Nottingham trial of faecal occult blood testing for colorectal cancer: a 20-year follow-up.

BACKGROUND: Three large randomised trials have shown that screening for colorectal cancer (CRC) using the faecal occult blood test (FOBt) can reduce the mortality from this disease. The largest of these trials, conducted in Nottingham since 1981, randomised 152,850 individuals between the ages of 45 and 74 years to an intervention arm receiving biennial Haemoccult (FOB) test kit or to a control arm. In 2006, the National Bowel Cancer Screening Programme was launched in England using the FOBt, with the expectation that it will reduce CRC mortality. AIMS: To compare the CRC mortality and incidence in the intervention arm with the control arm after long-term follow-up. METHODS: The 152,850 randomised individuals were followed up through local health records and central flagging (Office for National Statistics). RESULTS: At a median follow-up of 19.5 years there was a 13% reduction in CRC mortality (95% CI 3% to 22%) in the intervention arm despite an uptake at first invitation of approximately 57%. The CRC mortality reduction in those accepting the first screening test, adjusted for the rate of non-compliers, was 18%. There was no significant difference in mortality from causes other than CRC between the intervention and control arms. Despite removing 615 adenomas >10 mm in size from the intervention arm, there was no significant difference in CRC incidence between the two arms. CONCLUSIONS: Although the reduction in CRC mortality was sustained, further follow-up of the screened population has not shown a significant reduction in the CRC incidence. Moreover, despite the removal of many large adenomas there was no reduction in the incidence of invasive cancer which was independent of sex and site of the tumour.

Colorectal cancer, screening and survival: the influence of socio-economic deprivation.

OBJECTIVES: To determine the extent to which socio-economic deprivation explains colorectal cancer prevalence, subject participation in screening, and postoperative survival and life expectancy. METHODS: Regression analyses of clinical data from a large randomized controlled trial, augmented by geographical-based indices of deprivation. RESULTS: Deprivation appears to exert no significant impact on colorectal cancer prevalence but is a major factor explaining subject participation in screening. Cancer detection at later stages reduces life expectancy at time of treatment. Females from more-deprived areas have poorer post-treatment life expectancies and survival prospects, independently of their screening behaviour. CONCLUSIONS: Screening increases the chances of having a cancer treated at an earlier stage, and treatment at an earlier stage is associated with longer subsequent life expectancy. However, those from more-deprived areas are less likely to accept an invitation to be screened.

Effect of faecal occult blood screening on mortality from colorectal cancer: results from a randomised controlled trial.

BACKGROUND: Three large randomised trials have shown that screening for colorectal cancer using faecal occult blood (FOB) tests can reduce the mortality from this disease. Two national pilot studies have recently been launched in the UK to investigate the feasibility of population screening for colorectal cancer in the National Health Service. The largest of the randomised trials was conducted in Nottingham and randomised 152 850 individuals between the ages of 45 and 74 years to receive biennial Haemoccult (FOB) test kit (intervention group) or to a control group. AIMS: We have compared the mortality in the intervention group compared with the control group. METHODS: The 152 850 randomised individuals were followed up through local health records and central flagging (Office for National Statistics) over a median follow up period of 11 years. RESULTS: At a median follow up of 11 years there was a 13% reduction in colorectal cancer mortality (95% confidence interval 3-22%) in the intervention group despite an uptake at first invitation of only approximately 50%. The mortality reduction for those accepting screening was 27%. The reduction in mortality was independent of sex and site of tumour. There was no significant difference in mortality from causes other than colorectal cancer between the intervention and control groups. CONCLUSIONS: Although the reduction in colorectal cancer mortality was sustained, further follow up of this population is required to determine whether a significant reduction in the incidence of colorectal cancer will be achieved.

Psychiatric morbidity and screening for colorectal cancer.

BACKGROUND: Several studies have shown that faecal occult blood (FOB) screening reduces mortality from colorectal cancer. However, concern has been expressed that health screening may have adverse psychological effects, particularly for the group returning false positive tests. OBJECTIVES: To evaluate any adverse psychological effects associated with faecal occult blood screening. SETTING: Randomised controlled trial of faecal occult blood screening for colorectal cancer. METHODS: Psychiatric morbidity was measured, using the general health questionnaire (GHQ) before and 3 months after the offer of screening for colorectal cancer with FOB testing. Scores were related to acceptance of the screening test. A smaller cohort, who had returned positive FOB tests, had anxiety levels measured, using the Spielberger anxiety inventory (SAI), at different times during screening, investigation, and follow up. RESULTS: A GHQ was sent to 2184 subjects before the offer of screening, and 1541 (70.6%) were returned. Of the 1693 subjects offered the GHQ 3 months after the offer of screening, 1303 (77%) returned it. A GHQ score of 5 or more, indicating possible psychiatric morbidity, was present in 454 subjects (29.5%) before screening and in 386 (29.6%) subjects 3 months after screening (NS). Of the 454 subjects who scored 5 or more, 241 (53.1%) accepted screening and 213 (46.9%) refused. A total of 1081 subjects scored less than 5, and of these 521 (48.2%) accepted screening and 560 (51.8%) refused (NS). Anxiety scores were measured in 100 test positive patients and were highest after notification of a positive test and before investigation by colonoscopy. In patients with false positive results, scores fell the day after colonoscopy and remained low 1 month later. CONCLUSIONS: The receipt of a screening test does not cause sustained anxiety and the existence of psychiatric morbidity is not a factor affecting a person's decision to accept or refuse a screening test for colorectal cancer.

High prevalence of undetected ulcerative colitis: data from the Nottingham fecal occult blood screening trial.

OBJECTIVES: Inflammatory bowel disease (IBD) is usually diagnosed as a result of symptoms but occasionally is found during investigation for other conditions. An earlier report from Nottingham had found a high prevalence of previously undetected "asymptomatic" IBD detected as a result of colorectal cancer screening, and the aim of this study was to reassess the prevalence, symptoms, and outcome in these patients. METHODS: We investigated subjects found to be fecal occult blood (FOB) positive in a randomized trial of FOB screening for colorectal cancer. All FOB-positive subjects were investigated by colonoscopy or flexible sigmoidoscopy and barium enema. Subjects with IBD were referred back to their general practitioner for any further investigation and treatment. RESULTS: Seventy-five thousand two hundred fifty-three subjects (aged 45-74) were sent FOB tests and 44,838 (60%) completed a series of tests on one or more occasions. Of 133,000 test series, 1.5% were positive. During investigation 53 cases of previously undetected IBD (52 of ulcerative colitis) were found; 52% (27/52) had proctosigmoiditis only, whereas 25% (13/52) had pancolitis. Only 17% (9/52) were completely asymptomatic, with a half or more reporting some rectal bleeding (54%) or diarrhea (50%). The overall prevalence of undetected ulcerative colitis was 69/10(5) (95% CI = 50-88/10(5)) in people offered screening and 116/10(5) (95% CI = 85-147/10(5)) in people accepting screening and was higher in men. Of 32 subjects followed up 2-12 yr after diagnosis, 91% (29) continued to have few or no symptoms, with only 12 currently receiving any treatment for their colitis. CONCLUSIONS: In comparison with detected disease, undetected ulcerative colitis is relatively common but does usually cause some symptoms. It generally appears to follow a benign course, but a significant proportion have extensive colitis and may therefore be at an increased risk of colorectal cancer.

Randomized double-blind phase II survival study comparing immunization with the anti-idiotypic monoclonal antibody 105AD7 against placebo in advanced colorectal cancer.

The cancer vaccine 105AD7 is an anti-idiotypic monoclonal antibody that mimics the tumour-associated antigen 791T/gp72 (CD55, Decay Accelerating Factor) on colorectal cancer cells. Phase I studies in patients with advanced disease confirmed that 105AD7 is non-toxic, and that T cell responses could be generated. A prospective, randomized, double-blind, placebo-controlled survival study in patients with advanced colorectal cancer was performed. 162 patients were enrolled between April 1994 and October 1996. Patients attended at trial entry, and at 6 and 12 weeks, where they received 105AD7 or placebo. Study groups were comparable in terms of patient demographics, and time from diagnosis of advanced colorectal cancer (277.1 v 278.6 days). Baseline disease was similar, with 50% of patients having malignancy in at least 2 anatomic sites. Compliance with treatment was poor, with only 50% of patients receiving 3 planned vaccinations. Median survival from randomization date was 124 and 184 days in 105AD7 and placebo arms respectively (P = 0.38), and 456 and 486 days from the date of diagnosis of advanced disease (P = 0.82). 105AD7 vaccination does not prolong survival in patients with advanced colorectal cancer. The reasons for lack of efficacy are unclear, but may reflect the high tumour burden in the patient population, and poor compliance with immunization. Further vaccine studies should concentrate on patients with minimal residual disease.

Faecal occult blood screening for colorectal cancer at Nottingham: details of the verification process.

Cause specific mortality statistics derived from death certificates are highly dependent upon the accuracy of certification by the attending physician. In the Nottingham colorectal cancer screening trial, there were 12,624 deaths among the screening group and 12,515 among the control group during the period under consideration. There was no significant difference in all cause mortality rate (excluding deaths due to colorectal cancer) between the two study groups (rate ratio = 1.01, 95% confidence interval = 0.99 to 1.03). Disease specific mortality rates did not differ significantly between the two groups either. Overall, the agreement between verified and certified cause of death was 86%. Using the certified cause of death would have resulted in an underestimation bias of 6.27% for colorectal cancer deaths.

A prospective multicenter evaluation of new fecal occult blood tests in patients undergoing colonoscopy.

OBJECTIVE: Guaiac-based fecal occult blood (FOB) tests, in particular, Hemoccult II (HO), are commonly used to detect colorectal neoplasia. Because the sensitivity and specificity of these tests are critical to cost-effective screening programs, we aimed to investigate the improved performance characteristics of new FOB tests for known colonic lesions. METHODS: Nine centers worldwide performed FOB testing with guaiac-based tests (Hemoccult II [HO] and Hemoccult II SENSA [SENSA]) and immunochemical tests (HemeSelect [HS] and FlexSure OBT [FS]) on 554 patients referred for colonoscopy for predetermined indications. A combination testing strategy consisting of SENSA followed by HS or FS (which was considered positive only when both tests were positive) was also evaluated. Results of FOB tests were compared to findings on colonoscopy. RESULTS: Cancers were identified in 2.9% of subjects, whereas adenomas > or =10 mm were found in 39 patients. Small adenomas, colitis, and other lesions were identified in 141 patients. The positivity rate of HO for adenomas > or =10 mm was less than for SENSA (20.5% vs 35.9%, p < 0.05), whereas the positivity rate of HO, SENSA, FS, HS, or the combination tests for cancers was not statistically different. The overall positivity rates were significantly greater for FS (15.9%, p = 0.0002) and significantly lower using the combination tests (SENSA/FS 6.0%, p = 0.01; SENSA/HS 6.2%, p = 0.02) compared to HO (9.4%). In this study population, the relative specificity (i.e., true-negative tests/true-negatives + false-positives in patients without adenomas > or =10 mm or cancers) of HO (93.9%; 95% CI, 91.7-96.1) was similar to that of SENSA (92.8%; 95% CI, 90.4-95.2) and HS (90.1%; 95% CI, 87.4-92.8), and greater than FS (88.0%; 95% CI, 85.1-90.9, p < 0.001). When considering adenomas > or =10 mm, cancers alone or cancers and adenomas combined, the combination test using SENSA/FS was associated with significantly fewer false-positive tests than any of the individual tests. CONCLUSIONS: Compared to single tests, the combination test with the highly sensitive SENSA and an immunochemical test had slightly reduced sensitivity but significantly fewer false-positive tests than any single test. These data raise the possibility that a combination test (i.e., highly sensitive guaiac plus immunochemical) could reduce the costs of screening for colon cancer, and suggest that further study of combination test strategies is warranted.

Survival of patients with colorectal cancer diagnosed in a randomized controlled trial of faecal occult blood screening.

BACKGROUND: Analysis of survival of subjects with colorectal cancer diagnosed by different modalities can provide insight into the mechanism by which screening has an effect. It can also give an indication of the feasibility of using prognostic indicators as surrogate outcome measures to predict mortality in future studies. METHODS: This paper examines the survival of individuals with colorectal cancer diagnosed in the Nottingham trial and explores the role of selected prognostic factors as possible surrogate outcome measures. RESULTS: Survival was significantly better in subjects with screen-detected cancers than in controls, even after adjusting for tumour stage and accounting for lead-time bias. Survival was inversely related to stage of tumour, with patients with stage A tumours having the best survival. Subjects with well or moderately differentiated tumours had a significantly better survival than those with poorly differentiated tumours. CONCLUSION: Screening for colorectal cancer by means of faecal occult blood testing improved survival among subjects with screen-detected cancers. Differences in prognostic factors largely explain the differences in survival between both non-responders and subjects with interval cancers and those in the control group, but not the improved prognosis for patients with screen-detected cancers. The use of such factors as surrogate outcome measures may therefore be inappropriate.

The risks of screening: data from the Nottingham randomised controlled trial of faecal occult blood screening for colorectal cancer.

AIMS: To determine the harm that ensues from faecal occult blood (FOB) screening for colorectal cancer. METHODS: 150 251 people were randomly allocated either to receive biennial Haemoccult FOB tests (n =75 253) or not to be contacted (n=74 998). Study group patients returning positive tests were offered colonic investigation; 1774 underwent complete investigation of the colon. RESULTS: There was no significant difference in the stage at presentation of interval versus control group cancers. Survival in the interval cancer group was significantly prolonged compared with the control group. Sensitivity for colonoscopy or flexible sigmoidoscopy and double contrast barium enema (DCBE) was 96.7%. There were no complications of DCBE but seven (0.5%) complications of colonoscopy, of which six required surgical intervention. There were no colonoscopy related deaths. No patients without colorectal cancer died within 30 days of colonic investigation. Five patients died within 30 days of surgery for screen detected colorectal neoplasia and a further two died without having surgery. Six patients died after 30 days but within two years of surgery for screen detected benign adenomas or stage A cancers; in all cases the cause of death was not related to colorectal cancer. CONCLUSIONS: There was investigation related morbidity but no mortality and little to support overdiagnosis bias. The group returning falsely negative tests had a better outcome compared with the whole control group. There is a negative side to any screening programme but mortality reduction in this and other trials suggests that a national programme of colorectal cancer screening should be given consideration.

Increased activation of lymphocytes infiltrating primary colorectal cancers following immunisation with the anti-idiotypic monoclonal antibody 105AD7.

BACKGROUND: The anti-idiotypic monoclonal antibody 105AD7 mimics the tumour associated antigen 791Tgp72, expressed on 70-80% of colorectal cancers. Phase I studies have shown that the vaccine is non-toxic, and a number of patients have been immunised prior to resection of their primary tumours. AIMS: To assess lymphocyte activation at the tumour site by measuring expression of the alpha subunit of the interleukin 2 receptor (CD25). METHODS: Nineteen patients with primary colorectal cancer were immunised with varying doses of 105AD7 prior to resection of their primary tumours. Samples of normal bowel and tumour edge/centre from 16 patients were available for immunohistochemical staining with a monoclonal antibody against CD25. Samples from a matched control group were also stained. Fresh tumours from 14 immunised patients and 31 unimmunised control patients were disaggregated, and the lymphocytes obtained labelled for CD25. Samples were analysed blindly by flow cytometry. RESULTS: Median infiltration of lymphocytes expressing CD25, measured immunohistochemically, was higher in trial patients, as was the ratio of tumour to normal bowel infiltration. Flow cytometric analysis of fresh tumour from immunised patients showed a significantly higher percentage of lymphocytes expressing CD25 tumour infiltrating lymphocytes than their matched and unmatched controls. DISCUSSION: The alpha subunit of the interleukin 2 receptor is increased on tumour infiltrating lymphocytes, in patients immunised with the colorectal cancer vaccine 105AD7. This suggests a population of activated lymphocytes capable of targeting 791Tgp72 expressing tumour cells, such as circulating micrometastases. 105AD7 may have a role as adjuvant therapy in early stage disease.

Interval cancers in a randomized controlled trial of screening for colorectal cancer using a faecal occult blood test.

BACKGROUND: The sensitivity of unhydrated Haemoccult II has been examined in the context of a randomized controlled trial of faecal occult blood screening for colorectal cancer in Nottingham, UK. METHOD: Both traditional and proportional incidence methods were used to calculate sensitivity separately for both sexes, for two age groups at entry to the trial, for first screen and repeat screens and for three subsites within the large bowel. RESULTS: The traditional method of estimation yielded a sensitivity of 59% whereas the corresponding figure obtained using the proportional incidence method was 54%. The difference between the estimates using the two methods was greatest in subjects aged > or = 65 at entry to the trial and in cancers of the distal colon. CONCLUSIONS: The results suggest that there may be a higher proportion of slower growing tumours in subjects aged > or = 65 and that cancers occurring in the distal colon may have a longer mean sojourn time than cancers proximal to the sigmoid colon.

Direct mucosal targeting of colonic receptors by prokinetic drugs in an experimental model.

Isolated perfused segments of pig ileum and sigmoid colon were used as an extrinsically denervated model of intestinal fluid propulsion to compare the effects of intraluminal (IL) with intraarterial (IA) administration of cisapride and mebeverine. The ileal segments had a spontaneous mean activity of 0.008 (SEM 0.003) ml Krebs propelled aborally min-1, with propulsive waves at a mean frequency of 8.3 (1.6) min-1. The sigmoid colon segments ejected a mean of 0.013 (0.009) ml Krebs min-1, with propulsive waves at 3.9 (0.8) min-1. IL cisapride produced a dose-dependent response in the dose range 1 x 10(-9) M to 3 x 10(-1) & 1-3 x 10(-7) M in the ileum, and 3 x 10(-11) to 3 x 10(-9) M in the colonic segments, IL cisapride was significantly more effective than IA delivery of equivalent doses. IL instilled mebeverine (1 x 10(-6) M) inhibited the carbachol dose response of the ileal and colonic segments more than an equivalent dose of mebeverine infused IA. We conclude that the isolated perfused pig intestine is an effective model for studying the pharmacological effects of drugs and their routes of delivery. Cisapride and mebeverine were more effective per given concentration, when delivered IL than IA in both the ileum and sigmoid colon preparations. The qualitative effects of either IL or IA drug delivery were not affected by extrinsic denervation.

A comparison of an anti-gastrin antibody and cytotoxic drugs in the therapy of human gastric ascites in SCID mice.

The therapeutic effect of antibodies raised by the immunogen Gastrimmune was compared with both a CCKB/gastrin receptor antagonist, CI-988, and 5-Fluorouracil/leucovorin in a gastric cancer model. The human gastric ascites cell line, MGLVA1asc, produced and secreted progastrin and glycine-extended gastrin as determined by radioimmunoassay and immunocytochemistry. Cells were also stained with an antiserum directed against the human CCKB/gastrin receptor. MGLVAI asc cells were injected i.p. into SCID mice. Antibodies raised by Gastrimmune immunization of rabbits (affinity for G17 of 0.15 nM and GlyG17 of 0.47 nM) were passively infused i.p. and significantly enhanced survival by up to 5 days (p=0.0024 from vehicle controls). The enhancement in survival was not significantly different from that achieved by treatment with 5-Fluorouracil and leucovorin. A CCKB/gastrin receptor antagonist, CI-988, did not affect survival with cells injected at 7.5 x 10(5) cells/mouse but significantly increased the survival of mice injected with a lower cell innoculum of 5 x 10(5) cells/mouse from 30 to 35 days (p=0.0186). At this lower innoculum antibodies raised by Gastrimmune induced complete survival in 2 animals with the remaining dead by day 36 (p=0.0022). Thus, both endocrine and autocrine pathways mediated by precursor and mature gastrin molecules may be jointly operational in the gastric cancer scenario and may be important targets for therapeutic agents.

Antibodies raised by gastrimmune inhibit the spontaneous metastasis of a human colorectal tumour, AP5LV.

Both precursor forms of gastrin and mature amidated gastrin peptides can enhance proliferation of colorectal tumours and may regulate growth in an autocrine manner. The purpose of this study was to evaluate the effect of neutralization of precursor and amidated gastrin on primary and secondary in vivo growth of a human colorectal tumour. The human colorectal cell line, AP5LV, when injected into the muscle layer of the abdominal wall of severe combined immunodeficient (SCID) mice, grows as a well-vascularized primary tumour and metastasis to the lung. AP5LV expressed the precursor gastrin forms; progastrin and glycine-extended gastrin and gastrin/CCKB receptors, as assessed by immunocytochemistry. Gastrimmune is a gastrin immunogen in which the amino terminus of the gastrin-17 molecule is linked to diphtheria toxoid and induces antibodies which neutralise the amidated and glycine-extended forms of gastrin-17. Rabbit antiserum, raised against Gastrimmune, was administered intravenously into SCID mice bearing AP5LV tumours. Control animals were treated with antiserum raised against diphtheria toxoid only. Antibodies raised against Gastrimmune significantly limited the growth of primary AP5LV tumours, as assessed by median cross-sectional area (controls = 244 mm2; antibody-treated = 179 mm2; P = 0.033). In addition Gastrimmune-induced antiserum limited the growth of lung metastasis as assessed by nodule number (controls = 3.5; antibody-treated = 1.0; P = 0.0001) and nodule cross-sectional as assessed by image analysis (controls = 11.9 mm2; antibody-treated = 3.75 mm2; P = 0.0064). In conclusion in vivo neutralization of gastrin forms, which may potentially be fueling growth by an autocrine pathway, inhibited both primary growth and, to a greater degree, lung metastasis of a human colorectal tumour cell line. Immunization against tumour-associated gastrin forms may provide an effective therapy for advanced colorectal cancer.

Gastric carcinoid expresses the gastrin autocrine pathway.

BACKGROUND: In gastric adenocarcinoma the gastrin autocrine-paracrine pathway is activated. As enterochromaffin-like (ECL) cells originate from the same stem as epithelial cells, the aim of this study was to determine if the gastrin autocrine pathway is present in gastric carcinoid. METHODS: Samples from ten patients with gastric carcinoid were assessed by immunocytochemistry using primary antibodies directed against gastrin precursors and the gastrin/cholecystokinin B receptor and detected using the avidin-biotin immunoperoxidase system. RESULTS: A high level of expression of precursor and mature gastrin peptides, together with the gastrin receptor, was seen in all carcinoids screened. CONCLUSION: In common with the glandular epithelium of the stomach the gastrin gene is activated during the neoplastic process in ECL cells. This finding may explain why some carcinoids do not regress after surgical procedures that lower serum gastrin. Antigastrin agents may be a useful treatment for carcinoid either in their own right or as an adjunct to surgery.

Expression of CCKB/gastrin receptor isoforms in gastro-intestinal tumour cells.

Anti-serum raised against the human cholecystokinin B (CCKB)/gastrin receptor was used in Western blotting to differentiate the cellular locations of receptor isoforms expressed by human gastro-intestinal (GI) tumour cell lines. Using anti-serum directed against the amino-terminal extracellular tail of the CCKB/gastrin receptor, 8/9 cell lines were shown to express immunoreactive proteins of either m.w. 70 or 40 kDa, or both. Both isoforms were found to be associated with intracellular, non-nuclear membranes, whereas only the 70 kDa protein was expressed in the plasma membrane. Receptor expression was related to gastrin production and secretion. Both progastrin and glycine-extended gastrin-17 were produced and secreted by the tumour cell lines; however, carboxy amidated gastrin was not detected by radioimmunoassay. A CCKB/gastrin receptor transfectant NIH3T3 cell line did not produce detectable gastrin and showed exclusive expression of the 70 kDa receptor on the plasma membrane. One cell line had <50 pg/ml cell-associated progastrin and no detectable receptor form. Cell lines expressing 50-150 pg/ml had both 40 and 70 kDa receptor forms. Those expressing >150 pg/ml progastrin had only the 40 kDa isoform, which was shown to be exclusively expressed on intracellular, non-nuclear membranes, in one of the cell lines. Of the 4 cell lines exclusively expressing the lower m.w. receptor, 3 had gastrin present within the cell, which was not secreted. Thus, if cell-associated gastrin induces a proliferative effect, it may be by an intracrine pathway. Our study has identified the presence of CCKB/gastrin receptor isoforms in different cellular locations and may help toward understanding the complex autocrine and intracrine pathways mediated by gastrin peptides.

Screening for colorectal cancer reduces emergency admissions.

AIMS: Colorectal cancer is common and accounts for over 15,000 deaths annually in England and Wales. Up to 30% of these patients require emergency surgery. Screening for colorectal cancer can reduce the mortality of colorectal cancer. This study addresses the impact of a population-based screening study on emergency admissions with colorectal cancer. METHOD: From 1981 a randomized trial of Faecal Occult Blood (FOB) screening has been undertaken in the Nottingham area, recruiting over 150,000 patients. The present study examined the records of patients enrolled in this study who presented as an emergency with colorectal cancer. RESULTS: Colorectal cancer was identified in 1962 cases, of which 468 (23.9%) presented as emergencies. The overall compliance was 60% (proportion of individuals completing at least one test). There were significantly fewer emergencies in the Screen-detected group compared with the Control group (P = < 0.0001). This group also had a significantly reduced 30-day mortality and a lower stoma rate than the Control group. Conversely the Non-responders had a significantly greater proportion of emergency admissions and a significantly increased stoma rate compared with the Control group. CONCLUSIONS: Screening for colorectal cancer using a faecal occult blood test can significantly reduce the number of emergency presentations with colorectal cancer. It is likely that the introduction of a national programme of screening for colorectal cancer would lead to increased compliance and that this would lead to a significant reduction in the emergency workload on the National Health Service from colorectal cancer.

Faecal occult blood screening for colorectal cancer: is it cost-effective?

Recently published evidence from two large-scale clinical trials conducted in England and in Denmark suggests that faecal occult blood screening for colorectal cancer significantly reduces mortality. However, before screening can be advocated as part of national health policy, its cost-effectiveness must be demonstrated. The English screening trial has been the subject of a detailed economic evaluation over the past 10 years In this paper, cost-effectiveness estimates of screening are presented, based on cost and outcome data combined in a mathematical model developed from the trial's clinical findings The estimates of cost per quality-adjusted life-year gained from colorectal cancer screening show the procedure to be of similar cost-effectiveness to breast cancer screening in the short term. Over the longer term, however, the estimates for colorectal cancer screening appear superior.

Endoscopic screening of relatives of patients with colorectal cancer.

BACKGROUND: The risk of colorectal cancer is higher among relatives of those affected. The neoplastic yield reported from screening such individuals varies enormously between studies and depends on the age and strength of the family history of those screened. AIMS: To ascertain the neoplastic yield of endoscopic screening of first degree relatives of patients with colorectal cancer by age and familial risk. SUBJECTS: A total of 330 individuals with a family history of colorectal cancer. METHOD: Endoscopic screening conducted according to a protocol. RESULTS: Adenomas were found in 12%, and adenomas larger than 1 cm in 8%, of "high risk" individuals screened primarily by colonoscopy. Of those with neoplasia, 26% had lesions at or proximal to the splenic flexure. Neoplasia was found in 9.5% of individuals at lower familial risk, screened primarily by 60 cm flexible sigmoidoscopy, 4% of whom had neoplasia larger than 1 cm in size or cancer. Neoplastic yield was greatest in the fourth and fifth decades in those at highest risk, but increased with age in those at lower risk. CONCLUSIONS: For individuals with two or more first degree relatives, or relatives who have developed colorectal cancer at a young age, colonoscopy appears to be the only satisfactory method of screening, but 60 cm flexible sigmoidoscopy may be useful in those at lower levels of risk.