Colonoscopy in patients with a family history of colorectal cancer

Since 1982 it has been the second author's policy to advise all patients who have presented with a positive family history of bowel cancer and who are over the age of 30 years to undergo colonoscopy. In the period to August 1990, 600 such patients had at least one colonoscopy. Colorectal polyps or cancer were detected in 270 patients (45 percent). The incidence was essentially the same for the 171 patients with only second-degree relatives affected (43 percent), for the 194 patients with more than one affected relative (45 percent), and for the 429 patients with an affected first-degree relative (46 percent). Only the 55 patients with more than one affected first-degree relative had a higher incidence (67 percent). The incidence in the 136 totally asymptomatic patients was 36 percent but was 48 percent in the 464 with symptoms. In 37 patients carcinoma was diagnosed. Even in the 30- to 39-year age group there was a 29 percent incidence of polyps or carcinoma. Colonoscopic screening of patients with a family history of bowel cancer compares favorably with mass screening for breast cancer. It is currently advised that all patients over 30 years of age with a family history of colorectal cancer undergo colonoscopy on presentation and, if clear, every four years thereafter unless two first-degree relatives are affected, when it should be every two years.Read in part at the meeting of The American Society of Colon and Rectal Surgeons, Boston, Massachusetts, May 12 to 17, 1991.     

Colonoscopy in patients with a primary family history of colon cancer

Patients with a primary family history of colon cancer were recommended to have full colonoscopy for screening. The results of 125 such patients who also were asymptomatic, had no prior history of neoplasms, and had negative fecal occult blood, showed 15 patients (12 percent) with neoplasms. Only 6 (5.2 percent) had neoplasms that were detectable only by colonoscopy (i.e.,above 55 cm). These results suggest that colonoscopy may not be necessary to screen patients with a primary history of colon cancer.Read at the meeting of The Northeastern Society of Colon and Rectal Surgeons, St. Croix, United States Virgin Islands, November 14 to 18, 1988.     

Variables associated with the risk of colorectal adenomas in asymptomatic patients with a family history of colorectal cancer.

The results of screening individuals referred to the Family Cancer Clinic at St Mark's Hospital from 1986 are presented. Colonoscopy was performed in 644 asymptomatic individuals (from 436 families) with a family history of colorectal cancer. Sixty nine (15.8%) of the families fulfilled the Amsterdam criteria for the hereditary non-polyposis colorectal cancer syndromes (HNPCC). Seven cases of colorectal cancer were diagnosed at an average age of 49 years; six at Dukes's stage A and one at stage C, four in subjects from Amsterdam criteria families. One hundred and forty four (22.4%) subjects had one or more adenomas. The prevalence of adenomas in the subjects from Amsterdam criteria families was 34 of 127 (26.8%) compared with 110 of 517 (21.3%) in those from other families; the age and sex adjusted odds ratio (OR) was 1.76 (p = 0.02). Factors influencing the prevalence of adenomas in screened individuals were evaluated. Multivariate analysis showed that independent variables significantly related to the risk of adenomas were: age (p < 0.0001), sex (p = 0.0002), and the number of generations (> or = 2 v 1) of relatives affected by either colorectal cancer or adenomas (p = 0.0006). The latter variable was more highly predictive of the probability of finding an adenoma at colonoscopy than a family history of two generations with cancer only (p = 0.056). The OR of having colorectal adenomas increased with age, by about twofold for each decade, and was twice as high in men than women, and in subjects with two or more generations relative to those with one generation affected by colorectal cancer or adenomas. Six of seven patients with cancer and 46 of 144 (31.9%) with adenomas had lesions proximal to the splenic flexure only. The proportion of individuals with proximal adenomas only was 47.1% in Amsterdam criteria families and 27.3% in the others (p=0.03). These findings support the view that colonoscopy rather than sigmoidoscopy is the method of choice for screening high risk groups.     

Colonoscopy surveillance of individuals at risk of familial colorectal cancer

BACKGROUND: Individuals with first degree relatives affected with colorectal cancer (CRC) at a young age, or more than one relative affected but who do not fulfil the Amsterdam criteria for a diagnosis of hereditary non-polyposis colon cancer (HNPCC), are believed to be at an increased risk of CRC. However, there is a paucity of prospective data on the potential benefit of colonoscopic surveillance in such groups categorised by empiric family history criteria. We report a prospective study of 448 individuals seeking counselling about their perceived family history of CRC. PATIENTS AND METHODS: Following pedigree tracing, verification, and risk assignment by genetic counsellors, colonoscopy was undertaken for those at a moderate or high risk (HNPCC). Those classified as low risk were reassured and discharged without surveillance. Here we report our findings at the prevalence screen in the 176 patients of the 448 assessed who underwent colonoscopy. RESULTS: Fifty three individuals had a family history that met Amsterdam criteria (median age 43 years) and 123 individuals were classed as moderate risk (median age 43 years). No cancers were detected at colonoscopy in any group. Four individuals (8% (95% confidence limits (CL) 0.4-15%)) in the high risk group had an adenoma detected at a median age of 46 years and all four were less than 50 years of age. Five (4% (95% CL 0.6- 8%)) of the moderate risk individuals had an adenoma at a median age of 54 years, two of whom were less than 50 years of age. CONCLUSIONS: These findings indicate that the prevalence of significant neoplasia in groups defined by family history is low, particularly in younger age groups. These prospective data call into question the value of colonoscopy before the age of 50 years in moderate risk individuals.     

Colonoscopic screening of asymptomatic patients with a family history of colon cancer

The records of 201 asymptomatic patients who underwent colonoscopy based solely on a family history of colon cancer were reviewed. Eighty-five patients (42 percent) had a total of 166 lesions. Fifty-four (27 percent) patients of the screened population had neoplastic lesions, while 31 (15 percent) patients had nonneoplastic polyps. Four carcinomas were found. Twenty-five of the patients with polyps (29 percent) had no polyps distal to the splenic flexure; these proximal polyps (and two carcinomas) would have been missed on screening with fiberoptic sigmoidoscopy. Nineteen of these 25 patients had polyps smaller than 0.5 cm, which likely would have been missed with contrast enemas. Almost one half (47 percent) of all polyps discovered at screening colonoscopy were proximal to the descending colon. Only one patient younger than 40 years old had adenomas. The yield of polyps and cancer in patients with familial risk indicates screening colonoscopy should be considered after age 40.Read at the meeting of The American Society of Colon and Rectal Surgeons, Toronto, Canada, June 11 to 16, 1989. This paper received the Harry E. Bacon Foundation award.     

Race and colorectal cancer screening compliance among persons with a family history of cancer

AIM: To determine compliance to colorectal cancer (CRC) screening guidelines among persons with a family history of any type of cancer and investigate racial differences in screening compliance.METHODS: We used the 2007 Health Information National Trends Survey and identified 1094 (27.4%) respondents (weighted population size = 21959672) without a family history of cancer and 3138 (72.6%) respondents (weighted population size = 58201479) with a family history of cancer who were 50 years and older. We defined compliance with CRC screening as the use of fecal occult blood testing within 1 year, sigmoidoscopy within 5 years, or colonoscopy within 10 years. We compared compliance with CRC screening among those with and without a family member with a history of cancer.RESULTS: Overall, those with a family member with cancer were more likely to be compliant with CRC screening (64.9% vs 55.1%; OR = 1.45; 95%CI: 1.20-1.74). The absolute increase in screening rates associated with family history of cancer was 8.2% among whites. Hispanics had lowest screening rates among those without family history of cancer 41.9% but had highest absolute increase (14.7%) in CRC screening rate when they have a family member with cancer. Blacks had the lowest absolute increase in CRC screening (5.3%) when a family member has a known history of cancer. However, the noted increase in screening rates among blacks and Hispanics when they have a family member with cancer were not higher than whites without a family history of cancer: (54.5% vs 58.7%; OR = 1.16; 95%CI: 0.72-1.88) for blacks and (56.7% vs 58.7%; OR = 1.25; 95%CI: 0.72-2.18) for Hispanics.CONCLUSION: While adults with a family history of any cancer were more likely to be compliant with CRC screening guidelines irrespective of race/ethnicity, blacks and Hispanics with a family history of cancer were less likely to be compliant than whites without a family history. Increased burden from CRC among blacks may be related to poor uptake of screening among high-risk groups.     

Is colonoscopic screening appropriate in asymptomatic patients with family history of colon cancer?

Colonoscopy has been advocated by some investigators as the most appropriate means of screening asymptomatic patients with a positive family history of colorectal cancer. However, results of such screening have been widely disparate. The purpose of this study was to evaluate the yield of colonoscopy in a cohort of completely asymptomatic individuals with one or two first-degree relatives with a history of colorectal cancer and to compare this yield with that of colonoscopy in a group of patients with apparent anal bleeding. Patients with possible genetic disorders, such as familial polyposis, were excluded. A total of 160 asymptomatic patients and a comparison group of 137 patients with nonacute anorectal bleeding underwent colonoscopy. Colonoscopy was completed in 143 of the 160 study patients (89 percent) and in all of the comparison patients and did not result in any complications. Twenty-two adenomas were found in 17 study patients (10.6 percent); 16 of the 22 adenomas were less than 1 cm in size. In the comparison group, eight adenomas were identified (5.8 percent of patients). No cancers were identified. The difference in polyp frequency between groups was not significant. The relatively low yield of colorectal neoplasms discovered at colonoscopy in this study may in part be due to the small sample size or to the strict criteria used to define these asymptomatic patients but does not lend strong support to the notion that colonoscopy is an appropriate first step in screening the asymptomatic patient with one or two first-degree relatives with colon cancer.     

Histological patterns of gastritis in H. pylori-infected individuals with a family history of gastric cancer

OBJECTIVE: Different types of chronic gastritis, including antral predominant, corpus predominant, and multifocal pangastritis, are associated with Helicobacter pylori infection. Specific patterns of H. pylori gastritis that might characterize individuals with family histories of noncardia gastric cancer (GC) were investigated. METHODS: Histopathological changes associated with H. pylori gastritis were assessed in 111 individuals with family histories of GC and in 77 without from a region with high prevalence of H. pylori infection and GC. Gastric biopsies were taken from 12 sites (antrum, five; corpus, six; and cardia, one). RESULTS: Individuals (age < 36 yr) with family histories of GC developed pangastritis and had higher H. pylori bacterial scores (p < 0.05) in the gastric corpus, whereas those without family histories of GC typically had antral predominant gastritis. The correlation between density of polymorphonuclear leukocytes and density of H. pylori at each biopsy site was statistically significant (p < 0.01). Pangastritis was associated with a higher density of lymphoid aggregates and follicles (p < 0.05) in the corpus of younger individuals (age < 36) and in the antrum of older individuals (age > or = 48) with positive family histories of GC. CONCLUSIONS: Pangastritis and high lymphoid follicle density associated with H. pylori infection were found in patients with family histories of GC. Because a family history of gastric carcinoma is associated with increased risk of gastric cancer development, characterization of histological patterns of gastritis may be applicable to gastric cancer screening and surveillance, especially in relatively young at-risk populations.     

Yield from colonoscopic screening in people with a strong family history of common colorectal cancer

BACKGROUND AND AIMS: People with a strong family history of common (so-called 'sporadic') colorectal cancer are generally advised to undergo colonoscopic screening, but the starting age for this is unclear. An audit was performed to study the age-related yield of screening colonoscopy in this risk group. METHODS: A prospective audit of the outcome of screening colonoscopy was performed on a cohort of 232 people with a strong family history of common colorectal cancer. All were registrants in a familial bowel cancer service solely because of their family medical history. They had no bowel symptoms and no prior endoscopic investigation of the large bowel. RESULTS: Neoplastic lesions were detected by using colonoscopy in 33 participants. In 27 participants, the major lesion was a small tubular adenoma, four had an advanced adenoma and two had cancer. More neoplastic (P= 0.02) and advanced neoplastic (P= 0.03) lesions were found in those patients aged > or = 50 years. Only one advanced adenoma was detected in a participant below the age of 50 years. CONCLUSION: The yield from screening colonoscopy in young people (< 50 years) with a strong family history of common colorectal cancer is low, placing doubt on the need for colonoscopic screening before the age of 50 years.     

Accuracy of reporting of family history of colorectal cancer

BACKGROUND AND AIMS: Family history is used extensively to estimate the risk of colorectal cancer but there is considerable potential for recall bias and inaccuracy. Hence we systematically assessed the accuracy of family history reported at interview compared with actual cancer experience in relatives. METHODS: Using face to face interviews, we recorded family history from 199 colorectal cancer cases and 133 community controls, totalling 5637 first and second degree relatives (FDRs/SDRs). We linked computerised cancer registry data to interview information to determine the accuracy of family history reporting. RESULTS: Cases substantially underreported colorectal cancer arising both in FDRs (sensitivity 0.566 (95% confidence interval (CI) 0.433, 0.690); specificity 0.990 (95% CI 0.983, 0.994)) and SDRs (sensitivity 0.271 (95% CI 0.166, 0.410); specificity 0.996 (95% CI 0.992, 0.998)). There was no observable difference in accuracy of reporting family history between case and control interviewees. Control subjects similarly underreported colorectal cancer in FDRs (sensitivity 0.529 (95% CI 0.310, 0.738); specificity 0.995 (95% CI 0.989, 0.998)) and SDRs (sensitivity 0.333 (95% CI 0.192, 0.512); specificity 0.995 (95% CI 0.991, 0.995)). To determine practical implications of inaccurate family history, we applied family history criteria before and after record linkage. Only two of five families reported at interview to meet surveillance criteria did so after validation, whereas only two of six families that actually merited surveillance were identified by interview. CONCLUSIONS: This study has quantified the inaccuracy of interview in identifying people at risk of colorectal cancer due to a family history. Colorectal cancer was substantially underreported and so family history information should be interpreted with caution. These findings have considerable relevance to identifying patients who merit surveillance colonoscopy and to epidemiological studies.     

Colonoscopy as a screening test for colorectal cancer

Colonoscopy is the current gold standard for the diagnosis and treatment of colorectal neoplasms. Several gastroenterological and/or endoscopical societies recommend screening by colonoscopy in high risk patients for colorectal cancer whilst for average risk patients colonoscopy remains a valid option. In some countries screening colonoscopy is now covered by medical insurance. It is also the final common pathway of all colorectal cancer screening methods. This paper addresses the advantages and also limitations of colonoscopy as the first procedure for colorectal screening and emphasizes the importance of organized training and continuous assessment of competence of gastroenterologists and the necessity to have quality control audits of the endoscopy units.     

Screening for hemochromatosis in asymptomatic subjects with or without a family history

BACKGROUND: Hemochromatosis in white subjects is mostly due to homozygosity for the common C282Y substitution in HFE. Although clinical symptoms are preventable by early detection of the genetic predisposition and prophylactic treatment, population screening is not currently advocated because of the discrepancy between the common mutation prevalence and apparently lower frequency of clinical disease. This study compared screening for hemochromatosis in subjects with or without a family history. METHODS: We assessed disease expression by clinical evaluation and liver biopsy in 672 essentially asymptomatic C282Y homozygous subjects identified by either family screening or health checks. We also observed a subgroup of untreated homozygotes with normal serum ferritin levels for up to 24 years. RESULTS: Prevalence of hepatic iron overload and fibrosis were comparable between the 2 groups. Disease-related conditions were more common in male subjects identified by health checks, but they were older. Hepatic iron overload (grades 2-4) was present in 56% and 34.5% of male and female subjects, respectively; hepatic fibrosis (stages 2-4) in 18.4% and 5.4%; and cirrhosis in 5.6% and 1.9%. Hepatic fibrosis and cirrhosis correlated significantly with the hepatic iron concentration, and except in cases of cirrhosis, there was a 7.5-fold reduction in the mean fibrosis score after phlebotomy. All subjects with cirrhosis were asymptomatic. CONCLUSIONS: Screening for hemochromatosis in apparently healthy subjects homozygous for the C282Y mutation with or without a family history reveals comparable levels of hepatic iron overload and disease. Significant hepatic fibrosis is frequently found in asymptomatic subjects with hemochromatosis and, except when cirrhosis is present, is reversed by iron removal.     

The role of colonoscopy in screening persons with family history of colorectal cancer

Abstract First-degree relatives of colorectal cancer patients are at increased risk for developing colorectal neoplasms. In order to assess the potentiality of colonoscopy screening in this high-risk population, 213 asymptomatic family members (age range 30-69 years, mean 42.8 years) of those patients with colorectal cancer received colonoscopic examination at Chang-Gung Memorial Hospital from April 1992 to May 1994. Twenty-eight persons with 42 lesions (polyps or cancer) were identified, including 28 adenomas, nine hyperplastic polyps and five adenocarcinomas. The positive detection rate was 9.9% for adenoma and 2.3% for cancer. Colorectal neoplasms afflicted males more frequently than females (16.7 vs 5.7%, P < 0.05) and occurred less frequently in those < 40 years of age (5.5 vs 17.2%, P < 0.05). Forty-two per cent of the detected neoplastic lesions were beyond the reach of 60 cm flexible sigmoidoscopy and 36% of adenomas were < 0.5 cm in size and would be missed if patients were screened by air contrast barium enema. Cost analysis revealed that the charges of both screening colonoscopy and screening flexible sigmoidoscopy/air contrast barium enema were approximate. Colonoscopy also has a high acceptability and safety. It appears appropriate to use colonoscopy, rather than flexible sigmoidoscopy or air contrast barium enema, as an initial screening procedure for persons with a family history of colorectal cancer, especially those > 40 years of age.     

大肠癌术后患者结肠镜随访检查的意义

目的 通过大肠镜检查在临床的广泛应用,防止和降低多原发大肠癌的发生.方法 分析1986年6月至2007年6月大肠癌外科术后进行无症状定期结肠镜随访2762例患者的资料,随访方法为术后3～6个月内首次肠镜检查,以后每年1次,连续3年.并与1981年9月至1986年5月大肠癌术后有症状者结肠镜复查的218例资料进行对比.结果 2762例中发现多原发癌48例,其中同时多原发癌39例(1.4%),异时多原发癌9例(0.3%);TNM分类Ⅰ期癌6例,Ⅱ期癌31例,Ⅲ期癌11例.发现腺瘤583例(21.1%),病理检查证实17例(3.2%)为浸润性早期癌,58例(9.9%)为高级别上皮内瘤变.218例有症状检查者共发现多原发癌27例(12.4%),明确Ⅰ期癌4例,Ⅱ期癌6例,Ⅲ期癌16例.发现腺瘤29例(13.3%).结论 无症状定期结肠镜随访检查发现多原发癌明显低于有症状者,发现的早期癌、腺瘤比例高,说明无症状定期检查,能防止和降低多原发大肠癌的发生.     

Association between family history and mismatch repair in colorectal cancer

BACKGROUND AND AIMS: Germline mutations in mismatch repair (MMR) genes cause a greatly increased risk of cancer of the gastrointestinal and female reproductive tracts (hereditary non-polyposis colorectal cancer (HNPCC)). Loss of MMR expression is common in colorectal cancer (CRC) overall. Such loss is assumed to be acquired predominantly, although a population of CRC cases will include individuals with unrecognised MMR mutations. This study examines the association between MMR gene expression and family history of cancer among the CRC population. METHODS: Individuals with CRC were identified from two well characterised populations: (1) consecutive hospital patients (n = 644) and (2) a population based cases series (n = 249). CRC was examined for expression of hMLH1 and hMSH2 using immunohistochemistry, and expression was related to family history using logistic regression. RESULTS: hMLH1 and hMSH2 expression was assessed in 732 CRCs with 8% showing loss of expression. No association was seen overall for hMLH1 or hMSH2 expression and family history of CRC. Loss of hMSH2 was predicted by family history of extracolonic cancer (odds ratio (OR) 5.78 (95% confidence interval (CI) 0.95-35.18)) and family history suggestive of HNPCC (OR 27.84 (95% CI 4.37-177.56)). Loss of hMLH1 was not predicted by family history of extracolonic cancer or a family history suggestive of HNPCC but was for a family history of at least two affected relatives (OR 4.88 (95% CI 1.25-19.03)). CONCLUSIONS: Individuals with hMSH2 deficient CRC in the general population exhibit a family history and other characteristics suggestive of HNPCC, and may carry germline MMR mutations. Loss of hMLH1 is only associated with a strong family history of extracolonic cancer at older ages, suggesting a novel mechanism of susceptibility.     

Frequency of replication errors in colorectal cancer and their association with family history

Background—Replication errors (RERs) characterisetumours of hereditary non-polyposis colorectal cancer (HNPCC). RERstatus may therefore improve identification of such families previously diagnosed by family history alone.
Aims—To assess RER and HNPCC frequency within apopulation of colorectal cancer patients and a regional population offamily history defined (Amsterdam criteria) HNPCC families.
Methods—Family history was assessed by personalinterview in a population of 479 patients with colorectal cancerattending one follow up clinic. Seven fluorescently labelledmicrosatellites were used to investigate RER frequency in colorectalcancers from 89 patients of this population with varying degrees offamily history and 20 Amsterdam criteria positive families (four with aknown germline mutation, 16 with unknown mutation status) from theregional population.
Results—Only four of the follow up population(0.8%) came from families meeting the Amsterdam criteria with only oneshowing RERs. The frequency of RERs was similar in the early onsetcancer group (less than 50 years of age), those with a family history, and those with no family history of colorectal cancer. From the regional population, RERs were identified in 4/4 families with amutation but only 8/16 families with unknown mutation status.
Conclusions—No correlation was seen between RERstatus and strength of family history except in HNPCC families. Resultsalso indicate that half of the Amsterdam criteria defined families donot exhibit RERs, perhaps suggesting a different mechanism of tumorigenesis.

Keywords:hereditary non-polyposis colorectal cancer; replication errors