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Background and Aims: People with a strong family history of common (so-called 'sporadic') colorectal cancer are generally advised to undergo colonoscopic screening, but the starting age for this is unclear. An audit was performed to study the age-related yield of screening colonoscopy in this risk group., Methods: A prospective audit of the outcome of screening colonoscopy was performed on a cohort of 232 people with a strong family history of common colorectal cancer. All were registrants in a familial bowel cancer service solely because of their family medical history. They had no bowel symptoms and no prior endoscopic investigation of the large bowel., Results: Neoplastic lesions were detected by using colonoscopy in 33 participants. In 27 participants, the major lesion was a small tubular adenoma, four had an advanced adenoma and two had cancer. More neoplastic (P= 0.02) and advanced neoplastic (P= 0.03) lesions were found in those patients aged > or = 50 years. Only one advanced adenoma was detected in a participant below the age of 50 years., Conclusion: The yield from screening colonoscopy in young people (< 50 years) with a strong family history of common colorectal cancer is low, placing doubt on the need for colonoscopic screening before the age of 50 years.

Objective: To investigate the impact of predictive genetic testing on colonoscopic surveillance in an extended family with hereditary non-polyposis colorectal cancer (HNPCC)., Setting: Familial Bowel Cancer Service, The Royal Melbourne Hospital, Victoria., Subjects: 96 people registered with the Service who were apparently unaffected members of an extended family that met the classic Amsterdam criteria for HNPCC and carried an MLH1 gene mutation (IVS9 + 3insT)., Intervention: Predictive genetic testing was offered in a cascade manner to at-risk family members; mutation-positive individuals were advised to have annual colonoscopic surveillance, while mutation-negative individuals were withdrawn from surveillance., Main Outcome Measures: Previous compliance with recommended colonoscopic surveillance; uptake and results of genetic testing; expected effect of genetic test results on number of colonoscopies over five years., Results: 22 of the 96 family members (23%) were not complying with recommended surveillance. Of 48 individuals offered predictive genetic testing, 41 (85%) responded and 39 (81%) underwent testing. Seven of the 39 (18%) were positive for the family-specific mutation, and 32 (82%) were negative. The 39 tested individuals and 37 of their descendants who were registered with the screening program had undergone 70 colonoscopies in the five years before genetic testing. In the five years after testing, only 37 surveillance colonoscopies were planned (annual or two-yearly colonoscopies for the six mutation-positive individuals and five-yearly colonoscopies for four mutation-negative individuals with previously identified adenoma), an almost 50% reduction in colonoscopies., Conclusion: Predictive genetic testing in HNPCC families allows many individuals to be withdrawn from regular colonoscopic surveillance. It may therefore reduce costs, as well as have emotional benefits for many individuals.

Rectal epithelial cell kinetics are used as intermediate markers for colorectal cancer and relate to risk. In this study, measures of proliferation using direct immunohistochemistry for proliferating cell nuclear antigen (PCNA) were compared to in vitro labeling by bromodeoxyuridine (BrdUrd) and incubated biopsies that were later stained for PCNA (PCNA-I) in human rectal biopsies. The study group consisted of 20 sets of biopsies from 12 subjects participating in an intervention trial. Fresh nonincubated biopsies were fixed in methacarn and stained immunohistochemically for PCNA (clone 19A2). In parallel biopsies, BrdUrd was incorporated into the DNA of S-phase cells during a 2-h incubation at 37 degrees C under hyperbaric conditions and localized by immunohistochemistry. Additionally, biopsies were incubated under hyperbaric conditions for 2 h at 37 degrees C, fixed in methacarn, and stained for PCNA (PCNA-I). There was a highly significant difference in the labeling index between the three methods (P < 0.01), but there was no significant difference between subjects (P = 0.439). The mean labeling index was 2.3 +/- 0.1% for PCNA, 2.9 +/- 0.1% for PCNA-I, and 4.1 +/- 0.1% for BrdUrd. The proportion of labeled cells in the top two-fifths was significantly higher (P = 0.01) for BrdUrd (5.5 +/- 0.8%) and PCNA-I (6.4 +/- 1.1%) compared to PCNA (3.1 +/- 0.6%), and a significant difference was seen between subjects (P = 0.038). PCNA-I and BrdUrd methods had similar crypt heights with 73.5 +/- 1.8 and 71.2 +/- 1.3 cells/crypt column, respectively, but were significantly shorter (P < 0.001) than PCNA with 83.4 +/- 1.5 cells/crypt column, indicating a loss of cells during organ culture. The simplicity of the PCNA technique, which avoids potential perturbations occurring during organ culture, has considerable appeal as a marker for colorectal cancer risk, but additional studies are needed to correlate PCNA with neoplastic risk.

Background: Low fat and wheat bran interventions significantly reduced the growth of small to large adenomas and modestly suppressed rectal epithelial cell proliferation in the Australian Polyp Prevention Project., Aim: To study the effect of unprocessed wheat bran, unprocessed oat bran and processed wheat bran (Kellogg's All Bran) on rectal epithelial cell proliferation., Patients: Twenty subjects with recent adenomas and a high fat background diet were recruited., Methods: Rectal biopsy specimens were taken at entry and at the end of three six-week periods of oat bran (64 g/day), wheat bran (25 g/day) and All Bran (38 g/day), all in association with a diet < 25% energy as fat, in a randomised cross-over trial. Each of the bran supplements had a total of 11 g dietary fibre. The biopsy specimens were fixed in methacarn and stained immunohistochemically for presence of the proliferating cell nuclear antigen (PCNA). The kinetics used to measure proliferation were labelling index, whole distribution of labelled cells, and labelled cells in the top two-fifths of crypts using analysis of variance., Results: There were no significant differences in mean labelling indexes between the four diets or in the percentage of labelled cells in the top two-fifths (p = 0.59), but activity in the top two-fifths of crypts was lowest with wheat bran. The mean (SD) labelling indexes were 2.23 (0.11)% for control, 2.13 (0.08)% for wheat bran, 2.19 (0.09)% for oat bran, and 2.12 (0.08)% for All Bran. The proportion in the top two-fifths of the crypts was 2.6 (0.6)% for control, 2.15 (0.5)% for wheat bran, 3.3 (0.9)% for oat bran, and 3.1 (0.9)% for All Bran. On analysis of whole distribution, there was no significant overall effect of diets but there was a difference between subjects. Analysis including total fibre intake also did not identify effects on proliferation., Conclusion: In this study of high risk subjects with initial high fat diets, dietary fibre in association with a low fat diet had no effect on rectal epithelial cell proliferation, although wheat bran had the greatest effect on percentage of labelled cells in the top two-fifths of crypts.

The place of colonoscopy in the management of ulcerative colitis is restricted to clinical situations where the information provided will change clinical management. The information provided will be answers to the questions?inflammatory bowel disease, o r, in the patient with known colitis: inflammatory bowel disease?type?activity extent?dysplasia. Biopsy is pivotal to the diagnosis and provides the certainty of tissue diagnosis, assessment of activity and detection of dysplasia. Sigmoidoscopy is sufficient for providing information for clinical management in most circumstances, but colonoscopy is important where clinical features are disproportionate to sigmoidoscopic findings and systemic parameters of inflammatory activity; to determine type and extent of inflammatory bowel disease and when surveillance needs to start; and for biopsy to detect dysplasia. Ileoscopy is an important aspect of colonoscopy for differential diagnosis, and is the unique definer of total colonoscopy.

Screening average-risk people aged 55 to 70 years for colorectal cancer is now a public health priority in Australia. Pilot studies of faecal occult blood testing are required to find ways of achieving optimal compliance and cost efficiency in the Australian health care setting. Flexible sigmoidoscopy probably should be used as complementary screening but further trials are needed. High-risk groups (family history of colorectal cancer, or previous ulcerative colitis, adenomas or cancer) should already be in surveillance programs.

Hereditary non-polyposis colon cancer (HNPCC) comprises 2-6% of the total colorectal cancer burden. Two families are described that show linkage between the HNPCC susceptibility gene and the markers D2S123 and D2S119 on chromosome 2p, producing multipoint lod scores of 3.62 and 3.83, respectively, in the largest pedigree. In our third family the multipoint lod scores for D2S123 and D2S119, -2.97 and -3.12, excluded localization of a susceptibility gene in this region indicating that there is at least one more gene that causes predisposition to HNPCC. The exclusion was based on at least one genotype for an individual who had multiple primary colon and extracolonic tumours and could not be considered to have had common forms of cancer. Our results therefore encourage further gene mapping to pursue the localization of additional HNPCC genes. These findings confirm the presence of the susceptibility gene for HNPCC, COCA1, on chromosome 2p. They allow the immediate identification of a subset of HNPCC families, and provide the means for presymptomatic testing of family members if sufficient number of members are available for study.

If measures of rectal epithelial kinetics are to be used on a large scale, or as part of multicenter studies, the variance of repeated measures must be sufficiently small to detect the effect of clinical status and dietary, or chemoprevention interventions. Errors in measurement can be categorized as intra-reader (sigma 2I), inter-biopsy (sigma 2B), inter-laboratory (sigma 2L), and inter-reader (sigma 2R); the sum of these (sigma 2T) when compared to inter-subject variance (sigma 2S) is a measure of the precision with which cell kinetics can be estimated for a given subject. We estimated the variances of the component errors in four separate experiments, each involving 6 to 10 subjects, using the proliferating cell nuclear antigen (PCNA) technique. PCNA labeling index variances for a single laboratory study were sigma 2I = 0.02-0.07 and sigma 2B = 0.08-0.15. Inter-laboratory and inter-reader variances were sigma 2L = 0.08 and sigma 2R = 0.03. Summing the errors applicable within a laboratory gives a rounded estimate of 0.15. For inter-laboratory studies the total error (sigma 2T) is greater, estimated in our two-laboratory study as 0.3. In a separate study, the variation between biopsies (sigma 2B) could be accounted for by the variation between crypts within biopsies; an acceptable level of accuracy is achieved after counting 20-30 crypts. In contrast to the measurement errors, the variance between subjects, which includes a treatment effect of diet, was larger, estimated to be between 0.75 and 1.30.(ABSTRACT TRUNCATED AT 250 WORDS)

Background: Fat and total calories are closely correlated in the diet. Because of this correlation, studies of dietary fat and breast and colorectal cancer incidence have been peculiarly difficult to interpret., Methods: This article reviews the information from rodent models of breast and colorectal cancer and epidemiological studies addressing the separate effects of calories and fat in the diet. Various statistical approaches described for separating the effects of calories and fat are outlined, with a review of epidemiological case-control, cohort, and prospective controlled clinical studies of diet and breast and colorectal neoplasia., Results: Animal studies provide convincing evidence for a dominant effect of calorie restriction over fat modification in tumorigenesis. Individual case-control studies show no effect or are inconsistent in distinguishing calories from fat in colorectal carcinogenesis, and are largely null in breast cancer. However, a meta-analysis of these studies in breast cancer defines a relative risk (P < 0.05) of 1.40 for calories "solely" due to fat (1.48; P < 0.05). Cohort studies for colorectal cancer have reported variable results, but a recent large study of women implicates animal fats, particularly from red meat, as a risk for colon cancer, independently of calories. For breast cancer, a marginally significant effect of fat independent of calories was found in one recent cohort study, but earlier large cohort studies could not identify calories or fat as risk factors., Conclusion: Caloric restriction is likely to be important in inhibiting tumorigenesis based on animal studies. However, the influence of animal fats is seen both in animal studies and epidemiological studies of breast and bowel cancer. The differential effect of fats from different dietary sources in both colon and breast cancer points to a qualitative effect separate from calories in tumorigenesis. Extrapolation of significant analyses of trend to very low-fat diets should be interpreted cautiously without further information on concurrent nutrient deficiencies and competing illnesses. Randomized controlled trials of dietary intervention to prevent neoplasia are feasible and will enhance the quality of information available about diet and tumorigenesis.

Background: Hemoccult II, the guaiac-based fecal occult blood test used in most colorectal cancer screening programs, has an unsatisfactory sensitivity for asymptomatic colorectal neoplasms. We evaluated the relative performance of four fecal occult blood tests, directed against various components of the hemoglobin molecule., Methods: All tests, Hemoccult II, HemoccultSENSA (a more sensitive guaiac test), HemeSelect (an immunochemical test specific for human hemoglobin), and HemoQuant (the heme-porphyrin assay), were performed by 107 patients with symptomatic colorectal cancer and 81 patients with predominantly asymptomatic adenoma. Hemoccult-SENSA and HemeSelect were performed by 1,355 screenees., Results: HemeSelect and Hemoccult-SENSA had significantly higher sensitivity for colorectal cancer (97% and 94%, respectively) than the other tests. HemeSelect had the highest sensitivity for adenomas; in 45 patients with large (> or = 10 mm) adenomas, sensitivity was 76% for HemeSelect, 60% for HemoccultSENSA, and 42% for both Hemoccult and HemoQuant. In the screenees, estimated specificity was 97.8% for HemeSelect and 96.1% for Hemoccult-SENSA., Conclusions: HemeSelect and Hemoccult-SENSA have the highest levels of sensitivity for detection of colorectal neoplasia, but the immunochemical test HemeSelect provides the best combination of specificity and sensitivity.

Aims: To determine: (1) whether there is an association between collagenous colitis and coeliac disease or lymphocytic colitis; (2) the distribution of lymphocyte subsets and macrophages in the lamina propria and surface epithelial layer in collagenous colitis; and (3) the colorectal distribution of the disease and whether a mucosal biopsy specimen, using a flexible sigmoidoscope, is sufficient to diagnose it., Methods: The clinical data and colorectal biopsy specimens from 38 patients with collagenous colitis were studied. In 10, small bowel biopsy specimens were also available for review. Immunostaining of the mucosal lymphoid infiltrate with a panel of relevant antibodies was carried out on formalin fixed tissue in seven cases; in three the phenotyping was performed on fresh biopsy specimens separately frozen or fixed in B5 solution., Results: Coeliac disease was found in four out of the 10 patients with collagenous colitis who had had a small bowel biopsy, in contrast to the prevalence of the disease in Australia of 1 in 3000. Collagenous colitis did not respond to gluten withdrawal. Five of 29 (17%) of the patients had a mixed pattern of lymphocytic and collagenous colitis. Immunostaining of the lymphoid infiltrate showed that the striking increase in intraepithelial lymphocytes in collagenous colitis was due to an influx of CD8 positive cells. The occurrence and severity of collagenous colitis along the large bowel were independent of the anatomical site, and in more than 90% of cases biopsy specimens from the sigmoid colon or rectum were diagnostic., Conclusions: There is a very high incidence of coeliac disease among patients with collagenous colitis so that jejunal biopsy should be an essential part of their investigations, especially if symptoms persist. However, only a minority showed a mixed pattern of lymphocytic and collagenous colitis. The intraepithelial lymphocytes in collagenous colitis are CD8 positive cells. Collagenous colitis can be diagnosed from rectal or sigmoid colon biopsy specimens in more than 90% of cases.

Objective: To review the place of gastrointestinal endoscopy in the management of upper and lower gastrointestinal disorders., Data Sources: We reviewed articles on endoscopy reported over two decades. A Medline search complementing our experience and knowledge of the literature was used to identify the articles., Study Selection: Papers were selected which focused on indications, comparison with radiology, including clinical outcome measures, and complications. One hundred papers, including those from radiology journals, were reviewed., Data Extraction: Results of studies are referenced as appropriate., Data Synthesis and Conclusions: Endoscopy allows direct visualisation of the mucosa of the upper gastrointestinal tract, colon and terminal ileum. Subtleties of colour change, vascular pattern abnormalities and scarring are easily detected at endoscopy and are often of diagnostic importance. Endoscopy also provides access for tissue biopsy and allows a wide variety of therapeutic interventions. Traditionally barium studies have been the first step in the evaluation of many gastrointestinal symptoms and still retain cost advantages over endoscopy. However, endoscopy is frequently more sensitive and specific than barium studies. Costs associated with incorrect diagnoses may undermine the apparent cost benefits of barium studies. Advances in endoscopic design have allowed wider therapeutic options and increased safety. Gastrointestinal endoscopy should now be the first line of investigation where diagnostic precision is required or where therapeutic intervention is likely.

Previous studies have suggested that abnormal expression of enzymes characteristic of the intestinal brush border might accompany colonic neoplasia and possibly facilitate identification of epithelium at risk of malignancy. To test this possibility, the distribution of the brush border enzymes sucrase-isomaltase (SIM), maltase-glucoamylase (MGA), aminopeptidase-N (APN) and diamino-peptidylpeptidase-IV (DPPIV) were studied by the immunoperoxidase method in biopsies from the rectum and caecum of normal subjects, and neoplastic and non-neoplastic tissues from patients with adenoma or cancer. Brush border enzymes were detected by immunohistochemistry more frequently in the caecum than the rectum (P less than 0.05) of normal subjects. Diamino-peptidylpeptidase-IV and APN were present in highest concentration at the brush border of the most mature colonocytes on the luminal surface with less staining in the crypt, whereas SIM and MGA staining of the brush border was as prominent on crypt cells as surface cells. While all cancers expressed at least one enzyme, there was heterogeneity of staining within tumours and a tendency to lose polarity of enzyme expression in cells, sometimes with dense staining of the cytoplasm. Distally situated adenomas uncommonly expressed a brush border enzyme (25%) and the only enzyme expressed in them was SIM. These finding indicate that these brush border enzymes are not exclusively expressed in the small intestine; DPPIV and APN are markers of the normal mature colonocyte and should prove useful as markers of differentiation. However, the change associated with neoplasia would not appear to be of clinically predictive value.(ABSTRACT TRUNCATED AT 250 WORDS)

Spontaneous bacterial peritonitis (SBP) in cirrhotic patients with ascites carries a mortality rate ranging from 50% to 90%. Eleven patients were diagnosed at The Royal Melbourne Hospital over a 25-year period. Fever was present in eight, abdominal pain in eight, rebound tenderness in six and pre-coma in four. In two, the peritonitis was silent. All five diagnosed by paracentesis survived, but the three patients first diagnosed at laparotomy died. The experience shows that SBP can be successfully treated with antibiotics. Because of the variable clinical features, a diagnostic paracentesis is recommended in all cirrhotic patients presenting with ascites.

A double blind controlled trial has been conducted in 40 patients to compare the therapeutic effects of prednisolone metasulphobenzoate enemas with those of prednisolone-21-phosphate enemas. Both enemas brought about improvement in symptoms and sigmoidoscopic appearances in more than 70% of patients treated. The absorption of prednisolone from the metasulphobenzoate enema in three patients was less than from the 21-phosphate enema. In view of the low plasma prednisolone concentrations obtained, there are theoretical advantages in using a poorly absorbed enema to avoid the possibility of systemic steroid effects in patients requiring long term steroid treatment.

Non-compliance in screening programmes for colorectal cancer is likely to be the most important factor limiting the impact of screening on mortality. This study aimed to determine risk factors and correlates of compliance that could be readily identified by general practitioners. A total of 581 eligible subjects aged 40 to 75 years completed a questionnaire that covered demographic factors, personal medical history, family history of colorectal cancer and smoking status. Faecal occult blood tests were then offered by the general practitioner and compliance correlated with responses. The over-all compliance was 44% and increased to 51% for those who accepted the self-testing kit at consultation. For men, compliance increased with increasing level of education and was significantly greater for non-smokers than for smokers. For women, compliance increased with increasing age, and was greater for those with either symptoms and/or a family history of colorectal cancer. A doctor group-practice factor appeared to influence acceptance versus refusal of the test kit from the doctor. A triage approach to screening in general practice may improve over-all compliance and the yield of tumours. With this strategy, patients at high risk (for example, those with a family history of colorectal cancer or in older age groups) are identified first. Particular attention should be given during consultation to those at high risk who have poor compliance profiles (for example male smokers with a family history of colorectal cancer). High-risk subjects with high compliance profiles would need less attention and low-risk individuals would need least attention.

Successful introduction of screening for early colorectal cancer will depend, at least in part, on doctors' knowledge and attitudes. A 34-item questionnaire was sent to a random sample of one in five doctors in Victoria, with a final completion rate of 65%. The survey revealed gaps of knowledge, particularly about recognition of high-risk groups. Only 12% were aware of the degree of increased risk faced by first-degree relatives of patients with colorectal cancer and only 10% recognised the similar increase in risk for people with a history of resected colorectal cancer. While 73% of doctors order faecal occult blood tests, only 9% were aware that the more reliable quaiac method was used for their patients. Overall, 38% considered that faecal occult blood testing was a practical method for screening for colorectal cancer. Most of the doctors who accepted occult blood screening would follow up a positive test with digital rectal examination (80%) and barium enema (75%), but only 58% would want sigmoidoscopy performed and 34% colonoscopy. The diagnostic potential of digital rectal examination and sigmoidoscopy was over-estimated by half of the doctors surveyed. Recognition of subjects at high risk for colorectal cancer, and knowledge about the proper use, follow-up, and potential for screening of faecal occult blood tests need emphasis in medical educational programmes.

A new human colon cancer cell line (LIM1215) has been derived from a tumor arising in a member of a family known to have a high incidence of colorectal cancer. The tumor cell line is comprised of small pleomorphic cells that clone in liquid medium and form tumors in immunosuppressed mice. Ultrastructurally, the cells are capable of differentiation, with cells with multiple microvilli and cells resembling goblet cells being present in the one culture. The cells are pseudodiploid and contain a 13p+ marker chromosome.

This study was designed to determine if any constitutional chromosomal markers were linked with the expression of colorectal neoplasms in the inherited nonpolyposis colon cancer syndrome, using a number of cytogenetic techniques. High resolution G-banding in 12 affected and 17 unaffected family members did not reveal a structural chromosome abnormality. Increased C-band heteromorphism was not seen in either affected or unaffected individuals, and no heritable fragile sites were detected. Mean baseline and mitomycin C-induced sister chromatid exchanges were not elevated in affected patients compared with controls. Mapping of sister chromatid exchanges did not reveal any hot spots of exchange. A tumor cell line with the karyotype 46,XY,der(13),t(13;?)(p11;?) was established from one patient, but no constitutional abnormality of chromosome #13 was found. In addition, 11 patients with familial polyposis coli were studied with high resolution G-banding and no heteromorphism of chromosome #2 in the region 2q21.3 was detected.

A total of 581 people (33% male, 67% female) attending general practitioners completed a questionnaire mainly on health beliefs and were then offered a fecal occult blood test (Hemoccult II) free of charge. Eighty-six percent accepted the general practitioners' offer and took the Hemoccult kit home. Of these, 51% complied (i.e., returned specimens for laboratory testing). The Health Belief Model was found to account for 12% of the variance in screening behavior. Perceived barriers to taking the test and perceived susceptibility to bowel cancer were the only components contributing significantly in the multiple regression analysis. Health Belief Model components that were predictive of initial acceptance of the test offer differed from components predictive of ultimate compliance. The influence upon compliance of family history of colorectal cancer, history of colonic symptoms, smoking habits, perceived attitudes of spouses, attitude to detection tests, and subjective stress related to the threat of bowel cancer were also investigated.

The histopathological features and results of treatment of malignant polyps removed by endoscopic polypectomy from 60 patients are presented. The patients were followed for a minimum of five years. Forty six patients were treated by polypectomy alone as local excision was judged complete and the invasive carcinoma was well or moderately well differentiated. Thirty seven of these patients are alive and well after five years and the remaining nine have died of other causes up to four years later: there was no evidence of recurrence in any of these cases. Fourteen patients underwent a subsequent major surgical resection and residual tumour was found at the site of polypectomy in two cases but regional lymph nodes were not involved. Only one patient from this group with a high grade tumour developed metastases although the operative specimen was free of tumour. Malignant polyps can be successfully treated by polypectomy alone provided both the laboratory techniques of examination and the histopathological criteria are strictly applied.

Colorectal cancer in familial adenomatous polyposis is a preventable disease in at-risk relatives of patients with primary cases. Until the recent establishment of a register in Western Australia, there has been no registration of pedigrees or central organization of surveillance in Australia. In the present study, the experience of 20 such families who were associated with The Royal Melbourne Hospital was documented, with an analysis of the reasons for any failure of management. The impact of a hospital-based register on the management of the disease was studied. In each family, results were categorized according to whether "at-risk" relatives had been diagnosed at surveillance examinations, and whether the Hospital register were involved. Before involvement with the register, 24 family members presented with symptomatic polyposis after the first affected case had been diagnosed. Eighteen of these had colorectal cancer at diagnosis, and 16 subjects now are dead. Identifiable reasons for the failure of surveillance were family communication failure (two cases), family denial (two cases), failure of the hospital clinic (two cases) and a failure to cover extended branches of families who were living locally (nine cases), interstate (four cases) or overseas (three cases). In contrast, only two (6%) of 33 affected cases that were identified at a planned surveillance endoscopy had colorectal cancer at diagnosis. Without the active surveillance of at-risk family members, lethal delays in diagnosis are likely to occur. Most reasons for failure potentially are correctable by a dedicated registry that is responsible for notifying clinicians and patients about the timing of surveillance procedures.

Preliminary rehydration of Hemoccult II slides increases slide sensitivity for blood and lowers the false-negative rate for colorectal cancer. To test the effect of this modification on the false-positive rate due to peroxidase-containing foods, 156 healthy young subjects crossed between diets of differing peroxidase content. Hemoccult II slides were prepared in duplicate for testing with and without rehydration. When developed without rehydration, only seven (0.4%) of 1856 slides were positive, the positive results occurring with challenge diets containing 250 g rare red meat. With preliminary rehydration, 53 (5.7%) of 926 slides were positive, in 26 (17%) of the 156 subjects on a challenge diet that included rare red meat and uncooked fruit and vegetables. Well-cooked red meat also gave positive tests, Diets excluding red meat but with large quantities of uncooked fruit and vegetables produced only five positive results in 314 rehydrated tests, in 3 of 53 subjects. On a strict low-peroxidase diet, two of 310 tests, in 2 of 52 subjects, were positive. Rehydration of Hemoccult slides and exclusion of red meat and certain other high-peroxidase foods should give optimal sensitivity and specificity for colorectal cancer detection. The effect of these conditions on yield of lesions and false-positive rates should be tested in screening programs.

Patients who have undergone implantation of ureters into the sigmoid colon (ureterosigmoidostomy) are known to be at high risk of developing cancer of the colon many years later. The operation is often performed in infancy for congenital abnormalities of the bladder, thus creating a long term surveillance problem. Six of 34 patients (17.6 per cent) who had undergone ureterosigmoidostomy were found at a screening fibresigmoidoscopy to have adenomas of the left colon or severe dysplasia of the stoma, a mean interval of 22 years after their urinary diversion. Four other patients had previously had a sigmoid adenoma or cancer; thus, 29 per cent overall had developed colonic neoplasms, almost all closely related to their stomas. Another patient who, by error, was excluded from the surveillance, died of metastatic cancer of the sigmoid colon within the study period. Regular surveillance by fibresigmoidoscopy of patients who have had urinary diversion affords the opportunity to detect and remove potentially malignant sigmoid lesions. In addition to its clinical importance, it allows a closer study of this unique model of colon carcinogenesis.

The diagnostic and therapeutic benefits of colonoscopy are well known but most large-scale surveys, especially those involving multiple centres, may underestimate the range and incidence of complications. The detailed records of 5000 colonoscopies in a specialist unit have been analysed and conclusions drawn which may help to make the procedure safer. The incidence of haemorrhage was 1% and bowel perforation 0.1%. All the major haemorrhages occurred during polypectomies over 2 cm in size. Secondary haemorrhage was an unpredictable occurrence, one to 14 days later. Three deaths followed colonoscopy: one cardiorespiratory death was related to oversedation; a second was due to mismanaged ischaemic colitis developing two days after traumatic instrumentation, and the third was due to peritonitis. Minor complications included thrombophlebitis, abdominal distension, and vasovagal episodes. Because of experience during the first half of the series and also due to improvements in instrumentation, the complication rate of the later part of the series was halved. Recommendations include the avoidance of oversedation, review of previous barium enema films so as to be aware of large polyps which are more likely to bleed, and the recognition of situations where perforation or septicaemia is likely to occur.

Although Hemoccult (Smith Kline Diagnostics, Inc., Sunnyvale, Calif.) screening for colorectal cancer is based on detection of the peroxidase activity of blood, little is known about the relationship between patterns of bleeding from cancers or adenomas and sensitivity of the test slides. 51Cr-labeled blood loss was measured for a mean of 9.1 days in 46 patients with colorectal cancer and 28 with adenomas. Duplicate sets of Hemoccult II slides were prepared by the patients and mailed for testing with and without preliminary rehydration. Mean blood loss was significantly related to the site of the cancers, but was unrelated to Dukes' staging. Geometric mean levels of blood loss from the cancers were 9.3 ml/day for cecum and ascending colon, 1.5 ml/day for transverse and descending colon, 1.9 ml/day for sigmoid colon, and 1.8 ml/day for rectum. Rehydration increased Hemoccult sensitivity for blood independently of storage delay, almost doubling sensitivity at the levels of bleeding commonly encountered with cancers of the left side of the colon. Relating results to testing over 3 days, the Hemoccult false-negative rate for cancer was 31% without rehydration, falling to 9% with rehydration. With adenomas, blood loss and Hemoccult positivity were closely related to lesion size. The findings support the validity of 3-day occult blood testing as a method of screening for colorectal cancers and large adenomas, provided the test employed has a high sensitivity for blood. Further information is needed about the specificity of rehydrated Hemoccult slides in subjects following diets of differing peroxidase content. The degree to which rehydration of slides lowers the false-negative rate for cancer indicates that this modification of slide development should be evaluated in large population screening programs.

Three hundred and thirty patients having had previous colonoscopic polypectomy of adenomas were recalled for follow-up and submitted to all available diagnostic methods: occult blood testing, digital examination, rigid proctosigmoidoscopy, fibre-optic sigmoidoscopy, total colonoscopy and double contrast barium enema. Polyps up to 7 mm diameter were electro-coagulated during diagnostic endoscopy but larger polyps were left in situ for barium enema before polypectomy at a later date. Disparities between endoscopy and X-ray were rechecked by one or both procedures. Occult blood testing, digital examination and rigid proctosigmoidoscopy were found to be inaccurate or ineffective in diagnosis of the 37% of patients with further adenomas or carcinomas. Double contrast barium enema demonstrated 71% of larger lesions compared to the 92% shown by colonoscopy. The commonest sites of X-ray inaccuracy were in the sigmoid colon and caecum. Colonoscopy permits immediate electrocoagulation or snare polypectomy of any lesions seen, as well as being the more accurate investigation and is, therefore, the procedure of choice in post polypectomy follow-up. The mean time taken for diagnostic total colonoscopy in this series was 15.3 minutes, comparable to the time taken for barium enema. Postal questionnaire showed both procedures to be equally well tolerated by the patients. Thirty per cent of colonoscopies were, however, considered technically difficult by the endoscopist, and for these patients it is suggested that follow-up should be by the combination of fibre-sigmoidoscopy using carbon dioxide insufflation and immediate double contrast barium enema. Should this combination indicate a need for total colonoscopy, then almost all adenomas and cancers would be detected. Total examination of the colon by one or other means is essential, over half the patients with adenomas and three of the five patients with carcinoma showing no pathology in the territory of fibresigmoidoscopy or limited colonoscopy.

Research that involves healthy normal volunteers frequently is performed. This article examines ethical guide-lines for the recruitment of healthy volunteers in research projects. Ethical decisions on projects that are based on patient-volunteers or healthy normal volunteers should balance the risk to the volunteer and the collective benefit to the community. For healthy normal volunteers that risk should be minimal or trivial. Investigators should follow recruitment practices that avoid approaches to persons who are dependent upon them in some way, and should carry the day-to-day ethical responsibility even after institutional ethical approval has been granted. Pilot studies and self-experimentation readily can transgress ethical guide-lines. Compensation for mishaps or injuries that occur during research in which there is no question of negligence (for example, an unforeseeable reaction in a phase-1 drug trial) is an unresolved issue which should be addressed by the research community. It is recommended that action be taken to ensure that healthy volunteers who participate in approved research have redress in the rare event of an accident, whether this is a result of negligence, chance or misadventure. Hospitals/institutions or other bodies that sponsor research should extend their insurance to cover specifically such unforeseeable events in which there may be liability, and to have the facility for a payment of beneficence in the case of accidents in which liability cannot be established.

The study was designed to determine the prevalence of large bowel symptoms in an adult working population and to assess their value in screening for large bowel neoplasms. A symptom questionnaire was sent to workers in two large organizations and the results were compared with faecal occult blood testing in the same individuals using Haemoccult (Eaton Laboratories). Completed symptom questionnaires and Haemoccult test kits were returned by 916 out of a total of 1805 employees over the age of 40 (compliance 50.7 per cent). Twenty-eight (3.1 per cent) were Haemoccult positive and 114 (12.4 per cent) had one or more symptoms. All positives (129 persons) were examined by flexible sigmoidoscopy and barium enema. No cancer was found but 7 patients with adenomas greater than 10 mm diameter were discovered. Each of the 7 patients reported at least one symptom (dark red bleeding in 4, bright red bleeding in 2 and diarrhoea in 1) and 6 were Haemoccult positive. There was no individual with a Haemoccult positive adenoma without symptoms. Predictive values for adenomas over 10 mm for Haemoccult positive tests (21 per cent), self-reported dark bleeding (16 per cent) and diarrhoea (17 per cent), were significantly higher than for other symptoms. The predictive value rose significantly to 46 per cent for Haemoccult-positive patients who in addition had at least one symptom (P less than 0.05) and to 57 per cent for Haemoccult positive with dark bleeding. These combinations of Haemoccult- and symptom-positive results increased the specificity of 97.6 per cent for Haemoccult alone to values over 99 per cent without reducing sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)