Mismatch repair polymorphisms and colorectal polyps: hMLH1-93G>A variant modifies risk associated with smoking

BACKGROUND AND AIM: Mutations in the mismatch repair (MMR) enzymes hMLH1 and hMSH6 are known causes of hereditary nonpolyposis colorectal cancer and act by inducing a mutator phenotype characterized by microsatellite instability. The aim of our study was to determine if polymorphisms in the DNA MMR genes hMLH1 and hMSH6 are associated with an increased risk of colorectal polyps, and to evaluate interactions with exposures known to cause DNA damage. METHODS: In a Minnesota-based case-control study of individuals with adenomas (N=401), hyperplastic polyps (N=195), or both adenomas and hyperplastic polyps (N=123) versus polyp-free controls (N=624), we investigated the role of hMLH1-93G>A, hMLH1 I219V, and hMSH6 G39E polymorphisms in increasing the risk of colorectal polyps. Polytomous multivariate logistic regression analysis was used, adjusting for age, sex, body mass index, postmenopausal hormone use, aspirin use, and NSAID use. RESULTS: Overall, no evidence of an association between any of the three polymorphisms or hMLH1 haplotypes and colorectal polyps was observed. However, risk associated with the hMLH1-93A variant differed by smoking: smoking-associated risks were stronger among those with variant -93AA or -93AG genotypes, showing a twofold greater risk of adenoma with >25 pack-years of smoking compared with nonsmokers, and a corresponding eightfold greater risk of hyperplastic polyps (genotype smoking: p-interaction=0.02 for hyperplastic polyps and p-interaction=0.08 for adenomas). CONCLUSIONS: These data are consistent with the observation that smoking is associated with MMR in colorectal neoplasia and suggest that the risk increase with smoking may differ by hMLH1-93G>A genotype.     

Risk of proximal colorectal neoplasia among asymptomatic patients with distal hyperplastic polyps

PURPOSE: Many guidelines on colorectal cancer screening do not consider distal hyperplastic polyps to be a marker for proximal neoplasia. However, 11 of 17 published studies have shown an increased risk of proximal neoplasia in patients with distal hyperplastic polyps. Our goal is to assess the risk of proximal neoplasia in asymptomatic patients with distal hyperplastic polyps, compared to those with distal tubular adenomas or no distal polyps. METHODS: We assessed proximal (cecum, ascending, transverse colon and splenic flexure) and distal polyps in patients undergoing screening colonoscopy, classifying them into 3 groups: distal hyperplastic polyps only; distal adenomas with or without hyperplastic polyps; no distal polyps. The prevalence of proximal neoplasia and advanced neoplasia (polyps > or =1 cm, villous adenomas, or cancer) was compared among these groups. RESULTS: Of 2357 patients, 427 (18%) had neoplasia, including 103 (4%) with advanced neoplasia. Proximal neoplasia occurred in 175 (9%) of 1896 patients with no distal polyps, compared with 28 (12%) of 237 with distal hyperplastic polyps (P = 0.20) and 64 (29%) of 224 with distal adenomas (P <0.0001). Proximal advanced neoplasia occurred in 39 (2%) patients with no distal polyps, compared with 4 (2%) with distal hyperplastic polyps (P = 0.70) and 9 (4%) with distal adenomas (P = 0.13). CONCLUSIONS: Patients with distal hyperplastic polyps, unlike those with distal adenomas, do not exhibit an increased risk for proximal neoplasia or proximal advanced neoplasia compared to those with no distal polyps. The discovery of hyperplastic polyps on screening sigmoidoscopy should not prompt colonoscopy.     

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

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

Sex-influenced association of non-alcoholic fatty liver disease with colorectal adenomatous and hyperplastic polyps

AIM To investigate the relationship between non-alcoholic fatty liver disease(NAFLD) and colorectal adenomatous and hyperplastic polyps.METHODS A retrospective cross-sectional study was conducted on 3686 individuals undergoing health checkups(2430 males and 1256 females). All subjects underwent laboratory testing,abdominal ultrasonography,colonoscopy,and an interview to ascertain the baseline characteristics and general state of health. Multinomial logistic regression analysis was performed to examine the association between NAFLD and the prevalence of colorectal adenomatous and hyperplastic polyps.Furthermore,the relationship was analyzed in different sex groups. Subgroup analysis was performed based on number,size,and location of colorectal polyps.RESULTS The prevalence of colorectal polyps was 38.8% in males(16.2% for adenomatous polyps and 9.8% for hyperplastic polyps) and 19.3% in females(8.4% for adenomatous polyps and 3.9% for hyperplastic polyps). When adjusting for confounding variables,NAFLD was significantly associated with the prevalence of adenomatous polyps(OR = 1.28,95%CI: 1.05-1.51,P 0.05) and hyperplastic polyps(OR = 1.35,95%CI: 1.01-1.82,P 0.05). However,upon analyzing adenomatous and hyperplastic polyps in different sex groups,the significant association remained in males(OR = 1.53,95%CI: 1.18-2.00,P 0.05; OR = 1.42,95%CI: 1.04-1.95,P 0.05) but not in females(OR = 0.44,95%CI: 0.18-1.04,P 0.05; OR = 1.18,95%CI: 0.50-2.78,P 0.05). CONCLUSION NAFLD is specifically associated with an increased risk of colorectal adenomatous and hyperplastic polyps in men. However,NAFLD may not be a significant factor in the prevalence of colorectal polyps in women.     

Hyperplastic polyps and the risk of adenoma recurrence in the polyp prevention trial

BACKGROUND AND AIMS: Recent studies have suggested that some hyperplastic polyps may be associated with an increased risk of colorectal cancer. Prospective information on the risk of adenoma recurrence associated with hyperplastic polyps is limited. We sought to investigate whether the coexistence of hyperplastic polyps with adenomas increases the risk of adenoma recurrence. METHODS: We used unconditional logistic regression models to examine the association between baseline hyperplastic polyps and subsequent adenoma recurrence during a 3-year follow-up evaluation, among 1637 participants in the Polyp Prevention Trial. RESULTS: A total of 437 participants (26.7%) had hyperplastic polyps coexisting with adenomas at baseline. Of these, 132 (30.2%) had at least one hyperplastic polyp in the proximal colon, whereas 305 (69.8%) had only distal hyperplastic polyps. When compared with subjects without any hyperplastic polyps at baseline, there was no statistically significant association between the presence of baseline hyperplastic polyps and recurrence of any adenoma (odds ratio [OR], 1.19; 95% confidence interval [CI], 0.94-1.51) or advanced adenoma (OR, 1.25; 95% CI, 0.78-2.03). Also, there was no association between hyperplastic polyp location and adenoma recurrence (OR, 1.01; 95% CI, 0.69-1.48) for any proximal hyperplastic polyp (OR, 1.26; 95% CI, 0.96-1.65) and for distal hyperplastic polyps. CONCLUSIONS: The coexistence of hyperplastic polyps with adenomas, irrespective of location, does not confer an increased risk of adenoma recurrence beyond that of adenomas alone within 3 years of follow-up evaluation. Prospective long-term studies on adenoma recurrence risk associated with hyperplastic polyps in screening populations are needed.     

Risk of proximal colon neoplasia with distal hyperplastic polyps: a meta-analysis

BACKGROUND: Most guidelines for colorectal cancer screening do not consider distal hyperplastic polyps (HPs) to be markers for proximal colon neoplasia. However, many studies have shown an increased risk of proximal neoplasia (PN) in patients with distal HPs. We performed a systematic review to assess the association between distal HPs and PN. METHODS: We identified studies that compared the prevalence of PN and proximal advanced neoplasia in patients with distal HPs vs controls. Two masked investigators extracted data on individuals with distal HPs, distal adenomas, or no distal polyps. Using the DerSimonian and Laird method, we calculated summary risk ratios. Extensive subgroup analysis was performed. RESULTS: The prevalence of PN and proximal advanced neoplasia in persons with distal HPs was 26.0% and 4.4%, respectively. In studies comparing the risk of PN in patients with distal HPs vs those with no distal polyps, the summary risk ratio was 1.81 (95% confidence interval, 1.20-2.73). However, this increased risk disappeared if only high-quality studies on screening patients were considered. The risk ratio was 0.69 (95% confidence interval, 0.60-0.80) when comparing the risk of PN in those with distal HPs vs those with distal adenomas. CONCLUSIONS: Overall, patients with distal HPs have an intermediate risk of PN compared with those with distal adenomas or no distal polyps; however, in asymptomatic screening individuals, there is no increased risk of PN or proximal advanced neoplasia. The discovery of HPs on screening flexible sigmoidoscopy should not automatically prompt follow-up colonoscopy.     

Comparison of cyclo-oxygenase 2 expression in colorectal serrated adenomas to expression in tubular adenomas and hyperplastic polyps

BACKGROUND AND AIMS: Serrated adenoma (SA) is a newly defined category of colorectal neoplasia that contains features of both adenoma and hyperplastic polyp, and has two patterns, hyperplastic and cerebriform patterns. Since cyclooxygenase 2 (COX-2) has been found upregulated in colorectal cancers and adenomas, we examined whether either the hyperplastic or cerebriform pattern of SA has the potential for tumor progression and should be a target for clinical treatment. PATIENTS AND METHODS: An immunohistochemical scoring system was used to compare COX-2 expression in colorectal SAs (n=79), tubular adenomas (n=66), and hyperplastic polyps (n=21). RESULTS: COX-2 scores were significantly higher in SA of the cerebriform pattern (n=44) than in SA of the hyperplastic pattern (n=35). There was no difference in COX-2 scores between SA of the cerebriform pattern and tubular adenoma. In SA accompanied by hyperplastic polyp (n=26) the hyperplastic components expressed little COX-2, the same as traditional hyperplastic polyps. COX-2 expression in the SA component was similar to that in pure SA. CONCLUSION: SA of the cerebriform pattern should be treated similarly as traditional tubular adenomas. COX-2 induction may additionally be involved in progression from hyperplastic polyp to SA.     

Growth of colorectal polyps: redetection and evaluation of unresected polyps for a period of three years.

BACKGROUND, AIMS, AND PATIENTS: In a prospective follow up and intervention study of colorectal polyps, leaving all polyps less than 10 mm in situ for three years, analysis of redetection rate, growth, and new polyp formation was carried out in 116 patients undergoing annual colonoscopy. The findings in relation to growth and new polyp formation were applied to 58 subjects who received placebo. RESULTS: Redetection rate varied from 75-90% for each year, and was highest in the rectum and sigmoid colon. There was no net change in size of all polyps in the placebo group, however, polyps less than 5 mm showed a tendency to net growth, and polyps 5-9 mm a tendency to net regression in size, both for adenomas and hyperplastic polyps. This pattern was verified by computerised image analysis. Patients between 50 and 60 years showed evidence of adenoma size increase compared with the older patients, and the same was true for those with multiple adenomas (four to five) compared with those with a single adenoma. The new adenomas were significantly smaller and 71% were located in the right side of the colon. Patients with multiple adenomas had more new polyps at all the follow up examinations than patients with a single adenoma. One patient developed an invasive colorectal carcinoma, which may be evolved from a previously overlooked polyp. Two polyps, showing intramucosal carcinoma after follow up for three years, were completely removed, as judged by endoscopy and histological examination. CONCLUSIONS: The results show that follow up of unresected colorectal polyps up to 9 mm is safe. The consistency of growth retardation of medium sized polyps suggests extended intervals between the endoscopic follow up examinations, but the increased number of new polyps in the proximal colon indicates total colonoscopy as the examination of choice. The growth retardation of the medium sized polyps may partly explain the discrepancy between the prevalence of polyps and the incidence of colorectal cancer.     

Predictors of presence, multiplicity, size and dysplasia of colorectal adenomas. A necropsy study in New Zealand.

Three hundred and thirty six forensic necropsy specimens of large bowel were examined in order to identify subject related variables that independently predicted the following adenoma characteristics: presence, size (largest), multiplicity and high grade dysplasia. The variables were age, gender, body mass index, race (European origin versus Maori/Polynesian) and presence of hyperplastic (metaplastic) polyp(s). Subjects included 303 New Zealanders of European origin (M = 185, F = 118) yielding 149 adenomas and 251 hyperplastic polyps and 33 Maori/Polynesians (M = 25, F = 8) yielding five adenomas and one hyperplastic polyp. Independent predictors of adenoma presence as determined by regression analysis were age (p = 0.0001), presence of hyperplastic polyps (p = 0.0001) and male gender (p = 0.05). Models were poor at explaining variation in size, multiplicity, and dysplasia. Larger adenomas occurred more frequently in subjects with multiple adenomas (p = 0.03) and multiple adenomas were probably associated with hyperplastic polyps (p = 0.09) and male gender (p = 0.09) in Europeans. High grade dysplasia was more frequent in women (p = 0.05) and possibly in subjects with hyperplastic polyps (p = 0.2). Body mass index and ethnicity did not predict any adenoma characteristics, but hyperplastic polyp prevalence was influenced by European origin (p = 0.04) and to a lesser extent by body mass index (p = 0.08) as well as presence of adenoma (p = 0.0002) and age ( = 0.005). The association of hyperplastic polyp with presence, multiplicity but not size of adenoma and with a high risk group for colorectal cancer (New Zealanders of European origin) suggests that the hyperplastic polyp serves as a marker for a factor which influences neoplastic evolution at the stages of initiation/transformation but not promotion. Fifty nine per cent of individuals with adenoma(s) did not have hyperplastic polyp(s) emphasising that the last would serve only as a marker of populations and not individuals at high risk of bowel cancer. Low intracolonic butyrate may be the factor linking the expression of the two types of polyp.     

Immunohistochemical study of epithelial cell proliferation in hyperplastic polyps, adenomas, and adenocarcinomas of the large bowel

A monoclonal antibody to bromodeoxyuridine was used in tissue specimens previously incubated with bromodeoxyuridine to show S-phase cells by immunohistochemical technique. Biopsy specimens of normal mucosa (n = 10), hyperplastic polyps (n = 10), adenomas with low-grade dysplasia (n = 20), adenomas with high-grade dysplasia (n = 10), and invasive adenocarcinomas (n = 10) of the large bowel were studied. Labeling index and cell proliferative patterns were analyzed. No statistically significant difference was found in labeling index between normal mucosa and hyperplastic polyps or between adenomas with high-grade dysplasia and adenocarcinomas. The labeling index was significantly lower in normal mucosa and in hyperplastic polyps than in adenomas and adenocarcinomas (p less than 0.001). The difference in labeling index between adenomas with high-grade dysplasia and low-grade dysplasia was also statistically significant (0.01 less than p less than 0.05). In normal mucosa and in hyperplastic polyps the proliferative zone was confined to the lower two-thirds of the crypt; no kinetic activity was found in the upper portions of the crypt or in surface epithelium. In adenomas the labeled cells were either present in the upper third or scattered along the whole axis of the crypt and in the surface epithelium. Labeling patterns in invasive carcinomas were similar to those observed in adenomas with high-grade dysplasia. The difference in proliferative patterns between hyperplastic polyps and adenomas supports a different significance of the two polypoid lesions in the histogenesis of large bowel cancer; our results confirm the subsequent steps of the adenoma-carcinoma sequence. Immunohistochemical labeling patterns observed with monoclonal antibody to bromodeoxyuridine in polypoid and cancer lesions of the large bowel are similar to those described by autoradiographic studies.     

Diminutive polyps of large bowel should be an early target for endoscopic treatment

BACKGROUND AND AIMS: Aim of the present study is to ascertain the importance of diminutive colorectal polyps and define the need for removal according to their characteristics and malignant potential. PATIENTS AND METHODS: A total of 4,723 patients who underwent colonoscopy were evaluated and 624 patients with 826 polyps were recorded. There were 352 patients with 443 diminutive polyps, studied according to their distribution. Of these, 371 were removed, histologically examined and correlated to patient characteristics and occurrence of synchronous neoplasms. RESULTS: Of the right colon polyps, 81/115 were diminutive, versus 362/711 of the left colon (p<0.0001). Adenomas were more common in patients over 50 years of age, (p<0.0001). In all colonic segments, diminutive adenomas prevailed over hyperplastic polyps, whereas the proportion of diminutive adenomas predominated in the right colon (p=0.0015). Adenomas were classified as tubular 39%, tubulovillous 55.7% and villous 5.3%. The degree of dysplasia was mild in 45.5%, moderate in 51% and severe in 3.5%. The prevalence of synchronous neoplasms was 37.4%. They were more frequently found in males over 50 years of age and in patients with diminutive adenomas compared to those with diminutive hyperplastic polyps (p=0.0078). CONCLUSIONS: The majority of right colon polyps are diminutive. The proportion of diminutive adenomas is higher in patients over 50 years and in the right vs left colon. Diminutive polyps should be removed taking into account the high prevalence of adenomas with a villous component and their significant degree of dysplasia.     

结直肠息肉水通道蛋白3、4的表达

目的:观察水通道蛋白(aquaporin,AQP)3、4蛋白在结直肠息肉中的表达.方法:选择结直肠息肉患者103例,肠镜下收集115个息肉组织样本和10例正常人结直肠黏膜组织样本,采用免疫组织化学方法检测AQP3、4的蛋白表达.结果:AQP3、4蛋白在人结直肠黏膜上皮细胞呈阳性表达,均表达在细胞的基底部与侧面.AQP3、4蛋白在炎性息肉中的表达均明显高于正常组,差异有显著性意义(P<0.01,P<0.05);增生性息肉AQP3蛋白表达低于正常组,差异有显著性意义(P<0.01);腺瘤AQP4蛋白表达低于正常组,差异有显著性意义(P<0.01).AQP3与AQP4在结直肠息肉及正常结直肠黏膜中的表达呈正相关(r=0.61,P=0.000).结论:AQP3、4蛋白在结直肠息肉中存在异常表达,二者之间呈正相关.     

Mucin associated Tn and sialosyl-Tn antigen expression in colorectal polyps.

Sialosyl-Tn antigen and its immediate precursor, Tn antigen, are carbohydrate structures associated with the earliest steps of mucin O-linked glycosylation. Both antigens have been shown previously to be highly sensitive and specific markers of colorectal cancer. One hundred and three colorectal polyps (79 adenomatous; 24 hyperplastic) were examined for expression of Tn antigen using vicia villosa isolectin B4, and for sialosyl-Tn antigen by monoclonal antibody TKH2. Tn antigen was expressed by all of the polyps studied. Sialosyl-Tn, on the other hand was expressed weakly by a few cells in 7 of 24 (29%) hyperplastic polyps. Among the adenomatous polyps, 56% expressed sialosyl-Tn and expression correlated with larger adenoma size, greater villous component, and more severe grades of dysplasia. In individuals with two or more synchronous adenomas, the level of sialosyl-Tn expression within an adenoma was associated with the severity of cytological atypia. All the adenomas that contained a focus of invasive carcinoma expressed sialosyl-Tn. These results indicate that colorectal polyps manifest incomplete glycosylation, exposing antigens in the innermost region of mucin oligosaccharides. In addition, the correlation of sialosyl-Tn antigen expression with the adenoma-carcinoma sequence may make this a useful marker for studying malignant progression in the colon.     

A prospective study of the clinical, genetic, screening, and pathologic features of a family with hereditary mixed polyposis syndrome

In 1997, hereditary mixed polyposis syndrome (HMPS) was described in an Ashkenazi pedigree having colorectal polyps with mixed histology and risk for colorectal cancer (CRC). The mutation is now localized to 15q13-14. Since 1980, compliant relatives of an HMPS family were seen annually, tested genetically, and had colonoscopy offered every 1 to 2 yr from age 20 yr. The Israeli pedigree has 37 members (17 clinically affected by CRC or polyps), and seven of 13 available relatives entered our screening program. The others, followed-up elsewhere, provided clinical information. Half of our screened group had rectal bleeding; others were asymptomatic. Colonoscopy, performed a mean of four times, identified polyps in all seven patients (mean age 28 yr). Polyps were removed and included juvenile adenomas, mixed juvenile adenomas, hyperplastic polyps, mixed hyperplastic adenomas, serrated adenomas, and tubular adenomas. None of our screened patients developed CRC or extracolonic neoplasia. Linkage analysis localized their mutation to 15q13-14. This high-penetrance founder mutation so far is described only in Ashkenazim. The CRC pathway seems to be through juvenile and hyperplastic polyps. Mutation identification will aid screening for and evaluation of HMPS prevalence in Jewish and non-Jewish populations. Meanwhile, a cancer pedigree and correct classification of polyps will identify HMPS families. They require early and frequent colonoscopy, polypectomy, and elective extensive colectomy when indicated.     

Management of small and diminutive colorectal polyps: a review of the literature

Major advances in biomedical optics have increased our ability to detect more colorectal polyps. Increased small (6-9 mm) and diminutive (<6 mm) polyp detection has been reported however the impact of these increases in terms of colorectal cancer prevention is unknown. The same advances that have allowed increased detection have also made in vivo determination of polyp histology possible. As our in-vivo assessment accuracy improves, the need for resection of non neoplastic polyps and pathologic confirmation of low risk adenomas may eventually diminish. The clinical significance of small and diminutive polyps continues to be debated however both retrospective and prospective studies support a low prevalence of advanced pathology in colorectal polyps <10mm in size. Furthermore, natural history studies suggest these polyps exhibit little or slow growth and some may in fact regress over time. Though the overall risk of colonoscopy is low, polypectomy remains the single greatest risk factor, driving interest in methods to avoid polypectomy of non-neoplastic polyps thereby improving safety without reducing cancer prevention effectiveness. A "diagnose and discard" strategy for diminutive adenomas and a "diagnose and leave behind" strategy for diminutive hyperplastic polyps may offer risk and cost reduction without compromising effectiveness but will require the ability to make both accurate high confidence in-vivo polyp assessment and agreement in setting post-polypectomy surveillance intervals. As both our technology and our knowledge increase, we will be better equipped to confidently provide a complete colorectal screening, to manage detected polyps according to their chance for neoplasia, and to provide an accurate assessment of lifetime colorectal cancer risk and need for future surveillance examinations.     

High frequency of K-ras mutations in human colorectal hyperplastic polyps.

BACKGROUND: Hyperplastic polyps are common benign colorectal polyps, and are thought to have little association with malignant tumours in the colorectum. However, several reports suggest that some hyperplastic polyps may develop into colorectal neoplasms. AIM: To clarify genetic alterations in colorectal hyperplastic polyps. METHODS: Twenty eight colorectal polyps having serrated components were resected from patients endoscopically. The K-ras gene mutations in codons 12 and 13 were analysed by PCR-RFLP. Intranuclear p53 protein was immunostained by the avidin-biotin complex method. RESULTS: A mutation of the K-ras gene was detected in nine (47%) of 19 hyperplastic polyps, and five (56%) of nine adenomas. p53 protein nuclear accumulation was detected immunohistochemically in two (22%) of nine adenomas, but not in any of the hyperplastic polyps. CONCLUSION: Some hyperplastic polyps may be true neoplastic lesions, and could be precursors of malignant neoplasia.     

Small early tubular adenomas and mixed colonic polyps found on screening flexible sigmoidoscopy do not predict proximal neoplasia in males.

BACKGROUND & AIMS: Distal colonic adenomas found on flexible sigmoidoscopy are associated with proximal neoplasias, thus requiring a complete colonoscopic examination, but data regarding the association of distal mixed polyps with proximal neoplasia are lacking. We conducted this study to elucidate the significance of distal mixed colonic polyps in predicting proximal neoplasia. METHODS: We retrospectively analyzed data from patients who underwent a flexible sigmoidoscopic examination for colorectal cancer screening and a follow-up colonoscopic examination because of distal colonic polyps. Distal index polyps were classified by a pathologist as early tubular adenoma (ETA), serrated, or true mixed categories. Index polyps also were immunostained with a monoclonal antibody, Adnab-9, a marker for the colorectal adenoma carcinoma sequence. RESULTS: In 636 patients with distal index polyps, 6% were malignant, 55% were adenomas, 13% were ETAs, 6% were serrated, 4% were true mixed, and 17% were hyperplastic. Compared with distal hyperplastic index polyps, distal malignant polyps (P = 0.0006) and adenomas (P = 0.001) were associated with a significantly increased number of synchronous proximal neoplasia, but the small distal mixed, serrated, or ETA did not predict the increased incidence of proximal neoplasia. Large distal polyps of each category were significantly associated with an increased number of synchronous proximal neoplasias. In support of these findings, immunostaining of distal polyps with Adnab-9 showed predictability for proximal neoplasia only in the adenoma category (P < 0.05). CONCLUSIONS: Small ETAs, serrated, or mixed polyps found on flexible sigmoidoscopic examination do not increase the probability of synchronous proximal neoplasia.     

Prevention of colorectal cancer by colonoscopic surveillance in families with hereditary colorectal cancer

OBJECTIVE: In recent years persons at risk for colorectal cancers (CRC) have been subjected to follow-up with colonoscopy in many centres. There is, however, limited knowledge about the effect of such interventions. The objective of this study was to report the results of our observations during the past 15 years. MATERIAL AND METHODS: Healthy persons were included in the study according to their family history of CRCs, and prospectively followed with colonoscopies. RESULTS: Altogether, 1133 individuals were included and observed for a total of 3474 follow-up years from the first to the last colonoscopy initiated by our activity. Mismatch repair (MMR) mutations were detected in 6.5% of cases. A total of 1383 polyps were removed, 72% were less than 5 mm in diameter. Findings were scored as hyperplastic polyps (n=887), adenomas with mild to moderate dysplasia (n=460), adenomas with high-grade dysplasia (n=30) and cancers (n=6). Two cancers were observed after the first colonoscopy, compared with 2.6 expected by chance and more than 20 expected under the hypothesis of predominant inherited diseases in the families. Observed annual incidence rates for adenomas were similar in all groups, while in the mutation carriers there was a higher frequency of progression to severe dysplasia or infiltrating cancer. CONCLUSIONS: A simple explanation for the combined findings may be that all selected families had a similar tendency to produce adenomas, while mutation carriers more frequently demonstrated dysplasia/cancer in the adenomas. The low annual incidence rates for CRC indicated that the removal of adenomas may have prevented cancers.     

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.