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.

Long-term results of the Angelchik prosthesis for gastro-oesophageal reflux.

INTRODUCTION: Between 1982 and 1989, 46 patients had insertion of an Angelchik prosthesis for gastro-oesophageal reflux. Eleven patients (24 per cent) subsequently had the prosthesis removed, all but one for intractable dysphagia. METHODS: Thirty-six of the original patients were followed by questionnaire, and 32 of these had a barium marshmallow swallow investigation. RESULTS: A high proportion of patients (20 of 26) with a prosthesis in situ had symptoms of dysphagia. On objective evaluation by marshmallow swallow, the transit time was significantly slower than that of an age-matched control group (P < 0.01), but showed no significant deterioration with time compared with previous postinsertion studies. CONCLUSION: The Angelchik prosthesis causes long-term dysphagia in a high proportion of patients, severe enough in one-quarter to necessitate its removal. Its continued use cannot, therefore, be recommended.

Randomised controlled trial of faecal-occult-blood screening for colorectal cancer.

BACKGROUND: There is growing evidence that faecal-occult-blood (FOB) screening may reduce colorectal cancer (CRC) mortality, but this reduction in CRC mortality has not been shown in an unselected population-based randomised controlled trial. The aim of this study was to assess the effect of FOB screening on CRC mortality in such a setting. METHODS: Between February, 1981, and January, 1991, 152,850 people aged 45-74 years who lived in the Nottingham area of the UK were recruited to our study. Participants were randomly allocated FOB screening (76,466) or no screening (controls; 76,384). Controls were not told about the study and received no intervention. Screening-group participants were sent a Haemoccult FOB test kit with instructions from their family doctor. FOB tests were not rehydrated and dietary restrictions were imposed only for retesting borderline results. Individuals with negative FOB tests at the first screening, together with those who tested positive but in whom no neoplasia was found on colonoscopy, were invited to take part in further screening every 2 years. Screening was stopped in February, 1995, by which time screening-group participants had been offered FOB tests between three and six times. Screening-group participants who had a positive test were offered full colonoscopy. All participants were followed up until June, 1995. The primary outcome measure was CRC mortality. FINDINGS: Of the 152,850 individuals recruited to the study, 2599 could not be traced or had emigrated and were excluded from the analysis. Thus, there were 75,253 participants in the screening group and 74,998 controls. 44,838 (59.6%) screening-group participants completed at least one screening. 28,720 (38.2%) of these individuals completed all the FOB tests they were offered and 16,118 (21.4%) completed at least one screening but not all the tests they were offered. 30,415 (40.4%) did not complete any test. Of 893 cancers (20% stage A) diagnosed in screening-group participants (CRC incidence of 1.49 per 1000 person-years), 236 (26.4%) were detected by FOB screening, 249 (27.9%) presented after a negative FOB test or investigation, and 400 (44.8%) presented in non-responders. The incidence of cancer in the control group (856 cases, 11% stage A) was 1.44 per 1000 person-years. Median follow-up was 7.8 years (range 4.5-14.5). 360 people died from CRC in the screening group compared with 420 in the control group-a 15% reduction in cumulative CRC mortality in the screening group (odds ratio=0.85 [95%; CI 0.74-0.98], p = 0.026). INTERPRETATION: Our findings together with evidence from other trials suggest that consideration should be given to a national programme of FOB screening to reduce CRC mortality in the general population.

Detection of colorectal liver metastases using intraoperative ultrasonography.

Intraoperative ultrasonography of the liver has been carried out in 99 patients undergoing surgery for colorectal cancer. Palpation of the liver, preoperative abdominal ultrasonography and computed tomography scanning were also performed in all patients. Metastases were identified in 26 of the 99 patients (26 per cent). Intraoperative ultrasonography diagnosed more metastases than palpation, abdominal ultrasonography or CT scanning, identifying metastases in 24 of the 26 patients, including six patients in whom the metastases were not detected by any other technique. Identification and localization of impalpable liver metastases is therefore possible using intraoperative ultrasonography.

Screening for clinically unsuspected abdominal aortic aneurysms in patients with peripheral vascular disease.

In patients with abdominal aortic aneurysms, most fatalities occur from rupture before the patient can be brought to hospital. Even when seen in hospital the mortality is still approximately 50% in contrast to elective repair which has a substantially reduced mortality of less than 5%. In order to reduce the number of patients dying from rupture, they must be diagnosed early to allow elective intervention, hence there has been considerable renewed interest in screening for abdominal aortic aneurysms. We have studied a consecutive series of 104 patients with either claudication or ischaemic rest pain in the lower limbs to determine the incidence of aortic aneurysms in this type of patient.

Randomised, controlled trial of faecal occult blood screening for colorectal cancer. Results for first 107,349 subjects.

To assess the effectiveness of screening by faecal occult blood tests, 107,349 people without symptoms of colorectal disease identified from general practitioner records have been randomly allocated to test and control groups. 53,464 test subjects were invited to carry out the screening test; 27,651 (53%) of the 52,258 who received the tests did so. Further investigation of the 618 (2.3%) with positive tests showed 63 cancers (52% stage A) and 367 adenomas (266 subjects). Rescreening of subjects with negative results every 2 years (9510 first rescreen, 3639 second) has shown a significant fall in the rate of positive results (1.7% of 7344; 0.3% of 2906). Cancers have also been diagnosed in 20 subjects presenting in the interval between a negative test and rescreening, and in 83 non-responders. The incidence of cancer in the control group (123 subjects; 10.6% stage A) was 0.72 per 1000 person-years. Cancers detected by screening were at a less advanced pathological stage, but it is too early to show any effect of screening on mortality from colorectal cancer.

Oesophageal transit of marshmallow after the Angelchik procedure.

The oesophageal transit time of half a marshmallow was measured radiologically in 17 controls, 28 patients with gastro-oesophageal reflux pre-operatively, 36 patients soon after implantation of the Angelchik prosthesis (2-9 weeks) and in 23 patients later postoperatively (9-48 months). Sixteen postoperative patients also underwent oesophageal manometry. All control and pre-operative patients had a marshmallow transit time of less than 1 min; 67 per cent of the early postoperative patients had prolonged transit and 70 per cent of the late tests were similarly abnormal. Prolonged oesophageal transit as measured by marshmallow swallow correlated well with symptoms of solid food dysphagia. Most, but not all, patients with an abnormal marshmallow swallow had abnormal manometric findings. The oesophageal transit of solid food is significantly slowed after the Angelchik procedure and this is not a transient postoperative phenomenon.

Fecal occult blood screening for colorectal cancer in the general population. Results of a controlled trial.

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).

Evaluation of the plain abdominal X-ray in the acute abdomen.

The prognostic value of an erect and supine abdominal X-ray was studied prospectively in 97 patients with an acute abdomen. Although 64 (66%) of the radiographs showed an abnormality, the surgical registrar altered his clinical diagnosis on only seven occasions and changed his management on four. A consultant radiologist was the most accurate at reporting the X-rays even without seeing the patient, whilst junior surgical and radiological staff were as accurate as each other. A surgical registrar, however, was more accurate than junior radiologists in making a diagnosis. The investigation was of immediate clinical value in only 4% of the patients, and its use could probably be limited without detriment to patients.

A prospective study of thyroid ultrasound scan in the clinically solitary thyroid nodule.

Thyroid ultrasound differentiates solid from cystic lesions, solitary nodules from multinodular and diffuse enlargement, and extrathyroidal lesions. Two hundred consecutive patients with a clinically solitary thyroid nodule were investigated by ultrasound examination, thyroid function test, and thyroid auto-antibodies. Patients with confirmed solitary solid, or mixed solid and cystic nodules underwent surgery as well as those with cysts, multinodular or diffuse goitres with pressure symptoms, recurrent haemorrhage or relapsing hyperthyroidism. Comparison between the ultrasound and ultimate pathological findings in the 101 patients who underwent surgery showed that they were in agreement in 96 cases. The remaining 99 patients with cystic, multinodular or diffuse lesions have been followed up for a mean of two years. Nearly 50% of patients with a clinically solitary thyroid nodule have avoided surgery.

A comparison of an immunological faecal occult blood test Fecatwin sensitive/FECA EIA with Haemoccult in population screening for colorectal cancer.

Two faecal occult blood tests, a simple chemical test Haemoccult and an immunological test, Fecatwin Sensitive/Feca EIA, were offered to 3,225 asymptomatic individuals as screening for colorectal cancer. One thousand three hundred and four (44%) completed and returned the tests and of these 126 (9.7%) were found to be positive - Haemoccult 40 (3%) and Feca EIA 106 (8.1%). Five cancers (4 Dukes' Stage A, 1 Dukes' Stage C) and 23 adenomas greater than 1 cm were detected - rates of 3.8 per 1000 persons screened and 17.7 per 1000 persons screened respectively. Of the five cancers identified 5 were Feca EIA positive and 3 were Haemoccult positive. Of the 23 adenomas greater than 1 cm diameter identified, J1 were Feca EIA positive and 20 were Haemoccult positive. Seventy-eight Feca EIA positive subjects were investigated and no neoplastic disease was identified. Whilst this sensitive immunological test increases the yield of carcinomas, the high false positive rate makes it unsuitable for population screening for colorectal cancer in its present form.

A comparison of nuclear magnetic resonance and intravenous xeroangiography with conventional arteriography in popliteal artery imaging.

Twenty-nine patients with peripheral vascular disease had the popliteal artery segment assessed by xeroangiography and nuclear magnetic resonance (NMR) scanning. The result of each test was compared with conventional contrast arteriography. Nuclear magnetic resonance and xeroangiography correctly predicted popliteal artery patency in 97% and 100% of limbs, respectively, and occlusion was correctly predicted in 44% and 63% of limbs. The ability of xeroangiography to define the state of the popliteal artery accurately makes this a useful method in high-risk patients. The potential for NMR imaging appears very promising but more work is required to define its future clinical application.

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.

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.

Comparison of rigid and flexible fibreoptic sigmoidoscopy with double contrast barium enemas.

One hundred consecutive new patients attending a general surgical and gastrointestinal outpatient clinic had a flexible fibreoptic sigmoidoscopic examination before a double contrast barium enema. Colonic lesions were found in 45 patients and flexible sigmoidoscopy was superior to barium enemas in diagnosing lesions in the sigmoid colon. Two cancers, 1 histologically a Dukes' A lesion and 6 adenomatous polyps greater than 0.5 cm in diameter, in the sigmoid colon, were not detected by barium enemas. In 6 of these patients extensive diverticular disease was present. In patients with rectal bleeding found to have diverticular disease demonstrated radiographically, an endoscopic examination must be performed to exclude polyps or cancer. Flexible fibreoptic sigmoidoscopy may reduce the numbers needing barium enemas.

Outcome of endoscopy and barium radiography for acute upper gastrointestinal bleeding: controlled trial in 1037 patients.

A study was conducted to find whether the higher diagnostic yield of endoscopy compared with barium radiography improves management or survival in patients with acute upper gastrointestinal bleeding. A total of 1037 patients were entered into a randomised study comparing the outcomes after each investigation. The diagnostic yield in patients who underwent endoscopy was 73% (382 of 526 cases) and in those examined by radiography 55% (280 of 511 cases). A fifth of the patients in the radiology group and a tenth of those in the endoscopy group subsequently underwent the alternative investigation; in most cases, however, no additional diagnostic information was obtained. Operation rates were similar in two groups, though patients in the endoscopy group were generally operated on sooner. Mortality rates were also similar in the two groups, though postoperative mortality was higher in the endoscopy group. Endoscopy may be a more accurate means of diagnosis than radiography, but it offers no short-term benefits in management.

Screening for symptomless colorectal cancer by testing for occult blood in general practice.

1638 persons over the age of 45 were invited to test their faeces for occult blood, using the 'Haemoccult' method. The acceptance-rate was low (25%) in those over the age of seventy-five and was highest (56%) in those aged fifty-five to sixty. 3.8% of those using the test had at least one positive haemoccult test. Rigid sigmoidoscopy identified 2 persons with carcinoma of the rectum and 1 with adenoma of the rectum. Subsequent colonoscopy and barium enema identified two cases of adenoma of the sigmoid colon and one case of adenoma of the caecum.