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PURPOSE: The results of previous studies of colorectal neoplasia and fecal composition have been inconsistent, in part because the cases have been symptomatic and the studies small. We sought to test hypotheses relating to fecal bile acids, calcium, and pH in a large sample of asymptomatic subjects who had participated in fecal occult blood screening. METHODS: Fecal samples were obtained from 45 cases of cancer, 129 subjects with adenoma, 167 fecal occult blood-negative controls and 155 fecal occult blood-positive subjects in whom no cancer or adenoma was found. Concentrations of fecal bile acids, steroids, calcium, and pH were assessed blind to case-control status and compared between cases and 1) fecal occult blood-negative controls and 2) fecal occult blood-positive subjects. RESULTS: No association between colorectal cancer and fecal bile acids or pH was observed. Although there was no overall association between colorectal adenomas and fecal bile acids or pH, villous adenomas were associated with increasing concentrations of major bile acids and decreasing concentration of minor bile acids, and there was a suggestion of an inverse association with an acid pH. High levels of fecal calcium were associated with a reduced risk of both colorectal cancer and adenoma, but this was not statistically significant. CONCLUSION: The study does not support an association between colorectal cancer and fecal bile acids or pH. However, there is evidence that increases in major bile acids are associated with villous adenomas.

Although the aetiology of Barrett's oesophagus or columnar line oesophagus (CLO), remains unknown, bile reflux has been implicated as a factor in its pathogenesis. This study aimed to detect alkaline reflux in gastro-oesophageal reflux patients using dual probe pH monitoring. Thirty patients with histologically diagnosed CLO, 15 age and sex matched patients with oesophagitis (grade 1-3), and 15 healthy volunteers were studied by dual probe, 18 hour pH monitoring and analysis of the bile acid content of oesophageal refluxate. Total acid exposure and acid exposure in the upright and supine postures were greater in CLO subjects than in oesophagitis patients and controls. Furthermore, the number of reflux episodes lasting more than five minutes and the duration of the longest reflux episode were significantly greater in the CLO subjects than the oesophagitis and control subjects. Nine subjects with CLO and oesophagitis, however, were not identified as refluxers, although six had a bile acid concentration in their oesophageal aspirate higher than the 95th centile value of the controls. There was no correlation between the oesophageal pH and the bile acid contents of refluxate. It is concluded that dual probe pH monitoring is not useful in detecting alkaline refluxers. pH monitoring, although the only subjective test available to identify acid refluxers, is not a sufficiently sensitive test with which to define alkaline reflux.

OBJECTIVE--To examine the relation between the use of aspirin and non-steroidal anti-inflammatory drugs and the presence of asymptomatic colorectal adenomas. DESIGN--Case-control study of subjects participating in a randomised controlled trial of faecal occult blood screening for colorectal cancer. Data on analgesics and other drugs were obtained from a questionnaire which was mainly concerned with diet and was administered by an interviewer. SETTING--Nottingham. SUBJECTS--147 patients with positive results in faecal occult blood tests who were found to have colorectal adenomas (cases), 153 age and sex matched control subjects with negative results in such tests (negative controls), and 176 control subjects with positive results in the tests who were found not to have colorectal adenomas (positive controls). MAIN OUTCOME MEASURES--Relative risk of developing colorectal adenomas according to frequency and duration of use of analgesics. RESULTS--Cases reported taking less aspirin and non-steroidal anti-inflammatory drugs than the negative controls, with the estimated relative risk for any use being 0.49 (95% confidence interval 0.3 to 0.8). The inverse association was less strong when cases were compared with the positive controls (0.66 (0.4 to 1.1)). The association was specific for aspirin and non-steroidal anti-inflammatory drugs there being no association with paracetamol or other drugs. Prescribed use of non-steroidal anti-inflammatory drugs for longer than five years was associated with the lowest risk (0.21 (0.1 to 0.8)), although the numbers reporting prolonged prescribed use were small. CONCLUSIONS--These findings support the hypothesis that aspirin and non-steroidal anti-inflammatory drug use protects against the development of colorectal neoplasia.

Ninety-seven patients underwent Hartmann's procedure between 1981 and 1986 at the University Hospital, Nottingham. Sixty-one (63%) required this operation as an emergency procedure. There was an overall mortality of 22% and the morbidity rate was 56%. Infective and cardiovascular problems accounted for 77% of all complications encountered reflecting the age and underlying condition ofthe patients requiring this procedure. Thirty patients had successful restoration of intestinal continuity, the majority of these having their original procedure performed as an emergency for benign disease. There were no immediate postoperative deaths from reanastomosis and few short- or long-term anastomotic problems, however there was again considerable postoperative morbidity.

Most case-control studies of colorectal cancer have shown a positive association with energy intake. In contrast studies which have considered physical activity have found the most active to have a lower risk of colonic cancer and obesity appears to be no more than weakly related to colorectal cancer. We therefore compared energy intake determined by a diet history interview, self-reported height and weight, together with measures of lifetime job activity levels and leisure activity in the year prior to interview in 147 cases with colorectal adenomas and two control groups (a) 153 age-sex matched FOB-negative subjects (b) 176 FOB-positive subjects in whom no adenoma or carcinoma was found. Unconditional logistic regression was used to estimate relative risks (RR) and 95% confidence intervals () adjusted for age, sex and social class. No association with weight or body mass index was found. The only association with physical activity found with both control groups was an inverse association with running or cycling for half an hour continuously at least once a week RR 0.46 (0.2-1.3) compared with control group (a), and RR = 0.32 (0.1-0.8) compared with (b), but few subjects engaged in such activity. There was an inverse association with energy intake (trend chi 2 = 5.3, P < 0.025) in the comparison with control group (a) only, a finding which is consistent with those of two previous studies of asymptomatic adenoma.

Diets high in animal fat and protein and low in fibre and calcium are thought to be factors in the etiology of colorectal cancer. Intakes of these nutrients were determined in three groups participating in a randomised trial of faecal occult blood (FOB) screening. A diet history was obtained by interview from 147 patients with colorectal adenomas, 153 age and sex matched FOB-negative controls (a) and 176 FOB-positive controls without colorectal neoplasia (b). Unconditional logistic regression was used to estimate relative risks (RR) and 95% confidence limits (increases) adjusted for age, sex and social class. After adjustment for total energy intake, no associations were found with total, saturated or mono-unsaturated fat, or calcium intake. For total fibre intake there were non-linear relationships with both control groups with the crude RR for highest quintiles of total fibre intake compared to the lowest being 0.6, although this pattern was no longer apparent after adjustment for energy intake with group (a). In comparison with group (b) cereal fibre intake showed a more consistent inverse relationship with adenoma prevalence with the RR for ascending quintiles of intake being 1.0, 0.7 (0.3-1.6), 0.5 (0.3-1.1), 0.7 (0.4-1.4) and 0.3 (0.1-0.6) (trend chi 2 = 8.80, p = 0.003). In comparison with group (a), the adjusted RR for the highest quintile of cereal fibre intake compared with the lowest was 0.6, but no clear trend was apparent. There was an unexpected positive relationship between adenomas and polyunsaturated fat intake with the RR for having an adenoma being 1.0, 2.8 (1.3-6.1), 1.6 (0.7-3.4), 3.5 (1.6-7.5) and 2.3 (1.1-5.0) for ascending quintiles of polyunsaturated fat intakes (trend chi 2 = 4.8, P = 0.03) in comparison with group (a) only. Our data, while providing no support for the role of dietary animal fat or protein, do support the protective role of dietary cereal fibre in the etiology of colorectal adenomas.

Should patients with positive faecal occult blood screening tests who are free of colorectal neoplasia undergo upper gastrointestinal investigation? Altogether 16,985 faecal occult blood tests were completed in a group of 18,818 asymptomatic patients (45-75 years) offered screening at two yearly intervals. A total of 447 (2.6%) were positive and underwent large bowel investigations. No neoplastic disease was identified in 283 (63%) of them. Fourteen (5%) also underwent gastroscopy for upper gastrointestinal symptoms, benign conditions were identified in five and a gastric carcinoma in one. No further investigations were instituted in the remaining 269 subjects who have now been followed up for a median period of 5 years (2-8 years). Five have been referred for benign upper gastrointestinal conditions, but none for upper gastrointestinal malignancy. Thirty one subjects have died - one from gastric cancer (a patient who had undergone a previous partial gastrectomy for a duodenal ulcer and who had persistent upper gastrointestinal symptoms). The remaining deaths were unrelated to the upper gastrointestinal tract. Nineteen people who have left the trial area have been monitored for the development of malignant disease; none have presented with upper gastrointestinal malignancy. These data support the view that upper gastrointestinal investigations need not be performed routinely in this group of subjects, but may be reserved for those with relevant symptoms.

Background Published data suggest that screening might reduce the mortality rate from colorectal neoplasia. Faccal occult blood (FOB) testing suffers from poor sensitivity and significant numbers of interval cancers, both of which should be improved by the addition of flexible sigmoidoscopy (FOS). Methods This prospective, randomized study aimed to assess the compliance and neoplasia yield of FOB testing and FOS compared with that of FOB testing alone. From general practitioner registers, 6371 asymptomatic patients (3124 men, 3247 women ; age range 50-74 years) were invited for screening by means of FOB testing (3128 patients) performed at home, or a combination of FOB testing and FOS (3243 patients). Results Compliance with FOB testing alone was 50 per cent. In the FOB testing/FOS group, 48 per cent returned the FOB test but only 20 per cent went on to FOS. Despite the poor compliance. the neoplasia yield was four times greater in the FOB testing/FOS group. Conclusion FOS increases the neoplasia yield but strategies to improve compliance must be identified for this to become a population screening test.

Isolated perfused segments of pig ileum and sigmoid colon were used as an extrinsically denervated model of intestinal fluid propulsion to compare the effects of intraluminal (IL) with intraarterial (IA) administration of cisapride and mebeverine. The ileal segments had a spontaneous mean activity of 0.008 (SEM 0.003) ml Krebs propelled aborally min-1, with propulsive waves at a mean frequency of 8.3 (1.6) min-1. The sigmoid colon segments ejected a mean of 0.013 (0.009) ml Krebs min-1, with propulsive waves at 3.9 (0.8) min-1. IL cisapride produced a dose-dependent response in the dose range 1 x 10(-9) M to 3 x 10(-1)1-3 x 10(-7) M in the ileum, and 3 x 10(-11) to 3 x 10(-9) M in the colonic segments, IL cisapride was significantly more effective than IA delivery of equivalent doses. IL instilled mebeverine (1 x 10(-6) M) inhibited the carbachol dose response of the ileal and colonic segments more than an equivalent dose of mebeverine infused IA. We conclude that the isolated perfused pig intestine is an effective model for studying the pharmacological effects of drugs and their routes of delivery. Cisapride and mebeverine were more effective per given concentration, when delivered IL than IA in both the ileum and sigmoid colon preparations. The qualitative effects of either IL or IA drug delivery were not affected by extrinsic denervation.

The therapeutic effect of antibodies raised by the immunogen Gastrimmune was compared with both a CCKB/gastrin receptor antagonist, CI-988, and 5-Fluorouracil/leucovorin in a gastric cancer model. The human gastric ascites cell line, MGLVA1asc, produced and secreted progastrin and glycine-extended gastrin as determined by radioimmunoassay and immunocytochemistry. Cells were also stained with an antiserum directed against the human CCKB/gastrin receptor. MGLVAI asc cells were injected i.p. into SCID mice. Antibodies raised by Gastrimmune immunization of rabbits (affinity for G17 of 0.15 nM and GlyG17 of 0.47 nM) were passively infused i.p. and significantly enhanced survival by up to 5 days (p=0.0024 from vehicle controls). The enhancement in survival was not significantly different from that achieved by treatment with 5-Fluorouracil and leucovorin. A CCKB/gastrin receptor antagonist, CI-988, did not affect survival with cells injected at 7.5 x 10(5) cells/mouse but significantly increased the survival of mice injected with a lower cell innoculum of 5 x 10(5) cells/mouse from 30 to 35 days (p=0.0186). At this lower innoculum antibodies raised by Gastrimmune induced complete survival in 2 animals with the remaining dead by day 36 (p=0.0022). Thus, both endocrine and autocrine pathways mediated by precursor and mature gastrin molecules may be jointly operational in the gastric cancer scenario and may be important targets for therapeutic agents.

A biopsy gun which can be operated by one hand has been evaluated at post-mortem to determine its accuracy in biopsying impalpable lesions within the liver under intraoperative ultrasound control. Of 20 impalpable metastases identified positive histology was obtained in 90% demonstrating that this technique is of value in identifying and localising metastases in the liver.

Anti-serum raised against the human cholecystokinin B (CCKB)/gastrin receptor was used in Western blotting to differentiate the cellular locations of receptor isoforms expressed by human gastro-intestinal (GI) tumour cell lines. Using anti-serum directed against the amino-terminal extracellular tail of the CCKB/gastrin receptor, 8/9 cell lines were shown to express immunoreactive proteins of either m.w. 70 or 40 kDa, or both. Both isoforms were found to be associated with intracellular, non-nuclear membranes, whereas only the 70 kDa protein was expressed in the plasma membrane. Receptor expression was related to gastrin production and secretion. Both progastrin and glycine-extended gastrin-17 were produced and secreted by the tumour cell lines; however, carboxy amidated gastrin was not detected by radioimmunoassay. A CCKB/gastrin receptor transfectant NIH3T3 cell line did not produce detectable gastrin and showed exclusive expression of the 70 kDa receptor on the plasma membrane. One cell line had50 pg/ml cell-associated progastrin and no detectable receptor form. Cell lines expressing 50-150 pg/ml had both 40 and 70 kDa receptor forms. Those expressing150 pg/ml progastrin had only the 40 kDa isoform, which was shown to be exclusively expressed on intracellular, non-nuclear membranes, in one of the cell lines. Of the 4 cell lines exclusively expressing the lower m.w. receptor, 3 had gastrin present within the cell, which was not secreted. Thus, if cell-associated gastrin induces a proliferative effect, it may be by an intracrine pathway. Our study has identified the presence of CCKB/gastrin receptor isoforms in different cellular locations and may help toward understanding the complex autocrine and intracrine pathways mediated by gastrin peptides.

Mature and post-translational precursor gastrin forms are growth factors for colorectal tumours. The immunogen Gastrimmune is composed of the amino terminus of gastrin-17 linked to diphtheria toxoid and raises antibodies in situ which neutralise amidated and glycine-extended gastrin-17. The aim of the study was to determine the effect of treatment with 5-fluorouracil(5-FU)/leucovorin on the antibody titres induced by Gastrimmune and the effect of combination therapy on the growth of the rat colon tumour DHDK12. Gastrimmune was administered to rats s.c. at 3 weekly intervals. The rat colon tumour line DHDK12 was injected into the abdominal wall of BDIX rats. Combinations of 5-FU/leucovorin were injected i.v. on days 1, 3 and 5, with the cycle repeated every 4 weeks. Antibody titres were measured by an ELISA technique. Antibody titres were followed for 40 weeks after Gastrimmune (500 microg.ml(-1)) immunization, with titres peaking between 10 and 20 weeks after a single immunisation and falling by week 30. At termination, no effect was observed on either the histological appearance of the gastro-intestinal tract or the proliferation of the colonic mucosa. Pre- and post-treatment with 5-FU/leucovorin (30 mg.kg(-1)) had no effect on the kinetics and level of antibody response to Gastrimmune. Gastrimmune (200 microg.ml(-1)) and 5-FU/leucovorin combinations (12.5 and 20 mg.kg(-1)) increased the therapeutic effects on the in vivo growth of DHDK12 tumors when compared to the agents given singly. Gastrimmune immunisation may be a therapeutic option for the treatment of colorectal cancer in combination with 5-FU/leucovorin.

Activating mutations in the Ki-ras2 oncogene are frequently observed in sporadic colorectal adenomas and their incidence is reported to rise in large and tubulovillous adenomas to values close to those in carcinomas. This study shows that this property is a feature of adenomas growing in large bowel that has already demonstrated its propensity to engender malignant tumours: i.e., bowel in which there is a synchronous carcinoma. Adenomas from cancer-free bowel do not share this high incidence of Ki-ras mutations. This difference in mutation incidence between adenomas from cancer-free and cancer-bearing patients does not appear to derive from sampling bias relative to adenoma size, site, or patient age, nor is it found in another gene (APC) known to be of importance in adenoma formation. Large, dysplastic adenomas from cancer-bearing bowel, however, are particularly liable to carry Ki-ras mutations when they arise in patients over 70 years old. The observations suggest that the role of Ki-ras mutations may be more subtle than merely enhancing adenoma growth. Adenoma cells of cancer-prone individuals may suffer more mutational events than those in persons selected as cancer-free.

The effect of gastrin neutralization was evaluated on the in vivo growth of the rat colon line, DHDK12, which expressed cholecystokinin B/gastrin receptors and secreted glycine-extended gastrin-17 (G17). Gastrin neutralization was achieved by administration of the immunogen, Gastrimmune, which is composed of the amino terminal portion of G17 linked to a diphtheria toxoid. A rat-specific version of Gastrimmune was used to preimmunize rats, with control animals receiving diphtheria toxoid only. The antibodies raised neutralized both carboxy-amidated and glycine-extended G17. The tumor was implanted into the muscle layer of the abdominal wall, and rats immunized with Gastrimmune had significantly reduced median cross-sectional tumor areas (70.2% reduction; P = 0.005) and weights (56.5% reduction; P = 0.0078)) when compared to control rats. Histological analysis revealed that the tumors had an enhanced degree of necrosis, with the area of viable tumor in the Gastrimmune-immunized rat reduced to 40.3% compared to 58.6% in the control rats (P = 0.003). Immunization with Gastrimmune raised antibodies that inhibited the growth of a rat colon tumor. This could have been mediated by neutralization of both serum G17 and cell-associated precursor gastrin molecules.

The effect of the matrix metalloproteinase inhibitor batimastat was evaluated in two human colorectal cancer metastasis models involving: (a) the liver-invasive tumor C170HM2 and (b) the lung-invasive tumor AP5LV, both of which have been shown to express the M(r) 72,000 type IV collagenase. Batimastat at concentrations between 0.01 and 3.0 micrograms/ml had no direct cytotoxic effects on the in vitro growth of the cell lines. In the liver-invasive tumor model, batimastat administered i.p. from day 10 to termination of the therapy (day 39) at 40 mg/kg reduced both the mean number of liver tumors (35% of vehicle-treated control; P0.05) and the cross-sectional area of the tumors (43% of vehicle-treated control; P0.05). In the lung-invasive tumor model, batimastat administered daily (40 mg/kg i.p.) significantly reduced tumor weight within the lung (72% of vehicle-treated control; P0.05) but did not significantly affect nodule number. In the latter model, in which the take rate was unaffected, tumor cells were introduced into the lateral tail vein, and lung localization may have been a physical phenomenon not involving invasion. In the former model, tumor cells were introduced directly into the peritoneal cavity, and from there the cells adhered to and invaded the liver capsule. Because the take rate is significantly reduced, it may be that the matrix metalloproteinases are involved in this process. Batimastat may be a therapeutic modality for the treatment of colorectal cancer metastasis.

Retrospective studies have suggested that DNA tumor content (ploidy) has a significant effect on survival. This group has reported, prospectively, that among patients who had colorectal resections for carcinoma, the 2-year tumor recurrence rate was significantly greater for patients with aneuploid tumor than for those with diploid tumors. This paper reports the 5-year survival rates of this cohort of patients.Three hundred sixty-three patients who had colorectal resections for cancer between November, 1982, and March, 1988, were studied prospectively. The DNA tumor ploidy was measured from fresh and paraffin embedded tissues. These patients were followed regularly in a dedicated colorectal clinic for a minimum of 5 years or until death. Of the 363 patients studied, 2 were lost to follow-up.Forty percent of the tumors were diploid, the remainder aneuploid. The 5-year survival for patients who had curative resections was 76% for those with diploid tumors compared with 64% for aneuploid tumors (P = 0.05; Mantel-Cox, 3.7). On further analysis, the survival benefit conferred by a diploid tumor appeared to be confined to those with Stage B tumors. There was no relation between ploidy and sex, age of patient, stage, histologic grade, or site of tumor.Ploidy is a useful objective measurement of the aggressiveness of Stage B tumors. Patients with aneuploid Stage B tumors have a poor prognosis; this group may benefit from adjuvant therapy.

The aim of this study was to examine the effect of dietary restrictions on compliance with Haemoccult screening for colorectal carcinoma. One-hundred-and-fifty-three individuals were randomly allocated to perform Haemoccult tests with or without dietary restrictions, over 3 or 6 days. Those who failed to return completed tests within 6 weeks were sent a reminder letter. A small but significant improvement in compliance when testing over a 3-day period has been previously demonstrated but this difference was not seen in this study because of the small sample size. Overall, 72.8% compliance was achieved in those who were not asked to exclude certain foods during the test period compared with 51.8% in those in whom dietary restriction was requested (chi 2 = 7.45, P0.01). In a British population compliance with Haemoccult screening is adversely affected by the imposition of dietary restrictions.

Forty previously undiagnosed cases of acute sigmoid volvulus presenting over five years in Nottingham are retrospectively reviewed. The average age was 71.6 years with an even sex ratio. Fifteen (38%) patients lived in nursing homes or institutions. At presentation, all had clinical features of large bowel obstruction, confirmed on plain abdominal X-ray. Sigmoidoscopy and rectal tube decompression was successful in 23 cases. The remaining 17 patients were treated surgically, within 24 hours, at which time the sigmoid was sutured to the abdominal wall (2 cases), resected and brought out as a colostomy (10 cases) or resected and primarily anastomosed (5 cases). Whilst in hospital, of those treated conservatively five died, and three from those treated surgically, four from those in which a colostomy was formed died and three from those in which a primary anastomosis was fashioned died. Of those that survived 11 from the conservative group had at least one recurrence, but none recurred following surgery. In conclusion, acute sigmoid volvulus affects an old and infirm population and carries a poor prognosis. Conservative management is initially preferable, but if emergency surgery is necessary a colostomy rather than primary anastomosis is indicated.

A human antiidiotypic monoclonal antibody (105AD7) has been shown to induce antitumor cellular responses in animals and appears to prolong survival in patients with metastatic colorectal cancer without associated toxicity. Proliferative leukocyte responses to the targeted tumor antigen gp72 were observed in these patients and plasma interleukin 2 levels were increased following immunization. Autologous tumor tissue was not available in these patients, so antitumor cytotoxicity could not be measured. This issue has now been addressed in an adjuvant clinical study in primary rectal cancer patients. Six patients with rectal cancer were immunized preoperatively with 105AD7. Peripheral blood lymphocytes taken prior to immunization were tested against tumor cells extracted from biopsies also obtained prior to immunization or from natural killer (NK)-sensitive target cells. Cryopreserved lymphocytes taken before and after tumor immunization, fresh peripheral blood lymphocytes taken immediately prior to surgery, and lymphocytes from tumor-draining lymph nodes were tested against autologous cells from the resected specimen or NK-sensitive target cells. Significant killing of autologous tumor cells, which was not due to NK activity, was seen with cryopreserved lymphocytes or lymph node cells of three patients at 1-2 weeks postimmunization with 105AD7 but not on pretreatment biopsies. Enhanced NK activity was seen 2-3 weeks postimmunization in 3 of 6 patients. These results indicate that 105AD7 human monoclonal antibody immunization enhances cytotoxicity in rectal cancer patients by specific and nonspecific effector mechanisms.

Certain dietary constituents may cause guaiac-based faecal occult blood tests to be positive in the absence of blood loss. In a randomized controlled study of Haemoccult screening for the early detection of colorectal cancer, a policy of retesting with appropriate dietary restriction is used to minimize false-positive results. Delay associated with the retesting protocol may cause considerable anxiety. The aim of the study was to determine the likelihood of an initial positive result remaining positive after retesting. One-hundred-and-thirteen of 137 (35.6%) subjects whose initial test was5 squares positive remained positive in contrast to 52/59 (88.1%) withor = 5 squares positive, a significantly higher proportion (P0.001). This suggests that if five or more test squares are positive, then dietary interference is unlikely to be responsible. We conclude that, if dietary restriction retesting is practiced, individuals with strongly positive tests may be offered investigation without retesting, thus reducing their delay to further investigation.

The gastrointestinal tumour cell lines, MKN45G and C146 possessed oestrogen receptors (ER) of affinities 1.8 x 10(-8) and 5.2 x 10(-9) M respectively. C146 and MKN45G had enhanced proliferation in the presence of oestradiol (10(-8) and 10(-10) M). Fifty-six percent (5/9) of primary gastric and colorectal tumours had their proliferation enhanced by oestradiol. The anti-steroidal drug, danazol, inhibited the basal growth of MKN45G (10 micrograms ml-1 45% of the untreated control), C146 (10 and 5 micrograms ml-1, 20 and 48% of control, respectively) and 3/9 GI primary tumours (10 micrograms ml-1). Danazol competed with 3 [H]-Oestradiol for binding to ER on MKN45G and C146, at concentrations from 10 to 1 micrograms ml-1.

This paper models a range of feasible strategies for mass population screening for colorectal cancer. It uses both clinical and economic data derived from the major colorectal cancer screening trial currently under way in Nottingham, supplemented by data from concurrent Scandinavian trials. Costs and yields for 12 strategies are modelled, and optima are identified according to a number of evaluation criteria. The cost-effectiveness condition for the desirability of introducing a programme of colorectal screening is also established.

The successful treatment and understanding of fistula-in-ano requires knowledge of the anatomy of the anal canal, the pelvic musculature and the pathogenesis of fistula-in-ano. Sir Alan Parks made a number of contributions to our understanding of this problem, in the classification and pathogenesis of fistula-in-ano and in particular the importance of sepsis in the intersphincteric plane

The purpose of tumour staging for colorectal cancer (CRC) is to help define clinical management, facilitate communication between physicians, provide a basis for stratification and analysis of treatment results in prospective studies, and provide some prognostic information for patients and their families. The World Congresses of Gastroenterology, Digestive Endoscopy, and Coloproctology, Working Party on staging for CRC studied six commonly used systems to review their strengths and weaknesses. Although it was concluded that defining a new staging system was unnecessary, it was recognized that there is a need to define a terminology to describe the full anatomic extent of spread of CRC. Furthermore, we note that there are several additional features, derived from both clinical and pathology information, which have had prognostic significance shown by appropriately constructed multivariate analyses and which can be used to formulate a more accurate prognostic index than that provided by a description of anatomical tumour spread. Thus the Working Party came to two principal conclusions. First, a standard format should be adopted for the collection of the essential data required for prospective studies, and we recommend the 'International Documentation System (IDS) for CRC' for this purpose. Second, a nomenclature which describes the full anatomical extent of tumour spread and residual tumour status in CRC has been defined and should be adopted, from which all currently used staging systems can be derived. We have called this nomenclature the 'International Comprehensive Anatomical Terminology (ICAT) for CRC'. In the event that these recommendations are adopted, we envision that there will be improved clarity in the documentation of treatment outcome for patients with CRC and improved communication of results derived from prospective studies. Furthermore, an acceptance of IDS and ICAT would set the scene to develop a prognostic index for individual patients with CRC by the expansion of anatomical clinicopathology staging information to include additional factors which have independent prognostic significance.

Tumor cell DNA (ploidy) content was measured prospectively in samples from 320 patients resected for colorectal cancer with a minimum follow-up time of 2 years. All patients were followed and those with recurrence were investigated carefully. There was no correlation between tumors with an abnormal cellular DNA content (aneuploid or tetraploid) and patient age, sex, tumor site, pathologic stage, or histologic grade. In 236 patients who underwent potentially curative operations, 75 (32%) had local and/or distant recurrence. The recurrence rate was significantly higher (test statistic, 4.3; P = 0.04) for those patients with aneuploid tumors (52 of 142, 37%) compared with those with diploid tumors (23 of 94, 24%). The subgroups of patients where ploidy exerted an effect were in patients with Stage B tumors or mobile tumors and in patients over 65 years of age. Further analysis showed that there was a twofold increase in local recurrence and a threefold increase in distant recurrence in patients with aneuploid tumors, but no excess of patients who had both local and distant recurrence. Measurement of DNA ploidy can identify a group of patients undergoing curative surgery for colorectal cancer at high risk for recurrence. In combination with clinicopathologic factors, DNA ploidy may be useful in analyzing the results of trials and in planning adjuvant therapy.

Owing to dehydration during storage, faecal occult blood tests have been found to lose sensitivity; accordingly, test rehydration before development has been advocated, although this practice has yet to be subjected to an economic evaluation. In this paper, the results from two major screening trials in Sweden and England, one using rehydration and the other not, are so evaluated, based on a costing model developed within the English trial. The higher sensitivity resulting from rehydration was found to be accompanied by losses in specificity, such that, although more cancers are detected, the costs of screening and of cancer detection are actually considerably higher under the rehydration regimen than with non-hydration.

Sixty consecutive patients undergoing anterior restorative resection of the rectum for cancer were studied. After full mechanical bowel preparation and intravenous antibiotic prophylaxis, colorectal anastomosis was performed with the EEA (Autosuture) staple gun. The median height of the anastomosis above the anal verge was 9 cm (range 3-15 cm) and no patient had a protecting colostomy fashioned. All 'doughnuts' were checked and following instillation of saline into the pelvis the anastomosis was tested by air insufflation through the rectum. There was a statistically significant association between an incomplete 'doughnut' and peroperative anastomotic leakage (P less than 0.001); however, of the 11 patients shown to have a leak, only seven had deficient 'doughnuts'. All 11 patients had repair of the defect identified by escape of air and none of these patients developed a clinical leak.

Recent developments in screening, diagnosis and treatment of colon cancer could lead to a reduction in mortality from this disease. Removal of adenomas, identification of risk factors, appropriate application of accurate diagnostic tests, and aggressive anatomic-surgical resection of colon cancers may already be having a favourable impact. Screening of average-risk populations over the age of 50 also offers promise in the control of this important cancer. The disease is of sufficient magnitude to deserve detection at an early stage with better prospects of patient survival, since screening tests with moderate sensitivity and high specificity are available. Flexible sigmoidoscopy and faecal occult blood tests are sufficiently acceptable to be included in case-finding among patients who are in the health care system. The results of current controlled trials involving more than 300,000 individuals for evaluating the impact of screening on mortality from colon cancer are needed before this approach can be recommended for general public health screening of the population. Further research is required to develop better screening tests, improve patient and physician compliance, and answer more definitively critical questions on cost-effectiveness. Mathematical modelling using current and new data can be used to determine the effectiveness of screening in conjunction with recommendations for primary prevention.

Gastrointestinal (GI) tract motility was depicted in four human volunteers with the high-speed echo-planar imaging technique: modulus blipped echo-planar single-pulse technique (MBEST). Data acquisition times of 64 and 128 msec obviate image degradation due to motion without the need for gut paralysis and allow imaging of the GI tract in real time. Peristaltic patterns of the gastric antrum and proximal small intestine were depicted for fasting and fed subjects and subjects in whom peristalsis had been pharmacologically stimulated. The potential for quantitative measurements of GI tract motion with this new technique was demonstrated.

A classification of anal fistulas is presented, which is the result of an analysis of 400 cases treated over the past IS years, based on the pathogenesis of the disease and the normal muscular anatomy of the pelvic floor. Four main types were found but numerous variations of each occur, which are described. It is hoped that this will alert the surgeon to the various complex situations that he may encounter.

1 Intravenous bolus doses of porcine glucagon of 0.001-0.05 mg kg-1 caused intense stimulation of the duodenum and jejunum of the dog. 2 Intravenous infusion of porcine glucagon at 0.025-0.05 mg kg-1 h-1 caused similar stimulation. In both cases the stimulation was phasic in nature. 3 Stimulation of the duodenum and jejunum following glucagon was accompanied by a decrease in frequency of the intestinal basic electrical rhythm (BER). No change was seen in the intervals between successive periods of phase III motor activity.

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 (x2 = 8.0, P = < 0.001). Cancer 58:397–403, 1986.