High-magnification Chromoscopic Colonoscopy Research Articles

The distribution of human rectal aberrant crypt foci and criteria for defining the counting area.

Aberrant crypt foci (ACF) are considered as a useful surrogate biomarker for colorectal cancer, although their biological significance still remains controversial. We conducted this study to clarify whether differences in the ACF counting area might have led to the discrepancies in the ACF counts among previous reports. A endoscopist proficient in ACF counting performed high-magnification chromoscopic colonoscopy in 45 subjects and investigated the distribution of ACF in four bowel segments (middle Houston valve to the dentate line and distal rectum 0-5, 5-10 and 10-15 cm). We also investigated whether the patient physique might affect the distance from the middle Houston valve to the dentate line. The prevalence of ACF was 84% and most of the ACF (170/210, 81%) were located in the bowel segment from the middle Houston valve to the dentate line. The number of ACF was significantly correlated with the bowel segment in which the counting was performed: Dentate line to the middle Houston valve and distal rectum within 0-15 cm (r=0.94, P<0.001). The patient physique did not affect the distance from the middle Houston valve to the dentate line. In conclusion, the definition of the ACF counting area may not affect the results of ACF counting.

Abstract A12: Validity of aberrant crypt foci using as a surrogate biomarker for colorectal cancer

Abstract Introduction: Aberrant crypt foci (ACF) are considered to be useful as surrogate biomarker for colorectal cancer (CRC), but the biological significance of ACF remains controversial. We attempted to investigate the relationship between the presence of ACF and human colorectal carcinogenesis using a relatively large sample size. Methods: We performed high-magnification chromoscopic colonoscopy to identify ACF in 861 subjects undergoing a diagnostic endoscopy at the Yokohama City University Hospital. The present study compared the prevalence and number of ACF in three subject groups (normal subjects, adenoma cases, and CRC cases). The correlations between the demographic and behavioral characteristics of the subjects and the prevalence of ACF were also assessed. Results: The prevalence of ACF was 64%, 88% and 95%, and the mean number of ACF was 3.6, 6.2 and 10.1, in normal subjects, adenoma cases, and CRC cases, respectively. Older age and men had increased prevalence and number of ACF. When differences in the prevalence and number of ACF among age- and sex-stratified subject groups were examined, significant stepwise increments from normal subjects to adenoma cases to CRC cases were apparent (P&amp;lt;0.001). Moreover, an age- and sex-adjusted multiple logistic regression analysis revealed that smoking and alcohol habits had a synergistic effect, increasing the prevalence of ACF as well as the risk of CRC (P&amp;lt;0.001). Conclusions: These results suggested that ACF may serve as a reliable surrogate biomarker for human colorectal carcinogenesis. The use of ACF as an endpoint may enable the size, duration, and cost of CRC chemoprevention studies to be reduced. Citation Information: Cancer Prev Res 2011;4(10 Suppl):A12.

Investigation of the Prevalence and Number of Aberrant Crypt Foci Associated with Human Colorectal Neoplasm

Aberrant crypt foci (ACF) are considered to be useful as surrogate biomarker for colorectal cancer (CRC), but the biological significance of ACF remains controversial. We attempted to investigate the relationship between the presence of ACF and human colorectal carcinogenesis using a relatively large sample size. We carried out high-magnification chromoscopic colonoscopy to identify ACFs in 861 subjects undergoing a diagnostic endoscopy at the Yokohama City University Hospital. The present study compared the prevalence and number of ACFs in three subject groups (normal subjects, adenoma cases, and CRC cases). The correlations between the demographic and behavioral characteristics of the subjects and the prevalence of ACFs were also assessed. The prevalence of ACF was 64%, 88%, and 95%, and the mean number of ACF was 3.6, 6.2, and 10.1, in normal subjects, adenoma cases, and CRC cases, respectively. When differences in the prevalence and number of ACFs among age- and sex-stratified subject groups were examined, significant stepwise increments from normal subjects to adenoma cases to CRC cases were apparent (P < 0.001). Moreover, an age- and sex-adjusted multiple logistic regression analysis revealed that smoking and alcohol habits had a synergistic effect, increasing the prevalence of ACFs as well as the risk of CRC (P < 0.001). These results suggested that ACF may serve as a reliable surrogate biomarker for human colorectal carcinogenesis. The use of ACF as an endpoint may enable the size, duration, and cost of CRC chemoprevention studies to be reduced.

Abstract LB-436: Rectal aberrant crypt foci for estimate of colorectal tumor recurrence: 3-year follow up study

Abstract Background and Aims: Endoscopic screening and removal of colorectal tumor can reduce colorectal cancer, although surveillance colonoscopy is currently recommended after the initial screening and removal of colorectal tumor due to the possibility of newly developing tumor. Aberrant crypt foci (ACF) serve as surrogate biomarkers of human colorectal carcinogenesis. In this study we aimed to investigate the relationship between ACF and the recurrence of colorectal tumor after endoscopic polypectomy. Methods: We performed high-magnification chromoscopic colonoscopy to identify lower rectal ACF on 82 subjects who underwent endoscopic polypectomy, and surveillance colonoscopy 3 years after baseline polypectomy at Yokohama City University Hospital. Results: Marked elevation of the ACF number at baseline findings was observed in the tumor recurrence patients in comparison with the non recurrence patients (p &amp;lt; 0.01). ROC analysis showed high specificity of the number of ACF for diagnosis of any tumor recurrence. Conclusion: This is the first study to investigate relation between ACF and the recurrence of colorectal tumor after endoscopic polypectomy. These results suggested that ACF is useful for predictive factors for the recurrence of tumor. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-436. doi:10.1158/1538-7445.AM2011-LB-436

Aberrant crypt foci as biomarkers predictive of colorectal carcinoma.

Background: Aberrant crypt foci (ACF) are the first neoplastic lesions of the colorectum that are seen by the use of a stereomicroscope or highmagnification chromscopic endoscopy. The association of ACF with colorectal carcinoma (CRC) is supported by shared histological features with colonic polyps and adenomas. ACF exhibit many of the molecular and genetic abnormalities that are involved in the patogenetic cascade of CRC development. Regarding histopathology, ACF are classified as hyperplastic and dysplastic. Hyperplastic ACF display characteristics similar to hyperplastic polyps. They are more common in sporadic cases than in familial adenomatous polyposis (FAP) patients, while dysplastic ACF are much more frequent in FAP patients. Dysplastic ACF are generally accepted as precursors to CRC, but the significance of hyperplastic ACF in tumor progression is less well established. However, ACF provide an opportunity to investigate and characterize the earliest genetic and molecular alterations in CRC development. As high-magnification chromoscopic colonoscopy (HMCC) now allows detection and biopsy of ACF in the mucosa of the large bowel, ACF might serve as a valid biomarker of subsequent adenoma and carcinoma formation. Conclusions: The present article describes the characteristics of ACF as well as their role as a potent biomarker of CRC risk in clinical practice by means of high-resolution chromoendoscopy.

Advanced Colon Polypectomy

Advanced Colon Polypectomy

The Detection of Flat and Depressed Colorectal Lesions: Which Endoscopic Imaging Approach?

The secondary prevention of colorectal cancer (CRC) assumes that early detection and resection of precursor lesions disrupts the adenoma– carcinoma sequence and halts progression to invasive neoplastic disease. The adenoma– carcinoma sequence has until now formed the rationale for endoscopic therapies directed at reducing the incidence of CRC. The fact that snare polypectomy of exophytic lesions fails to prevent progression to carcinoma in up to 24% of cases has prompted reevaluation of the prevalence and clinicopathologic significance of flat and depressed colorectal lesions in Western population cohorts. Such lesions, although well-described in the Japanese literature, have only recently been reported in Western population cohorts. Debate has continued regarding their prevalence, anatomic localization, histopathologic characteristics, and proposed imaging modality of choice. Within this perspective, we summarize the key data pertinent to recently described endoscopic diagnostic modalities and detail their clinical applicability both for the detection of flat neoplastic lesions occurring in the “sporadic” patient cohort, familial polyposis syndromes, and chronic ulcerative colitis.

Aberrant crypt foci as precursors in colorectal cancer progression

Colorectal cancer progression originates when accumulated genetic and epigenetic alterations cause genomic instability and a malignant phenotype. Subsequent molecular pathway deregulation leads to histopathologic changes that are clinically evident as aberrant crypt foci (ACF) and visualized by high-magnification chromoscopic colonoscopy. ACF are biomarkers of increased colorectal cancer risk, particularly those with dysplastic features. Genetic profiling using genomic instability, loss of heterozygosity, and methylation analysis has revealed a minority population of ACF genotypically analogous to cancer.

Impact of Wide-Angle, High-Definition Endoscopy in the Diagnosis of Colorectal Neoplasia: A Randomized Controlled Trial

It is essential to optimize standard colonoscopy technique to be able to increase polyp detection. We sought to compare the performance of colonoscopy using a high-definition, wide-angle endoscope (HDE) versus a standard colonoscope (SC) for the detection of colorectal neoplasia. All consecutive consenting adult patients referred from primary care centers were included and randomly assigned at a 1:1 ratio to undergo HDE or SC. Times to reach and withdraw from the cecum were measured. Morphology, size, location, and pathologic diagnosis of each polyp were recorded. Sample size calculation resulted in a total of 682 patients needed. A total of 693 consecutive patients fulfilled all inclusion criteria (73 excluded owing to insufficient bowel preparation). Each arm included 310 patients with no baseline characteristic differences. Time to reach the cecum was slightly superior for SC (8.9 +/- 4.8 minutes vs 8.2 +/- 4.5 minutes; P = .055). Pathology examination was feasible in 418 lesions (272 adenomas, 109 hyperplastic polyps, and 37 inflammatory lesions). Both techniques detected a similar number and type of lesions, and there were no differences in the distribution along the colon, in the degree of dysplasia, or morphology of adenomas. The per-patient basis analyses demonstrated that there were no differences between the 2 arms of the study in the detection rates of polyps (SC, 0.84 +/- 1.59; HDE, 0.83 +/- 1.30), adenomas (0.45 +/- 1.07 vs 0.43 +/- 0.87), small adenomas (0.22 +/- 0.71 vs 0.28 +/- 0.78), flat adenomas (0.30 +/- 0.91 vs 0.21 +/- 0.63), or hyperplastic polyps (0.16 +/- 0.50 vs 0.18 +/- 0.54). HDE did not detect significantly more colorectal neoplasia than SC.

Detection and Treatment of Early Flat and Depressed Colorectal Cancer Using High-Magnification Chromoscopic Colonoscopy: A Change in Paradigm for Western Endoscopists?

Japanese researchers reported flat and depressed colorectal lesions in the 1980s. Such lesions were thought irrelevant to Western populations and described as "Phantom" or "Akitas" carcinoma. Many depressed neoplasms arise through the de novo pathogenic sequence and demonstrate early invasive characteristics. All investigators report difficulties in identifying flat and depressed lesions using conventional colonoscopy. Failure to detect and treat such lesions may be responsible for the current shortfalls in secondary colorectal cancer prevention. Given the introduction of colorectal cancer screening programs in the United Kingdom, Europe, and the United States, it is essential to re-evaluate the significance of flat lesions as applicable to Western cohorts and explore the safety and efficacy of new endoscopic technology and interventional therapeutics.

Novel colorectal endoscopic in vivo imaging and resection practice: a short practice guide for interventional endoscopists.

Colorectal cancer remains a leading cause of cancer death in the UK. With the advent of screening programmes and developing techniques designed to treat and stage colorectal neoplasia, there is increasing pressure on the colonoscopist to keep up to date with the latest practices in this area. This review looks at the basic principles behind endoscopic mucosal resection and forward to the potential endoscopic tools, including high-magnification chromoscopic colonoscopy, high-frequency miniprobe ultrasound and confocal laser scanning endomicroscopic colonoscopy, that may soon become part of routine colorectal cancer management.

Olympus Lucera High-resolution Vascular Ectasia Mapping in Combination With the Type V Crypt Pattern for the Invasive Depth Estimation and Nodal Disease Estimation in Paris Type II Colorectal Cancers

Flat and depressed neoplastic lesions of the colorectum [Paris type (PT) 0-II] localized to the superficial submucosal (sm) layer can be managed using endoscopic mucosal resection. Successful endoluminal management can be enhanced using endoscopic or ultrasound tools that help predict the degree of sm invasion. Previous studies addressing invasive depth estimation using high-magnification chromoscopic colonoscopy showed a low specificity for deep sm layer 3 invasion with miniprobe ultrasound demonstrating better nodal and T stage in vivo prediction. High-resolution vascular mapping of lesions can show microvascular superficial changes that may predict sm invasive disease. Vascular mapping in combination with high-magnification chromoscopic colonoscopy (HMCC) may provide an accurate tool for the invasive depth estimation of PT type II neoplastic lesions as compared with high frequency 20/12.5 MHz miniprobe ultrasound. Sixty-eight patients with a known diagnosis of PT II neoplasia were imaged using 3 "back to back" imaging modalities. Phase 1-vascular ectasia mapping; phase 2-HMCC with crypt analysis according to Nagata criteria; phase 3-12.5/20 MHz miniprobe ultrasound. Lesions predicted as T0/1/N0 were resected using endoscopic mucosal resection with the remaining referred for surgery. Each imaging modality was then compared with the resected histopathologic specimen used as the "gold standard." N=68 lesions (19 sm1/13 sm2/36 sm3). Overall accuracy of Nagata criteria, Nagata criteria combined with vascular mapping, and ultrasound staging was 65%, 78%, and 94%, respectively (P<0.001) when observing the between phase differences. Fifty-two lesions were resected surgically. The prevalence of node positive disease was 16% (8/52) with the remaining 44/52 (84%) being confirmed pN0 at histopathology. The kappa coefficient of agreement between invasive depth estimation (using histopathology as the gold standard), Nagata stage, Nagata stage plus vascular ectasia mapping and ultrasound stage was 0.47, 0.65, and 0.9, respectively. A significant improvement in between phase differences was observed (P=0.001). This is the first study to address the in vivo clinical utility of vascular mapping in combination with HMCC for the T and N staging of PT II neoplasia. Combination imaging may provide an adequate clinical tool for both T and N stage assessment in vivo and help stratify those patients at high risk for T2/N1 disease that may benefit from further high-frequency miniprobe ultrasound (HFUS) assessment and possible primary surgical excision. This is important in the clinical context, given the high overall costs of a second HFUS examination, limitation of HFUS resources, and safe selection of patients undergoing primary endoscopic resection versus surgical resection.

Novel clinical in vivo roles for indigo carmine: high-magnification chromoscopic colonoscopy

Since the adenoma–carcinoma sequence was first proposed by Morson in the 1970s, it has become widely accepted that detection and subsequent removal of polypoid adenomas from the colon reduces the incidence of colorectal cancer. These adenomas are relatively easy to detect by conventional colonoscopy; however, large population studies have shown that despite resection of polypoid adenomas, interval colorectal cancers still occurred. Recent advances in technology have given today's endoscopists access to high-resolution and high-magnification scopes, which has facilitated detection of flat and depressed colorectal lesions. Current data suggest that such morphologically distinct lesions may account for up to 30% of all colorectal adenomas. Furthermore, flat and depressed lesions of the large bowel may confer greater malignant potential compared to polypoid adenomas. The majority of flat lesions show only subtle changes by conventional colonoscopy, but the use of stains, such as indigocarmine, in addition to magnification colonoscopy can enhance their detection significantly. In this paper, we discuss the rationale for detecting flat colorectal lesions. We explore the use of high-magnification colonoscopy and chromoendoscopy, with particular reference to the application of indigocarmine, in this patient group. We also discuss the novel therapeutic techniques now available for these lesions.

High-magnification chromoscopic colonoscopy in ulcerative colitis: a valid tool for in vivo optical biopsy and assessment of disease extent

Colonoscopy with mucosal biopsy is currently considered to be the "gold standard" investigation for the evaluation of disease activity and disease extent in ulcerative colitis. Conventional colonoscopic criteria are inadequate for assessing disease extent and for predicting clinical relapse, however. Histopathological markers of relapse, such as microscopic crypt abscess formation and mucin depletion cannot be identified using conventional endoscopy. The aim of this study was to evaluate the efficacy of high-magnification chromoscopic colonoscopy for the in vivo assessment of histopathological inflammation and disease extent using standardised endoscopic and histopathological criteria. Total colonoscopy using the Olympus CF240Z magnifying colonoscope was performed prospectively in 325 consecutive patients with a known diagnosis of ulcerative colitis. A "biphasic" examination of all five colonic segments and the rectum was performed with conventional endoscopy followed by magnification imaging and biopsy. Disease activity was documented using Baron's classification, modified Saitoh criteria for magnification imaging, and Matts' histopathological grading. A total of 1800 images from 300 patients were analyzed (25 patients were excluded). The kappa coefficients of agreement between Saitoh's magnification criteria grades 1/2, 3/4, and 5/6 and Matts' histopathological grades 1/2, 3a/b, and 4/5 were 0.96, 0.62, and 0.51, respectively. Mild, moderate, and severe histopathological disease (Matts' grades 1/2, 3a - 4, and 5) were represented more accurately using Saitoh's criteria than by conventional Baron scores for all clinical parameters ( R = 0.976; P < 0.001). Magnification imaging was significantly better than conventional colonoscopy for predicting disease extent in vivo ( P < 0.0001). This is the largest prospective study and the only Western group to report on this application of magnification imaging. High-magnification imaging provides a sensitive and specific in vivo "virtual biopsy" in ulcerative colitis and so an instant biomarker for disease relapse, while accurately predicting disease extent. High-accuracy optical biopsy can limit the number of biopsies required, with significant cost savings for pathology services.

Reply to Hurlstone et al.

We would like to thank Dr. Hurlstone and his colleagues for his discerning comments about the place of high-magnification chromoscopic colonoscopy (HMCC) and endoscopic ultrasonography in establishing the indication for endoscopic mucosal resection (EMR) for early colonic neoplasia. As mentioned by Hurlstone et al., many publications, including Western papers, have assessed the feasibility, reproducibility, and safety of EMR in the treatment of colonic polyps. EMR is currently regarded as a curative method of treatment for well-differentiated colonic cancer limited to the mucosa or invading less than one-third of the submucosa (sm1). In assessing the results with this method, our study was specifically designed to analyze both local recurrences and the risk of distant metastases after EMR procedures carried out exclusively in patients with early colorectal cancer.

Chromoendoscopy: A new vision for colonoscopic surveillance in IBD

Chromoendoscopy: A new vision for colonoscopic surveillance in IBD

High Resolution Colonoscopy With Chromoscopy Versus Standard Colonoscopy for the Detection of Colonic Neoplasia: A Randomized Study

High-resolution colonoscopy with chromoscopy (HRC) is a technique designed to improve the detection of colonic neoplasias. We prospectively compared standard colonoscopy (SC) and HRC in a randomized multicenter trial. Patients (n = 203; age, 58 +/- 10 years; sex ratio, 1) were recruited according to the following criteria: (1) a history of either familial or personal colonic neoplasia or (2) alarm symptoms after the age of 60 years. After randomization, an SC was performed in 100 patients (resolution, < or = 410,000 pixels) and a HRC in 103 patients (Fujinon EC485ZW, 850,000 pixels). In the HRC group, each colonic segment was examined before and after spraying with indigo carmine 0.4%. Two hundred seventy-six polyps were detected in 198 patients. One hundred sixty of them were hyperplastic polyps, 116 were adenomas, and 2 were carcinomas. The numbers of hyperplastic polyps and purely flat adenomas were significantly higher in the HRC group than in the SC group (1.1 +/- 1.6 vs 0.5 +/- 1.4 and 0.22 +/- 0.68 vs 0.07 +/- 0.29, respectively; P = .01 and P = .04), but there was no significant difference in the total number of adenomas per patient (primary end point) detected between the HRC and the SC groups (0.6 +/- 1.0 vs 0.5 +/- 0.9, respectively). Although HRC improves detection of purely flat adenomas and hyperplastic polyps, the overall detection of colonic adenomas in a population at increased risk of neoplasia is not significantly improved. These findings do not support the routine use of HRC in clinical practice.

High-Magnification Chromoscopic Colonoscopy: Caution Needs to Be Exercised Before Changing Screening Policy

High-Magnification Chromoscopic Colonoscopy: Caution Needs to Be Exercised Before Changing Screening Policy

Nonpolypoid (Flat and Depressed) Colorectal Neoplasms

Nonpolypoid (Flat and Depressed) Colorectal Neoplasms

Indigo Carmine-Assisted High-Magnification Chromoscopic Colonoscopy for the Detection and Characterisation of Intraepithelial Neoplasia in Ulcerative Colitis: A Prospective Evaluation

Recent data suggest that panchromoscopy using methylene blue can improve the detection of intraepithelial neoplastic lesions in the context of surveillance colonoscopy for patients with chronic ulcerative colitis. This method has also been shown to provide a more accurate diagnosis of the extent of disease and inflammatory activity. Interval cancers are known to occur in patients with chronic ulcerative colitis despite the adoption of currently accepted surveillance biopsy protocols. We hypothesised that targeted chromoscopy alone, with high-magnification imaging, may increase the total number of intraepithelial neoplastic lesions detected, compared with conventional colonoscopy and biopsy surveillance according to current protocols. A total of 350 patients with long-standing ulcerative colitis (>or=8 years) underwent surveillance colonoscopy using high-magnification chromoscopic colonoscopy (HMCC). Quadrantic biopsies at 10-cm intervals were taken on extubation in addition to targeted biopsies of abnormal mucosal areas. Defined lesions were further evaluated using modified Kudo crypt pattern analysis. These data were compared with data from 350 disease duration- and disease extent-matched control patients who had undergone conventional colonoscopic surveillance between January 2001 and April 2005. Significantly more intraepithelial neoplastic lesions were detected in the magnification chromoscopy group compared with controls (69 vs. 24, P<0.0001). Intraepithelial neoplasia was observed in 67 lesions, of which 53 (79%) were detected using magnification chromoscopy alone. Chromoscopy increased the number of flat lesions with intraepithelial neoplasia detected compared with controls (P<0.001). Twenty intraepithelial neoplastic lesions were detected from 12,850 non-targeted biopsies in the HMCC group (0.16%), while 49 intraepithelial neoplastic lesions were detected from the 644 targeted biopsies in the HMCC group (8%). From 12,482 non-targeted biopsies taken in the control group patients, 18 (0.14%) showed intraepithelial neoplasia. The yield of intraepithelial neoplastic lesions from targeted biopsies in the control group (i. e. without HMCC imaging), however, was only modestly improved at 1.6% (6/369). Using modified Kudo criteria, the sensitivity and specificity for differentiating neoplastic from non-neoplastic lesions using HMCC were 93% and 88% respectively. The total procedure time was significantly longer in the HMCC group compared with controls (P<0.02). Magnification chromoscopy improves the detection of intraepithelial neoplasia in the endoscopic screening of patients with chronic ulcerative colitis. Neoplastic and non-neoplastic mucosal change can be predicted with a high overall accuracy using magnification techniques. These adjunctive endoscopic techniques have important clinical implications and may lead to changes in current practice guidelines.