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Objectives . To determine the extent to which socio-economic deprivation explains colorectal cancer prevalence, subject participation in screening, and postoperative survival and life expectancy. Methods . Regression analyses of clinical data from a large randomized controlled trial, augmented by geographical-based indices of deprivation. Results . Deprivation appears to exert no significant impact on colorectal cancer prevalence but is a major factor explaining subject participation in screening. Cancer detection at later stages reduces life expectancy at time of treatment. Females from more-deprived areas have poorer post-treatment life expectancies and survival prospects, independently of their screening behaviour. Conclusions . Screening increases the chances of having a cancer treated at an earlier stage, and treatment at an earlier stage is associated with longer subsequent life expectancy. However, those from more-deprived areas are less likely to accept an invitation to be screened.

Both precursor forms of gastrin and mature amidated gastrin peptides can enhance proliferation of colorectal tumours and may regulate growth in an autocrine manner. The purpose of this study was to evaluate the effect of neutralization of precursor and amidated gastrin on primary and secondary in vivo growth of a human colorectal tumour. The human colorectal cell line, AP5LV, when injected into the muscle layer of the abdominal wall of severe combined immunodeficient (SCID) mice, grows as a well-vascularized primary tumour and metastasis to the lung. AP5LV expressed the precursor gastrin forms; progastrin and glycine-extended gastrin and gastrin/CCKB receptors, as assessed by immunocytochemistry. Gastrimmune is a gastrin immunogen in which the amino terminus of the gastrin-17 molecule is linked to diphtheria toxoid and induces antibodies which neutralise the amidated and glycine-extended forms of gastrin-17. Rabbit antiserum, raised against Gastrimmune, was administered intravenously into SCID mice bearing AP5LV tumours. Control animals were treated with antiserum raised against diphtheria toxoid only. Antibodies raised against Gastrimmune significantly limited the growth of primary AP5LV tumours, as assessed by median cross-sectional area (controls = 244 mm2; antibody-treated = 179 mm2; P = 0.033). In addition Gastrimmune-induced antiserum limited the growth of lung metastasis as assessed by nodule number (controls = 3.5; antibody-treated = 1.0; P = 0.0001) and nodule cross-sectional as assessed by image analysis (controls = 11.9 mm2; antibody-treated = 3.75 mm2; P = 0.0064). In conclusion in vivo neutralization of gastrin forms, which may potentially be fueling growth by an autocrine pathway, inhibited both primary growth and, to a greater degree, lung metastasis of a human colorectal tumour cell line. Immunization against tumour-associated gastrin forms may provide an effective therapy for advanced colorectal cancer.

Colorectal cancer is common and accounts for over 15,000 deaths annually in England and Wales. Up to 30% of these patients require emergency surgery. Screening for colorectal cancer can reduce the mortality of colorectal cancer. This study addresses the impact of a population-based screening study on emergency admissions with colorectal cancer.From 1981 a randomized trial of Faecal Occult Blood (FOB) screening has been undertaken in the Nottingham area, recruiting over 150,000 patients. The present study examined the records of patients enrolled in this study who presented as an emergency with colorectal cancer.Colorectal cancer was identified in 1962 cases, of which 468 (23.9%) presented as emergencies. The overall compliance was 60% (proportion of individuals completing at least one test). There were significantly fewer emergencies in the Screen-detected group compared with the Control group (P =0.0001). This group also had a significantly reduced 30-day mortality and a lower stoma rate than the Control group. Conversely the Non-responders had a significantly greater proportion of emergency admissions and a significantly increased stoma rate compared with the Control group.Screening for colorectal cancer using a faecal occult blood test can significantly reduce the number of emergency presentations with colorectal cancer. It is likely that the introduction of a national programme of screening for colorectal cancer would lead to increased compliance and that this would lead to a significant reduction in the emergency workload on the National Health Service from colorectal cancer.

Onapristone is a progesterone antagonist which inhibits the growth of mammary tumours in mice. The effect of Onapristone and concomitant oestrogen (E2) supplements on the growth of five human gastrointestinal cancer xenografts was examined. E2 stimulated RD19 (gastric tumour) tumour growth in female mice and tumours grew less well when also treated with Onapristone (P0.05). Onapristone had no effect on male mice bearing RD19 tumours or mice of either sex bearing MKN45G (gastric) tumours. PAN-1 (pancreatic) tumours were significantly stimulated by E2 (by 64% of control, P = 0.02) and Onapristone treatment inhibited E2 stimulated growth (52% reduction of E2 control, P0.05). C146 (colorectal) tumour growth was not stimulated by E2 nor inhibited by Onapristone. E2 stimulated formation of AP5LV (colorectal) tumour nodules (in lungs) (mean 38-52, P = 0.001). Onapristone significantly reduced the number of nodules (mean 32, P0.05) only in female mice not given E2. Xenografts of some GI tumour cell lines grow at different rates in male and female mice. E2 may cause additional growth stimulation and E2 stimulated growth can be reversed by Onapristone to basal levels.

Summary 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 16118 (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=0026). 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.

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 neoplasmsor = 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 neoplasmsor = 1 cm progressively fell to 6.8%35, 3.6%20, 2.7%18 and 1.5%12, compared with 1.1% and eight neoplasmsor = 1 cm for Haemoccult. In spite of the unit cost of the Hemeselect test being greater than Haemoccult, the cost per neoplasmor = 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.

A hepatic invasive human colorectal xenograft model was derived in nude mice by selection through the liver of the parental cell line, C170. Following intraperitoneal injection, tumours selectively grew on the liver in > 80% of the animals within 15–20 days. The liver-invading xenograft line, renamed C170HM2, had a significantly greater expression of the LewisX antigen compared to C170 (mean linear fluorescence per cell > 1000 compared with 500 for C170, P < 0.02). C170HM2 had significantly elevated proliferation (when compared with C170) in the presence of epidermal (P < 0.001) and basic fibroblast growth factor (P < 0.001). C170HM2 also mitogenically responded to type I collagen (derived from rat tails), unlike C170. C170HM2 tumours when invading the liver expressed both interstitial collagenase and gelatinase activity at the invading edge.

The rat pancreatic cell line, AR42J possessed high-affinity gastrin and somatostatin receptors and its growth was stimulated by physiological gastrin-17 concentrations between 5 x 10(-11) mol/l and 10(-9) mol/l as measured by [75Se]selenomethionine uptake. The somatostatin analogue, octreotide (2 x 10(-7) to 2 x 10(-11) mol/l), reduced this stimulated growth. Gastrin-stimulated AR42J growth was also inhibited by proglumide (3 x 10(-4) mol/l) and lorglumide (3 x 10(-5) mol/l) at maximal G17 concentrations of 5 x 10(-11) and 10(-10) mol/l, respectively, and the analogues competed with [125I] gastrin-17 (5 x 10(-10) mol/l) for binding to gastrin receptors on AR42J (50% inhibitory concentrations, less than or equal to 10(-3) mol/l and 4 x 10(-6) mol/l, respectively. Octreotide reduced the basal growth of the human gastric cell line, MKN45G, (which is associated with intracellular gastrin immunoreactivity) in serum-free medium to 73% of control at a concentration of 2 x 10(-8) mol/l, which was reversed by gastrin-17 (10(-10) mol/l). Lorglumide (3 x 10(-5) mol/l) also reduced the basal growth to 30% of control, which was reversed to 78% by 10(-5) mol/l gastrin. Proglumide had no effect on the basal growth of MKN45G.

Diagnosis for colorectal cancer is commonly made using either colonoscopy or double contrast barium enema techniques. To data, little attention has been paid to the comparative costs of these two procedures and the paper presents estimates of hospital costs for each, using data from the colorectal study being undertaken in Nottingham, U.K. Consideration is also given to procedure sensitivity and the frequency of referral to the alternative technique in cases of incomplete diagnosis. The paper presents the conditions under which a given technique may be considered cost-superior to its alternative but concludes that the absence of conclusive clinical trial data and other considerations precludes the identification of a definitively optimum technique from the economic point of view.

Screening represents an alternative possibility of influencing the mortality of colorectal cancer in a population. It may reduce mortality in two ways. Firstly by the detection of tumours early in their natural history before they have produced symptoms and when the tumour is amenable to surgical treatment and secondly, by the detection and removal of premalignant adenomas with a resulting decrease in the future incidence of colorectal cancer.

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.

Colonic motility has been monitored using a pressure sensitive radiotelemetry capsule and portable receiving equipment in ambulatory subjects. Data from 24 hour recordings were stored on miniature cassette tape and subsequently replayed on a standard unit interfaced to a BBC B microcomputer. The computer program provides a semi-automated analysis and calculates a motility index allowing objective quantitative measurements to be made which can be rapidly and accurately presented. This method of analysis has been shown to be resistant to interobserver bias and in comparison with the analysis of analogue paper traces shown to be reproducible.

This paper describes a hospital costing analysis of 85 colorectal cancer patients treated in the context of a randomised control trial at the Queen's Medical Centre, Nottingham. Estimates are presented for investigation, surgical and inpatients costs. Comparisons between study and control group patients reveal only a small difference in overall costs of treatment.

BBC microcomputers are being used in multiple roles in the computerization of a randomized colorectal screening study, of 120,000 people with a minimum seven year follow-up. They perform six distinct and essential functions in the management of the large population screening database, linked with a remote mainframe for bulk storage of data.

The effects of intrarectal metronidazole and intraincisional povidone iodine on sepsis after emergency appendicectomy were compared in a double-blind randomised controlled trial in 496 patients. Wound sepsis occurred in 12.3% of metronidazole-treated patients compared with 24% in the povidone-iodine group and 23.5% in an untreated control group. The metronidazole-treated patients left hospital approximately 2 days earlier than patients in the other two groups. They returned to work sooner and receiver fewer visits from the district nursing service. A short six-dose course of metronidazole significantly reduces the wound-infection rate in patients over the age of 12 undergoing emergency appendicectomy. If the clinical and economic benefits of metronidazole shown by this study are confirmed, the drug should be considered for routine use in emergency appendicectomy.

Mean delay between the onset of symptoms and treatment was 30·5 weeks in a hundred patients with colonic carcinoma and 38 weeks in a hundred patients with rectal carcinoma. Most of this delay occurred outside hospital and delays attributable to the patient and family doctor were almost equal in duration. Patient delay is largely the result of not knowing the importance of bowel symptoms, while delay with the family doctor was the result of not examining patients with possible rectal carcinomas and not recognising symptoms suggestive of colonic carcinoma. 42% of patients with colonic carcinoma were admitted for emergency treatment, 76% having already consulted their doctor about symptoms on one or more occasions. Hospital delay consisted mainly in waiting for investigations, poor quality barium enemas, and inadequate sigmoidoscopy. There was no relation between the duration of symptoms and the Dukes stage of the tumour.

An immunological test for faecal occult blood is described, which is suitable for screening purposes. Fluorescein-labelled rabbit anti-human-haemoglobin serum is mixed with an aqueous faecal suspension, and free antibody is bound to a membrane sampler coated with human haemoglobin. The fluorescence on the membrane sampler is measured in a fluorometer, and the level of haemoglobin in the suspension is estimated. Advantages over chemical tests include absence of cross-reaction with animal haemoglobins, minimal observer error, and an adjustable sensitivity.