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Biomedical subjects

P Sherlock

Publications and source records attributed to P Sherlock.

At least 19 recordsLinked to original sources
PubMed1987

Screening for colorectal cancer in a high-risk population. Results of a mathematical model.

A mathematical model was used to estimate the cost-effectiveness of colorectal cancer screening strategies for people who are at high risk because of a first-degree relative with colorectal cancer. The model uses indirect evidence about such factors as cancer incidence, sensitivity and specificity of different tests, and treatment effectiveness. The analysis indicates that for screening people over 40 yr old an annual fecal occult blood test may reduce colorectal cancer mortality by about one-third, either colonoscopy or barium enema may reduce mortality by approximately 85%, a 3-5-yr frequency for endoscopies or barium enemas preserves 70%-90% of the effectiveness of an annual frequency, and beginning screening at age 50 reduces effectiveness by 5%-10%. Although both barium enemas and colonoscopies appear to be effective in reducing mortality, the lower cost of the barium enema makes it a more cost-effective strategy. All of these estimates depend on the baseline estimates of each of the factors incorporated in the model; the conclusions are most sensitive to assumptions about the natural history of adenomatous polyps, the bleeding of adenomas and presymptomatic cancers, and the sensitivity of the fecal occult blood test. Recommendations about colorectal cancer screening must also consider factors such as discomfort, inconvenience, and the availability of various technologies.

Colonic Neoplasms↗
PubMed1985

Gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine: role of gastrectomy and duodenal reflux.

The effect of gastrectomy and duodenal reflux on gastric carcinogenesis was studied because gastrectomized patients may be considered at "high risk" for the development of gastric stump cancer. Wistar rats received N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) (83 mg/liter) ad libitum in the drinking water for either four, eight, or twelve weeks. A control group received tap water. After MNNG administration animals were antrectomized. Antrectomy was not performed in a control group. Bowel continuity was restored either with a Billroth II (BIL) or with a ROUX en Y (ROUX) procedure. Duodenogastric reflux is possible after the BIL but not after the ROUX procedure. Eight months after the beginning of the experiment the stomachs of the animals were studied. In both operated and unoperated animals, the number of cancers observed was significantly related to the duration of MNNG administration. Animals receiving MNNG plus the BIL procedure had a significantly higher number of anastomotic cancers than the ROUX animals, indicating that duodenogastric reflux played a promotional role in gastric carcinogenesis. Three BIL gastrectomized rats not receiving the carcinogen had an adenocarcinoma on the anastomotic line further emphasizing the risk attached to the duodeno-gastric reflux.

Animals↗
PubMed1984

Barrett's esophagus with adenocarcinoma in scleroderma.

The gastrointestinal manifestations of scleroderma are varied. Esophageal problems are common especially in patients with Raynaud's phenomenon. An adenocarcinoma complicating a Barrett's esophagus was identified in a patient with the CREST variant of scleroderma. The significance of this association and its relationship to chronic reflux esophagitis is discussed. Patients with scleroderma should be considered to be at an increased risk of developing this premalignant condition of the esophagus.

Adenocarcinoma↗
PubMed1983

Nutrition and cancer.

Nutrition and cancer interact at several levels. Both dietary deficiencies and dietary excesses have been linked with changes in prevalence of certain human cancers. With respect to one particular nutrient, riboflavin, a dietary deficiency may decrease the development of spontaneous tumors in experimental animals but increase carcinogenesis due to certain agents. Cancer itself has profound effects upon nutritional status, and neoplastic tissue appears in general to resist dietary deficiency more effectively than normal tissues. Nutrition has a major role in therapy of cancer, but as an adjunct to the treatment plan rather than as an alternative. Parenteral nutrition, either peripheral or total, can provide support that is critically needed when patients cannot eat or swallow, have obstruction or malabsorption, or are otherwise unable to utilize dietary nutrients in adequate amounts. The advent of home parenteral nutrition now provides a means for long-term rehabilitation of cancer patients.

Animals↗
PubMed1983

A morphologic and kinetic basis for the more invasive character of N-methyl-N'-nitro-N-nitrosoguanidine induced duodenal tumors following pyloroplasty.

Pyloroplasty increased the invasiveness of duodenal tumors in Wistar rats receiving N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) for 12 weeks (83 mg/l in drinking water) (Arch. Surg., 117, 768-771). To assess morphologic and kinetic alterations, analyses of tritiated thymidine (3HTdR) pulse-labeled fundic, antral and duodenal mucosa were carried out. The normal appearance of MNNG-treated antral and duodenal mucosa was characterized by the appearance of elongated hyperactive columns exhibiting elevated levels of DNA synthesis. Pyloroplasty in carcinogen-treated rats induced both a 3-fold enhancement in the number of these elongated columns and an elevation in the number of proliferating cells within them (P less than 0.001). In the MNNG and pyloroplasty treated duodenal mucosa 26% of columns contained over 130 cells/column rather than an average of 100 cells in normal appearing MNNG-treated mucosa. DNA synthesis was increased by 23% within these hyperactive glands (11.3 proliferative cells/column vs. 9.4/column in normal appearing mucosa). Pyloroplasty creates both an increase of gastric bile reflux and an increase of the gastric evacuation rate, conditions which influence cell proliferation. Such alterations in antro-pyloro-duodenal physiology contribute to the increased cellular activity observed, promote malignant transformation and foster the expression of invasiveness.

Animals↗
PubMed1983

Tissue concentrations and proliferative effects of massive doses of ascorbic acid in the mouse.

The effect of ascorbic acid supplementation on CF1 mice fed ascorbic acid for approximately six months at dose levels of 1%, 5%, and 10% of diet was investigated by analysis of tissue ascorbic acid concentration in the liver, kidney, stomach, small intestine, and large bowel. The effect on epithelial cell proliferation was also examined in the small and large bowel but only at the 5% level. In the control animals, ascorbic acid concentration was lowest in the liver (0.406 +/- 0.07 mg/g) and highest in the small bowel (0.754 +/- 0.16 mg/g). Dietary intake of 5% and 10% ascorbic acid significantly elevated levels in the liver (0.741 +/- 0.13; p less than 0.05), and all doses of ascorbic acid significantly raised tissue concentrations in the kidney and colon. No difference was observed in the percentage of DNA-synthesizing cells in the jejunum of controls or animals fed 5% ascorbic acid at 1 or 24 hours after 3HTdR injection. However, at 1 hour a significantly decreased level of proliferation was observed in the distal colon of ascorbic-acid-treated mice compared with controls (labeling index [L.I.] = 7.3 +/- 0.28 vs. 10.1 +/- 1.15; p less than 0.05), and an even greater suppression of DNA synthesis was achieved by 24 hours (L.I. = 11.4 +/- 1.06 vs. 18.6 +/- 1.61; p less than 0.01). None of the doses of ascorbic acid employed was toxic to the experimental mice.

Animals↗
PubMed1982

Surveillance for colorectal cancer in average-risk patients, familial high-risk groups, and patients with adenomas.

New concepts and technological advances have stimulated a heightened interest in the secondary prevention of colorectal cancer; the identification and eradication of premalignant lesions, and the detection of early cancer before the development of life-threatening consequences. This approach must be selective based on risk factors. Fecal occult blood testing and sigmoidoscopy have been applied to the average-risk patients, whereas x-rays, endoscopy, biopsy, and cytology have been applied to the high-risk groups for case findings and screening. Program results to date are encouraging for average-risk patients. Compliance with fecal occult blood testing and sigmoidoscopy has been high in motivated groups self-selected for entry into screening programs. The rate of positive slides, false-positivity, and predictive value for neoplasia has been acceptable. Dukes' staging of cancers has been favorable. False-negativity and mortality data are not yet available. Flexible sigmoidoscopy has been shown to be an effective substitute for rigid sigmoidoscopy in trained hands. Familial polyposis and Gardner's syndrome families have been well studied, but interest in the nonpolyposis inherited colon cancer families is relatively new. Followup procedures after polypectomy have been variable and only recently has there been an organized attempt to prospectively study the effectiveness of different followup plans. The National Polyp Study has been developed to address this issue.

Adenoma↗
PubMed1982

Primary gastrointestinal lymphoma: a 30-year review.

The authors reviewed all cases of non-Hodgkin's lymphoma primarily involving the gastrointestinal tract treated at Memorial Hospital during the period from 1949-1978. Complete clinical records were available in 104 cases. Slides of original pathology specimens were available in 81 cases. Tumors were classified by Rappaport, Lukes-Collins and modified Kiel classifications. All patients were staged retrospectively, using modified Ann Arbor staging. The primary tumor was in the stomach in 76 patients, in the small bowel in 15 and in the large bowel in 13. The life-table survival for all patients at five years was 44% and for the 81 Stage I and II patients it was 53%. We found a trend toward improved survival for patients treated in the last decade (P = 0.05). Using Cox regression analysis, survival was found to be correlated with stage (P less than 0.0001) and involvement of adjacent structures (P = 0.007). For Stage I patients, resection and radiation therapy were equally effective alone in controlling local tumor even though factors responsible for the selection of either treatment could not be identified. For Stage II patients, resection combined with radiation therapy controlled local disease better than either treatment alone. For Stage II, patient survival was correlated with the pattern of nodal involvement (P less than 0.0001). Neither the choice of treatment (resection, radiation therapy, or resection with radiation therapy; P = 0.17) nor the involvement of resected margins (P = 0.22) affects survival. Among 81 Stage I and II patients, 68% had recurrences outside the primary field of treatment and 60% outside the abdomen. Systemic multiple modality therapy should be considered for patients at high risk for recurrence.

Adult↗
PubMed1982

Cancer induction after pyloroplasty in rats: treatment with N-methyl-N'-nitro-N-nitrosoguanidine.

Nineteen male Wistar rats received N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in drinking water (83 mg/L) to initiate glandular adenocarcinoma of the stomach; eight control rats received tap water. After 12 weeks a pyloroplasty was performed on nine rats receiving MNNG and three control rats. Ten MNNG-treated rats and five control rats had no operation. All were observed for 38 weeks before being killed. No difference in the incidence of antral adenocarcinomas was found between the MNNG-treated groups; however, those without operation showed in situ changes in the duodenum and those treated with pyloroplasty showed five invasive adenocarcinomas. In this model pyloroplasty alone did not increase the risk of gastric cancer but increased the risk of duodenal tumors. Pyloroplasty apparently accelerated the gastric evacuation rate, resulting in greater insult to the duodenal mucosa. Such a condition may require a higher proliferative rate in the duodenum and may increase subsequent formation of malignant tumors.

Adenocarcinoma↗
PubMed1982

Primary gastric lymphoma. A review of 50 cases.

The records of 50 patients with localized primary gastric lymphoma were reviewed and clinical and prognostic factors characterized. Pathologic material was reclassified according to Rappaport's, Lukes-Collins, and Lennert's Kiel classifications. Factors with the greatest prognostic significance included initial stage as determined by surgery and pathology, absolute tumor size, degree of penetration through the stomach wall, and histologic grade of the lymphoma. After surgical resection for cure, the overall 5-year disease-free survival was 47%. For stage I disease, this was 78% vs 29% for stage II (P = 0.006). Patients with lymphomas less than 5 cm in diameter had 58% 5-year disease-free survival vs 32% for those with tumors greater than 10 cm (P = 0.06). Full-thickness penetration decreased 5-year survival from 75% to 38% (P = 0.06). Patients with histologically low-grade lymphomas had a better prognosis than those with high-grade lymphomas. The most significant correlation of histology to survival was seen with the Kiel classification with a 5-year survival of 39% for centroblastic polymorphous lymphoma vs 66% for LP immunocytoma. When lymphoma recurred it developed outside the abdomen in a majority of patients. The addition of abdominal radiation therapy to surgical resection made no significant impact on survival for either stage I or II disease.

Adult↗