression, and be valuable biomarkers for reduction of risk of colorectal cancer (CRC). For this review, we searched PubMed, and reference lists of recent publications, for studies which reported on associations of features of ACF in humans, such as number or size, with subject characteristics, such as age or family history of CRC. Over 150 papers have reported on ACF in humans. However, the vast majority of these publications are concerned with molecular and morphological features of biopsied lesions, and not their epidemiology. None of the epidemiological studies were of optimum design, primarily due to their absence of a well-defined subject sampling frame or method. Given their 'first-generation' nature, consistent findings were of increased ACF number with age and with synchronous advanced colonic neoplasia. One study reported a higher mean number of ACF in subjects with a family history of CRC than in those without. The strongest evidence on the ability of ACF to predict a diagnosis of CRC will be from prospective studies with baseline ACF assessment in a large sample of diseasefree persons (many thousands) who are followed carefully for many years. In the interim, because ACF are asymptomatic, well-designed cross-sectional studies are feasible and will yield valuable information on the relation of ACF to the known risk factors for CRC. This information can then be used to improve the design of prospective studies, and of clinical intervention trials that use ACF as an intermediate endpoint.

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“…The increased number of ACF was further observed in patients with flat adenoma and cancer (9). Seike et al showed that ACF could be a predictive factor for advanced rectal cancer by multivariate analysis (10). Thus, magnifying endoscopy has become a common methodology to observe ACF.…”

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confidence: 99%

Aberrant Crypt Foci as Precursors of the Dysplasia-Carcinoma Sequence in Patients with Ulcerative Colitis

Kukitsu¹,

Takayama²,

Miyanishi³

et al. 2008

Clinical Cancer Research

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Purpose: Long-standing ulcerative colitis (UC) predisposes patients to the development of colorectal cancer, but surveillance of colitis-associated cancer by detecting the precancerous lesion dysplasia is often difficult because of its rare occurrence and normal-looking appearance. In sporadic colorectal cancer, aberrant crypt foci (ACF) have been reported by many investigators to be precursor lesions of the adenoma-carcinoma sequence. In the present study, we analyzed the genetic background of ACF to determine whether they could be precursors for dysplasia, and we examined the usefulness of endoscopic examination of ACF as a surrogate marker for surveillance of colitis-associated cancer. Experimental Design: ACF were examined in 28 UC patients (19 patients with UC alone and 9 patients with UC and dysplasia; 2 of those patients with dysplasia also had cancer) using magnifying endoscopy. K-ras, APC, and p53 mutations were analyzed by two-step PCR RFLP, in vitro^synthesized protein assay, and single-strand conformation polymorphism, respectively. Methylation of p16 was analyzed by methylation-specific PCR. Results: ACF that appeared distinct endoscopically and histologically were identified in 27 out of 28 UC patients. They were negative for K-ras, APC, and p53 mutations but were frequently positive for p16 methylation (8 of 11; 73%). In dysplasia, K-ras and APC mutations were negative but p53 mutation (3 of 5; 60%) and p16 methylation (3 of 5; 60%) were positive. There was a significant stepwise increase in the number of ACF from patients with UC alone to patients with dysplasia and to patients with cancer. Univariate and multivariate analyses showed significant correlations between ACF and dysplasia. Conclusions: We have disclosed an ACF-dysplasia-cancer sequence in colitis-associated carcinogenesis similar to the ACF-adenoma-carcinoma sequence in sporadic colon carcinogenesis. This study suggests the use of ACF instead of dysplasia for the surveillance of colitis cancer and warrants further evaluation of ACF as a surveillance marker in large-scale studies.It is commonly recognized that long-standing ulcerative colitis (UC) predisposes patients to the development of colorectal cancer (1). However, the detection of early colorectal cancer is often difficult in patients with UC because there is inflammation in the background mucosa and it predominantly represents flat-type ill-delineated lesions (2, 3). Therefore, colitis-associated cancer is often detected at an advanced stage and is characterized by a very poor prognosis. One approach to overcome this difficulty is to use dysplasia, which is considered to be a precancerous lesion in colitis-associated cancer, as a surrogate marker for early detection of colitis-associated cancer (4, 5). However, identification of dysplasia by endoscopy requires greater skill than detection of cancer itself because of its rare occurrence and apparently normal-looking appearance (6).We previously succeeded in identifying aberrant crypt foci (ACF) in non-UC subjects using ...

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Assessment of Rectal Aberrant Crypt Foci by Standard Chromoscopy and its Predictive Value for Colonic Advanced Neoplasms

Abstract: Chromoscopic assessment of rectal ACF by conventional techniques is useful for predicting colonic advanced neoplasms.

Cited by 42 publications

References 25 publications

Aberrant crypt foci: endoscopic assessment and cell kinetics characterization

Aberrant crypt foci: endoscopic assessment and cell kinetics characterization

Epidemiology of colonic aberrant crypt foci: Review and analysis of existing studies

Aberrant Crypt Foci as Precursors of the Dysplasia-Carcinoma Sequence in Patients with Ulcerative Colitis

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