High Risk For Colorectal Neoplasia Research Articles

Investigation of the Birt–Hogg–Dubé tumour suppressor gene (FLCN) in familial and sporadic colorectal cancer

BackgroundBirt–Hogg–Dubé (BHD) syndrome is an autosomal dominant multisystem disorder with skin (fibrofolliculomas or trichodiscomas), lung (cysts and pneumothorax) and kidney (renal cell carcinoma) tumours. Although colorectal neoplasia was reported initially...

Nonlaxative PET/CT Colonography: Feasibility, Acceptability, and Pilot Performance in Patients at Higher Risk of Colonic Neoplasia

CT colonography without bowel preparation is a safer and better-tolerated alternative to full laxation protocols, but comparative sensitivity and specificity are potentially reduced. Uptake of (18)F-FDG by colonic neoplasia is well described, and combining PET with nonlaxative CT colonography could improve accuracy. The purpose was to prospectively test the technical feasibility and acceptability of combined nonlaxative PET/CT colonography in patients at higher risk of colorectal neoplasia and to provide pilot data on diagnostic performance. Fifty-six patients (median age, 64 y; 30 women) at high risk of colonic neoplasia underwent nonlaxative PET/CT colonography with barium fecal tagging within 2 wk of scheduled colonoscopy. Colonic segmental distension was graded 1 (poor) to 3 (good). A radiologist, experienced in CT colonography, and nuclear medicine physician in consensus analyzed the datasets. The diagnostic performance for standalone CT colonography and combined PET/CT colonography was compared with the reference colonoscopy. Patient experience for 25 items (each scored from 1 to 7) pertaining to satisfaction, worry, and physical discomfort was canvassed after both PET/CT colonography and colonoscopy. Distension was good in 298 of 334 segments (89%; 95% confidence interval [CI], 85%-92%). Patients experienced more physical discomfort during colonoscopy (median, 4; interquartile range [IQR], 2-7) than during PET/CT colonography (median, 5; IQR, 3-7; P = 0.03) and were more willing to undergo PET/CT colonography again (36/43 [84%; 95% CI, 73%-95%] vs. 31/43 [72%; 95% CI, 59%-86%]; P = 0.001). Twenty-one patients had 54 polyps according to colonoscopy (10 with at least 1 polyp >or=6 mm and 8 with at least 1 polyp >or=10 mm). Of 14 polyps 6 mm or greater, 12 (86%; 95% CI, 67%-100%) were (18)F-FDG-avid, including all those 10 mm or greater (mean standardized uptake value, 10.1). CT colonography sensitivity for polyps 6 mm or larger was 92.9% (95% CI, 79.4%-100%) and was not improved by the addition of PET. However, combined PET/CT colonography review improved per-patient positive predictive value for a polyp 10 mm or greater from 73% (95% CI, 39-92) to 100% (95% CI, 60-100). In this feasibility study, simultaneous PET acquisition during nonlaxative CT colonography is technically feasible, is well tolerated, and potentially improves specificity.

T1310 Almost One Half of Inflammatory Bowel Disease (IBD) Patients at High Risk of Colorectal Neoplasia Do Not Undergo Endoscopic Surveillance: A Clinical Practice Study Nested in the CESAME Cohort

T1310 Almost One Half of Inflammatory Bowel Disease (IBD) Patients at High Risk of Colorectal Neoplasia Do Not Undergo Endoscopic Surveillance: A Clinical Practice Study Nested in the CESAME Cohort

Abstract 1851: Investigation of the Birt-Hogg-Dubé tumour suppressor gene (FLCN) in familial and sporadic colorectal cancer

Abstract Birt-Hogg-Dubé (BHD) syndrome is an autosomal dominant multisystem disorder with skin (fibrofolliculomas or trichodiscomas), lung (cysts and pneumothorax) and kidney (renal cell carcinoma) tumours. Although colorectal neoplasia was reported initially to be part of the BHD phenotype, some recent studies have not confirmed this association. We undertook a series of clinical and laboratory studies to investigate possible relationships between colorectal neoplasia and the BHD gene (FLCN). Thus we investigated whether individuals with familial colorectal cancer of unknown cause might have unsuspected germline FLCN mutations, looked for somatic FLCN C8 tract mutations in microsatellite unstable sporadic colorectal cancers and assessed the risk of colorectal neoplasia and possible genotype-phenotype correlations in BHD patients. Although we found previously that germline FLCN mutations can be detected in ∼5% of patients with familial renal cell carcinoma, we did not detect germline FLCN mutations in 50 patients with familial non-syndromic colorectal cancer. Analysis of genotype-phenotype correlations for two recurrent FLCN mutations identified in a subset of 51 families with BHD demonstrated a significantly higher risk of colorectal neoplasia in c.1285dupC mutation (within the exon 11 C8 mononucleotide tract) carriers than in c.610delGCinsTA mutation carriers (χ2=5.78 P=0.016). Somatic frameshift mutations in the FLCN exon 11 C8 mononucleotide tract were detected in 23% of sporadic colorectal cancers with microsatellite instability suggesting that FLCN inactivation might contribute to colorectal tumourigenesis. Our findings suggest that the previously reported clinical heterogeneity for colorectal neoplasia may reflect allelic heterogeneity and the risk of colorectal neoplasia in BHD syndrome requires further investigation. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1851.

Comparison of the Detection Rate of Colorectal Neoplasia by Colonoscopy in Average-Risk Patients Ages 40-49 vs. 50-59 Years

Purpose: The USPSTF recommendations for the prevention of colorectal cancer to begin screening at age of 50 are based on data which shows an increased incidence of colorectal cancer during the sixth decade. However, a recent study of colonoscopy in average risk individuals showed a similar prevalence in colorectal adenomas among individuals aged 40-49 compared with those aged 50-59. The aim of our study was to assess the rate of colorectal neoplasia by age detected during colonoscopy among average risk patients. Methods: In this retrospective review, we included consecutive patients ages 40-59 undergoing their first colonoscopy from 2004 to 2008 for a total of 994 colonoscopies (247 ages 40-49, 747 ages 50-59). We excluded colonoscopies that did not reach the cecum and any patients at an increased risk for colorectal cancer. The primary endpoint was the prevalence of colorectal neoplasia by age. Secondary endpoints included the prevalence of colorectal neoplasia by gender, ethnicity and BMI. Results: Among patients aged 40-49 the prevalence of colorectal neoplasia was 12.1% (30 patients with adenomas, 5 with advanced polyps, no cancers). Patients aged 50-59 had a 22.6% prevalence of colorectal neoplasia (168 patients with adenomas, 39 with advanced polyps, 3 with cancer). Compared with individuals aged 40-49 there was a significantly higher prevalence of adenomas in individuals aged 50-59 (χ2=12.72, p=0.0004) as well as advanced adenomas and cancer (χ2=5.73, p=0.01). After adjusting for gender, race and BMI the effect of age remained statistically significant (OR 0.5, p=0.001, 95% CI 0.32-0.76). Higher BMI was associated with an increased risk of colorectal neoplasia (OR 1.03, p=0.02, 95% CI 1.00-1.06). Conclusion: We found the prevalence of colorectal neoplasia among patients aged 40-49 to be 12% which is similar to the published literature. There was a statistically significant higher prevalence of adenomas and advanced adenomas including cancer among individuals aged 50-59. The validity of these results is supported by our adenoma detection rate in patients aged 50-59 which is in line with recommended standards. After adjusting for gender, race and BMI the probability of having a lesion detected was 50% higher in the group aged 50-59. The number needed to screen to detect one additional advanced lesion in the 40-49 age group was 50 compared to a number of 19 in those aged 50-59. Increasing BMI was also associated with a higher risk of colorectal neoplasia. We conclude that individuals aged 40-49 have a lower but measurable risk for colorectal neoplasia compared to those aged 50-59 and that screening guidelines should be modified in conjunction with other factors such as gender, race and BMI.

Avaliação do desempenho da colonografia tomográfica computadorizada (colonoscopia virtual) no diagnóstico de pólipos colorretais

Computed tomographic colonography has been proposed for detection of colorectal polyps instead of colonoscopy in colorectal cancer screening programs. To evaluate the performance of computed tomographic colonography in the detection of colorectal polyps with colonoscopy used as the gold standard. We prospectively studied 20 patients at high risk for colorectal neoplasia (14 men and 6 women; mean age, 55 years and 59 years). Computed tomographic colonography was performed immediately before colonoscopy. We inserted a rectal balloon catheter and insufflated the colon with room air to the level that a good distension was observed. Twenty milligrams of hioscin was given immediately before computed tomographic imaging of the abdomen and pelvis in order to minimize the degree of smooth-muscle spasm and peristalsis and to reduce the patient's discomfort. Computed tomographic colonography images were considered satisfactory in all cases. Colonoscopy detected 85 polyps in 19 of 20 patients (95%). All the observed polyps were successfully removed and examined histologically. The radiological examination correctly identified 8 of 10 polyps 10 mm or more in diameter, 2 of 19 (18,2%) with 5-9 mm, and just 1 of 53 <5mm (9,1%). Seventeen of the 43 adenomatous polyps were > or =5 mm. Eight (47%) were correctly identified on computed tomographic colonography. None of the neoplasias <5 mm were identified on colonography. Nineteen patients preferred colonoscopy in the event of having to repeat on of the two examinations. For the detection of colorectal polyps, computed tomographic colonography seems to be useful only when the result is positive, as the negative results of this examination cannot eliminate the presence of these lesions.

Sporadic Duodenal Adenoma and the Association With Colorectal Neoplasia: A Case-Control Study

Sporadic duodenal adenomas are an uncommon finding. It is not clear whether patients with sporadic duodenal adenoma have a greater risk for colorectal neoplasia and should undergo colonoscopy. The aims of the present study were to estimate the prevalence of colorectal neoplasia in patients with sporadic duodenal adenoma, and to compare colorectal neoplasia rates in patients with sporadic duodenal adenomas versus those without them. A retrospective case-control study was conducted to identify sporadic duodenal adenoma patients using the databases of two academic and one regional hospital in the Netherlands. Colonoscopic findings in the sporadic duodenal adenoma patients were compared with those of a control group of patients who underwent both gastroduodenoscopy and colonoscopy. Furthermore, the frequency of colorectal cancer in the sporadic duodenal adenoma patients was compared with the population incidence of colorectal cancer. During the period 1991-2006, 102 patients in total with sporadic duodenal adenomas were identified. Colonoscopy was performed in 49 patients (48%), and colorectal neoplasia was present in 21 of these patients (43%). There was a significantly higher rate of both colorectal neoplasia (43%vs 17%, odds ratio [OR] 3.6, 95% confidence interval [CI] 1.7-7.4) and advanced colorectal adenoma (18%vs 3%, OR 7.8, 95% CI 2.1-29.4) in the patients with sporadic duodenal adenoma compared to that in the control group. Also, the incidence of colorectal cancer was higher in sporadic duodenal adenoma patients compared to that in the population (P= 0.02). Individuals with sporadic duodenal adenomas appear to be at a significantly higher risk of colorectal neoplasia, and therefore should undergo colonoscopy.

Review article: the relevance of surveillance endoscopy in long‐lasting inflammatory bowel disease

Development of colitis-associated colorectal cancer is an important clinical problem in patients with colonic inflammatory bowel disease (IBD). British and American guidelines recommend to start surveillance after a disease duration of 8-10 or 15-20 years for patients with extensive or left-sided colitis, respectively. To assess the evidence level of current surveillance strategies. A PubMed-based literature search using the search terms inflammatory bowel disease, ulcerative colitis, Crohn's disease, dysplasia, colorectal cancer and surveillance was performed. Low-grade and high-grade dysplastic lesions progress to cancer in a high percentage of patients. Furthermore, concurrent cancer is found in approximately one-third of the patients with colonic dysplasia. Low-level evidence showing reduced colorectal cancer-related mortality in patients who were undergoing surveillance is available. Patients with concomitant primary sclerosing cholangitis form a subgroup of IBD patients with an even higher risk of colorectal neoplasia. Colonic surveillance prolongs life expectancy of patients with long-lasting IBD.

Diagnostic performance of computed tomography colonography in symptomatic patients and in patients with increased risk for colorectal disease

To evaluate the diagnostic performance (colorectal lesions) of computed tomography (CT) colonography in 111 patients, a majority of whom were at high risk for colorectal neoplasia. After bowel preparation, CT colonography was performed, immediately followed by conventional colonoscopy. The diagnostic performance of CT colonography was analyzed relative to lesion size, histological diagnosis, and diagnostic certainty. The sensitivity of CT colonography increased with lesion size (P<0.001), and was 91% (21/23) for lesions > or = 10 mm. All 10 carcinomas and 86% (19/22) of adenomas > or = 5 mm were detected. Unconfirmed or false-positive CT findings were generally small and/or reported with low diagnostic certainty. The specificity of CT colonography would be 45% (30/66; 95% CI 34% to 57%) if patients with findings of any size and any diagnostic certainty were selected for follow-up, and 92% (85/92; 95% CI 85% to 96%) if only patients with CT findings > or = 10 mm classified as certain were selected. CT colonography had a high sensitivity for lesions > or = 5 mm. The diagnostic performance increased with lesion size and degree of diagnostic certainty, and was higher for adenomas.

Recent advances in chromoscopic colonoscopy and endomicroscopy

The basic rationale for secondary prevention of colorectal carcinoma is by endoscopic polypectomy. New technologies in the form of high-magnification or "zoom" colonoscopy complemented by chromoscopic agents permit early detection of neoplastic colorectal lesions, particularly flat and depressed types. Detailed morphologic characteristics of the surface crypt or "pit pattern" can be obtained with these techniques, enabling an in vivo "optical biopsy" and staging tool. Establishing suitability for endoscopic resection or surgical excision can be enhanced using these techniques. Furthermore, chromoscopic colonoscopy may have a role in routine endoscopic colorectal cancer surveillance programs in patients at high risk for colorectal neoplasia, such as those with long-standing ulcerative colitis and familial colorectal cancer syndromes. This review summarizes recent data regarding the prevalence and histopathologic characteristics of flat and depressed colorectal lesions in Western cohorts and describes how their detection and management can be improved by chromoscopy and magnification technology. We outline these techniques from a clinical perspective and describe the basic principles of endoscopic mucosal resection.

Colonic Perforation at CT Colonography: Assessment of Risk in a Multicenter Large Cohort

To assess retrospectively the incidence, clinical features, and treatment of colonic perforation at computed tomographic (CT) colonography in a large multicenter cohort. The study was performed in accordance with the institutional ethics committees' requirements of a retrospective review in each of the participating centers, and no informed consent was required. A review of all patients who underwent CT colonography between January 2001 and December 2004 in 11 medical centers representing more than 95% of studies performed in a single country was performed to determine the rate of colorectal perforation. Data about patient demographics and patient- and procedure-related risk were recorded. Information about the location of the perforation, its likely mechanism, and treatment was collected. Analysis included calculation of rates of colonic perforation and surgical treatment and of 95% confidence intervals. A total of 11 870 CT colonographic studies were performed in 6837 (57.6%) men and 5033 (42.4%) women (mean age, 59.9 years; range, 38-90 years) with seven cases of colorectal perforation, yielding a risk rate of 0.059% (one of 1696 studies; 95% confidence interval: one of 974, 971 of 6537). The mean age of the patients with perforation was 77.8 years. Six (84%) of seven cases of perforation occurred in symptomatic patients at high risk for colorectal neoplasia, and one (16%) occurred in an asymptomatic average-risk patient. All studies were performed after insufflation of room air. Six (84%) cases of perforation occurred in patients in whom a rectal tube was inserted, and in five of them, a balloon was inflated. Five (71%) cases of perforation occurred in the sigmoid colon; and two (29%), in the rectum. Four (57%) patients (one in 2968 patients; 95% confidence interval: 1.5 in 10 000, 14.7 in 10 000) required surgical treatment. Possible factors that contributed to perforation were left inguinal hernia containing colon (n = 4), severe diverticulosis (n = 3), and obstructive carcinoma (n = 1). Perforation of the colon and rectum is a rare complication of CT colonography. Older age and underlying concomitant colonic disease were present in patients with perforation.

Practical Uses of Chromoendoscopy and Magnification at Colonoscopy

New technologies in the form of high-magnification or zoom colonoscopy complemented by chromoscopic agents permits early detection of neoplastic colorectal lesions, particularly flat and depressed types. Establishing suitability for endoscopic resection or surgical excision can be enhanced using these techniques. Chromoscopic colonoscopy may play an important role in the routine endoscopic colorectal cancer surveillance programs in patients assuming a high risk of colorectal neoplasia. This article summarizes recent data regarding the prevalence and histopathologic characteristics of flat and depressed colorectal lesion in Western cohorts and describes how their detection and management can be improved by chromoscopy and magnification technology. The techniques required for chromoscopic colonoscopy and magnification imaging are outlined along with a review of the literature on these subjects.

XRCC2 and XRCC3 Polymorphisms Are Not Associated with Risk of Colorectal Adenoma

The XRCC2 and XRCC3 proteins participate in homologous recombination and DNA double-strand break repair to maintain chromosomal stability. Coding-region variants in XRCC2 (Arg188His) and XRCC3 (Thr241Met) have been associated with cancers at several sites (1-3). The XRCC3 241Met homozygous variant has also been associated with increased DNA adduct levels, suggesting a role for this protein in repairing DNA adducts (2).We assessed the association between XRCC2 R188H, XRCC3 T241M, and two intronic XRCC3 polymorphisms and risk of colorectal adenoma in two case-control studies nested in the Nurses' Health Study (NHS) and the Health Professionals Follow-up Study (HPFS) cohorts. We hypothesize that XRCC2 and XRCC3 polymorphisms modify risk of colorectal adenoma associated with smoking and alcohol intake; both established risk factors for colorectal adenoma (4). In addition, we examine the XRCC2 and XRCC3 polymorphisms and their potential interaction with plasma and dietary folate in relation to risk of colorectal adenoma.Detailed information about the design of the NHS (cases, n = 556; controls, n = 557) and HPFS (cases, n = 376; controls, n = 725) nested case-control studies has been published previously (4). Genotyping of coding region XRCC2 R188H (rs3218536) and XRCC3 T241M (rs861539), and intronic XRCC3 A&gt;G 4541 (rs1799794) and XRCC3 A&gt;G 17893 (rs1799796) single nucleotide polymorphisms was carried out using the TaqMan allelic discrimination system (Applied Biosystems, Foster City, CA). Plasma folate was measured for some of the NHS nested case-control participants (cases, n = 345; controls, n = 333) (5). Odds ratios and 95% confidence intervals were calculated using conditional and unconditional logistic regression and were adjusted for established colorectal cancer risk factors (4). Interactions between genotype and exposure to smoking, dietary folate, plasma folate, and alcohol intake were tested by the likelihood ratio test.The distribution of the XRCC2 and XRCC3 genotypes conformed to Hardy-Weinberg expectations and these polymorphisms were not in linkage disequilibrium. We observed no association between XRCC2 and XRCC3 genotype and risk of colorectal adenoma in separate and combined analyses of women and men from the NHS and HPFS cohorts, respectively (Table 1). In addition, no difference in risk was found between early (tubular histology and &lt;1 cm in diameter) and advanced (villous or tubulovillous histology and ≥1 cm in diameter) lesions in men and women (data not shown). No statistically significant interactions were observed between genotype and smoking, alcohol intake, dietary folate, or plasma folate (data available from www.channing.harvard.edu/nhs/pub.html#xrcc2004). Cigarette smoking increased risk of colorectal adenoma in our study for both men and women, regardless of XRCC2 or XRCC3 genotype. In addition, alcohol intake increased risk of colorectal adenoma in men for all genotypes. There was no evidence that the effect of XRCC2 or XRCC3 genotype varied by plasma or dietary folate in NHS.In the present study, we observed no association between XRCC2 and XRCC3 and risk of colorectal adenoma. We had &gt;80% power to detect risk ratios of 1.6 (XRCC2 R188H), 1.7 (XRCC3 T241M), 1.7 (XRCC3 A&gt;G 17893), and 2.4 (XRCC3 A&gt;G 4541) for homozygous carriers of the variant alleles in both groups. XRCC2 and XRCC3 are required for the formation of the protein complex necessary for homologous recombination repair of DNA double-strand breaks, which, if not repaired, can lead to chromosome rearrangement and genomic instability. DNA double-strand breaks can arise during DNA replication and are also induced by some carcinogens. High alcohol consumption has been related to higher risk of colorectal neoplasia through an antifolate effect, which may lead to uracil misincorporation into DNA and result in chromosomal breaks (4). DNA in human colon cells can also be damaged by adduct forming carcinogens derived from tobacco smoke (6). The XRCC2 and XRCC3 polymorphisms analyzed here did not modify the association between smoking, plasma folate, dietary folate, alcohol consumption, and adenoma risk. Our results suggest that cigarette smoking and high alcohol intake increase the risk of colorectal adenoma in men and women regardless of XRCC2 and XRCC3 genotypes.We thank the participants of the Nurses' Health Study and the Health Professionals Follow-up Study for their cooperation and participation. The authors are grateful to Hardeep Ranu for technical assistance.

Epidemiologic Studies of Folate and Colorectal Neoplasia: a Review

Dietary folate influences DNA methylation, synthesis and repair. Aberrations in these DNA processes may enhance carcinogenesis, particularly in rapidly proliferative tissues such as the colorectal mucosa. DNA methylation abnormalities may influence the expression of cancer-related genes, and inadequate levels of folate may lead to uracil misincorporation into DNA and to chromosomal breaks. Folate deficiency enhances intestinal carcinogenesis in several animal models. An increasing number of epidemiologic studies indicate that higher intakes of folate either from dietary sources or from supplements may lower the risk of colorectal adenoma and cancer. More limited data also suggest that dietary methionine, which might also influence methylation, may have a similar protective role. High alcohol consumption, which has a strong antifolate effect, also has been related to higher risk of colorectal neoplasia. The deleterious effects of alcohol are accentuated when folate or methionine intake is low. Some evidence also suggests that the risk of colorectal neoplasia may vary according to genetic polymorphisms in methylenetetrahydrofolate reductase, an enzyme that is involved in folate metabolism. The cumulative data indicate that maintaining adequate folate levels may be important in lowering risk of colorectal cancer.

Neoplasia in adult exstrophy patients.

To document the incidence of neoplasia in a cohort of 103 patients born with classical exstrophy. The notes of patients born before 1964 with exstrophy were reviewed retrospectively. The patients were divided into two groups; 42 were thought to be at high risk of developing neoplasia because they had (at some time) had mixing of urine and faeces in a colorectal reservoir, whereas 61 had never been exposed to such a mixture and were thought to have a low risk of neoplasia. At a minimum of 35 years of follow-up, complete data were available for 61 patients; 42 were lost to follow-up, of whom 14 were at high risk and 28 at low risk of neoplasia. In the high-risk group, there were three with colonic carcinoma (two of whom presented before 1980 and died), one with carcinoma in situ of the colon, 10 with benign colonic neoplasms and three with bladder cancer (two of whom died). In the low-risk group, there was one patient with bladder cancer (who died) and one with a clear cell carcinoma of the kidney. Three of the four patients with bladder cancer had undergone cystectomy before 5 years of age. Assuming that all the lost patients are alive and free of neoplasia, the risk of neoplasia in adults born with exstrophy is 17.5%. The main risk is in those who have been exposed to mixing of urine and faeces in a colorectal reservoir (38%). Even in low-risk patients the risk of malignant neoplasia is 3.3% at a median (range) age of 42 (40-44) years, which is 27 times higher than that of the age-matched general population. Annual colonoscopy of patients deemed at high risk of colorectal neoplasia appears to be an effective screen for colorectal carcinoma, by identifying a premalignant stage, as there were no deaths after this was introduced. Despite bladder closure or diversion surgery within the first few years of life, patients with exstrophy have an almost 700-fold greater incidence of carcinoma of the bladder than the age-matched general population. Early cystectomy is not protective.

I1307K APC gene variant has no clinical implication in Israeli jews at average or high risk for colorectal neoplasia

I1307K APC gene variant has no clinical implication in Israeli jews at average or high risk for colorectal neoplasia

I1307K APC gene variant has no clinical implication in Israeli jews at average or high risk for colorectal neoplasia

I1307K APC gene variant has no clinical implication in Israeli jews at average or high risk for colorectal neoplasia

Colon Cancer Screening: Sigmoidoscopy or Colonoscopy

Colorectal cancer is a common neoplasia with high morbidity and mortality. With endoscopy it is possible to identify its precursor lesion, the adenoma, and early localized cancer. Early detection and removal of adenomas can reduce the incidence and mortality of this disease. Studies using fecal occult blood testing (FOBT) and sigmoidoscopy for screening asymptomatic patients demonstrate a reduction in mortality from colorectal cancer. Colonoscopy, however, has the highest yield for detecting polyps. Most authorities and organizations now recommend screening the asymptomatic population over age 50 for colorectal neoplasia. The estimated cost of colon cancer screening is well within the benchmark figure of $40,000 per year of life saved, which is considered by the government to be cost effective. Controversies still exist regarding which colon cancer screening strategy is the most sensitive, specific, acceptable to the population, and cost effective. The American Cancer Society recommends a combination of FOBT and flexible sigmoidoscopy, but some experts believe that a one-time colonoscopy at age 60 may be a more cost-effective method. If the costs of colonoscopy are reduced, it is more cost effective than other techniques. Colonoscopy also may help to stratify at-risk patients, and those with negative initial colonoscopy may not need further screening. Advances in molecular biology may provide markers for screening or identifying people who are at high risk for colorectal neoplasia. This development may allow screening to be directed at high-risk groups.

Possible causes of a positive Haemoccult-II test in a population screening study for colorectal neoplasia.

In a population study for colorectal neoplasia possible relationships were sought between faecal occult bleeding and clinical findings. Samples were taken from three different stools, collected during biennial screening from 1985 to 1994 in the age group 45-75 years at the beginning of the study. A total of 943 persons had positive Haemoccult-II (H-II) tests in at least one of the five screening rounds, and 87% had a complete colonoscopy. Of the 20,672 persons accepting initial screening, 1% had a positive test, the figure increasing to 1.8% during the fifth screen. The degree of positivity (1-3 slides) decreased with time. Positive tests were most frequent in men. Predictive values (PVpos) for colorectal cancer (CRC) increased with increasing number of positive slides from 6 to 31%. The average PVpos decreased from 17% during the initial screen to 8% during the fifth. Average PVpos for possible precursors (adenomas) varied from 40% at the beginning to 33% at the end. PVpos for CRC and inflammatory bowel disease increased when visible blood in the stools was present. Marcoumar increased PVpos for adenomas. Colorectal examination in the 943 persons revealed 114 persons with CRC and further 377 with adenomas. Early CRC (Dukes' stage A) was detected in 46 of the 114 with CRC, a more favourable distribution than that found in symptomatic patients. The study defined a group of people with a high risk of colorectal neoplasia, with a good prognosis, out of a group who had been selected at random from a normal population.

Egg consumption and risk-markers for colorectal neoplasia.

A strong positive relationship between dietary intake of eggs and risk of colorectal cancer has been observed in a number of epidemiological surveys. In this study we investigated the relationship between egg consumption and intermediate biomarkers of crypt cell proliferation in the colon and rectum of 75 patients who had adenomatous polyps or no evidence of bowel disease. Biopsies of normal flat mucosa were obtained at colonoscopy, and microdissected crypts were used to measure crypt length, frequency of mitosis per crypt and spatial distribution of mitoses within the crypt. There was no significant difference in the consumption of eggs by patients with adenomatous polyps (n = 53) and those without (n = 22). There was no significant positive correlation between frequency of egg consumption and any of the parameters of crypt cell proliferation in the group as a whole, nor when the patients with polyps were analysed separately. This study provides no biological evidence of any relationship between egg consumption and abnormal cell proliferation among patients at relatively high risk of colorectal neoplasia.