Screening for colorectal cancer with an immunological faecal occult blood test: 2-year follow-up.

This study is a 2-year follow-up of an average-risk population offered screening with both Haemoccult and Hemeselect tests to determine the interval cancer rate, and thus sensitivity. The effect on compliance with Hemeselect of testing over 1 day rather than 3 days was investigated in a separate cohort. In the first study, 3948 subjects received tests; 1489 (37.7 per cent) completed both tests and 148 had a positive result, 17 (1.1 per cent) were Haemoccult positive and 145 (9.7 per cent) were Hemeselect positive. Investigation of 142 patients revealed ten with cancer (Dukes stage A, seven; B, one; C, two). All were detected by Hemeselect but only one was Haemoccult positive. After a median follow-up of 35 (range 26-43) months, seven further patients developed colorectal cancer (stage A, one; B, three; C, three) but none followed a negative Hemeselect test (100 per cent sensitivity). In the second study 2703 subjects were offered Hemeselect tests. Compliance for testing over 1 day (48.6 per cent) was significantly better than that over 3 days (43.1 per cent) (chi 2 = 8.1, 1 d.f., P < 0.01). Hemeselect is a promising screening test for the early detection of colorectal cancer.

Is an immunological faecal occult blood test better than Haemoccult? A cost-benefit study.

Immunological faecal occult blood (FOB) tests have theoretical advantages over their guaiac counterparts in that they are specific for human haemoglobin. HemeSelect is a semi-quantitative immunological FOB text. Faecal material is eluted into test diluent and serial dilutions are performed. The manufacturers recommend that erythrocyte agglutination at 1:8 dilution is considered a positive reaction. However, further serial dilutions can be carried out and the highest dilution at which the test remains positive determined. At 1:8 dilution, the test has been shown to be more sensitive for symptomatic colorectal cancer than Haemoccult. The aim of this study is to compare the positive rates, neoplastic yield and costs of Haemoccult with HemeSelect at various dilutions in asymptomatic average risk subjects aged 50-74. 1489 subjects satisfactorily completed both tests, 145 (9.7%) returned positive Hemeselect tests (read at 1:8 dilution, 38 patients with neoplasms > or = 1 cm) and 17 positive Haemoccult tests (1.1%). All positive Hemeselect tests were further serially diluted. As the Hemeselect dilution increased to 1:16, 1:32, 1:64 and 1:128 so the positive rate and yields of neoplasms > or = 1 cm progressively fell to 6.8% & 35, 3.6% & 20, 2.7% & 18 and 1.5% & 12, compared with 1.1% and eight neoplasms > or = 1 cm for Haemoccult. In spite of the unit cost of the Hemeselect test being greater than Haemoccult, the cost per neoplasm > or = 1 cm was lower for Hemeselect at 1:8 and 1:16 dilutions than Haemoccult. However, for an equivalent neoplastic yield, Haemoccult was cheaper. Hemeselect is a versatile test whose positive rate can be tailored according to the risk of the group being screened.

Population screening for colorectal cancer: comparison between guaiac and immunological faecal occult blood tests.

There is concern about the low sensitivity of the guaiac-based Haemoccult test in mass population faecal occult blood (FOB) screening for the early detection of colorectal carcinoma. Hemeselect, an immunological FOB test, has been shown to be more sensitive for symptomatic colorectal cancer and may prove to be a more reliable screening method. In Brighton and Guildford, 4018 asymptomatic subjects aged 50-75 years were offered screening with Haemoccult and Hemeselect. A total of 1489 (37.7 per cent) completed both tests, of which 17 (1.1 per cent) were positive for Haemoccult and 145 (9.7 per cent) positive for Hemeselect (a total of 148 subjects had positive tests). Seven subjects (4.7 per cent) refused to be investigated. Colonic investigation in the remainder revealed nine cancers and 49 patients with 67 adenomas (32 tumours 1 cm or more in size). All cancers (Dukes A, six; B, one; C, two) were detected by Hemeselect (positive predictive value 6.2 per cent) but only one patient was Haemoccult positive (positive predictive value 5.9 per cent). Hemeselect detected 65 adenomas (31 of 1 cm or more) in 48 patients (positive predictive value 33.1 per cent) compared with 11 adenomas (seven of 1 cm or more) in eight patients who were positive for Haemoccult (positive predictive value 47.1 per cent). The test specificity for neoplasia was respectively 94.9 and 99.6 per cent. The Hemeselect positive rate is high but its substantial positive predictive value for cancer warrants continuing evaluation.

Ultrasound of the common bile duct in patients undergoing cholecystectomy.

One hundred patients undergoing cholecystectomy underwent ultrasonography of the biliary tree on the day prior to surgery. At operation a per-operative cholangiogram was performed unless stones were palpable in the duct. Pre-operative biliary ultrasonography accurately identified dilatation of the common bile duct (sensitivity 96%, specificity 95%) but was less accurate at detecting common duct stones (sensitivity 36%, specificity 98%). Thirty three percent of patients with dilated ducts on ultrasound did not have stones in the duct, while 20% of patients with common duct stones had normal sized ducts. We conclude that ultrasonography alone cannot reliably select patients who require exploration of the common bile duct, or select patients for operative cholangiography. Although pre-operative demonstration of common bile duct dilation is an absolute indication for operative cholangiography, by itself it does not indicate the need for exploration.

Varicose vein surgery using a pneumatic tourniquet: reduced blood loss and improved cosmesis.

A prospective controlled randomised study has been performed of 100 consecutive patients undergoing varicose vein surgery. One group underwent saphenofemoral flush ligation and multiple lower leg avulsions with the leg exsanguinated with a Rhys-Davies cuff, and ischaemia maintained with a pneumatic tourniquet. The other group underwent identical surgery but with a 30 degree head down tilt only. Blood loss was significantly less (13.5 +/- 12 ml vs 133 +/- 78 ml; P less than 0.01) and postoperative cosmesis was significantly improved in patients in the tourniquet group. Operating time was similar (27 +/- 11 min vs 30 +/- 13 min) in the two groups.

The success of in situ vein grafting: early results in comparison with the reversed vein technique.

In a 6-year retrospective analysis of 341 consecutive femorodistal autogenous vein bypasses, results from 104 in situ veins (IS) were compared with 209 reversed veins (RV). The groups were comparable for age, sex, diabetes, indication for surgery and calf vessel run-off, but a significantly higher proportion of the in situ group had a lower distal anastomosis (16% IS, 6% RV, chi 2 = 7.1 P less than 0.01). Overall, operative mortality was 2% and early graft failure was similar in both groups (11% IS, 12% RV, P = NS). Cumulative graft patency rates were 74% IS, 79% RV at one year and 71% IS, 71% RV (P = NS) at three years. Cumulative limb survival rates were 81% IS, 85% RV at one year and 79% IS, 81% RV [P = NS) at 3 years. These results demonstrate that the in situ technique has been used in a wider variety of patients and yielded similar early and intermediate term results to reversed vein.

Management of acute lower gastrointestinal haemorrhage in a surgical unit over a 4-year period.

Over a 4-year period 107 patients, 5% of all emergency admissions, were admitted to one surgical unit with significant lower gastrointestinal haemorrhage (requiring more than a 2-unit transfusion of blood). Twenty-three individuals required more than 3 units of blood, and 7 life-saving surgery. All subjects undergoing surgery required more than 3 units of blood in the first 24 hours of admission. Arteriography was diagnostic in 5 of the 9 subjects in whom it was performed. Arteriography was positive if performed in the first 24 hours of admission. A flow chart of the management of patients with lower gastrointestinal haemorrhage is presented.

Faecal occult blood screening of first degree relatives of patients with colorectal cancer.

A full first-degree family history was taken from 161 patients with colorectal cancer (Group 1) and from a group of 203 subjects previously investigated and found to have no colorectal neoplasia (Group 2). Twenty-six (16%) of patients in Group 1 compared with 23 (11%) in Group 2 had at least 1 first-degree relative with colorectal cancer (p = 0.23). Contact of first-degree relatives was possible in 123 patients in Group 1. Of these, 4 were members of 'cancer families' with 26 available first-degree relatives. The remaining 119 patients had 341 contactable first-degree relatives. They were approached by post and offered faecal occult blood (FOB) screening. One hundred and sixty-two (47%) completed FOB tests of which 12 (8%) were positive. Investigation of these individuals detected 4 adenomas. In the subgroup of 20 patients with 1 or 2 first-degree relatives with colorectal cancer, there were 78 potential relatives of whom 71 were contacted. Thirty-two (45%) FOB tests yielded 1 positive found to have an adenoma. A control group of 332 individuals was selected randomly from general practitioners' lists and offered FOB testing. One hundred and fifty-five (47%) complied of whom 7 (4.5%) were positive. Investigation yielded 1 adenoma. Thirteen of the 26 relatives of the 4 'cancer family' patients were investigated by endoscopy and 2 (15%) had large polyps detected. Although there may be an increased risk of colorectal neoplasia in first-degree relatives of patients with sporadic colorectal cancer, this risk is not sufficiently high to justify separate screening.

An assessment of occult blood testing to determine which patients with large bowel symptoms require urgent investigation.

One hundred and fifty-two consecutive patients with symptoms suggestive of colorectal disease were offered occult blood testing before undergoing barium enema examination or colonoscopy; one hundred and thirty-nine successfully completed the test. Thirty-four had positive results of whom thirteen had a cancer and eight an adenomatous polyp (diagnostic yield for neoplasia of 59 per cent). No false negative results occurred, a sensitivity of 100 per cent, and only 21 false positives occurred, a specificity for malignancy of 84 per cent. Subjects attending outpatients should be offered occult blood testing; those with a positive test should undergo colonoscopy. The cost-benefit of such a scheme is emphasized.

The localization of an anti-tumour monoclonal antibody (791T/36) in gastrointestinal tumours.

Fifty-six patients with gastrointestinal cancers and four patients with benign colorectal tumours have been injected with radiolabelled anti-tumour monoclonal antibody ( 791T /36) to assess the degree of localization of the antibody by external scintiscanning and measurements on resected specimens. Twenty-nine patients with primary colorectal cancer showed increased uptake of the radiolabelled antibody in the resected tumours, with a tumour to normal tissue (T:NT) ratio of 2.5:1. All but two of fifteen patients with recurrent or metastatic tumour showed positive images of the deposits on external scintiscanning. Twelve patients with noncolonic gastrointestinal malignancy were studied and in only two patients were tumours demonstrated by external scanning. There were no positive images in four patients with benign colonic disease nor could increased uptake of radiolabelled antibody be demonstrated in the resected specimens. Immunohistology and autoradiography have shown that the antibody can be demonstrated in the pseudoacini and stroma of colon cancer. There are indications that this may represent localization to a cell surface antigen which becomes detached in the processing of the histological sections. It seems that in the gastrointestinal tract the monoclonal antibody 791T /36 is consistently taken up by colorectal cancer. Only a few noncolonic cancers and no benign colonic tumours take up the antibody. This antibody uptake may prove of value in the detection of occult metastases and in the targeting of antitumour agents.

Colorectal screening by a self-completion questionnaire.

The prevalence and significance of colorectal symptoms within a group of 1533 individuals was assessed using a self-completion questionnaire and results compared with faecal occult blood screening. One hundred and twenty eight individuals listed one or more symptoms, while only 12 had a positive blood occult test. Of the subjects studied, 6.6% had noticed bleeding from the rectum in the last six months, 8.7% diarrhoea, and 12.3% a change in bowel habit. Examination of these individuals revealed one (0.8%) to have an adenoma of the colon. By comparison, occult blood testing identified two patients with carcinoma and four with adenoma. Both of the patients with carcinoma and three out of the four with adenoma had replied negative to the questionnaire suggesting the self-completion questionnaire to be of little value in the early detection of colorectal neoplasia.

Intervention in large bowel carcinogenesis--does screening improve prognosis?

Cancer of the large bowel is the second most common malignant tumour in the western world, with approximately 20,000 new cases registered each year in England and Wales. No improvement in the survival figures has occurred in the past 30 years, and since 1970 the number of deaths per annum in Great Britain has been rising. The prognosis of the disease is related directly to the degree of centrifugal spread of the tumour. Patients with cancer limited to the bowel wall have a corrected 5-year survival of about 90%, whereas those with tumours with lymphatic spread have a 5-year survival of about 30%. The prognosis for early colorectal tumours is therefore good, but a method of identifying such lesions is required. If early tumours bleed, the detection of occult blood in the faeces may be a valuable screening test for colorectal cancer. In one town, 8,925 asymptomatic people over the age of 40 were invited to be screened for faecal occult bleeding using Haemoccult slides. The invitation was accepted by 2,439 patients, a compliance rate of 27%. On Haemoccult screening 121 patients were positive initially, but 39 of these were found to be false-positive after further investigation. Haemoccult therefore gives a false-positive incidence of 30%. Twelve tumours of the bowel were identified, eight polyps and four cancers. Another patient who had been negative in the screening survey was identified within 2 months of the end of the experiment as having large-bowel cancer. This means that Haemoccult gives a false negative rate, in our hands, of 20%. The ability of a cancer screening procedure to identify and cure early tumours depends upon the compliance of the population, the sensitivity of the test and the availability of effective treatment. The poor compliance of our population and the disappointing sensitivity of Haemoccult mean that occult blood screening for early large bowel cancer remains theoretically possible but practically inefficient.

Localisation of human osteosarcoma by antitumour monoclonal antibody.

Immunoscintigraphy using radioisotope-labelled monoclonal antibody prepared against osteosarcoma 791T cells was used to detect a primary osteosarcoma. The eight-centimetre tumour was detected using rectilinear scintigraphy of 131I-labelled antibodies. Image enhancement was achieved by subtraction of blood-pool radioactivity labelled with technetium-99m. The ratio of tumour to non-tumour uptake of radioactivity (5:1) suggested that antibody targeting of therapeutic agents is feasible.

Flexible fiberoptic sigmoidoscopy and double-contrast barium-enema examination in the identification of adenomas and carcinoma of the colon.

To assess the accuracy of the flexible fiberoptic sigmoidoscope, 227 consecutive patients (mean age 61.8 +/- 13 years) requiring investigation of colonic symptoms were evaluated using rigid and flexible sigmoidoscopy (PAF and KDV) and double-contrast barium enema (SSA). Patients with equivocal findings or adenomatous polyps underwent colonoscopy (TWB). Thirty-four patients had carcinoma and 50 patients had one or more adenomatous polyps (greater than 5mm). The neoplastic yield from rigid sigmoidoscopy was 12 per cent, flexible fiberoptic sigmoidoscopy 90 per cent, and double-contrast barium enema only 76 per cent. Barium enema failed to identify eight carcinomas and 13 adenomatous polyps; seven of the eight carcinomas were polypoid Dukes' Stage A lesions, and associated diverticular disease was present in 62.5 per cent of cases. Flexible fiberoptic sigmoidoscopy failed to identify seven carcinomas and one adenomatous polyp. Five of the carcinomas were beyond range of the instrument; in one patient, a stricture was seen that was caused by the carcinoma; and in the seventh patient, the examination was terminated because of angulation spasm. Double-contrast barium enema is inaccurate in detecting lesions in the sigmoid colon, with flexible sigmoidoscopy being superior.

Accuracy of occult blood tests over a six-day period.

The false negative rate of the stabilized guaiac faecal occult blood tests, Fecatest and Haemoccult, was determined in 61 patients with known colorectal cancer. When subjects tested their stools over three days, 9.7% of the Fecatest slides and 27.8% of the Haemoccult slides were negative (p less than 0.02). Extending the number of days of testing from three to six reduced the false negative rate of Fecatest to 4.8% and Haemoccult to 9.7% (p less than 0.05). There was no significant difference between the false negative rate of Fecatest and Haemoccult test when subjects performed six-day testing. Haemoccult false negative results occurred mainly in patients with well differentiated left sided carcinomas.

Controlled trial of faecal occult blood testing in the detection of colorectal cancer.

20 525 patients from general practitioners' lists were randomly allocated into test and control groups. The 10 253 test subjects were invited to perform haemoccult faecal occult blood testing over 3 days. 3613 (36 . 8%) of the 9807 who received their invitations completed the test. Compliance was improved by direct invitation from the general practitioner and by prior health education by letter or interview. 77 people (2 . 1%) had a positive test result, and 50% of these on investigation had neoplastic disease--12 had invasive carcinomas (9 Dukes' stage A, 2 stage B, 1 stage C) and 27 had 40 adenomas (12 over 2 cm, 2 of which contained areas of severe dysplasia). In the year following the screening test 1 carcinoma (stage C) has presented in the group which accepted the test, and 10 carcinomas (4 stage B, 4 stage C, 2 stage D) have presented in the control group. This respresents a 3 . 6 times greater detection rate per 1000 persons in the test group than in the control group. Only 8 adenomas have presented in the control and non-responding groups. Fibreoptic sigmoidoscopy identified the 10 carcinomas within its range and 39 of the 40 adenomas. Double-contrast barium enema identified only 9 of the 12 carcinomas and 24 (62%) of the 40 adenomas. All 3 carcinomas not identified by barium enema were polypoid Dukes' stage-A lesions.

Localized amyloid of the ureter--case report and review of the literature.

An unusual case of localized amyloidosis of the ureter is described and a review of the 12 previously reported cases is presented. No case had been diagnosed prior to surgery. Loin pain, with or without haematuria, associated with a sterile pyuria and an abnormal pyelogram were the commonest clinical signs. In the case reported an incidental small renal cell carcinoma was also present and the association of amyloidosis and neoplasia is discussed.

Endoscopic review of patients who have had gastric surgery.

Seventy one patients who had had operations on their stomachs over 15 years previously were examined by endoscopy and multiple mucosal biopsy sampling. Sixty six had histologically proved gastritis (56 chronic atrophic gastritis, 10 superficial gastritis), 38 intestinal metaplasia, and 11 epithelial dysplasia. In three cases the epithelial dysplasia was severe (carcinoma in situ). One patient had an infiltrating carcinoma and another, whose biopsy appearances were reported as severe dysplasia, developed a carcinoma of the stomach eight months later. All patients having undergone gastric surgery more than five years previously should be screened endoscopically and any found to have moderate dysplasia subjected to regular endoscopic screening thereafter. Patients with severe dysplasia (carcinoma in situ) should be considered for radical surgery.