A prospective clinicopathological and endoscopic evaluation of flat and depressed colorectal lesions in the United Kingdom

OBJECTIVES: Flat and depressed colorectal lesions are now reported in Western populations. The malignant potential, anatomical distribution, and other clinicopathological features have not been established in this group. This study aimed to assess prospectively the prevalence, clinicopathological, and endoscopic features of flat and depressed colorectal lesions in the United Kingdom. METHODS: A single endoscopist performed colonoscopy on 850 consecutive patients presenting for routine colonoscopy. All endoscopies were performed using a high magnification colonoscope with chromoscopy to facilitate detection of flat and depressed colorectal lesions. RESULTS: A total of 458 flat lesions were identified. Of these, 173 (38%) were hyperplastic and 285 (62%) adenomatous or beyond. Of the 173 hyperplastic flat lesions, 162 (94%) were located in the recto-sigmoid region. Of the 267 adenomas, 66 (25%) had areas of high grade dysplasia (HGD), with 54/66 (82%) being present in the right colon. Flat lesions <8 mm in diameter was more likely to contain HGD than those <8 mm (p<0.001). Nine of the 10 (90%) flat invasive adenoacarcinomas were in the right colon and all had a depressed morphological component. In contrast, HGD was observed in 58/466 (12%) of protuberant (sessile/pedunculated) adenomas of which 95% (55/58) were located in the left colon. In addition, HGD was present in 17% of all sessile adenomas versus 44.6% of flat lesions >8 mm in diameter (p=0.001). Of the 14 protuberant carcinomas, 13/14 (93%) were in the left colon. Synchronous lesions were found in 96/816 (12%) of cases. Of the 816 patients with two or more left-sided protuberant adenomas <8 mm (with or without HGD), 89 (11%) had one or more flat lesions in the right colon with HGD. CONCLUSIONS: Flat adenomas and carcinomas have a high malignant potential compared to protuberant lesions and have a propensity for developing in the right hemi-colon. Total colonoscopy is required to detect such lesions, as only 18% of flat lesions would be in reach of the flexible sigmoidoscope.     

Detection of colorectal adenomas by routine chromoendoscopy with indigocarmine

OBJECTIVES: Nonpolypoid adenomas, which can be important precursors of colorectal cancers, are difficult to find during routine colonoscopy. The aim of this study was to evaluate the usefulness of routine chromoendoscopy in Korea, where the incidence of colorectal cancer is low compared with western countries. METHODS: Colonoscopy with chromoendoscopy was performed in 74 consecutive patients (48 men, 26 women; mean age 53.0 yr). After a careful examination of the whole colon, a defined segment of the sigmoid colon and rectum (0-30 cm from the anal verge) was stained with 20 ml of 0.2% indigocarmine solution with a spraying catheter. Nonpolypoid lesions were classified as flat or depressed types. Biopsies were taken from all lesions detected before or after staining with indigocarmine. RESULTS: Indications for colonoscopy included routine check-up (21 patients), diarrhea or loose stool (14 patients), abdominal pain (12 patients), constipation (7 patients), bleeding (6 patients), and others (14 patients). Before staining, 58 lesions were found in 30 patients (43.2%). Histology showed tubular adenoma in 41 lesions, hyperplastic or inflammatory changes in 14 lesions, adenocarcinoma in 2 lesions, and villous adenoma in 1 lesion. After indigocarmine staining for normal-looking distal 30 cm colorectal mucosa, 176 lesions were found in 46 patients (62.2%). Histologically, 158 lesions were hyperplastic or inflammatory in nature, and 17 lesions (from 11 patients) were tubular adenomas. There was one serrated adenoma. Eighteen adenomas seen only after spraying indigocarmine were 2.6 +/- 0.6 mm in diameter, and all of them were classified as flat adenomas. There was no depressed-type adenoma. No adenoma with high grade dysplasia, villous histology, or cancer was found after staining. Presence of macroscopic adenomatous lesions or carcinoma before staining could not predict the existence of adenoma after staining. CONCLUSIONS: In a large proportion of patients, flat or depressed adenomas could be found after spraying indigocarmine for normal-looking colorectal mucosa in Korea. The clinical significance of these diminutive adenomas that can be found only after spraying contrast agent needs to be further investigated.     

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.     

Flat adenoma in colon: Two decades of debate

The existence of flat adenomas in the colon is well recognized. Whether they represent a distinct disease with a pathogenetic pathway different from that of the classical adenoma-carcinoma sequence in colorectal tumorigenesis and have higher malignant potential remains a matter of debate. To review the epidemiology, clinical features, detection and management of flat and depressed (non-polypoid) colonic neoplasm, we performed a thorough literature review on studies focusing on the prevalence, histological features, genetics, detection and treatment of flat and depressed (non-polypoid) colonic neoplasm. A high percentage of severe dysplasia in flat colonic adenomas has not been consistently demonstrated. Their malignant potential appears to be size-dependent. Flat adenomas are found to have a lower incidence of major genetic abnormalities involved in the classical adenoma-carcinoma sequence and that has raised suspicions that they may have a different pathogenesis. The depressed type of colorectal carcinoma is uncommon but shows more aggressive behavior. More advanced colonoscopic techniques, such as chromoendoscopy, may enhance the detection of small and inconspicuous colonic neoplastic lesions that lack a protruding configuration. It is essential for endoscopists to appreciate the existence and clinical significance of flat and depressed colonic lesions as an important variant of colonic neoplasms so that the goal of reducing colorectal carcinoma incidence by polypectomy can be better achieved.     

Chromoendoscopic colonoscopy for detecting preneoplastic lesions in hereditary nonpolyposis colorectal cancer syndrome.

BACKGROUND & AIMS: In hereditary nonpolyposis colorectal cancer (HNPCC) syndrome, flat and small adenomas are particularly prone to malignant transformation but might be missed by standard colonoscopy. We prospectively studied the diagnostic yield of high-resolution colonoscopy coupled with chromoendoscopy for preneoplastic and neoplastic colorectal lesions in patients with HNPCC syndrome. METHODS: Thirty-six consecutive asymptomatic patients (mean age, 42 years) belonging to HNPCC families and receiving genetic counseling were enrolled in this prospective study. Colonoscopy was performed in 2 steps. Conventional colonoscopy was performed first, followed by a second colonoscopy with chromoendoscopy with indigo carmine (.4%) dye sprayed onto the entire proximal colon. RESULTS: Conventional colonoscopy identified 25 lesions (mean size, 4 +/- 3 mm) in 13 patients. Seven lesions, detected in 5 patients, were adenomas, 3 of which were located in the proximal colon. Chromoendoscopy identified additional 45 lesions (mean size, 3 +/- 1 mm) in 20 patients; most of these lesions were flat and hyperplastic. Eleven additional adenomas were detected in the proximal colon of 8 patients, and 8 of these 11 lesions were flat. The use of chromoendoscopy significantly increased the detection rate of adenomas in the proximal colon, from 3 of 33 patients to 10 of 33 patients (P = .045). CONCLUSION: Relative to conventional colonoscopy, high-resolution colonoscopy with chromoendoscopy markedly improves the detection of adenomas in patients with HNPCC syndrome and might help to prevent colorectal carcinoma in these patients with a very high risk of colorectal cancer.     

Flat adenomas in the National Polyp Study: is there increased risk for high-grade dysplasia initially or during surveillance?

BACKGROUND & AIMS: The flat adenoma may be a more aggressive pathway in colorectal carcinogenesis. Sessile adenomas from the National Polyp Study cohort were reclassified histopathologically as flat or polypoid and compared with initial and surveillance pathology. METHODS: A total of 933 sessile adenomas detected during 1980-1990 were reclassified as follows: (1) adenoma thickness (AT): < or =1.3 mm, and (2) adenoma ratio (AR): adenoma thickness <2x normal mucosa thickness. Logistic regression was used to assess whether flat adenomas had an effect on risk for high-grade dysplasia initially, and a Cox proportional hazards model assessed the risk for advanced adenomas at surveillance. RESULTS: The analysis encompassed 8401 person-years of follow-up evaluation. AT and AR measures of adenoma flatness were 95% concordant. By the AT measure, flat adenomas (n = 474) represented 27% of all baseline adenomas. Flat adenomas were found to be no more likely to exhibit high-grade dysplasia than sessile (polypoid) or pedunculated adenomas, the odds ratio for high-grade dysplasia was 1.91 (95% confidence interval [CI], 0.66-5.47; P = 0.23) for sessile (polypoid) vs. flat adenomas and 1.78 (95% CI, 0.63-5.02; P = 0.28) for pedunculated vs. flat adenomas adjusted for size, villous component, and location, and corrected for correlation of risk within an individual patient. Patients with flat adenomas at initial colonoscopy were not at greater risk for advanced adenomas at surveillance compared with those with polypoid adenomas only, the odds ratio was 0.76 (95% CI, 0.4-1.42; P = .39), adjusted for multiplicity, age, and family history of colorectal cancer. CONCLUSIONS: Flat adenomas identified in the National Polyp Study cohort at baseline were not associated with a higher risk for high-grade dysplasia initially, or for advanced adenomas at surveillance.     

Flat colonic adenomas in Malaysia: Fact or fancy?

BACKGROUND: Some two-thirds of colorectal carcinomas arise from adenomatous polyps, and as such, screening by colonoscopy and polyp removal should significantly reduce colorectal cancer. This has not been the case, as evidenced by recent studies, which revealed that endoscopy failed to prevent up to 50% of all subsequent carcinomas. Flat or depressed adenomas, frequently reported from Japan but rarely elsewhere, might explain the 'missed carcinomas.' Detection of flat adenomas has not been previously reported from Malaysia. METHODS: In the present prospective study, 426 consecutive patients underwent colonoscopic examination between March 1997 and January 2000, for a variety of bowel symptoms. The examinations were performed by an experienced endoscopist using a standard colonoscope and methylene blue dye spraying technique. Macroscopically, flat adenomas were defined using the criteria proposed by Sawada. RESULTS: Twenty-nine adenomas were identified in 12 patients, of which 15 were polypoid and 14 were flat, with no depressed lesions. Eight polypoidal lesions and all the flat adenomas contained mild or moderate areas of epithelial dysplasia. Seven severely dysplastic polyps were identified. One Duke's A polypoidal cancer and two advanced carcinomas were also found. All the severely dysplastic lesions and Duke's A carcinomas were found in polyps greater than 10 mm in mean size. The flat adenomas were all less than 5 mm in size. CONCLUSIONS: A significant proportion of colonic adenomas in Malaysian patients appear as small flat lesions, which could easily be missed during endoscopy. Increased recognition and treatment of flat adenomas among colonoscopists is warranted.     

Computed virtual chromoendoscopy for classification of small colorectal lesions: a prospective comparative study

OBJECTIVES: Standard colonoscopy offers no reliable discrimination between neoplastic and nonneoplastic colorectal lesions. Computed virtual chromoendoscopy with the Fujinon intelligent color enhancement (FICE) system is a new dyeless imaging technique that enhances mucosal and vascular patterns. This prospective trial compared the feasibility of FICE, standard colonoscopy, and conventional chromoendoscopy with indigo carmine in low- and high-magnification modes for determination of colonic lesion histology. METHODS: Sixty-three patients with 150 flat or sessile lesions less than 20 mm in diameter were enrolled. At colonoscopy, each lesion was observed with six different endoscopic modalities: standard colonoscopy, FICE, and conventional chromoendoscopy with indigo carmine (0.2%) dye spraying in both low- and high-magnification modes. Histopathology of all lesions was confirmed by evaluation of endoscopic resection or biopsy specimens. Endoscopic images were stored electronically and randomly allocated to a blinded reader. RESULTS: Of the 150 polyps, 89 were adenomas and 61 were hyperplastic polyps with an average size of 7 mm. For identifying adenomas, the FICE system with low and high magnifications revealed a sensitivity of 89.9% and 96.6%, specificity of 73.8% and 80.3%, and diagnostic accuracy of 83% and 90%, respectively. Compared with standard colonoscopy, the sensitivity and diagnostic accuracy achieved by FICE were significantly better under both low (P < 0.02) and high (P < 0.03) magnification and were comparable to that of conventional chromoendoscopy. CONCLUSIONS: The FICE system identified morphological details that efficiently predict adenomatous histology. For distinguishing neoplastic from nonneoplastic lesions, FICE was superior to standard colonoscopy and equivalent to conventional chromoendoscopy.     

结直肠肿瘤样病变内镜活检与黏膜切除术后病理诊断比较

背景：结直肠肿瘤样病变内镜黏膜切除术（EMR）后病理诊断与术前内镜活检病理诊断的差异未明。目的：评估放大色素内镜指导下EMR获得的结直肠肿瘤样病变标本的诊断价值。方法：连续收集接受EMR治疗的直径≤2cm的无蒂型或平坦、凹陷型结直肠肿瘤样病变纳入研究,分析EMR病理诊断与术前活检病理诊断的差异。结果：共纳入EMR切除病灶90个,无蒂型25个,平坦、凹陷型65个,后者为高度异型增生（HGD）或腺癌的可能性略高于前者（41．5％对20．0％,P〉0．05）。术前活检病理诊断的总体准确性为68．9％,28个（31．1％）病灶的诊断于术后发生改变．其中4个增生性病变术后均诊断为低度异型增生（LGD）,14个LGD诊断为HGD,5个LGD诊断为腺癌,5个HGD诊断为腺癌。病灶形态学表现及其浸润深度与病理诊断结果的改变无关。结论：放大色素内镜指导下的EMR病理诊断纠正了本组近1／3结直肠肿瘤样病变的术前活检病理诊断,具有完善诊断和治疗的双重作用。     

USEFULNESS OF MULTI DETECTOR ROW COMPUTED TOMOGRAPHY FOR DETECTION OF FLAT AND DEPRESSED COLORECTAL CANCER

Background: Recently, the clinical usefulness of colorectal cancer screening by CT colonography has been reported in Europe and the USA. However, in Japan, the diagnosis of flat or depressed colorectal cancer lesions has been emphasized, and the question of whether CT colonography facilitates visualization of these lesions remains to be answered. In the present study, we compared the visualization of flat and depressed colorectal cancer lesions by CT colonography with that of protruding lesions. Methods: We investigated 33 Dukes A colorectal cancer lesions that had been examined by 3D‐CT, colonoscopy, and barium enema prior to surgery. In all patients, CT colonography was performed immediately after colonoscopy. Volume rendering was used for 3‐D rearrangement, and imaging findings were examined with respect to morphology, tumor diameter, and tumor height. Results: All (14/14) of the protruding‐type lesions were visualized by CT colonography, whereas 78.9% (15/19) of the flat and depressed‐type lesions were visualized. There was no significant difference in tumor diameter between protruding‐type lesions and flat and depressed‐type lesions. With respect to tumor height, 100% of the lesions measuring 2 mm or more in height were visualized, whereas only 42.9% of those measuring less than 2 mm in height were visualized; the difference was significant (P < 0.001). Conclusions: These results suggest that the visualization capacity of CT colonography is associated with tumor height, but not with tumor diameter. Currently, lesions measuring 2 mm or more in height can be visualized reliably by CT colonography.     

Comparison of the clinicopathologic features between flat and polypoid adenoma

Objective. Several reports have suggested that flat colorectal adenomas might exhibit a higher potential for malignancy compared to polypoid adenomas. Although the clinical importance of the shape of polyps is stressed, the controversy surrounding the malignant potential of flat adenomas continues. The aim of this study was to compare the clinicopathologic characteristics, including degree of dysplasia and malignancy, between flat and polypoid adenomas 5 mm in size or larger. Material and methods. A total of 3263 polyps (254 flat adenomas and 3009 polypoid adenomas), ≥5 mm in size, diagnosed in 1883 patients by colonoscopy were analyzed. Results. Flat adenomas were found in 10% of patients, which represented 7.8% of all adenomas removed. The flat adenomas were larger in diameter than the polypoid adenomas (14.8±12.6 mm versus 8.6±5.0 mm, p <0.01), had a higher rate of villous components (18.5% versus 11.4%, p <0.01), a higher rate of high-grade dysplasia (9.4% versus 4.2%, p <0.01), and a higher rate of malignancy (10.2% versus 3.6%, p <0.01) than polypoid adenomas. However, there was no difference in the rate of high-grade dysplasia or carcinoma between flat and polypoid adenomas of equal size. It was shown by multivariate analysis that rectosigmoid location, larger size, and presence of a villous component were associated with a higher rate of malignancy, but not with flat morphology. Conclusions. Flat adenomas, which were of a relatively large size in this study, were not associated with a higher risk for high-grade dysplasia and carcinoma compared with polypoid adenomas.     

Advanced diagnostic tools: virtual colonoscopy and magnifying chromoendoscopy

Early endoscopic diagnosis of colorectal cancers (CRCs) represents the best tool for the reduction of CRC mortality, but the conventional colonoscopic view seems unable to clarify faint changes of colorectal mucosa. For these reasons, during the last few decades, two new techniques have been developed in order to better define, diagnose and treat colorectal lesions: chromoendoscopy (CE) and magnifying chromoendoscopy (MC). The authors herein highlight the benefits of both and compare the results of conventional endoscopy and CE with 0.2% indigo carmine solution, evaluating 995 consecutive selected patients referred for colonoscopy between January 1999 and March 2003 at the International Health Union of Rome. CE showed new neoplastic patterns not detectable with conventional endoscopy in 102 patients (10.2%). The incidence of high-grade dysplasia and early carcinomas was 9.9% for protruded, 13.1% for flat and 60% for depressed lesions. Our comparative study on 995 consecutive selected patients confirmed the existence of flat and depressed neoplasms in Italy and shows the high accuracy rate of CE over conventional endoscopy for the detection of non-polypoid lesions. CE should be used routinely in order to enhance the early diagnosis of CRCs, while MC in experienced hands represents a significant advance in colonoscopic practice improving the diagnosis of every single lesion, enhancing therapeutic efficacy of colorectal tumours.     

放大色素内镜在结直肠肿瘤内镜黏膜切除治疗中的应用

目的 评估内镜黏膜切除术(EMR)结合放大色素内镜诊治结直肠肿瘤的有效性和安全性.方法 收集结肠镜检查患者中符合EMR指征的无蒂型或平坦、凹陷型病灶.观察病灶形态学与EMR术后组织学结果 的相关性,评估放大色素内镜判断病灶浸润深度的准确性.结果 81例患者经EMR切除病灶90个(无蒂型25个,平坦、凹陷型65个).组织学显示低级别上皮内瘤变(LGD)58个,高级别上皮内瘤变(HGD)20个,腺癌12个.其中HGD和癌变病灶直径大于LGD病灶[(1.4±0.5)cm和(1.6±0.5)cm比(1.05:0.4)cm],但组间差异无统计学意义(P>0.05).平坦、凹陷型病灶较无蒂型病灶更易出现HGD或癌,但差异亦无统计学意义[41.5%(27/65)比20.0%(5/25),P=0.084].病灶表面有凹陷者出现HGD或癌的比例显著高于无凹陷者[51.0%(25/49)比17.1%(7/41),P<0.01)].放大色素内镜判断病灶浸润深度的准确性为97.8%(88/90).完整的组织学切除占所有病灶的95.6%(86/90).结论 凹陷型和平坦型伴中央凹陷的结直肠病变的恶性倾向高.应用放大色素内镜能准确判断病灶浸润深度,从而使EMR治疗更安全有效.     

Colonoscopic surveillance of patients with a family history of colon cancer and a history of normal colonoscopy: is a five-year interval between colonoscopies appropriate?

BACKGROUND & AIMS: Patients with a family history of colon cancer are advised to undergo surveillance colonoscopy 5 years after a normal screening colonoscopy. No prospective study has evaluated the prevalence of adenomas found at surveillance colonoscopy in these patients. The aims of this trial were (1) to determine the percentage of these patients with adenomas; (2) to determine the percentage of these patients with advanced adenomas (i.e., villous adenomas, adenomas > or = 10 mm, adenomas with high grade dysplasia); and (3) to assess risk factors for adenomas in these patients. METHODS: Consecutive patients with a family history of colorectal cancer and a normal screening colonoscopy 5 years earlier were offered a surveillance colonoscopy. Patients also completed a questionnaire about potential risk factors for adenomas. Multiple logistic regression analysis assessed associations between risk factors and adenomas. RESULTS: One hundred patients completed the trial. The male/female ratio was 54/46, the mean age was 56.2 +/- 8.8 years, and 91% were white. Eight percent (8 of 100) of patients had advanced adenomas at surveillance colonoscopy, and 33% (33 of 100) had adenomas. Among patients with adenomas, 39% (13 of 33) had no adenomas in the left side of the colon (i.e., distal to the splenic flexure). Among patients with advanced adenomas, 25% (2 of 8) had no adenomas in the left side of the colon. Multiple logistic regression analysis showed a significant negative association between adenomas and NSAID use (odds ratio, 0.26 [95% confidence interval, 0.09-0.79]), and male gender had a positive association with adenomas (odds ratio, 2.79 [95% confidence interval, 1.01-7.74]). CONCLUSIONS: These data support a 5-year interval between screening and surveillance colonoscopy for patients with a family history of colorectal cancer and a normal screening colonoscopy.     

Preoperative diagnosis of a small,depressed rectal cancer complicating ulcerative colitis

PURPOSE: This study was designed to clarify the importance of detecting small, depressed colorectal cancer complicating ulcerative colitis. METHODS: A 39-year-old Japanese male, who had an 18-year history of left-sided ulcerative colitis, was admitted to Fukuoka University Hospital for further evaluation of his colitis. Colonoscopy with a dye spraying method clearly revealed a small, depressed lesion and flat plaque-like lesions in the rectum. Biopsies taken from a depressed lesion and plaque-like lesions revealed a signet-ring cell carcinoma and dysplasia, respectively. Total colectomy was performed. RESULTS: Sections from the depressed rectal lesion, measuring 7X8 mm in size, revealed a signet-ring cell carcinoma that diffusely invaded the muscularis propria. Lymph node metastasis was evident. Flat plaques and mucosa around the depressed lesion were positive for dysplasia. CONCLUSION: This is the first report of a case of small, depressed rectal cancer complicating ulcerative colitis diagnosed by preoperative colonoscopy. To improve outcome of colonoscopic surveillance in ulcerative colitis, detecting such small, depressed lesions are important, and colonoscopy with a dye spraying method would be useful in detecting them.     

Colorectal flat neoplasia

BACKGROUND AND AIMS: An attempt has been made to evaluate the clinicopathological characteristics of flat colorectal neoplastic lesions, and analyse the factors associated with the malignancy. PATIENTS AND METHODS: A total of 115 flat neoplastic lesions, > or = 5 mm in size, diagnosed in 87 patients by colonoscopy, were investigated. RESULTS: The rectum was the most common location. Almost half (49.6%) of the flat neoplasms were small (5-10 mm), 27.8% were 11-20 mm and the remainder (22.6%) larger than 20 mm. The surface was smooth in 55.7%, granular in 20.0% and nodular in 24.3%. Histologically, the flat lesions were tubular, tubulovillous and villous adenomas in 69.6%, 20.9% and 5.2%, respectively. Five lesions (4.3%) were composed of carcinomas without adenoma. High-grade dysplasia, intramucosal carcinoma and invasive carcinoma were diagnosed in 9.6%, 7.8% and 6.1% of all flat neoplasms, respectively. Univariate analysis demonstrated that the location, size, surface pattern and histologic type of the flat lesions were factors associated with malignancy. However, in multivariate analysis, the size of the flat lesions was the only significant risk factor for malignant transformation. CONCLUSIONS: Flat neoplastic lesions of the colorectum have a relatively high rate of malignancy, and size is the most important factor associated with malignancy.     

Flat adenomas exist in asymptomatic people: important implications for colorectal cancer screening programmes

BACKGROUND: Flat adenomas are non-exophytic with a flat top or central depression and histologically the depth of dysplastic tissue is never more than twice the mucosal thickness. Flat adenomas frequently contain severely dysplastic tissue, and may progress rapidly through the adenoma-carcinoma sequence. Flat lesions have never been described in a British asymptomatic population. AIMS: To determine whether flat adenomas exist in an asymptomatic population participating in a large randomised controlled trial of flexible sigmoidoscopy screening. PATIENTS: A total of 3000 subjects (aged 55-64 years) underwent screening by flexible sigmoidoscopy. METHODS: All polyps were removed and sent for histology. The number of polyps with endoscopic and histological features of flat adenomas was recorded. RESULTS: Three subjects had a total of four flat lesions--that is, one per 1000 people screened. Three contained severely dysplastic tissue, one a focus of adenocarcinoma. Three of the four lesions were less than 5 mm in size and the fourth was 15 mm in diameter. CONCLUSIONS: Flat lesions with severe dysplasia exist in the asymptomatic population. This has major implications for gastroenterologists who should be trained to identify them. Their existence is of importance to molecular biologists and epidemiologists investigating the aetiology of colorectal cancer.     

Magnifying colonoscopy with narrow band imaging system for the diagnosis of dysplasia in ulcerative colitis: a pilot study

BACKGROUND: Narrow-band imaging (NBI) is a novel illumination technology for endoscopy that enhances vasculature of the GI tract. OBJECTIVE: The aim was to elucidate whether NBI colonoscopy can identify dysplasia in patients with ulcerative colitis (UC). DESIGN: Cross-sectional study of eligible patients. SETTING: Single center. PATIENTS: 46 patients with UC. INTERVENTIONS: Apparently flat mucosa at each segment and visible protruding lesions were observed by magnifying NBI colonoscopy. The surface structure was classified into honeycomb-like, villous, or tortuous pattern. The grade of dysplasia was determined in the specimens obtained from protrusions and from flat mucosa. MAIN OUTCOME MEASUREMENTS: The positive predictive value of conventional and NBI colonoscopy for the diagnosis of dysplasia. RESULTS: A total of 296 sites (20 protruding lesions and 276 flat areas) were examined by NBI colonoscopy. The surface pattern was determined to be honeycomb like in 161 sites, villous in 85 sites, and tortuous in 50 sites. Five dysplastic lesions were detected in 3 patients. A patient had 3 dysplastic lesions and the other 2 had a dysplastic lesion each. The positive rate of dysplasia was higher in protrusions (2/20 sites, 10%) than in flat mucosa (3/276 sites, 1.1%, P = .038; however, correction for the multiple testing of data removes this significance). When the surface pattern was taken into account, the rate of positive dysplasia was higher in the tortuous pattern (4/50 sites, 8%) than in the honeycomb-like or villous patterns (1/246 sites, 0.4%, P = .003). LIMITATIONS: Uncontrolled study. CONCLUSIONS: The tortuous pattern determined by NBI colonoscopy may be a clue for the identification of dysplasia during surveillance for UC.     

Improved detection of colorectal neoplasms with selective use of chromoendoscopy in 2005 consecutive patients

Background Colorectal cancer mortality is decreased by endoscopic polypectomy, but conventional colonoscopy may be inadequate for detecting subtle colonic lesions. Methods We selectively performed chromoendoscopy in all patients undergoing colonoscopy between January 1999 and December 2005 at the International Health Union of Rome. Patients with a history of colorectal polyps, inflammatory bowel disease, colorectal surgery or coagulopathy and those with poor bowel preparation were excluded from this analysis. Whenever colonoscopy revealed suspicious mucosal areas, dye-spraying with 0.2% indigo carmine solution was also performed. Findings from conventional and dyespraying views were classified morphologically, and specimens were analyzed histologically. Non-adenomatous lesions were classified as negative findings. Results A total of 2005 patients underwent conventional colonoscopy and in 305 cases (15%) chromoendoscopy was also performed. Conventional colonoscopy identified 508 neoplasms in 381 patients (19%). Selective chromoendoscopy found an additional 244 neoplasms in 212 patients (11%). Thus, chromoendoscopy was positive in 212 (70%) of 305 patients in whom the examination was performed. Overall, 56 large, ulcerated, advanced cancers and 696 non-advanced neoplasms were found. Of the 696 nonadvanced neoplasms, 448 (65%) were polypoid and 248 (35%) were non-polypoid. All but 4 non-polypoid lesions were only detected with chromoendoscopy. Of the 248 non-polypoid lesions, 12 (5%) were depressed and 236 (95%) were flat. Advanced histology was present in 39 non-polypoid lesions (15%) and was more common in depressed lesions than in flat ones (58% vs. 13%; p<0.001). Conclusions Our study confirms the existence of flat and depressed neoplasms in an Italian population. The vast majority of non-polypoid lesions were only detected by chromoendoscopy, and many lesions with advanced histology were missed by conventional colonoscopy. We therefore recommend selectively performing chromoendoscopy when conventional colonoscopy provides clues for non-polypoid lesions. Therefore, endoscopists should be trained in the detection of these subtle mucosal clues, as well as in the use of chromoendoscopy to enhance their detection. An erratum to this article is available at .     

p53 overexpression in flat serrated adenomas and flat tubular adenomas of the colorectal mucosa

The expression of the p53 protein was investigated in flat serrated neoplasias as well as in other histological phenotypes of flat or exophytic hyperplasias or neoplasias of the colorectal, mucosa. A total of 104 such lesions were analyzed: 24 were flat serrated neoplasias (22 flat serrated adenomas and 2 flat serrated adenocarcinomas), 26 flat tubular adenomas, 17 flat hyperplastic polyps, 29 exophytic tubular and/or villous neoplasias (23 adenomas and 6 exophytic adenocarcinomas) and the remaining 8, exophytic hyperplastic polyps. Deparaffinized, rehydrated sections were treated immunohistochemically to detect those overexpressing the p53 protein. Lesions having slight (+), moderate (++) or intense (+++) staining were considered immunoreactive. The results showed that 50% of the flat serrated adenomas with low-grade dysplasia (LGD) and 66.7% of those with high-grade dysplasia (HGD) had p53 immunoreactivity. None of the flat tubular or of the exophytic adenomas with LGD expressed p53, but immunoreactivity was present in 61.5% of the flat tubular adenomas with HGD and in 52.3% of the exophytic adenomas with HGD. All adenocarcinomas had an intense p53 reaction. Weak p53 expression was demonstrated by 11.7% of the flat hyperplastic polyps but none of the exophytic polyps reacted. The occurrence of p53 expression in flat serrated adenomas with LGD suggested that, despite its low histological profile, one-half of those lesions could be biologically already committed to independent growth. The occurrence of p53 expression in nearly 12% of the flat hyperplastic polyps was totally unexpected and deserves further investigation. Flat serrated adenoma emerges as a novel, independent histological entity among the various phenotypes of flat neoplasias of the colorectal mucosa.