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W S Atkin

Publications and source records attributed to W S Atkin.

36 records · Page 2Linked to original sources
PubMed1998

Predicting the risk of metachronous colorectal cancer in patients with rectosigmoid adenoma using quantitative pathological features. A case-control study.

The prognostic value of quantitative pathological features in rectosigmoid adenomas was investigated, in search of more precise identifiers of adenoma-bearing patients at high risk of metachronous colorectal cancer. In a "nested case-control study" design, 21 cases with metachronous colon cancer during an average follow-up time of 16 years (range 3-30 years) after polypectomy and 67 controls were selected from a cohort of 1618 patients. The most advanced adenoma of each patient was analysed. Cases were matched with up to three controls simultaneously for size, grade of dysplasia, histological type, and number of adenomas, as well as for duration of follow-up. The patients did not undergo any post-polypectomy surveillance. Geometric characteristics of tumour nuclei, the arrangement of nuclei in the epithelium, and glandular changes were measured, and mitoses were counted. Several quantitative features measuring nuclear polymorphism and crowding showed significant prognostic value, while those measuring glandular changes and mitotic activity did not. A multivariate combination of the average distance between nuclei and the standard deviation of nuclear area discriminated an unfavourable group (n = 44) with 17 metachronous cancers from a favourable group (n = 44) with four metachronous cancers (P = 0*001, RR = 6*3). With the optimum cut-off, 28 patients without any metachronous cancer were discriminated from a group of 60 patients with 21 metachronous cancers. In conclusion, in the present study, quantitative pathological features assessed in rectosigmoid adenomas showed prognostic value additional to traditional measures. These features may therefore be useful in guiding post-polypectomy surveillance.

Adenoma↗
PubMed1998

Flexible sigmoidoscopy as a mass screening tool.

Endoscopic removal of premalignant adenomas from the distal bowels of the entire population, 3 to 5-yearly from age 50, is advocated in the US as a feasible method of reducing colorectal cancer mortality rates. In the UK, a single flexible sigmoidoscopy (FS) is regarded as a more cost-effective option. Although more acceptable than colonoscopy, FS and polypectomy are expensive and invasive procedures carrying a small risk of serious harm. We believe that, before implementing mass screening, precise estimates are required of the magnitude of the reduction in mortality and costs (financial, physical and emotional). Several randomized trials, including a large British study, are currently evaluating these aspects.

Adenoma↗
PubMed1998

Uptake, yield of neoplasia, and adverse effects of flexible sigmoidoscopy screening.

BACKGROUND: A multicentre randomised controlled trial to evaluate screening by "once only" flexible sigmoidoscopy (FS) for prevention of bowel cancer is in progress. AIMS: To pilot the trial protocol examining rates of attendance, yield of neoplasia, and adverse effects. SUBJECTS: A total of 3540 subjects aged 55-64 years in Welwyn Garden City (WGC) and 19,706 in Leicester (LE). METHODS: Subjects responding positively to an "interest in screening" questionnaire were randomised to invitation for screening or control arms. Small polyps were removed during screening. Colonoscopy was undertaken for high risk polyps (more than two adenomas, size at least 1 cm, villous histology, severe dysplasia, or malignancy). The remainder were discharged. RESULTS: In WGC and LE respectively, 59% and 61% indicated an interest in screening, of which 74% and 75% attended. Adenomas were detected in 10% and 9%, respectively, and cancers in 7 per 1000 (in both centres), 55% at Dukes's stage A. The colonoscopy referral rate was 6% in both centres. Mild, short lived bleeding occurred in 3%. One person died following surgery. CONCLUSIONS: Compliance rates, yield of adenomas, and referral rate for colonoscopy were as expected, but cancer detection rates were higher. Adverse effects following sigmoidoscopy or colonoscopy were mild and transient, but there was one postoperative death. A randomised trial is necessary to evaluate fully the risks and benefits of this intervention.

Adenoma↗
PubMed1998

Flat adenomas exist in asymptomatic people: important implications for colorectal cancer screening programmes.

BACKGROUND: Flat adenomas are non-exophytic with a flat top or central depression and histologically the depth of dysplastic tissue is never more than twice the mucosal thickness. Flat adenomas frequently contain severely dysplastic tissue, and may progress rapidly through the adenoma-carcinoma sequence. Flat lesions have never been described in a British asymptomatic population. AIMS: To determine whether flat adenomas exist in an asymptomatic population participating in a large randomised controlled trial of flexible sigmoidoscopy screening. PATIENTS: A total of 3000 subjects (aged 55-64 years) underwent screening by flexible sigmoidoscopy. METHODS: All polyps were removed and sent for histology. The number of polyps with endoscopic and histological features of flat adenomas was recorded. RESULTS: Three subjects had a total of four flat lesions--that is, one per 1000 people screened. Three contained severely dysplastic tissue, one a focus of adenocarcinoma. Three of the four lesions were less than 5 mm in size and the fourth was 15 mm in diameter. CONCLUSIONS: Flat lesions with severe dysplasia exist in the asymptomatic population. This has major implications for gastroenterologists who should be trained to identify them. Their existence is of importance to molecular biologists and epidemiologists investigating the aetiology of colorectal cancer.

Adenomatous Polyps↗
PubMed1996

Screening for colorectal cancer by once only sigmoidoscopy: a feasibility study in Turin, Italy.

OBJECTIVES: To assess the impact on compliance of three invitation methods, as well as the acceptability and efficacy of two bowel preparation regimens, for endoscopic screening in the general population. METHODS: 1170 subjects (men and women aged 55 to 59, in the rosters of a sample of general practitioners (GPs) in Turin), were randomly allocated to one of three invitation groups (A: personal letter, signed by GP, with a pre-fixed appointment; B: same as for A + letter supporting the study by a well known scientist; C: letter signed by the study coordinator, NS) and two preparation regimens (i: one enema, self administered at home two hours before the test; ii: two enemas, administered the night before and two hours before the test). A postal reminder was mailed to non-attenders. A sample of non-responders was contacted for a telephone interview by a trained nurse. Written consent was obtained from all subjects undergoing the test. RESULTS: A total of 278 subjects attended for sigmoidoscopic screening. An invitation from the GP alone produced the highest response rate (compliance: A = 29.3%; B = 24.9%; C = 26.8%). A single enema was as effective as two enemas in achieving satisfactory preparation for the test: the proportion of subjects invited to repeat the test was 8.1% in the single enema group, and 9.6% in the group receiving two enemas. CONCLUSIONS: Compliance with this screening procedure tends to be low. One enema, self administered two hours before sigmoidoscopy, can ensure a satisfactory bowel preparation.

Colorectal Neoplasms↗
PubMed1995

Variables associated with the risk of colorectal adenomas in asymptomatic patients with a family history of colorectal cancer.

The results of screening individuals referred to the Family Cancer Clinic at St Mark's Hospital from 1986 are presented. Colonoscopy was performed in 644 asymptomatic individuals (from 436 families) with a family history of colorectal cancer. Sixty nine (15.8%) of the families fulfilled the Amsterdam criteria for the hereditary non-polyposis colorectal cancer syndromes (HNPCC). Seven cases of colorectal cancer were diagnosed at an average age of 49 years; six at Dukes's stage A and one at stage C, four in subjects from Amsterdam criteria families. One hundred and forty four (22.4%) subjects had one or more adenomas. The prevalence of adenomas in the subjects from Amsterdam criteria families was 34 of 127 (26.8%) compared with 110 of 517 (21.3%) in those from other families; the age and sex adjusted odds ratio (OR) was 1.76 (p = 0.02). Factors influencing the prevalence of adenomas in screened individuals were evaluated. Multivariate analysis showed that independent variables significantly related to the risk of adenomas were: age (p < 0.0001), sex (p = 0.0002), and the number of generations (> or = 2 v 1) of relatives affected by either colorectal cancer or adenomas (p = 0.0006). The latter variable was more highly predictive of the probability of finding an adenoma at colonoscopy than a family history of two generations with cancer only (p = 0.056). The OR of having colorectal adenomas increased with age, by about twofold for each decade, and was twice as high in men than women, and in subjects with two or more generations relative to those with one generation affected by colorectal cancer or adenomas. Six of seven patients with cancer and 46 of 144 (31.9%) with adenomas had lesions proximal to the splenic flexure only. The proportion of individuals with proximal adenomas only was 47.1% in Amsterdam criteria families and 27.3% in the others (p=0.03). These findings support the view that colonoscopy rather than sigmoidoscopy is the method of choice for screening high risk groups.

Adenoma↗
PubMed1993

Prevention of colorectal cancer by once-only sigmoidoscopy.

There is no national screening programme for colorectal cancer in the UK despite the fact that the annual death toll from this disease exceeds that of breast and cervical cancer. Faecal occult blood testing (FOBT) is under evaluation for screening, but screening by sigmoidoscopy is not considered viable. This situation contrasts with the USA where both annual FOBT and screening by flexible sigmoidoscopy every 3 to 5 years are recommended from 50 years old. We seek to demonstrate that most of the benefit from the US screening policy would accrue from a single flexible sigmoidoscopy examination at age 55 to 60 years with appropriate colonoscopic surveillance for the 3% to 5% found to have high-risk adenomas (> or = 1 cm or villous histology). If applied nationally, this screening regimen could prevent about 5500 colorectal cancer cases and 3500 deaths in the UK each year, thus saving 40,000 years of life. We estimate that there would be little net cost to the National Health Service because savings obtained from treating fewer patients would largely offset the cost of screening. We recommend that a randomised trial to evaluate screening by single flexible sigmoidoscopy should start without delay. Such a trial would involve about 120,000 participants, and 15 years of follow-up would be required to obtain a clear answer on mortality, although information on incidence reduction would be available sooner.

Adult↗
PubMed1992

Long-term risk of colorectal cancer after excision of rectosigmoid adenomas.

BACKGROUND AND METHODS: Surveillance by repeated colonoscopy is currently recommended for patients with colorectal adenomas. We assessed the long-term risk of colorectal cancer after rigid-instrument sigmoidoscopy and polypectomy in 1618 patients with rectosigmoid adenomas (tumor of the rectum or distal sigmoid colon) who did not undergo surveillance. A total of 22,462 person-years of observation were accrued (mean, 14 years per patient). RESULTS: The incidence of subsequent rectal cancer in these patients was similar to that in the general population (standardized incidence ratio, 1.2; 95 percent confidence interval, 0.7 to 2.1). Most rectal cancers developed in patients whose adenomas had been inadequately removed; the risk was very low after complete removal. The risk of subsequent colon cancer depended on the histologic type, size, and number of adenomas in the rectosigmoid. Among 842 patients with a rectosigmoid adenoma that was tubulovillous, villous, or large (greater than or equal to 1 cm), colon cancer developed in 31 patients. The standardized incidence ratio was 3.6 (95 percent confidence interval, 2.4 to 5.0) overall and 6.6 (95 percent confidence interval, 3.3 to 11.8) if there were multiple rectosigmoid adenomas. Among the remaining 776 patients with only small, tubular adenomas (whether single or multiple), colon cancer developed in only 4 patients. The standardized incidence ratio in this group was 0.5 (95 percent confidence interval, 0.1 to 1.3). CONCLUSIONS: Follow-up colonoscopic examinations may be warranted in patients with tubulovillous, villous, or large adenomas in the rectosigmoid, particularly if the adenomas are also multiple. In patients with only a single, small tubular adenoma that is only mildly or moderately dysplastic (43 percent of our series), however, surveillance may not be of value because the risk of cancer is so low.

Adenoma↗
PubMed1987

Value of flow cytometric determination of ploidy as a guide to prognosis in operable rectal cancer: a multivariate analysis.

The DNA content of 203 cases of rectal cancer, with at least 15 years follow-up, was analysed by flow cytometry. One hundred and twenty-nine (64%) were DNA aneuploid and corrected survivals were significantly influenced by ploidy distribution (p less than 0.01). The DNA content and details of stage and grade were subjected to multivariate analysis using the Cox regression model. Ploidy was entered into models including Dukes' stage alone, tumour differentiation alone, Dukes' stage and differentiation in combination and a more comprehensive range of discrete stage- and grade-related parameters. All four models demonstrated its independent contribution to survival. However, its contribution was very small (5%, 18%, 5%, 4% respectively). These findings illustrate that results based on new technological developments should not be viewed in isolation, but their values must be assessed in combination with traditionally available data by means of multivariate analysis.

Adenocarcinoma↗
PubMed1987

Mucinous carcinoma of the rectum.

We have studied and compared 316 mucinous and 45 signet ring cell carcinomas of the rectum with 413 non-mucinous carcinomas. Mucinous carcinomas were subdivided according to the amount of mucus which was gauged subjectively as either more or less than 75% of the tumour volume. Five year survivals for non-mucinous, mucinous (less than 75%), mucinous (greater than 75%) and signet ring cell carcinoma were 62%, 60%, 53% and 13%. Mucinous carcinomas (less than 75%) were relatively well differentiated and showed an age distribution identical to their non-mucinous counterparts, but differed in their strong association with villous adenoma. Mucinous carcinomas (greater than 75%) were less well differentiated and, like signet ring cell carcinomas, occurred in younger patients and showed no special association with villous adenoma. Clinically important and independent predictive variables were found by the method of multivariate regression analysis to be number of lymph node metastases, extent of spread in continuity, character of invasive margin and peritumoural lymphocytic infiltration. After adjustment for these factors, typing of rectal cancer as mucinous, non-mucinous and signet ring cell gave no additional, clinically useful prognostic information.

Adenocarcinoma, Mucinous↗
PubMed1986

The grading of rectal cancer: historical perspectives and a multivariate analysis of 447 cases.

The grade of a tumour is gauged on the subjective assessment of a number of histopathological parameters. The problems associated with this exercise were viewed from a historical perspective and survival analysis of 447 patients receiving surgery for rectal adenocarcinoma was undertaken. Only deaths from rectal adenocarcinoma were included as events in the survival analysis. Seven grade-related parameters were scored by one observer. A grading system was constructed using the Cox regression model. The variables in the best-fitting parsimonious model comprised lymphocytic infiltration, tubule configuration and pattern of growth. Scores were derived from the model and a four grade system was created in which the groups were of similar size. Good reproducibility of the selected histopathological parameters was demonstrated. Grade-related parameters were then allowed to compete with stage-related parameters in an overall model of pathological prognostic categories. The parameters selected in the best model were number of affected lymph nodes, the presence of lymphocytic infiltration and extent of spread through bowel wall. A set of five prognostic categories was developed from this model.

Adenocarcinoma↗
PubMed1976

Long-term low-dose co-trimoxazole in prophylaxis of childhood urinary tract infection: clinical aspects.

Long-term low-dosage prophylaxis may be used in children with recurrent urinary tract infection to prevent reinfection of the urinary tract while the underlying cause of infection persists. Co-trimoxazole in a dose of 2 mg trimethoprin combined with 10 mg sulphamethoxazole per kg body weight daily has proved very effective: only six of 130 children receiving this treatment during a total period of 2637 months developed a reinfection. Co-trimoxazole was acceptable, compliance was good, and there were no important adverse effects. Supportive measures during prophylaxis are important. Sixty-five children were follow up after completion of their co-trimoxazole prophylaxis. Twenty-seven developed reinfections with fresh organisms, over two-thirds occurring within three months of discontinuing prophylaxis. Each one of these reinfections was sensitive to trimethoprin. The rectal flora were similarly sensitive.

Child↗
PubMed1976

Long-term low-dose co-trimoxazole in prophylaxis of childhood urinary tract infection: bacteriological aspects.

The bacteriological consequences of giving long-term low-dose co-trimoxazole to children to prevent reinfection of the urinary tract were studied. Only six "break-through" infections occurred during 2637 child-months of prophylaxis. The children complied well with treatment. During prophylaxis the number of rectal coliform bacilli recovered was greatly and rapidly reduced, but at least 70% of the surviving coliform organisms remained sensitive to the two components of co-trimoxazole. Changes in sensitivity pattern were evident within a month of starting treatment and the proportion of rectal organisms resistant to sulphonamide or trimethoprim did not increase with time. After stopping co-trimoxazole prophylaxis the number of rectal organisms recoverable returned rapidly to normal, as did their sensitivities to trimethoprim and sulphonamide. Further episodes of urinary tract infection developing after prophylaxis was stopped were caused by organisms sensitive to a wide range of antimicrobial agents, including trimethoprim.

Child↗