结直肠癌筛查发现的7 408例肠道病变临床特征及病理类型分析

目的 探讨结直肠病变患者临床与病理特征,为结直肠癌早期临床诊断与干预提供依据。方法 基于2007至2012年海宁市32万余40～74岁目标人群结直肠癌筛查结果,对筛查检出的肠道病变进行临床特征（包括性别、年龄、大小、部位、形态、数目）及病理类型等分析探讨。结果 共完成初筛286 470例,顺应率88.96％;完成结肠镜检查29 069例,检出肠道病变7 408例,检出率25.48％;男性检出率高于女性（32.62%比19.48%,P＜0.001）;40～49岁组检出率18.30％,70～74岁组检出率35.06％,显示年龄越大检出率越高（P＜0.001）。7 408例肠道病变中,左半结肠约占69.40%,多发性病变占37.23％,＞1.0 cm病变占19.60％。检出结直肠癌205例（早期癌161例、中晚期癌44例）,进展期腺瘤1 365例,早诊率为97.20％。手术切除的5 030例病变病理提示腺瘤型及以上病变所占比重最大（63.00％）。直径＞1.5 cm病变癌变率为34.08%。结论 在高危人群中男性肠道病变检出率明显高于女性,年龄越大检出率越高;病理类型以腺瘤所占比重最高。     

Prognosis in familial non-polyposis colorectal cancer.

Familial cases of non-polyposis colorectal cancer have attracted much interest but little is known of their natural history. Using a population based study we have determined whether a positive family history of bowel cancer is an independent prognostic factor. All patients under 55 years with histologically confirmed colorectal cancer in Northern Ireland during the period 1976-8 were studied. The family history was validated in 95% of all nonpolyposis cases (n = 205). Medical history or cause of death were verified for 98% of 1811 first degree relatives. The strength of the family history was assessed using a score that compares the mortality from bowel cancer in the family against the average population mortality, taking account of family size and age structure. The family history score was not predictive of survival neither in univariate analysis or in a Cox's proportional hazards multivariate analysis controlling for age, sex, stage, site, and duration of symptoms. In conclusion, a positive family history does not independently influence prognosis in patients with bowel cancer.     

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.     

Epidemiology of familial adenomatous polyposis in Finland: impact of family screening on the colorectal cancer rate and survival.

The incidence and prevalence rates of familial adenomatous polyposis (FAP) in Finland between 1961 and 1990 were estimated from Finnish polyposis registry data comprising 81 FAP families, including 251 affected patients. In addition, the effect of family screening on the occurrence of colorectal carcinoma was evaluated by comparing the call up and proband groups and calculating the proportion of FAP among all patients with colorectal carcinoma. The incidence of FAP was 0.62 to 2.38 per million and the prevalence increased steadily from 0.88 to 26.3 million during the study period suggesting improving prognosis. Altogether 76 of 116 probands (65.5%) had colorectal carcinoma compared with only five of 76 call up patients (6.6%). Consequently, the life expectancy of the call up patients was significantly better than that of the probands from the age of 31 years and above. However, at most, 0.53% of all colorectal carcinomas were associated with FAP in 1966-70, and the diminishing frequency of this proportion was more a result of an increase in sporadic colorectal carcinomas in Finland than of family screening for FAP. Family screening is very effective in FAP and must always be undertaken when a new proband is diagnosed.     

Chemical and immunological testing for faecal occult blood in screening subjects at risk of familial colorectal cancer.

BACKGROUND: People with a family history of colorectal cancer have an increased risk of the disease themselves. Many centres are advocating family history screening by endoscopy. AIMS: The performance of chemical and immunological faecal occult blood tests (Haemoccult and Hemeselect) in 212 subjects with a family history of colorectal cancer was assessed. RESULTS: Both Hemeselect and Haemoccult were positive in the only patient with colorectal cancer. Hemeselect was more sensitive than Haemoccult for adenomas (40% compared with 20%) (adenomas larger than 1 cm 75% compared with 50%). No additional abnormality was detected by the addition of Haemoccult or Hemeselect to 60 cm flexible sigmoidoscopy in screening people at lower levels of familial risk. A false positive rate of 16% for Hemeselect resulted in a high proportion of additional colonoscopies in this group. CONCLUSIONS: At present faecal occult blood tests are not sufficiently sensitive or specific to replace endoscopy in screening people at risk of familial colorectal cancer.     

Value of screening of familial adenomatous polyposis for the prevention of colorectal cancer]

Familial adenomatous polyposis coli is a hereditary autosomal dominant disease which spontaneously and inevitably leads to degeneration of colorectal adenomas and requires preventive surgical treatment. The aim of this study was to evaluate the age of colorectal degeneration and the need for a screening technique in family members. Between 1983 and 1989, 141 patients were treated for familial adenomatous polyposis in our surgical center. Mean age at surgery was 32 years and 64 patients (45.4 percent) had a colorectal carcinoma. Thirty had an in situ tumor (mean age: 30 years) and 34 had an invasive adenocarcinoma (mean age: 45 years), 7 of whom died of their cancer. No colonic cancer was found in patients younger than 20. Thirty-eight percent of the patients under 40 years of age, 73 percent of the patients older than 40 years and 81 percent of those older than 50 had an adenocarcinoma. Fifty percent of the patients with carcinoma were younger than 40 years and 7 percent were less than 25 years old. Seventy-one patients were symptomatic at the time of operation (mean age: 40 years), 32 (45 percent) had a colonic cancer. In 70 patients, familial adenomatous polyposis was detected by screening (mean age: 24) and 2.8 percent had a colonic carcinoma. We conclude that the age-related risk of developing colonic carcinoma requires prophylactic surgery in asymptomatic patients before 20 years of age, and that routine familial screening would be of some benefit.     

A practical approach to familial and hereditary colorectal cancer.

Recent genetic research has isolated the primary genetic defect underlying many of the hereditary colorectal cancer syndromes. Obtaining a detailed family history is the first step in identifying individuals at increased risk of developing colorectal cancer. Once identified, individuals and their families may benefit from earlier, more intensified surveillance, prophylactic surgery, cancer risk assessment and education, and genetic testing. Clinicians, especially those with many patients with colorectal cancer in their practice, must be able to address the complex issues associated with the familial and hereditary colorectal cancer syndromes. A well-integrated partnership among colorectal surgeons, gastroenterologists, oncologists, and medical geneticists is necessary to address these complex issues and provide comprehensive medical care.     

Familial colorectal cancer and familial adenomatous polyposis

Familial adenomatous polyposis (FAP) affects around 1 in 10,000 individuals; the gene for this condition was recently shown to be located on chromosome 5, and it is only a matter of time before its precise location and function are determined, making prephenotypic, and even prenatal, diagnosis more generally available and reliable. In the mean time, care of FAP families will continue to depend on careful registration of family information, prophylactic bowel surgery and surveillance for other potentially serious manifestations of the disease. Upper gastrointestinal malignancies and desmoid tumours have overtaken colorectal cancer as the leading causes of death in some centres. Other dominantly-inherited colorectal cancer syndromes produce less striking phenotypes, but affect far more individuals than FAP. It appears that there are two patterns of hereditary non-polyposis colorectal cancer (HNPCC) syndromes, one involving cases of bowel cancer alone, the other associated with breast and gynaecological cancers; these may prove to be variable expressions of a common gene abnormality. More effort is required by clinicians managing cases of colorectal cancer to identify affected families in order to offer surveillance and appropriate treatment in the hope that such measures may prevent cancer in family members.     

Noninvasive colorectal cancer screening

Abnormal mucin with the STn epitope is produced by colorectal cancer cells and is immunologically distinguishable from normal colonic mucin. Herein we describe a technique of detecting abnormal mucin in fecal samples as a method of screening for colorectal neoplasia. Soluble glycoproteins from fecal samples of patients with symptoms of bowel disease and asymptomatic volunteer subjects were isolated by centrifugation and ethanol precipitation. The protein content of the soluble fraction was normalized and tested by immunoassay (slot dot). Anti-COTA monoclonal antibody SP-21, which reacts with STn epitope, was applied in the reaction, and the optical density of each slot dot was determined by imaging densitometer. Quantitative values of samples were determined from the standard curve obtained with highly purified COTA. COTA values >15 g/ml were considered positive for neoplasia. Results indicated that 5/6 colon cancers, 6/22 adenomas, 1/8 colitis cases, and 2/58 normal patients were positive in the test. The pilot study revealed that COTA assay is sensitive and more specific than Hemoccult screening for colorectal neoplasia.     

Hereditary familial non polypoid colorectal cancer

The most common form of hereditary CRC is hereditary non-polyposis colorectal cancer (HNPCC), several mutator genes have been identified in this syndrome. The molecular genetic discoveries are providing news insights into the pathogenesis of CRC. The CRC in Lynch syndrome shows microsatellite instability and it also shows a special histology now referred to as an undifferentiated medullary or solid cribriform carcinoma. This histology is uncommon in various populations. In addition CRC in HNPCC shows an excess of mucoid features as well as peritumoral lymphocyte infiltration and Crohn-like reaction. It is very important to make a diagnosis based on the natural history features of a particular cancer syndrome in combination with a well orchestrated family history. We report the case of a 44 year old man with colon cancer and adenomatous polyps, without family history of adenomatous polyps but with familial antecedent of colon cancer in his father, with a suspicion of Lynch syndrome.     

结直肠癌的遗传异质性与分子分型

结直肠癌中存在明显的遗传异质性,可分为染色体不稳定及微卫星不稳定及甲基化等,不同类型具有不同临床表型,可以依据遗传异质性对结直肠癌进行分子分型。     

Molecular and prognostic heterogeneity of microsatellite-unstable colorectal cancer

Colorectal cancers(CRCs)with a high level of microsatellite instability(MSI-H)are clinicopathologically distinct tumors characterized by predominance in females,proximal colonic localization,poor differentiation,mucinous histology,tumor-infiltrating lymphocytes,a Crohn’s-like lymphoid reaction and a favorable prognosis.In terms of their molecular features,MSI-H CRCs are heterogeneous tumors associated with various genetic and epigenetic alterations,including DNA mismatch repair deficiency,target microsatellite mutations,BRAF mutations,a CpG island methylator phenotype-high(CIMP-H)status,and a low level of genomic hypomethylation.The molecular heterogeneity of MSI-H CRCs also depends on ethnic differences;for example,in Eastern Asian countries,relatively low frequencies of CIMP-H and BRAF mutations have been observed in MSI-H CRCs compared to Western countries.Although the prognostic features of MSI-H CRCs include a favorable survival of patients and low benefit of adjuvant chemotherapy,there may be prognostic differences based on the molecular heterogeneity of MSI-H CRCs.Here,we have reviewed and discussed the molecular and prognostic features of MSI-H CRCs,as well as several putative prognostic or predictive molecular markers,including HSP110 expression,beta2-microglobulin mutations,myosin 1a expression,CDX2/CK20 expression,SMAD4expression,CIMP status and LINE-1 methylation levels.     

Cost-effectiveness of colorectal cancer screening

Colorectal cancer (CRC) screening in France is based on a faecal occult blood test every two years in average risk subjects 50-74 years of age while other endoscopic or non-endoscopic screening methods are used in Europe and in the USA. Beside the reduced incidence of and mortality from CRC found in available studies, cost-effectiveness data need to be taken into account. Because of the delay between randomized controlled trials and clinical results, transitional probabilistic models of screening programs are useful for public health policy makers. The aim of the present review was to promote the implementation of cost-effectiveness studies, to provide a guide to analyze cost-effectiveness studies on CRC screening and, to propose a French cost effectiveness study comparing CRC screening strategies. Most of these trials were performed by US or UK authors and demonstrate that the incremental cost-effectiveness ratio varies between 5 000 and 15 000 US dollars/one year life gained, with wide variations: these results were highly dependent on the unit costs of the different devices as well as the predictive values of the screening tests. Although CRC screening programs have been implemented in several administrative districts of France since 2002, and the results of these randomized controlled trials using fecal occult blood have been updated, cost-effectiveness criteria need to be integrated; especially since the results of screening campaigns based on other tools such as flexible sigmoidoscopy should be available in 2007.