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Biomedical subjects

M H Robinson

Publications and source records attributed to M H Robinson.

At least 37 records · Page 2Linked to original sources

Should we be screening for colorectal cancer?

Mass population screening for asymptomatic neoplastic disease is now national policy in the UK for breast cancer and has been established for many years in the early diagnosis of carcinoma of the cervix. Cancer screening is based on the concept that treatment is more effective when the disease is localised and aims to detect it when it is at a less advanced clinico-pathological stage prior to the development of symptoms. Because colorectal cancer develops in benign adenomatous polyps which are often amenable to endoscopic resection, screening may both reduce the incidence of the disease as well as improving outcome from it. Flexible sigmoidoscopy screening focuses mainly on the detection of potentially malignant adenomas, their endoscopic removal producing a decrease in colorectal cancer incidence. It is a promising approach but conclusive data on effectiveness from a Medical Research Council-sponsored multicentre randomised controlled trial will not be available before 2006. Faecal occult blood testing aims to preferentially detect early stage invasive disease. Three randomised controlled trials of faecal occult blood screening show that the disease can be detected earlier in its development leading to reduced mortality from the disease--and that this is achieved at reasonable cost. The Department of Health is currently giving consideration to its national implementation.

Colorectal Neoplasms↗

Localised non-Hodgkin's lymphoma: the Sheffield Lymphoma Group experience (1970-1995).

We report a retrospective study of all patients with localised non-Hodgkin's lymphoma referred to the Sheffield Lymphoma Group (1970-1995). A total of 1,979 patients with non-Hodgkin's lymphoma were seen: 553 (28%) presented with stage I or II disease, 411 (21%) extranodal, 142 (7%) nodal. The commonest extranodal sites were head and neck, gastrointestinal tract, skin and central nervous system, accounting for 87% of patients. Most patients received primary localised radiotherapy. Overall observed survival was 52.5% at 5 years in the extranodal group and 65% in the nodal group. For both groups the 10-year observed survival was 42.5%. An age of 45 years and over was a poor prognostic factor in both groups (p<0.001). Patients with skin and non-Waldeyer's head and neck lymphomas survived best (5-year observed survivals 67 and 70% respectively) and CNS worst (5-year survival 38%). There is no cause for complacency in the management of localised non-Hodgkin's lymphoma, particularly for the less common extranodal sites where multicentre clinical studies are still essential.

Adult↗

The association between nm23 gene expression and survival in patients with sarcomas.

The relationship between the expression of nm23, a putative metastasis-suppressor gene and prognosis was determined for 88 patients with sarcomas. Immunohistochemistry using immunopurified anti-nm23 peptide antibodies was performed and the results of each case graded according to the degree of staining. Univariate and multivariate analyses were carried out to determine the prognostic significance of nm23 staining for sarcoma patients. Expression of nm23 was found to increase in line with metastatic potential in many cases but this did not reach significance for the study as a whole. However, the possibility of nm23 loss occurring in association with metastasis cannot be ruled out in some more aggressive sarcomas, as was demonstrated for six patients with low-scoring, unclassified and synovial sarcomas that had metastasized. The time to metastasis was longer for patients with grade 3 sarcomas (50-75% of tumour cells staining) than similar patients in other staining groups. These results suggest that expression of nm23 genes in sarcomas is variable and has no value as a prognostic indicator for these mesenchymal tumours.

Adolescent↗

Chemical and immunological testing for faecal occult blood in screening subjects at risk of familial colorectal cancer.

BACKGROUND: People with a family history of colorectal cancer have an increased risk of the disease themselves. Many centres are advocating family history screening by endoscopy. AIMS: The performance of chemical and immunological faecal occult blood tests (Haemoccult and Hemeselect) in 212 subjects with a family history of colorectal cancer was assessed. RESULTS: Both Hemeselect and Haemoccult were positive in the only patient with colorectal cancer. Hemeselect was more sensitive than Haemoccult for adenomas (40% compared with 20%) (adenomas larger than 1 cm 75% compared with 50%). No additional abnormality was detected by the addition of Haemoccult or Hemeselect to 60 cm flexible sigmoidoscopy in screening people at lower levels of familial risk. A false positive rate of 16% for Hemeselect resulted in a high proportion of additional colonoscopies in this group. CONCLUSIONS: At present faecal occult blood tests are not sufficiently sensitive or specific to replace endoscopy in screening people at risk of familial colorectal cancer.

Adenoma↗

CT virtual simulation.

Advances in computer technology and software design have enabled the concept of virtual simulation, first suggested by George Sherouse, to be realized. This article reviews the hardware and software requirements that provide a system that feels like a simulator and can facilitate the 3D planning process. Fast digital reconstruction of a radiograph from a CT data set provides true verification of treatment field design within the constraints of the virtual method. The clinical application of this technique is discussed in detail in relation to particular treatment sites.

Breast Neoplasms↗

Randomised controlled trial of faecal-occult-blood screening for colorectal cancer.

BACKGROUND: There is growing evidence that faecal-occult-blood (FOB) screening may reduce colorectal cancer (CRC) mortality, but this reduction in CRC mortality has not been shown in an unselected population-based randomised controlled trial. The aim of this study was to assess the effect of FOB screening on CRC mortality in such a setting. METHODS: Between February, 1981, and January, 1991, 152,850 people aged 45-74 years who lived in the Nottingham area of the UK were recruited to our study. Participants were randomly allocated FOB screening (76,466) or no screening (controls; 76,384). Controls were not told about the study and received no intervention. Screening-group participants were sent a Haemoccult FOB test kit with instructions from their family doctor. FOB tests were not rehydrated and dietary restrictions were imposed only for retesting borderline results. Individuals with negative FOB tests at the first screening, together with those who tested positive but in whom no neoplasia was found on colonoscopy, were invited to take part in further screening every 2 years. Screening was stopped in February, 1995, by which time screening-group participants had been offered FOB tests between three and six times. Screening-group participants who had a positive test were offered full colonoscopy. All participants were followed up until June, 1995. The primary outcome measure was CRC mortality. FINDINGS: Of the 152,850 individuals recruited to the study, 2599 could not be traced or had emigrated and were excluded from the analysis. Thus, there were 75,253 participants in the screening group and 74,998 controls. 44,838 (59.6%) screening-group participants completed at least one screening. 28,720 (38.2%) of these individuals completed all the FOB tests they were offered and 16,118 (21.4%) completed at least one screening but not all the tests they were offered. 30,415 (40.4%) did not complete any test. Of 893 cancers (20% stage A) diagnosed in screening-group participants (CRC incidence of 1.49 per 1000 person-years), 236 (26.4%) were detected by FOB screening, 249 (27.9%) presented after a negative FOB test or investigation, and 400 (44.8%) presented in non-responders. The incidence of cancer in the control group (856 cases, 11% stage A) was 1.44 per 1000 person-years. Median follow-up was 7.8 years (range 4.5-14.5). 360 people died from CRC in the screening group compared with 420 in the control group-a 15% reduction in cumulative CRC mortality in the screening group (odds ratio=0.85 [95%; CI 0.74-0.98], p = 0.026). INTERPRETATION: Our findings together with evidence from other trials suggest that consideration should be given to a national programme of FOB screening to reduce CRC mortality in the general population.

Adenoma↗

Screening for colorectal cancer with an immunological faecal occult blood test: 2-year follow-up.

This study is a 2-year follow-up of an average-risk population offered screening with both Haemoccult and Hemeselect tests to determine the interval cancer rate, and thus sensitivity. The effect on compliance with Hemeselect of testing over 1 day rather than 3 days was investigated in a separate cohort. In the first study, 3948 subjects received tests; 1489 (37.7 per cent) completed both tests and 148 had a positive result, 17 (1.1 per cent) were Haemoccult positive and 145 (9.7 per cent) were Hemeselect positive. Investigation of 142 patients revealed ten with cancer (Dukes stage A, seven; B, one; C, two). All were detected by Hemeselect but only one was Haemoccult positive. After a median follow-up of 35 (range 26-43) months, seven further patients developed colorectal cancer (stage A, one; B, three; C, three) but none followed a negative Hemeselect test (100 per cent sensitivity). In the second study 2703 subjects were offered Hemeselect tests. Compliance for testing over 1 day (48.6 per cent) was significantly better than that over 3 days (43.1 per cent) (chi 2 = 8.1, 1 d.f., P < 0.01). Hemeselect is a promising screening test for the early detection of colorectal cancer.

Aged↗

Faecal occult blood testing and colonoscopy in the surveillance of subjects at high risk of colorectal neoplasia.

Colonoscopy is the established method of surveillance of subjects at high risk of developing colorectal neoplasia but the procedure is expensive, time consuming and occasionally hazardous. Faecal occult blood tests can be prepared at home and are cheap, simple and safe. Hemeselect is an immunological faecal occult blood test that is more sensitive for colorectal cancer than Haemoccult. The aim of this study was to determine the sensitivity of the Hemeselect test for asymptomatic colorectal neoplasia in subjects at high risk of the disease who were undergoing colonoscopy, thus assessing its suitability as an alternative means of screening high-risk groups. A total of 919 asymptomatic subjects were asked to complete Hemeselect tests. These were completed satisfactorily by 808 individuals (compliance rate 88 per cent) and were positive in 164 patients (20 per cent). At colonoscopy 11 cancers were detected in ten patients (seven Hemeselect positive) and 36 (16 Hemeselect positive) had at least one adenoma 1 cm or more in diameter. The test sensitivites of Hemeselect for carcinoma and large (1 cm or more) adenomas were 70 and 44 per cent respectively. In a subset of 417 subjects who also completed Haemoccult tests, the sensitivities were 33 and 18 per cent. Hemeselect specificity is 88 per cent compared with 98 per cent for Haemoccult. While the sensitivity of Hemeselect is higher than that of Haemoccult, it is still insufficient to replace colonoscopy in high-risk groups.

Colonoscopy↗

Nonsteroidal antiinflammatory drug-induced colonic stricture. An unusual cause of large bowel obstruction and perforation.

Nonsteroidal antiinflammatory drugs (NSAIDs) are widely prescribed drugs that can result in gastroduodenal ulceration. Adverse effects upon the small and large intestine are now more often recognized. Small intestinal obstruction secondary to both mucosal diaphragms and broad-based stenoses is reported, but colonic strictures appear to be less common. A case of NSAID-induced colonic stricture leading to large bowel obstruction and secondary cecal perforation (previously unreported) is presented. Twelve additional cases of NSAID-induced colonic stricture are reviewed from the literature and its possible pathogenesis is discussed.

Acetaminophen↗

Is an immunological faecal occult blood test better than Haemoccult? A cost-benefit study.

Immunological faecal occult blood (FOB) tests have theoretical advantages over their guaiac counterparts in that they are specific for human haemoglobin. HemeSelect is a semi-quantitative immunological FOB text. Faecal material is eluted into test diluent and serial dilutions are performed. The manufacturers recommend that erythrocyte agglutination at 1:8 dilution is considered a positive reaction. However, further serial dilutions can be carried out and the highest dilution at which the test remains positive determined. At 1:8 dilution, the test has been shown to be more sensitive for symptomatic colorectal cancer than Haemoccult. The aim of this study is to compare the positive rates, neoplastic yield and costs of Haemoccult with HemeSelect at various dilutions in asymptomatic average risk subjects aged 50-74. 1489 subjects satisfactorily completed both tests, 145 (9.7%) returned positive Hemeselect tests (read at 1:8 dilution, 38 patients with neoplasms > or = 1 cm) and 17 positive Haemoccult tests (1.1%). All positive Hemeselect tests were further serially diluted. As the Hemeselect dilution increased to 1:16, 1:32, 1:64 and 1:128 so the positive rate and yields of neoplasms > or = 1 cm progressively fell to 6.8% & 35, 3.6% & 20, 2.7% & 18 and 1.5% & 12, compared with 1.1% and eight neoplasms > or = 1 cm for Haemoccult. In spite of the unit cost of the Hemeselect test being greater than Haemoccult, the cost per neoplasm > or = 1 cm was lower for Hemeselect at 1:8 and 1:16 dilutions than Haemoccult. However, for an equivalent neoplastic yield, Haemoccult was cheaper. Hemeselect is a versatile test whose positive rate can be tailored according to the risk of the group being screened.

Aged↗

Serum thymidine kinase in colorectal neoplasia.

Thymidine kinase (TK), an enzyme known to be associated with DNA synthesis, has been measured in the serum of patients with asymptomatic colorectal adenomas (n = 40), asymptomatic colorectal carcinoma (n = 21) and patients known to have hepatic metastases form colorectal tumours (n = 33); enzyme levels have been compared with an age-matched group of asymptomatic people with no evidence of colorectal neoplasia at screening colonoscopy (n = 26). TK activity in patients with metastatic disease (median 4.23; range 2.03-14.12 pmol/ml/h) and in patients with adenomas (median 2.33; range 1.59-8.73 pmol/ml/h) was significantly higher than in the normal controls (median 2.04; range 1.29-5.40 pmol/ml/h). However TK activity in patients with asymptomatic cancer (median 1.85; range 1.00-4.50 pmol/ml/h) was not significantly different from the control group.

Adenoma↗

Effect of retesting with dietary restriction in Haemoccult screening for colorectal cancer.

OBJECTIVES: To determine the detection rate, false positive and false negative rates associated with a policy of retesting with dietary restriction after an initial positive Haemoccult screening test for colorectal cancer, in order to compare the cost effectiveness of such a policy with the alternative, in which all subjects with a positive test would proceed directly to diagnostic colonoscopy. METHODS: Over four years in a large randomised control trial in Nottingham 35,260 subjects had a mean of 1.5 screening rounds each at two-yearly intervals, and were followed up for a minimum of 27 months. During this period subjects with positive screening tests were asked to repeat the test with dietary restrictions. Estimates of costs of the initial screening and of diagnostic colonoscopy were used to estimate the cost for each cancer detected by the different policies. RESULTS: 1209 subjects had a positive initial screening test and 1033 (85.4%) completed the retests. Four hundred and ninety nine subjects were investigated and 89 cancers detected. In the 710 subjects with negative retests six interval cancers were diagnosed in the two years after screening. If these had been detected by screening under a policy of immediate colonoscopy, test sensitivity would have been improved from 53.6% to 57.2% (P = 0.02), but the cost for each cancer detected would have increased from pound 773 to pound 1509. CONCLUSION: Retesting with dietary restrictions reduces costs and maximises the benefit of limited colonoscopy resources, but results in a small but significant reduction in test sensitivity compared with a policy for immediate colonoscopy.

Colonoscopy↗

Population screening for colorectal cancer: comparison between guaiac and immunological faecal occult blood tests.

There is concern about the low sensitivity of the guaiac-based Haemoccult test in mass population faecal occult blood (FOB) screening for the early detection of colorectal carcinoma. Hemeselect, an immunological FOB test, has been shown to be more sensitive for symptomatic colorectal cancer and may prove to be a more reliable screening method. In Brighton and Guildford, 4018 asymptomatic subjects aged 50-75 years were offered screening with Haemoccult and Hemeselect. A total of 1489 (37.7 per cent) completed both tests, of which 17 (1.1 per cent) were positive for Haemoccult and 145 (9.7 per cent) positive for Hemeselect (a total of 148 subjects had positive tests). Seven subjects (4.7 per cent) refused to be investigated. Colonic investigation in the remainder revealed nine cancers and 49 patients with 67 adenomas (32 tumours 1 cm or more in size). All cancers (Dukes A, six; B, one; C, two) were detected by Hemeselect (positive predictive value 6.2 per cent) but only one patient was Haemoccult positive (positive predictive value 5.9 per cent). Hemeselect detected 65 adenomas (31 of 1 cm or more) in 48 patients (positive predictive value 33.1 per cent) compared with 11 adenomas (seven of 1 cm or more) in eight patients who were positive for Haemoccult (positive predictive value 47.1 per cent). The test specificity for neoplasia was respectively 94.9 and 99.6 per cent. The Hemeselect positive rate is high but its substantial positive predictive value for cancer warrants continuing evaluation.

Aged↗

Colorectal cancer screening and quality of life.

To evaluate the quality of life of patients following surgery for colorectal cancer, and to compare the quality of life between patients whose cancer was detected as a result of faecal occult blood screening with that of patients whose cancer presented symptomatically, an analysis was conducted within the context of the randomized controlled trial of colorectal cancer screening, University Hospital, Nottingham, UK. A total of 418 survivors of the trial's test and control groups and 33 randomly selected cancer patients completed quality of life questionnaires (Nottingham Health Profile and Health Measurement Questionnaire). The mode of entry to diagnosis and treatment (screening vs. non-screening) appeared to exert no major impact on post-intervention quality of life. The stage of cancer progression was not closely related to outcome life quality. A quality of life coefficient for surviving patients based on the Rosser classification was estimated to lie within the range 0.948-0.981. This figure accords well with the estimates of other studies of interventions in populations of similar age. Overall, there are no grounds for believing that faecal occult blood screening for colorectal cancer per se significantly influences patients' post-intervention quality of life.

Aged↗

Congenital hypertrophy of the retinal pigment epithelium and mandibular osteomata as markers in familial colorectal cancer.

Congenital hypertrophy of the retinal pigment epithelium (CHRPE) and multiple mandibular osteomata are markers of familial adenomatous polyposis (FAP). We have assessed their prevalence in non-polyposis familial colorectal neoplasia. Multiple mandibular osteomata were present in 1/29 (3%) patients with familial colorectal neoplasia. CHRPE was present in 11/33 (33%) patients with familial colorectal neoplasia compared with 3/36 (8%) with sporadic disease (P = 0.01) and 4/32 (12.5%) control subjects (P = 0.04). Seven patients with familial colorectal neoplasia had multiple areas of CHRPE compared with one with sporadic disease (P = 0.02) and one control subject (P = 0.02). There was no obvious correlation between calculated familial colorectal cancer risk and the presence of multiple areas of CHRPE. A proportion of patients with familial colorectal cancer have a marker found in FAP and may therefore have a constitutional genetic defect, at least in part responsible for their cancer, making them an interesting group for genetic study. Ophthalmoscopy may contribute to risk assessment in familial colorectal cancer.

Adult↗