A randomised study of screening for colorectal cancer using faecal occult blood testing: results after 13 years and seven biennial screening rounds.

BACKGROUND: Three randomised trials have demonstrated reduction in mortality from colorectal cancer (CRC) by repeated screening with faecal occult blood tests, including the trial presented here, which is the only one still in progress. AIMS: To evaluate reduction in mortality after seven screening rounds and the possible influence of compliance on mortality from CRC. METHODS: At Funen in Denmark, random allocation to biennial screening with Hemoccult-II in 30 967 subjects aged 45-75 years and 30,966 controls was performed in 1985 from a population of 137,485 of the same age. Only participants who completed the first screening round were invited for further screening. Colonoscopy was offered if the test was positive. The primary end point was death from CRC, and the 10 year results were published in 1996. RESULTS: From the beginning of the first screening to the seventh round, mean age increased from 59.8 to 70.0 years in the screening and control groups, and the male/female ratio decreased from 0.92 to 0.81. Those who accepted screening were younger than non-responders. Positivity rates varied from 0.8% to 3.8%, the cumulative ratio of a positive test was 5.1% after seven rounds, and 4.8% of patients had at least one colonoscopy. Mortality from CRC was significantly less in the screening group (relative risk (RR) 0.82 (0.69-0.97)), and the reduction in mortality was most pronounced above the sigmoid colon. After seven rounds, RR was reduced to less than 0.70 compared with controls. Mortality rates from causes other than CRC did not differ. Non-responders had a significantly increased risk of death from CRC compared with those who accepted the full programme. Subjects who accepted the first screening, but not subsequent ones, demonstrated a tendency towards increased risk. CONCLUSIONS: The persistent reduction in mortality from CRC in a biennial screening program with Hemoccult-II, and a reduction in RR to less than 0.70 in those adhering to the programme, support attempts to introduce larger scale population screening programmes. The smaller effect on mortality from CRC in the rectum and sigmoid colon suggests evaluation by additional flexible sigmoidoscopy with longer intervals.

The pattern of recurrent colorectal cancer in a prospective randomised study and the characteristics of diagnostic tests.

In a prospective randomised study, 597 patients subjected to curative surgery for colorectal cancer were allocated to either a group with frequent follow-up or a control group with follow-up every 5 years. The pattern of recurrence is reviewed. An equal number of recurrences was detected in the two groups, but the recurrence was diagnosed 9 months earlier in patients followed frequently, and the diagnostic characteristics of various tests dependent upon how often they were used. It is unlikely that frequent follow-up after curative surgery for colorectal cancer has a large positive influence upon survival, but a small benefit from an intensive follow-up program cannot be ruled out. The present results indicate that clinical examination, digital rectal examination, proctoscopy, colonoscopy and chest x-ray should be included in such a programme, whereas others (blood haemoglobin, faecal occult blood test, double contrast braium enema, serum alanine aminotransferase, and serum bilirubin) should be avoided, having a low sensitivity for detecting recurrent colorectal cancer.

Booster vaccination against diphtheria and tetanus in man. Comparison of calcium phosphate and aluminium hydroxide as adjuvants--II.

Diphtheria and tetanus antibody levels were measured before and four weeks after booster vaccination of 313 Danish military recruits participating in a clinical trial to compare aluminium hydroxide and calcium phosphate as adjuvants in diphtheria-tetanus vaccines (DT). Twenty-eight percent of the men had a diphtheria pre-vaccination content below a protective level of 0.01 IU ml-1. The calcium phosphate adsorbed vaccine showed the highest efficacy for both antigens. Adverse reactions were rare but more frequent in the calcium group than in the aluminium group. No correlation was found between pre- or post-vaccination levels and adverse reactions and both vaccines gave rise to specific IgE formation. The results show that calcium phosphate is more effective but not a safer alternative to aluminium hydroxide when compared in vaccines containing 1.0 mg ml-1 of Ca or of Al.

[Rectoscopy and Hemoccult-II as initial diagnosis. A procedure in patients with symptoms of irritable colon]. / Rektoskopi og Haemoccult-II prøve som initial diagnostik. Procedure hos patienter med symptomer på colon irritabile.

The diagnostic accuracy for colorectal cancer (CRC) of rigid sigmoidoscopy and faecal occult blood test (Hemoccult-II) (H-II) was investigated in patients with irritable bowel syndrome in general practice in a three year period and the results were compared with those of the previous three years, where rigid sigmoidoscopy and double contrast barium enema (DCBE) were the initial preferred examinations. Colonoscopy was recommended in patients with positive H-II, but also in patients with repeated negative H-II within three months, provided that the symptoms persisted. CRC was detected in 141 of 630 patients with positive H-II and in 52 of 8697 with negative H-II. The number of CRC's in the two study periods was similar, in spite of a pronounced reduction in DCBE's from 12,196 to 5656 and a small increase in colonoscopies from 3053 to 4127. It was concluded that the new strategy was no worse than the previous one and the major savings in DCBE's could be used to exchange the rigid sigmoidoscopy with a 60 cm flexible sigmoidoscopy, increasing diagnostic accuracy, shortening delay of diagnosis and removing more adenomas, which eventually may reduce the future incidence of CRC and thereby the mortality from CRC.

[Colonoscopy after radical surgery for colorectal cancer. A 10-year prospective study of 309 patients]. / Kolonoskopi efter radikal kirurgi for kolorektal cancer. Ti års prospektiv af 309 patienter.

Experience from ten year colonoscopic follow-up in patients after radical surgery for colorectal cancer is presented. In all, 309 patients below 76 years were included from 1978 to 1983. All had preoperative proctoscopy and barium enema. Colonoscopy was performed perioperatively, every six months the first three years, four and five years, seven to eight years and ten years after surgery. A minority had double-contrast barium enemas. Synchronous adenomas were removed during surgery and at perioperative colonoscopy and these patients had the same risk of metachronous cancer as those without synchronous adenomas. Five patients with six metachronous cancers, all had new curative surgery. Patients with synchronous adenomas had a higher risk of metachronous adenomas, but had a better prognosis than those without synchronous adenomas. Colonoscopically demonstrated intraluminal local recurrence in the colon could not be treated with new radical surgery in contrast to four out of eight intraluminal recurrences in the rectum. Most local recurrences were extraluminal and were diagnosed by other means.

[Rectoscopy and Hemoccult II in irritable colon. A prospective study]. / Rektoskopi og Hemoccult-II ved colon irritabile. En prospektiv undersøgelse.

It was investigated whether Hemoccult-II test (H-II) could reduce the number of colonic examinations in patients with the irritable bowel syndrome, with normal rigid proctoscopic findings. A negative H-II was obtained in 299 patients from general practice and a positive test in nine. Colonoscopy was done in 157 and double contrast barium enema in 142 after random allocation. The nine patients with positive H-II all had colonoscopy. Among the 299 with negative H-II, colonic adenomas were detected in ten and an early cancer in an adenoma in the sigmoid colon; overlooked rectal adenomas were found in three, rectal cancer in one, rectal carcinoid in another and a coecal cancer, which could be palpated, in a third patient. Two patients with colonic cancer and one with adenoma were detected among those with positive H-II. All patients were followed by clinical examination after one year. In conclusion, colonic examination should carry a low priority in patients with symptoms of irritable bowel, negative Hemoccult-II and normal rigid proctoscopic findings performed by an experienced examiner. The investigation confirmed the recommendation of total colonoscopy in patients with a positive H-II and added support for increasing number of endoscopy services in contrast to those of diagnostic radiology, which should be reduced.

Initial mass screening for colorectal cancer with fecal occult blood test. A prospective randomized study at Funen in Denmark.

A Danish study allocated at random 30,970 persons to screening with Hemoccult-II and 30,968 as controls in a population of 140,000 between 45 and 74 years old. Persons with known colorectal cancer, adenoma, and distant spread from all types of cancer were excluded. The test was completed in 20,672 persons from August 1985 to September 1986, and 215 (1%) were found to be positive. Colonoscopy in 203 and double-contrast barium enema in 6 detected 37 persons with cancer and 86 with adenomas. Dukes A cancer was detected in 19 in the screening group, in contrast to 2 among controls. Synchronous adenomas were found in 23 with a positive test and 10 controls. Interval cancer was found in nine persons within 1-11 months after a negative test. Eighteen persons got cancer before invitation and six defectors as well. In all, colorectal cancer was detected in 70 persons in the screening group and in 38 controls; the figures for adenomas alone were 103 and 38, respectively. The study is designed to detect a possible reduction in mortality from colorectal cancer of 25% within 5 years after three screenings with intervals of 2 years. The second screening will begin in September 1987. It remains to be shown whether a reduction may be obtained both in mortality and in incidence of colorectal cancer.