Five-year colon surveillance after screening colonoscopy

BACKGROUND & AIMS: Outcomes of colon surveillance after colorectal cancer screening with colonoscopy are uncertain. We conducted a prospective study to measure incidence of advanced neoplasia in patients within 5.5 years of screening colonoscopy. METHODS: Three thousand one hundred twenty-one asymptomatic subjects, age 50 to 75 years, had screening colonoscopy between 1994 and 1997 in the Department of Veterans Affairs. One thousand one hundred seventy-one subjects with neoplasia and 501 neoplasia-free controls were assigned to colonoscopic surveillance over 5 years. Cohorts were defined by baseline findings. Relative risks for advanced neoplasia within 5.5 years were calculated. Advanced neoplasia was defined as tubular adenoma greater than > or =10 mm, adenoma with villous histology, adenoma with high-grade dysplasia, or invasive cancer. RESULTS: Eight hundred ninety-five (76.4%) patients with neoplasia and 298 subjects (59.5%) without neoplasia at baseline had colonoscopy within 5.5 years; 2.4% of patients with no neoplasia had interval advanced neoplasia. The relative risk in patients with baseline neoplasia was 1.92 (95% CI: 0.83-4.42) with 1 or 2 tubular adenomas <10 mm, 5.01 (95% CI: 2.10-11.96) with 3 or more tubular adenomas <10 mm, 6.40 (95% CI: 2.74-14.94) with tubular adenoma > or =10 mm, 6.05 (95% CI: 2.48-14.71) for villous adenoma, and 6.87 (95% CI: 2.61-18.07) for adenoma with high-grade dysplasia. CONCLUSIONS: There is a strong association between results of baseline screening colonoscopy and rate of serious incident lesions during 5.5 years of surveillance. Patients with 1 or 2 tubular adenomas less than 10 mm represent a low-risk group compared with other patients with colon neoplasia.     

Endoscopic mucosal resection of colorectal adenomas>20mm:Risk factors for recurrence

AIM: To evaluate risk factors for local recurrence after endoscopic mucosal resection of colorectal adenomas 20 mm.METHODS: Retrospective data analysis of 216 endoscopic mucosal resections for colorectal adenomas 20 mm in 179 patients(40.3% female; median age 68 years; range 35-91 years). All patients had at least 1 follow-up endoscopy with a minimum control interval of 2 mo(mean follow-up 6 mo/2.0-43.4 mo). Possible factors associated with local recurrence were analyzed by univariate and multivariate analysis. RESULTS: Median size of the lesions was 30 mm(20-70 mm),69.0% were localized in the right-sided(cecum,ascending and transverse) colon. Most of the lesions(85.6%) showed a non-pedunculated morphology and the majority of resections was in piecemeal technique(78.7%). Histology showed carcinoma or high-grade intraepithelial neoplasia in 51/216(23.6%) lesions including 4 low risk carcinomas(pT1 a,L0,V0,R0- G1/G2). Histologically proven recurrence was observed in 33/216 patients(15.3%). Patient age65 years,polyp size30 mm,non-pedunculated morphology,localization in the right-sided colon,piecemeal resection and tubular-villous histology were found as associated factors in univariate analysis. On multivariate analysis,only localization in the rightsided colon(HR = 6.842/95%CI:1.540-30.394; P=0.011),tubular-villous histology(HR = 3.713/95%CI: 1.617-8.528;P=0.002) and polyp size30 mm(HR=2.563/95%CI:1.179-5.570; P=0.017) were significantly associated risk factors for adenoma recurrence. CONCLUSION: Meticulous endoscopic follow-up is warranted after endoscopic mucosal resection of adenomas localized in the right-sided colon larger than 30 mm,with tubular-villous histology.     

Präkanzerosen im Kolon

Preneoplastic lesions of colorectal carcinoma can be divided in non-serrated and serrated lesions. Non-serrated lesions include conventional adenomas (tubular, tubulovillous and villous) and dysplasias associated with inflammatory bowel disease like flat intraepithelial neoplasia, dysplasia-associated lesions or masses (DALM) and adenoma-like masses (ALM). Conventional adenomas are mostly sporadic, but also found in hereditary adenomatous-polyposis syndromes. Hamartous polyposis syndromes are also associated with colorectal cancer. Serrated lesions include hyperplastic polyps, sessile serrated adenomas and traditional serrated adenomas. Based on these precancerous colorectal lesions different molecular subtypes were identified. Histological subtype, size and grade of dysplasia of polyps are essential for risk assessment of colorectal cancer.     

Distal colonic neoplasms predict proximal neoplasia in average-risk, asymptomatic subjects

Flexible sigmoidoscopy has been recommended as a screening method to reduce the incidence of colorectal cancer in asymptomatic, average-risk subjects through the early detection and removal of polyps. However, the association between distal and proximal colonic neoplasia and, hence, the requirement for colonoscopic follow up of screen-detected distal neoplasms is unclear. Our aims were: (i) to evaluate the risk of having proximal neoplasms in those with distal colonic neoplasms; and (ii) to determine whether the risk was dependent on the number, size, histology or morphology of the distal lesions. We prospectively evaluated asymptomatic subjects in a flexible sigmoidoscopy based screening programme. Those with rectosigmoid neoplasia underwent colonoscopy. The number, size, histology and morphology of the polyps were recorded. Advanced lesions were defined as adenomas > 1 cm or with a villous component or severe dysplasia, carcinoma in situ or cancer. Adenomatous polyps were found in 17% (135) of screening flexible sigmoidoscopies. At colonoscopy, up to 30% of subjects with distal colonic neoplasms had synchronous proximal lesions at colonoscopy and up to 20% had advanced proximal lesions. The risk of proximal colonic neoplasia was increased in those with distal sessile colonic neoplasms but appeared independent of distal lesion size, number or morphology. In conclusion, distal colonic neoplasia predicts proximal neoplasia in up to 30% of subjects and these were advanced lesions in up to 20%. We recommend that all subjects with biopsy proven distal colonic neoplasia undergo colonoscopy.     

Prevalence of colorectal neoplasia in smokers

OBJECTIVES: Smoking has been linked with colorectal neoplasia. Previous colonoscopy screening studies have omitted smoking and have examined only gender, age, and family history. Our aim was to use a screening population to measure the prevalence of neoplasia in smokers, the anatomic location of these lesions, and the strength of this association relative to other risk factors. METHODS: Data collected from the charts of 1988 screening colonoscopy patients included colonic findings, histology, risk factors for colorectal neoplasia, and smoking pattern. Current smokers were defined as those who had smoked more than 10 pack-years and were currently smoking or who had quit within the past 10 yr. Our outcomes were any adenomatous lesion and significant colonic neoplasia, which included adenocarcinoma, high grade dysplasia, villous tissue, large (>1 cm) adenomas, and multiple (more than two) adenomas. RESULTS: Multivariate analysis revealed that current smokers were more likely to have any adenomatous lesion (odds ratio [OR] = 1.89; 95% CI = 1.42-2.51; p < 0.001) as well as significant neoplasia (OR = 2.26; 95% CI = 1.56-3.27; p < 0.001) than those who had never smoked. The increased risk for smokers was predominantly for left-sided neoplasia. The risk for significant neoplasia was greater for smokers than for patients with a family history of colorectal cancer (OR = 1.20; 95% CI = 0.75-1.92; p > 0.05). CONCLUSIONS: Smoking is a significant risk factor for colorectal neoplasia in a screening population, especially for significant left-sided lesions. In our sample population, smoking posed a greater risk than family history of colorectal cancer.     

Incidence and recurrence rates of colorectal adenomas estimated by annually repeated colonoscopies on asymptomatic Japanese

BACKGROUND: Whereas high recurrence rates of colorectal adenomas after polypectomy are widely recognised, little is known of the natural incidence in those with no neoplastic lesions initially. It is also known that single colonoscopy has a significant miss rate. AIMS: To elucidate the incidence and recurrence rates of colorectal neoplasms from a large cohort of asymptomatic Japanese patients on the basis of annually repeated colonoscopies. METHODS: A total of 6225 subjects (4659 men and 1566 women) participating in an annual colonoscopic screening programme and completing three or more colonoscopies were analysed during the 14 year period between 1988 and 2002. Patients were divided into three groups according to the findings of the initial two colonoscopies: 4084 subjects with no neoplasm, 1818 with small adenomas <10 mm, and 323 with advanced lesions, including carcinoma in situ, severe dysplasia, or large adenomas > or =10 mm. Mean age at the second colonoscopy was 48.8 years. RESULTS: For all types of colorectal neoplasms, the incidence rate in those with no initial neoplasm was 7.2%/year whereas recurrence rates in those with small adenomas and advanced lesions were 19.3% and 22.9%/year, respectively. For advanced colorectal lesions, the incidence rate was 0.21%/year whereas recurrence rates in those with small adenomas and advanced lesions were 0.64% and 1.88%/year, respectively. Colorectal neoplasms were in general more likely to develop in males and older subjects. CONCLUSIONS: Although recurrence rates after polypectomy were elevated, the incidence rates in subjects with no neoplastic lesions initially were quite high.     

The yield of lower endoscopy in patients with constipation: survey of a university hospital,a public county hospital,and a Veterans Administration medical center

BACKGROUND: The role of endoscopy in the evaluation of constipation is controversial. The aim of this study was to clarify the yield of lower endoscopy in patients with constipation. METHODS: Endoscopic databases from 3 diverse hospitals were searched for procedures with constipation as an indication. Detection of neoplasia was the main outcome of interest. RESULTS: Among 19,764 sigmoidoscopies or colonoscopies, constipation was a procedure indication for 563 patients (mean age 61 [16] years, 52% women); 58% had procedure indications in addition to constipation. Colorectal cancer was diagnosed in 8 (1.4%), adenomas in 82 (14.6%), and advanced lesions (cancer or adenoma with malignancy, high-grade dysplasia, villous features, or size > or = 10 mm) in 24 (4.3%). In the 358 patients who underwent colonoscopy, cancer was detected in 1.7%, adenomas in 19.6%, and advanced lesions in 5.9%. Two patients with cancer were less than 50 years of age. In as many as 6 patients with cancer, the tumor may have caused partial obstruction. CONCLUSIONS: The range of neoplasia in patients with constipation evaluated with lower endoscopy was comparable with what would be expected in asymptomatic subjects undergoing colorectal cancer screening. Although chronic constipation alone may not be an appropriate indication for lower endoscopy, age-appropriate colorectal cancer screening should be pursued when patients with constipation seek medical care.     

Screening colonoscopy in asymptomatic average-risk African Americans

BACKGROUND: Recent data indicate that colorectal cancer incidence and mortality in white Americans have been declining since 1985 at a rate of 2% to 3% per year. In African Americans, however, mortality from colorectal cancer appears to be increasing. We sought to evaluate the prevalence of colonic neoplasia in asymptomatic African Americans. METHODS: We performed a cross-sectional colonoscopy screening study to determine the prevalence of colonic neoplasia in asymptomatic African Americans older than 50 years of age. RESULTS: One hundred sixty-six subjects were evaluated for the study of whom 121 (69 women) were deemed to be asymptomatic average-risk persons and completed colonoscopy. Forty-two individuals (35%) had a total of 72 adenomas (67 tubular and 5 tubulovillous); 47 (65.3%) of these were proximal to the splenic flexure. Three subjects had an adenoma 1 cm or greater in diameter and none had severe dysplasia. CONCLUSIONS: The overall prevalence of adenomas in asymptomatic average-risk African Americans was comparable to that of previously described populations. The predominance of right-sided adenomas in this study confirms previous findings and is an area requiring further study. Until this issue is resolved, we suggest the use of colonoscopy rather than sigmoidoscopy for screening for colorectal neoplasia in asymptomatic, average-risk African Americans.     

Interval faecal occult blood testing in a colonoscopy based screening programme detects additional pathology

BACKGROUND: Colonoscopic based surveillance is recommended for patients at increased risk of colorectal cancer. The appropriate interval between surveillance colonoscopies remains in debate, as is the "miss rate" for colorectal cancer within such screening programmes. AIMS: The main aim of this study was to determine whether a one-off interval faecal occult blood test (FOBT) facilitates the detection of significant neoplasia within a colonoscopic based surveillance programme. Secondary aims were to determine if invitees were interested in participating in interval screening, and to determine whether interval lesions were missed or whether they developed rapidly since the previous colonoscopy PATIENTS: Patients enrolled in a colonoscopic based screening programme due to a personal history of colorectal neoplasia or a significant family history. METHODS: Patients within the screening programme were invited to perform an immunochemical FOBT (Inform). A positive result was followed by colonoscopy; significant neoplasia was defined as colorectal cancer, adenomas either > or =10 mm or with a villous component, high grade dysplasia, or multiplicity (>/=3 adenomas). Participation rates were determined for age, sex, and socioeconomic subgroups. Colonoscopy recall databases were examined to determine the interval between previous colonoscopy and FOBT offer, and correlations between lesion characteristics and interval time were determined. RESULTS: A total of 785 of 1641 patients invited (47.8%) completed an Inform kit. A positive result was recorded for 57 (7.3%). Fifty two of the 57 test positive patients completed colonoscopy; 14 (1.8% of those completing the FOBT) had a significant neoplastic lesion. These consisted of six colorectal cancers and eight significant adenomas. CONCLUSIONS: A one off immunochemical faecal occult blood test within a colonoscopy based surveillance programme had a participation rate of nearly 50% and appeared to detect additional pathology, especially in patients with a past history of colonic neoplasia.     

Incidence and prognosis of colorectal dysplasia in inflammatory bowel disease: a population-based study from Olmsted County, Minnesota

BACKGROUND AND AIMS: The risk, fate, and ideal management of colorectal dysplasia in inflammatory bowel disease (IBD) remain debated. We estimated the incidence, long-term outcome, and risk factors for progression of colorectal dysplasia (adenomas [adenoma-associated lesions or masses (ALMs)], flat dysplasia, and dysplasia-associated lesions or masses [DALMs]) in a population-based IBD cohort from Olmsted County, Minnesota. MATERIALS AND METHODS: The Rochester Epidemiology Project was used to identify cohort patients with colorectal dysplasia. Medical records were reviewed for demographic and clinical characteristics. Histology slides were reviewed by a pathologist blinded to previous pathology reports. The cumulative incidence of dysplasia was estimated, and the association between patient characteristics and recurrence/progression of dysplasia was assessed using proportional hazards regression. RESULTS: Twenty-nine (4%) IBD patients developed flat dysplasia (n = 8), DALMs (n = 1), ALMs in areas of IBD (n = 18), or ALMs outside areas of IBD (n = 2). Among 6 patients with flat low-grade dysplasia (fLGD) who did not undergo colectomy, none progressed during a median of 17.8 (range 6-21) years of observation with a median of 3 (range 0-12) surveillance colonoscopies. Four (22%) patients with ALMs in areas of IBD who did not undergo surgery developed LGD or DALMs. Primary sclerosing cholangitis and dysplasia located proximal to the splenic flexure were significantly associated with risk for recurrence/progression of dysplasia. CONCLUSIONS: This population-based cohort study from Olmsted County, Minnesota did not confirm an increased risk of cancer related to fLGD, whereas 22% of patients with ALMs in areas of IBD developed fLGD or DALMs.     

Predictors of proximal neoplasia in patients without distal adenomatous pathology

BACKGROUND: Previous colorectal cancer screening studies have observed that some patients may have advanced proximal neoplasia without distal findings. Since these studies have included only gender, age, and family history as risk factors, they are limited in their ability to identify predictors of isolated proximal neoplasia. METHODS: Data were collected from the charts of 1,988 patients who presented for colonoscopy. Information gathered included endoscopic findings, histology, known risk factors for colorectal neoplasia, and smoking pattern. Our main outcome was the presence of proximal adenomatous neoplasia in patients who had no distal adenomas. We defined significant neoplasia as adenocarcinoma, high-grade dysplasia, villous polyps, adenomas 1 cm or greater or more than two adenomas of any size. RESULTS: Fifty-five patients had isolated significant proximal neoplasia that would have been missed on a flexible sigmoidoscopy. While patients older than 60 yr had a greater risk for this neoplasia (odds ratio = 3.01: 95% CI = 1.66-4.23; p < 0.001), those who took a daily aspirin had a reduced risk (OR = 0.60; 95% CI = 0.30-0.88; p < 0.05). A family history of colorectal cancer increased the patient's risk of having any adenomas (OR = 2.01; 95% CI = 1.33-3.40; p < 0.01) or villous tissue (OR = 2.03; 95% CI = 1.27-3.51; p < 0.05) in the proximal colon without distal findings. Smoking was associated with an increased risk of large (> 1 cm) isolated proximal tubular polyps (OR = 2.71; 95% CI = 1.64-4.46; p < 0.01) as well as isolated significant proximal neoplasia (OR = 2.30; 95% CI = 1.59-3.31; p < 0.01). CONCLUSIONS: Age greater than 60 yr, a history of at least 10 pack-years of smoking, and a family history of colorectal cancer increased the risk of finding significant proximal polyps in patients without distal pathology.     

Endoscopic follow-up after colorectal cancer resection: An Italian multicentre study

BACKGROUND: Endoscopic follow-up is advised in patients operated for colorectal cancer due to a high risk for both metachronous colorectal cancer and adenomas. Such issue has been scarcely addressed in Italy. This study aimed to evaluate the incidence of neoplastic lesions at a scheduled endoscopic follow-up and to identify the patients at higher risk of recurrence. METHODS: Colorectal cancer patients diagnosed in the three participating hospitals (one North, one Centre and one South Italy) were scheduled for colonoscopies at 1, 3 and 5 years after surgery. Incidence of adenomas, advanced adenomas and colorectal cancer was assessed in all patients. Neoplastic incidence in patients with and without synchronous lesions at entry was also compared. RESULTS: Overall, 318 consecutive patients were prospectively enrolled including 108 (34%, group A) with a synchronous lesion and 210 (group B) without it. A cumulative neoplastic incidence of 20.1, 32.4 and 44% was observed at 1, 3 and 5 years of follow-up, respectively. The cumulative incidence of all the lesions was 70% in group A and 30.2% in group B at 5-year follow-up, being 39.5 and 15.5% after excluding the lesions detected at 1-year examination. A neoplastic lesion was detected more frequently in group A at 1year (30.5% versus 14.7%; p = 0.0013), 3 years (21.4% versus 7.6%; p = 0.0008) and at 5years (18.1% versus 7.8%; p = 0.02). CONCLUSIONS: Our data showed that the incidence of adenomas in patients operated for colorectal cancer is fairly high. Colorectal cancer patients with synchronous lesions are at higher risk of neoplastic recurrence at follow-up as compared to those without them.     

Pathology of early lower GI cancer

Early colorectal cancer can be treated with curative resection if the depth of invasion is limited to the submucosa (pathologic T category pT1 in the TNM classification). Macroscopically early colorectal cancer and its precursor lesions present as elevated polyps or non-polypoid flat lesions. Microscopically, precursor lesions are characterized by intraepithelial neoplasia and present as classic adenomas or serrated adenomas. Precursor lesions may already contain foci of early colorectal cancer. Early colorectal cancer can be treated by endoscopic resection. Careful handling of the specimen is required in order to optimally identify the factors that may predict an adverse outcome. Whenever a favourable tumour grade is found, without vascular invasion and tumour budding, there seems to be a low risk for adverse outcome and laparotomy may thus be avoided.     

The Vienna classification of gastrointestinal epithelial neoplasia

BACKGROUND: Use of the conventional Western and Japanese classification systems of gastrointestinal epithelial neoplasia results in large differences among pathologists in the diagnosis of oesophageal, gastric, and colorectal neoplastic lesions. AIM: To develop common worldwide terminology for gastrointestinal epithelial neoplasia. METHODS: Thirty one pathologists from 12 countries reviewed 35 gastric, 20 colorectal, and 21 oesophageal biopsy and resection specimens. The extent of diagnostic agreement between those with Western and Japanese viewpoints was assessed by kappa statistics. The pathologists met in Vienna to discuss the results and to develop a new consensus terminology. RESULTS: The large differences between the conventional Western and Japanese diagnoses were confirmed (percentage of specimens for which there was agreement and kappa values: 37% and 0.16 for gastric; 45% and 0.27 for colorectal; and 14% and 0.01 for oesophageal lesions). There was much better agreement among pathologists (71% and 0.55 for gastric; 65% and 0.47 for colorectal; and 62% and 0.31 for oesophageal lesions) when the original assessments of the specimens were regrouped into the categories of the proposed Vienna classification of gastrointestinal epithelial neoplasia: (1) negative for neoplasia/dysplasia, (2) indefinite for neoplasia/dysplasia, (3) non-invasive low grade neoplasia (low grade adenoma/dysplasia), (4) non-invasive high grade neoplasia (high grade adenoma/dysplasia, non-invasive carcinoma and suspicion of invasive carcinoma), and (5) invasive neoplasia (intramucosal carcinoma, submucosal carcinoma or beyond). CONCLUSION: The differences between Western and Japanese pathologists in the diagnostic classification of gastrointestinal epithelial neoplastic lesions can be resolved largely by adopting the proposed terminology, which is based on cytological and architectural severity and invasion status.     

Comparison of malignant potential between serrated adenomas and traditional adenomas

BACKGROUND: Serrated adenoma is a discrete colorectal epithelial neoplastic lesion that can evolve into colorectal cancer. However, the degree of malignant potential has not been firmly established as yet. The purpose of the present paper was to compare the malignant potential and clinicopathological features between serrated and traditional adenomas. METHODS: A total of 124 serrated adenomas from 116 patients were assessed, and 419 traditional adenomas from 200 were randomly selected. The combination of nuclear dysplasia and serration of > or =20% of crypts was regarded as serrated adenoma. The clinicopathological features of serrated and traditional adenomas were compared, and multivariate analysis performed to confirm whether the malignant potential of serrated adenoma was similar to that of traditional adenoma. RESULTS: The differences in age, sex, total number of adenomas, and synchronous lesions including adenoma with high-grade dysplasia and carcinoma between subjects with and without serrated adenoma were not significant. Serrated adenomas were more frequently located in the rectum and sigmoid colon (P < 0.001), and the average size of serrated adenomas was greater than that of traditional adenomas (P < 0.05). The incidence of malignant lesions including high-grade dysplasia and carcinoma in serrated adenomas was found to be lower than in traditional adenomas (3.2% vs 9.3%, P < 0.05). In the multivariate analysis, adenoma type and polyp size constituted the risk factors for the incidence of high-grade dysplasia and carcinoma. CONCLUSIONS: Serrated adenoma is a premalignant lesion, but it has a lower potential for the development of malignancy than traditional adenomas.     

Colorectal adenomas: morphologic features and the risk of developing metachronous adenomas and carcinomas in the colorectum

The morphologic features of 307 colorectal adenomas among 159 patients are reviewed. Most adenomas (66.4%) were located in the sigmoid colon and the rectum, and the percentage decreased proximally to the right colon. The 307 adenomas comprised 244 (79.5%) tubular, 41 (13.3%) tubulovillous, and 22 (7.2%) villous adenomas. The epithelial dysplasia was graded as mild in 260 (84.7%) adenomas, moderate in 33 (10.7%), and severe in 14 (4.6%). The percentage of severe dysplasia was greater in villous adenomas than in tubular adenomas (p less than 0.05) and correlated with the increasing size (greater than 5 mm) of the adenomas (p less than 0.01). The risk of metachronous adenomas could be evaluated among 56 patients, 34 men and 22 women with a history of removed adenoma(s). Fourteen of 56 patients (25%) with 6:1 male to female ratio developed 18 new adenomas, after an average of 34.3 months (range, from 12 to 88 months). Eleven of the 14 patients had multiple adenomas at the initial examination. In addition, a carcinoma of the rectum was found in one male patient. Of the 48 patients, 17 men and 31 women, operated on for colorectal cancer 16 patients (34%) with 1.3:1 male to female ratio had 40 new adenomas after an average of 51.8 months (range, 12 to 252 months) after the surgical excision of their carcinomas. One patient had a recurrent carcinoma at the site of the anastomosis 22 months after anterior resection of his carcinoma. Our data suggest that a history of colorectal carcinoma, multiple adenomas, and male sex predict a higher risk of having future colorectal tumours.     

DNA microsatellite instability and mismatch repair protein loss in adenomas presenting in hereditary non-polyposis colorectal cancer

BACKGROUND AND AIM: Hereditary non-polyposis colorectal cancer (HNPCC), as its name implies, is associated with few adenomas, and the early evolution of colorectal neoplasia is poorly understood. In this study our aim was to clarify the genetic profiles of benign polyps in subjects with HNPCC using a combined molecular and immunohistochemical approach. METHODS: Thirty adenomas and 17 hyperplastic polyps were obtained from 24 affected HNPCC subjects. DNA was extracted from paraffin embedded tissue by microdissection and analysed for the presence of microsatellite instability (MSI) and mutations in five genes known to be targets in mismatch repair deficiency (TGFbetaRII, IGF2R, BAX, hMSH3, and hMSH6). Serial sections were stained by immunohistochemistry for hMLH1 and hMSH2. RESULTS: Twenty four (80%) of 30 adenomas showed MSI. Of MSI positive adenomas, 66.7% showed MSI at more than 40% of markers (high level of MSI (MSI-H)). Two of 17 hyperplastic polyps revealed MSI at one marker (low level of MSI (MSI-L)). A significant association was found between MSI-H and high grade dysplasia in adenomas (p=0.004). Eight of nine adenomas with mutations of coding sequences revealed high grade dysplasia and all nine were MSI-H. Four of the nine ranged in size from 2 to 5 mm. The presence of the hMSH6 mutation was significantly correlated with high levels of MSI (80% of markers) (p<0.02). Twenty four adenomas gave evaluable results with immunohistochemistry. One of six (17%) microsatellite stable, six of seven (86%) MSI-L, and 11 of 11 (100%) MSI-H adenomas showed loss of either hMLH1 or hMSH2. CONCLUSIONS: Most adenomas in subjects with a definite diagnosis of HNPCC show MSI (80%). The finding of MSI-L is usually associated with loss of expression of hMLH1 or hMSH2, unlike the situation in MSI-L sporadic colorectal cancer. The transition from MSI-L to MSI-H correlated with the finding of high grade dysplasia and mutation of coding sequences and may be driven by mutation of secondary mutators such as hMSH3 and hMSH6. Advanced genetic changes may be present in adenomas of minute size.     

结直肠肿瘤表面凹陷形态对判断病变性质及浸润深度的作用

目的评估应用放大色素内镜观察结直肠肿瘤表面凹陷形态判断病灶性质和浸润深度的作用。方法连续收集符合内镜黏膜切除术（EMR）指征的无蒂或平坦、凹陷型病灶。应用放大色素内镜,对伴有中央凹陷的病灶根据凹陷面形态分为1型（星芒状）和2型（圆盘形）。根据EMR术后病理诊断,分析病灶表面凹陷形态与病变性质和浸润深度的相关性。结果EMR切除病灶90个（无蒂型25个,平坦、凹陷型65个）。病灶中央有凹陷者占54．4％（49／90）,出现高度异型增生（HGD）或癌的比例（51．0％）显著高于没有凹陷者（17．1％）（P〈0．001）。其中,2型凹陷出现HGD或癌的比例（89．5％）又显著高于1型凹陷（26．7％、）（P〈0．001）。根据凹陷面形态区分黏膜下浅层（m·sm1）和黏膜下深层（sm2-sm3）浸润的总体准确性为83．7％（41／49）。结论根据结直肠平坦、凹陷型和无蒂肿瘤表面凹陷形态能够判断病变程度和浸润深度,从而指导EMR治疗。     

Adenoma prevalence and cancer risk in familial non-polyposis colorectal cancer.

BACKGROUND AND AIMS: Polypectomy in the colon has been shown to prevent colorectal cancer in both the general population and in familial colorectal cancer. Individuals with a family history of colorectal cancer have an increased risk of the disease. Over a period of 10 years, 304 subjects at risk were included in ongoing surveillance with regular colonoscopies. To compile the medical findings and experience generated during this period, a retrospective cross sectional study was performed. SUBJECTS: Subjects were classified into three family groups: families with hereditary non-polyposis colorectal cancer (HNPCC); families with hereditary colorectal cancer (HCC, non-Lynch syndrome); and a third group of families with only empirical risk estimates based on a family history of two close relatives (TCR) with colorectal cancer. METHODS: The risk population was studied with regard to age at onset, prevalence, number, cancer risk, size, dysplasia, and distribution of adenomas. A comparison was made within the family groups and with a reference group representing the general population. RESULTS: In total, 195 adenomas and six cancers were detected among 85 individuals. The relative risk of having an adenoma in the whole risk population compared with the general population was 2.6. Subjects from TCR families had most adenomas and HNPCC subjects had the least. A shift from proximal adenomas to distal carcinomas in families with HCC and TCR suggested a higher cancer risk in distal adenomas in these syndromes. HNPCC families showed a younger age at onset and adenomas with a higher degree of dysplasia. In HNPCC, there was a similar localisation of adenomas and carcinomas, suggesting a high risk of cancer in all adenomas. CONCLUSIONS: There was clear overrepresentation of adenomas in all three family types compared with the reference population. In HNPCC, we found earlier onset of adenomas and faster progression to cancer. Families with HCC, and even more so TCR subjects, had a later onset and lower risk of cancer from proximal adenomas. Based on these results, surveillance protocols in Sweden have been revised.     

Prospective cohort comparison of flavonoid treatment in patients with resected colorectal cancer to prevent recurrence

AIM： To investigate biological prevention with flavonoids the recurrence risk of neoplasia was studied in patients with resected colorectal cancer and after adenoma polypectomy. METHODS： Eighty-seven patients, 36 patients with resected colon cancer and 51 patients after polypectomy, were divided into 2 groups： one group was treated with a flavonoid mixture （daily standard dose 20 mg apigenin and 20 mg epigallocathechin-gallat, n = 31） and compared with a matched control group （n = 56）. Both groups were observed for 3-4 years by surveillance colonoscopy and by questionnaire. RESULTS： Of 87 patients enrolled in this study, 36 had resected colon cancer and 29 of these patients had surveillance colonoscopy. Among the flavonoid-treated patients with resected colon cancer （n = 14）, there was no cancer recurrence and one adenoma developed. In contrast the cancer recurrence rate of the 15 matched untreated controls was 20% （3 of 15） and adenomas evolved in 4 of those patients （27%）. The combined recurrence rate for neoplasia was 7% （1 of 14） in the treated patients and 47% （7 of 15） in the controls （P = 0.027）. CONCLUSION： Sustained long-term treatment with a flavonoid mixture could reduce the recurrence rate of colon neoplasia in patients with resected colon cancer.