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D J St John

Publications and source records attributed to D J St John.

At least 19 recordsLinked to original sources
PubMed1996

RNA-based mutation screening in hereditary nonpolyposis colorectal cancer.

Hereditary nonpolyposis colorectal cancer (HNPCC) is a cancer syndrome inherited in an autosomal dominant fashion. Four susceptibility genes are known, which code for DNA mismatch repair enzymes. The purpose of this study was to identify the HNPCC gene defects in a cohort of Australian HNPCC families and to evaluate the use of RNA-based screening methods. Six mutations were identified, four in the hMLH1 gene and two in hMSH2, by using a combination of DNA-based and RNA-based methods. One of the hMLH1 defects was a missense mutation, and the other five mutations would be expected to result in a shortened protein. These included a rare type of mRNA splicing mutation in hMLH1 exon 17. By use of reverse-transcriptase (RT) PCR, defective transcripts were detectable for three of the hMLH1 mutations but not for the fourth one, which was predicted to cause skipping of exon 15. Furthermore, many more alternative transcripts for the hMLH1 gene were found than previously described, and these were more abundant in the RNA samples prepared from whole blood than from lymphoblastoid cell lines. This confounded RNA-based screening for HNPCC mutations, because it was difficult to determine which aberrant RT-PCR fragment was the real hereditary defect. One of the splice-site mutations reported here causes skipping of exons 9 and 10, which also occurs as an alternative transcript. When the protein-truncation test was used, the results were indistinguishable between the patients in this family and controls. Other aberrant transcripts were also observed that varied in size between individuals but were unrelated to the hereditary defects. This study has important implications for the design of reliable diagnostic tests for HNPCC gene defects.

Cell Line↗
PubMed1995

Prevention of colorectal cancer: guidelines based on new data. WHO Collaborating Center for the Prevention of Colorectal Cancer.

Recently published good quality data are the basis for this update. The newly reported studies include randomized trials, non-randomized cohort studies, and case-control studies; some of the data had mortality reduction as the endpoint. These guidelines, which were developed by the WHO Collaborating Center for the Prevention of Colorectal Cancer at Memorial Sloan-Kettering Cancer Center in conjunction with an International Advisory Committee, include primary prevention, screening of average-risk individuals, screening of individuals with heritable factors for colorectal cancer, surveillance of patients with colorectal polyps, and surveillance of patients with chronic ulcerative colitis. A list of papers reviewed for this update are cited, including recently published trials evaluating faecal occult-blood testing, case-control studies of sigmoidoscopy, the National Polyp study, and familial colon cancer studies. These guidelines will help inform patients and guide physicians in their approach to the prevention of colorectal cancer.

Colorectal Neoplasms↗
PubMed1993

Cancer risk in relatives of patients with common colorectal cancer.

OBJECTIVE: To quantify any risk for colorectal cancer in first-degree relatives of patients with common colorectal cancer and to define possible markers for increased risk. DESIGN: Case-control family study. PATIENTS: Relatives of colorectal cancer patients and of matched control patients from a one-surgeon practice. METHODS: Family medical histories were obtained for 7493 first-degree relatives and 1015 spouses of 523 case-control pairs. Reported diagnoses of colorectal cancer in relatives were verified in 79% of instances. RESULTS: By case-control analysis, the odds ratio was 1.8 (95% CI, 1.2 to 2.7) for one and 5.7 (CI, 1.7 to 19.3) for two affected relatives. By matched analysis of risk in relatives, the increased risk to parents and siblings was 2.1 times greater for case patients than for control patients (CI, 1.4 to 3.1); 3.7 times greater (CI, 1.5 to 9.1) with case patients diagnosed before 45; and 1.8 times greater (CI, 1.2 to 2.9) with case patients diagnosed at 45 years or older; and was independent of gender, type of relative, site of cancer, and type of cancer (single or multiple). The cumulative incidence among first-degree relatives was greater for case patients than for control patients (P < 0.001), and in case patients, greater for those diagnosed before 55 years of age (P < 0.001). The cumulative incidence (+/- S.E.) to age 80 was 11.1% +/- 1.3%, 7.3% +/- 0.8%, and 4.4% +/- 1.0% among relatives of case patients diagnosed before age 45 years, between 45 and 54 years, and at 55 years or older, respectively, and was 2.4% +/- 0.6% in relatives of control patients. CONCLUSIONS: First-degree relatives of patients with common colorectal cancer have an increased risk for colorectal cancer. This risk is greater if diagnosis was at an early and is greater when other first-degree relatives are affected. This increased risk should be considered when formulating screening strategies.

Adult↗
PubMed1993

Evaluation of new occult blood tests for detection of colorectal neoplasia.

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.

Adenoma↗
PubMed1992

Comparison of the specificity and sensitivity of Hemoccult and HemoQuant in screening for colorectal neoplasia.

OBJECTIVE: To compare the Hemoccult II and HemoQuant tests regarding their specificity and sensitivity in screening for colorectal neoplasia. DESIGN: Cross-sectional study in which subjects underwent the two tests in parallel, after excluding dietary hemes and peroxidase-rich foods. HemoQuant results were analyzed for three different upper limits of normality (1.5, 2.0, 3.0 mg/g feces). SETTING: A university hospital and the surrounding community. PARTICIPANTS: A total of 150 healthy volunteers, 124 patients with colorectal cancer, and 86 patients with adenoma. MAIN OUTCOME MEASURES: Blinded comparison of the specificity and the sensitivity of the two tests for colorectal cancer and adenoma. RESULTS: Test specificity was 99.3% with Hemoccult and was 92.7%, 94.7%, and 97.3% with HemoQuant, depending on the cutoff point; differences between Hemoccult and HemoQuant were significant when cutoffs of 1.5 and 2.0 mg/g were used in HemoQuant testing (6.6% [95% CI, 2.3 to 11.1] and 4.7% [CI, 0.8 to 8.5], respectively). Test sensitivity for colorectal cancer at all sites was 89.5% with Hemoccult and was 83.1%, 74.2% and 62.9% with HemoQuant, for the 1.5, 2.0, and 3.0 mg/g cutoffs, respectively; differences were significant with the 2.0 and 3.0 mg/g cutoff points (6.4% [CI, 6.7 to 24.0] and 26.6% [CI, 17.4 to 35.9%], respectively). The two tests had similar levels of sensitivity for cancers proximal to the splenic flexure, but sensitivity was substantially lower with HemoQuant for the more distal cancers. For all adenomas, test sensitivity was 30.2% with Hemoccult and ranged from 45.4% to 22.1% with HemoQuant. CONCLUSIONS: Although HemoQuant provides a precise measurement of fecal heme and its porphyrin degradation products, the test's performance characteristics in the detection of colorectal neoplasia are less satisfactory than those of Hemoccult II, a qualitative test for the presence of heme.

Adenoma↗
PubMed1992

Readability and sensitivity of a new faecal occult blood test in a hospital ward environment. Comparison with an established test.

OBJECTIVE: To compare the readability and sensitivity of a new guaiac faecal occult blood test, HemoccultSENSA, with those of a standard guaiac-based test, Hemoccult, in a normal working environment. DESIGN: The two tests were performed in parallel on routine clinical and contrived faecal specimens; those developing the tests were blinded as to the test type. SETTING: All tests were carried out in the hospital ward environment under normal conditions by nurses working in the ward. SAMPLES: Fifty faecal samples from healthy volunteer subjects (low concentrations of haemoglobin were added to 40 of these samples) and 145 faecal samples from 65 inpatients likely to have gastrointestinal bleeding. MAIN OUTCOME MEASURES: Test positivity rate, and graded measures of colour intensity, colour stability and colour pattern. RESULTS: With patients' samples, the new test gave a greater number of positive results than the standard test (73.1% v. 65.5%; 95% confidence interval of the difference, 3.3%-11.9%). With contrived samples, the blue colour produced during development was more intense (P less than 0.0003), more stable (P less than 0.0025) and covered a larger area (P less than 0.01) with the new test compared with the standard test. CONCLUSIONS: These results demonstrate the better readability and slightly higher sensitivity of the new test. They justify its use in the ward environment or doctor's office. Patients being tested should consume a low peroxidase diet until the specificity of the new test has been fully evaluated.

Color↗
PubMed1991

Clinical profile in Barrett's esophagus: who should be screened for cancer?

A retrospective survey identified 96 patients (58 males) with Barrett's esophagus, diagnosed at the Royal Melbourne Hospital between 1978 and 1986. The age at presentation varied from 20 to 93 years, and 43% were greater than 70 years. Heartburn was a presenting symptom in 71%, regurgitation into the pharynx in 54%, dysphagia in 31% and hematemesis or melena in 29%. At endoscopy, the length of Barrett's epithelium ranged from 3 cm to 15 cm. Macroscopic esophagitis was observed in 69%, benign esophageal strictures in 14% and a co-existent adenocarcinoma of the lower esophagus in 10% of patients. Only 30% of the patients were cigarette smokers at the time of diagnosis, but 64% drank alcohol (9% greater than 80 g alcohol daily). Patients with esophageal cancer at presentation were more likely to be male and cigarette smokers (Fisher's exact probability test). It has been suggested that patients with Barrett's esophagus should be screened to detect the early development of esophageal cancer. If patients who already have cancer, the elderly (age greater than 70 years) and those with a chronic alcohol problem (greater than 80 g intake daily) are excluded from endoscopic cancer surveillance, only 42% of the patients described in this survey would be eligible for enrollment in such a program. This represents a recruitment of only 5 new patients yearly in a large teaching hospital endoscopy unit.

Adenocarcinoma↗
PubMed1990

Colorectal cancer.

Explore the source record for details and available documents.

Colorectal Neoplasms↗
PubMed1989

Impact of a hospital-based register on the management of familial adenomatous polyposis.

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.

Adenomatous Polyposis Coli↗
PubMed1989

Gastrointestinal blood loss from a new buffered aspirin (Ostoprin): measurement by radiochromium and Hemoquant techniques.

Occult gastrointestinal blood loss induced by a new buffered aspirin preparation (Ostoprin, 4.0 g per day) was compared with that from an enteric-coated aspirin (Ecotrin, 3.9 g per day) in 40 patients with osteoarthritis. Blood loss was measured by the radiochromium method and compared with the HemoQuant assay of fecal heme and heme-derived porphyrins. By radiochromium, mean daily blood loss during the first week of treatment with Ostoprin increased 1.6 ml above basal compared to 0.8 ml above basal with Ecotrin (p = 0.06). When aspirin was ceased, blood loss returned more rapidly towards normal in the Ostoprin group (p less than 0.01). By HemoQuant, mean fecal hemeporphyrin excretion rose 0.63 mg hemoglobin equivalent per g feces during the first week of treatment by Ostoprin compared with 0.40 mg/g for Ecotrin (p = 0.06). There was a significant linear relationship between the two methods (r = 0.65, p less than 0.001). Serum salicylate levels achieved with both preparations were almost identical and encompassed the therapeutic range. HemoQuant is sufficiently sensitive to detect low-level aspirin-induced bleeding. Ostoprin appears to be a safe alternative to Ecotrin and has similar bioavailability.

Adolescent↗
PubMed1989

Effect of ingestion of hemoproteins on fecal excretion of hemes and porphyrins.

Stools from asymptomatic volunteers on diets containing red meat, whole blood, or high fiber were analyzed for their content of hemes and dicarboxylic (heme-derived) porphyrins by the "HemoQuant" assay, the "Hemoccult" test, and "high-performance" liquid chromatography (HPLC). In 49 subjects, ingestion of red meat increased HemoQuant-determined combined fecal heme plus dicarboxylic porphyrins by an average 375%; the contribution of heme-derived porphyrins to total fecal porphyrins increased from 37% to 78%. Of subjects on a red-meat diet, 27% passed stools with a porphyrin content suggestive of a porphyria, compared with only 4% on a red-meat-free diet. These increases were due largely to protoporphyrin and its derivatives pemptoporphyrin and deuteroporphyrin, all of which were present in feces as iron-free porphyrins and iron-ligated (heme) forms. Ingestion of blood had an effect similar to that of red meat, but ingestion of fiber had no effect. These effects of dietary and endogenous hemoproteins must be considered when such methods are used to test feces for occult blood or to test for excess fecal porphyrins as an indicator of a porphyria.

Adolescent↗
PubMed1988

Extracorporeal shock-wave lithotripsy and the management of common bile-duct calculi.

Endoscopic sphincterotomy is the treatment of first choice for stones that remain in the bile duct after cholecystectomy. There is a small group of patients in whom this technique is not successful; many of these patients carry a high risk for surgery because of their age or associated medical conditions. A variety of non-surgical techniques is available; however, none is well established. We have used an in-vitro model to show that human gallstones are fragmented readily by shock-wave lithotripsy. Two elderly frail patients with difficult bile-duct stones have been treated successfully by extracorporeal shock-wave lithotripsy. The bile ducts were cleared of stones and the patients suffered no adverse effects. Extracorporeal shock-wave lithotripsy is a new and promising alternative to the current non-surgical techniques for the management of bile-duct stones.

Aged↗