Results from the first three rounds of the Scottish demonstration pilot of FOBT screening for colorectal cancer.

OBJECTIVES: To assess the effects of the first three rounds of a pilot colorectal screening programme based on guaiac faecal occult blood testing (gFOBT) and their implications for a national population-based programme. METHODS: A demonstration pilot programme was conducted in three Scottish NHS Boards. Residents aged between 50 and 69 years registered on the Community Health Index were included in the study. RESULTS: In the first round, the uptake was 55.0%, the positivity rate was 2.07% and the cancer detection rate was 2.1/1000 screened. In the second round, these were 53.0%, 1.90% and 1.2/1000, respectively, and in the third round, 55.3%, 1.16% and 0.7/1000, respectively. In the first round, the positive predictive value of the gFOBT was 12.0% for cancer and 36.5% for adenoma; these fell to 7.0% and 30.3% in the second round and were maintained at 7.5% and 29.1% in the third round. The percentage of screen-detected cancers diagnosed at Dukes' stage A was 49.2% in the first round, 40.1% in the second round and 36.3% in the third round. CONCLUSIONS: These results are compatible with those of previous randomised trials done in research settings, demonstrating that population-based colorectal cancer screening is feasible in Scotland and should lead to a comparable reduction in disease-specific mortality.

COX-2 expression in sporadic colorectal adenomatous polyps is linked to adenoma characteristics.

AIMS: To assess cyclooxygenase-2 (COX-2) expression in sporadic colonic adenomas and to explore the association of COX-2 positivity with adenoma characteristics linked to increased risk of malignant transformation. METHODS AND RESULTS: COX-2 expression and localization were assessed in 64 colorectal adenomas and 35 paired adjacent normal colonic mucosal biopsy specimens. The number of adenoma specimens was then extended to include polyps exhibiting an increasing degree of epithelial dysplasia. Forty colonic hyperplastic polyps were also identified from the pathology diagnostic database and included in the analysis. Immunohistochemistry was performed with the Envision+ peroxidase-linked biotin-free system incorporating a signal amplification step. There was a statistically significant increase in COX-2 expression in colonic polyps compared with paired adjacent normal mucosa, chi(2) = 40.1, P = 0.001. The probability of COX-2 expression increased along with increasing adenoma size and increasing degree of epithelial dysplasia. Fifty-five per cent of the hyperplastic polyp specimens expressed COX-2. CONCLUSIONS: This study associates COX-2 epithelial expression with a number of adenoma characteristics that convey an increased risk of malignant transformation. This is in keeping with a positive role for COX-2 in early colorectal carcinogenesis.

Evidence that a polymorphism within the 3'UTR of glutathione peroxidase 4 is functional and is associated with susceptibility to colorectal cancer.

Low selenium (Se) status has been associated with increased risk of colorectal cancer (CRC). Se is present as the amino acid selenocysteine in selenoproteins, such as the glutathione peroxidases. Se incorporation requires specific RNA structures in the 3' untranslated region (3'UTR) of the selenoprotein mRNAs. A single nucleotide polymorphism (SNP) occurs at nucleotide 718 (within the 3'UTR) in the glutathione peroxidase 4 gene. In the present study, Caco-2 cells were transfected with constructs in which type 1 iodothyronine deiodinase coding region was linked to the GPx4 3'UTR with either C or T variant at position 718. Higher reporter activity was observed in cells expressing the C variant compared to those expressing the T variant, under either Se-adequate or Se-deficient conditions. In addition, a disease association study was carried out in cohorts of patients with either adenomatous polyps, colorectal adenocarcinomas and in healthy controls. A higher proportion of individuals with CC genotype at the GPx4 T/C 718 SNP was present in the cancer group, but not in the polyp group, compared with the control group (P < 0.05). The present data demonstrate the functionality of the GPx4 T/C 718 SNP and suggest that T genotype is associated with lower risk of CRC.

Endoscopic findings in the upper gastrointestinal tract of faecal occult blood-positive, colonoscopy-negative patients.

BACKGROUND: Detection of faecal occult blood is recommended for colorectal cancer screening in average risk populations. However, many subjects do not have any cause found in the colon to account for the occult blood loss. AIMS: To determine the prevalence of upper gastrointestinal tract disease in faecal occult blood-positive, colonoscopy-negative patients. PATIENTS AND METHODS: Retrospective audit of 99 patients (56 females; mean age 60 years, range 18-83) who underwent same-day colonoscopy and upper gastrointestinal endoscopy over a 2-year period. RESULTS: Fifty-two of the 99 patients had a normal colonoscopy, 16 had diverticulosis and 2 had hyperplastic polyps; these 70 patients comprised the colonoscopy-negative group. Significant upper gastrointestinal tract disease was noted in 25 (36%) of the colonoscopy-negative group compared with 10 (34%) of the 29 colonoscopy-positive group (p=ns). Most of the upper gastrointestinal tract lesions identified were benign. Within the colonoscopy-negative group, patients with anaemia or upper gastrointestinal tract symptoms had a higher prevalence of positive findings in the upper gastrointestinal tract, but this association was not statistically significant. CONCLUSIONS: Endoscopic examination of the upper gastrointestinal tract in faecal occult blood-positive individuals reveals mostly benign disease, with an equal prevalence in colonoscopy-negative and colonoscopy-positive patients. Routine performance of upper gastrointestinal endoscopy in faecal occult blood-positive individuals is not indicated and should be undertaken only for appropriate symptoms.

A randomized trial comparing heater probe plus thrombin with heater probe plus placebo for bleeding peptic ulcer.

BACKGROUND & AIMS: This multicenter, double-blind, controlled trial compared the efficacy of combined endoscopic hemostatic treatment using the heater probe plus thrombin injection with that of the heater probe plus placebo injection as treatment for peptic ulcers with active bleeding or nonbleeding visible vessels. Efficacy was defined in terms of primary hemostasis, prevention of rebleeding, and need for urgent surgery. METHODS: Two hundred forty-seven patients presenting with major peptic ulcer bleeding were randomized to heater probe plus thrombin or to heater probe plus placebo. The groups were well matched for all risk categories including age, endoscopic stigmata, shock, and severity of comorbid diseases. Endoscopic therapy was applied using the heater probe followed by injection of thrombin or placebo. RESULTS: Successful primary hemostasis was achieved in 97% of patients. Rebleeding developed in 19 (15%) of thrombin plus heater probe patients and 17 (15%) of placebo plus heater probe patients. Emergency surgery was necessary in 16 and 13 patients, respectively. Eight patients in the thrombin group had adverse events compared with 4 in the placebo group. Eight (6%) of thrombin plus heater probe patients and 14 (12%) of placebo plus heater probe patients died (P = 0.21). CONCLUSIONS: The combination of thrombin and the heater probe does not confer an additional benefit over heater probe and placebo as endoscopic treatment for bleeding peptic ulcer. Our trial does not support the use of this combination of hemostatic therapy.