No abstract

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 oVered colonic investigation; 1774 underwent complete investigation of the colon. Results-There was no significant diVerence 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. (Gut 1999;45:588-592)

A total of 26,975 asymptomatic individuals were identified from family doctors' age/sex registers and randomly allocated to test or control group. The first test group (10,253) were offered 3-day fecal occult blood (FOB) testing; 3,613 (37%) completed the tests and 77 (2.1%) were found to be positive. In this group, 13 cancers were detected (3.5/1000 persons screened), of which 9 (70%) were Stage A. Of these subjects, 3349 have been rescreened at 2 years; 2799 (85%) completed the tests and 80 (2.8%) were found to be positive. Four cancers have been detected (three Stage A). In the whole test group followed for 2 years (10,462), 34 cancers have presented (17 screening detected, 3 interval cases in test responders, 14 symptomatic cancers in nonresponders), of which 14 (43%) were Stage A. In the control group (10,272 individuals), 17 patients have presented with symptomatic colorectal cancer during the 2-year follow-up, with rates of 0.9/1000 and 0.8/1000 persons/year in the first and second years of follow-up, respectively. No Stage A tumors were present. In the second test group (3,225) offered both guaiac (Hemoccult; Smith Kline Diagnostics) and immunologic (Feca EIA; Nordic) FOB tests, 1304 (44%) completed the tests, of which 126 (9.7%) were positive. Five cancers were detected (four Stage A), of which only three were positive by Hemoccult testing. In this group of test responders, one cancer has presented symptomatically at 1 year follow-up. Thus, at 2-year follow-up of the responding individuals of both cohorts of the initial screen of the test group, 5 of 21 cancers (24%) were negative by Hemoccult testing. Fecal occult blood testing has doubled the detection of colorectal cancer in the test group compared with the number presenting with symptoms in 2 years in the control group, and increased the proportion of early stage cancers (chi 2 = 8.0, P = less than 0.001).

Folate intake is inversely related to risk of developing colorectal neoplasia. Associations between risk of colorectal neoplasia and polymorphisms in genes coding for enzymes involved in folate metabolism have also been reported, suggesting a relationship between genotype and development of colorectal neoplasia. To further investigate the effects of folate metabolism genotypes on colorectal neoplasia, we genotyped 546 patients participating in a randomized controlled trial of folate supplementation for the prevention of colorectal adenoma recurrence. A significantly reduced risk of recurrence was observed in patients heterozygous for the MTRR A66G polymorphism [relative risk (RR), 0.64; 95% confidence interval (95% CI), 0.46-0.90] or heterozygous for the MTHFR A1298C polymorphism (RR, 0.71; 95% CI, 0.52-0.97). Furthermore, a significant reduction in recurrence risk was seen in MTRR A66G heterozygotes who received folate supplements but not in those who did not receive folate. Patients heterozygous for the MTHFR C677T polymorphism had a nonsignificant risk reduction (RR, 0.92; 95% CI, 0.69-1.23), as did patients with one or two variant alleles for the MTR A2756G polymorphism (RR, 0.82; 95% CI,. No influence on recurrence risk was observed for the TSER, TSER 3R G>C, and TS 1494del6 variants. These findings provide additional support for the hypothesis that germ line variants in folate metabolism genes influence the development of colorectal adenomas. (Cancer Epidemiol Biomarkers Prev 2006;15(9):1607 -13)

Paget's disease of the anus is a rare disorder of controversial origin and is frequently associated with malignancy. We studied eight patients and carried out immunohistochemical studies to determine whether particular functional profiles might be indicators of a malignant association. One patient presented with synchronous carcinoma and two developed carcinomas 3 and 10 years after excision of Paget's disease. Five patients underwent wide local excision and have not developed cancer (median follow-up 6 years, range 5-13 years). However, four patients developed recurrent Paget's disease. Immunohistochemical studies showed that in general Paget cells stained positively with CAM 5.2 (a cytokeratin marker), gross cystic disease fluid protein (a marker for apocrine cells), human milk fat globule glycoprotein (HMFG 1 and 2) and carcinoembryonic antigen but negatively for PR3A5 (a marker for colonic goblet cells). Three cases had a staining profile which was quite different from that usually observed and these were associated with malignancy. One showed an antigenic profile more typical of a large bowel carcinoma. Paget's disease of the anus appears to run one of two clinical courses: to develop malignancy; or to recur locally, often on repeated occasions. Wide local excision is the treatment of choice but long-term follow-up is necessary because of the cancer risk. An immunohistochemical staining pattern which is different from usual may indicate a higher malignant risk and/or identify some cases of Paget's disease as representing a downward 'pagetoid' extension from a anorectal adenocarcinoma rather than a true epidermotropic apocrine neoplasm of the perianal skin.

Summary Evidence as to the value of preoperative carcinoembryonic antigen (CEA)

Anal fissure is often treated surgically by sphincterotomy. There is growing concern over the effects of this procedure on continence. Nitric oxide donors such as glyceryl trinitrate are thought to cause a reversible 'chemical sphincterotomy', capable of healing the fissure. Twenty-one consecutive patients with chronic anal fissure (13 women, mean age 36 years) were treated for 4-6 weeks with 0.2 per cent glyceryl trinitrate ointment applied to the fissure twice daily. Maximum anal resting pressure (MARP) was measured before and after application of the ointment at the first visit. There were 16 posterior and five anterior fissures. Mean(s.d.) MARP fell from 118.7(45.0) to 70.3(34.1) cmH2O over 20 min after application of the ointment (P < 0.001). Healing was complete in 11 patients at 4 weeks and in 18 at 6 weeks. The fissure recurred in four patients after cessation of treatment; three were successfully treated by further glyceryl trinitrate. Mild headache occurred in four patients. Anal fissure can be successfully treated with 0.2 per cent glyceryl trinitrate ointment applied topically.

Background-The risk of colorectal cancer is higher among relatives of those aVected. 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. (Gut 1998;42:71-75)