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Biomedical subjects

S J Winawer

Publications and source records attributed to S J Winawer.

At least 73 records · Page 4Linked to original sources

Patient response to sigmoidoscopy. A randomized, controlled trial of rigid and flexible sigmoidoscopy.

Sigmoidoscopy could aid in the control of large bowel cancer by early detection of the 55% of colorectal cancers that develop in the rectosigmoid and by the identification and eradication of significant rectosigmoid adenomas. Rigid sigmoidoscopy has had poor patient acceptance and therefore has not been successful. The present study is a prospective randomized trial to evaluate patient response to flexible as compared with rigid sigmoidoscopy. Patients reported significantly less discomfort (10.1% versus 29.7%), anxiety (9.8% versus 27.6%) and embarrassment (5.2% versus 12.8%) during flexible as compared with rigid sigmoidoscopy. Flexible sigmoidoscopy appears to have better patient acceptance than rigid sigmoidoscopy (P less than 0.01). This could enhance its value as a cancer-control instrument. This article addresses the feasibility of sigmoidoscopy. Its validity also needs to be addressed within the framework of a long-term trial, evaluating mortality for rectosigmoid cancer.

Clinical Trials as Topic↗

Multiple primary malignant tumors.

Members of colon cancer-prone nonpolyposis families who had multiple primary malignant tumors were analyzed to determine the frequencies, locations, and stages of their cancers, and the duration of their survival. Colon cancers tended to be more proximal, were in a less advanced stage than in the general population, and in a majority of instances were associated with colonic adenomas. The multiple primary malignant tumors were more common in women, and occurred at a younger age than in the general population. Six or more multiple primary malignant tumors occurred in each of 4 patients. All patients survived for more than 10 yr after the diagnosis of the first cancer. Extracolonic cancers were most frequent in the breast and endometrium.

Actuarial Analysis↗

Outpatient management of esophageal cancer with endoscopic Nd:YAG laser.

In 50 inoperable patients with advanced malignant obstruction of the esophagus, endoscopic Nd:YAG laser treatment was used for palliation of dysphagia. In 30 of these patients, treatment was carried out entirely in an outpatient setting, providing more time at home and saving costs of hospitalization. Most patients had received prior radiation and chemotherapy. All were unable to swallow solid food; 16 had difficulty with liquids. Palliation was achieved in 69% allowing patients to eat a nearly normal diet. Therapy was least successful in cancers involving the cervical esophagus, in cancers more than 8 cm in length, and in cancers that were primarily infiltrating or extraluminal. Epidermoid carcinomas and adenocarcinomas were effectively treated, except for adenocarcinomas of the gastric cardia, which tended to be infiltrating. There were two serious but nonfatal complications, one perforation and one episode of bleeding, directly attributable to Nd:YAG laser therapy. An esophageal dilation prior to endoscopic Nd:YAG laser treatment facilitated outpatient management.

Adult↗

Screening for colorectal cancer.

Colorectal cancer is a good candidate for secondary prevention strategies. It appears to have a long lead time since most, if not all, of these cancers arise from premalignant adenomas, and several screening methods are available that might detect the cancer in a very early stage. However, there is little evidence at present to show that the available methods of early detection will actually decrease the mortality from colorectal cancer of a screened population as compared to a non-screened population. Studies that might convincingly provide this evidence are still in progress. This paper critically reviews the natural history of colorectal cancer, risk factors, screening trials and treatment.

Colonic Neoplasms↗

Malabsorption and mucosal abnormalities of the small intestine in the acquired immunodeficiency syndrome.

Diarrhea and weight loss may accompany the acquired immunodeficiency syndrome. We studied 30 patients with the syndrome, 20 of whom had diarrhea and weight loss and 10 of whom did not. Patients with identifiable enteric infections or small intestinal Kaposi's sarcoma were excluded. Malabsorption was common in the patients with diarrhea and weight loss, as shown by abnormal D-xylose and 14C-glycerol-tripalmitin absorption tests. In these patients, duodenal biopsy specimens showed a histiocytic infiltrate containing numerous acid-fast organisms in 5 and a mild-moderate chronic inflammation in 13. In asymptomatic patients, duodenal biopsy specimens were normal in 6 and showed chronic inflammation in 4. These results suggest that malabsorption is common in patients with the acquired immunodeficiency syndrome with chronic diarrhea and may contribute to their weight loss.

Acquired Immunodeficiency Syndrome↗

Surveillance and early diagnosis of colorectal cancer.

Colorectal cancer is a major health problem in western countries such as the United States. The annual incidence of more than 130,000 new cases, and the annual mortality of more than 60,000 people justifies a consideration of efforts for its control. New concepts of risk, better understanding of the adenoma-adenocarcinoma natural history, and new screening and diagnostic technology have provided a basis for possible preventive approaches. Trials are in progress evaluating the fecal occult blood test and sigmoidoscopy screening tests, and colonoscopy as a diagnostic and surveillance test. Evaluation of data from the trials requires many considerations regarding bias and validity. Although the data from screening trials appear to be promising, they are still preliminary. In the interim, guidelines have been proposed for screening strategies related to average risk and high risk groups. Considerably more work will be required in order to provide the scientific basis for the control of large bowel cancer. In addition, efforts will have to be directed toward the effective communication of new concepts, data and techniques to the majority of physicians who interact with the at-risk population. Efforts will also have to be directed to the public at large to enhance their compliance with the approaches to increase their awareness of colorectal cancer as an important disease and to eliminate their misconceptions. Finally the cost effectiveness of various screening strategies will have to be examined once data indicates a benefit of such approaches.

Clinical Trials as Topic↗

Unscheduled DNA synthesis in mononuclear leukocytes from patients with colorectal polyps.

The mononuclear leukocytes from peripheral blood samples of individuals with (n = 30) and without (n = 48) colonic polyps were examined for their abilities to carry out unscheduled DNA synthesis (UDS) induced by N-acetoxy-N-2-fluorenylacetamide (N-AcO-2-FAA). Individuals with polyps had significantly reduced UDS values compared to the nonpolyp group (P less than 0.01). Furthermore, in a more comprehensive study, patients with hyperplastic polyps had N-AcO-2-FAA-induced UDS values not significantly different from control individuals who were asymptomatic and free from colonic disease as judged by complete colonoscopy. However, patients who had had adenomatous polyps in their large bowel had significantly reduced levels of N-AcO-2-FAA-induced UDS in their mononuclear leukocytes (P less than 0.005). When N-AcO-2-FAA binding to DNA determinations were made in parallel and DNA repair proficiency indices were calculated (i.e., N-AcO-2-FAA-induced UDS/N-AcO-2-FAA binding to DNA), the patients with adenomatous polyps were still shown to be deficient in carrying out DNA repair synthesis. Since adenomatous polyps of the large bowel are considered the premalignant lesion for colorectal cancer, we postulate that reduced UDS may be a genetically sensitive marker that is useful in studying the mechanisms of genetic predisposition to colorectal cancer.

Acetoxyacetylaminofluorene↗

Degraded carrageenan-induced colitis in CF1 mice. A clinical, histopathological and kinetic analysis.

Delivery of 10% carrageen (degraded carrageenan, Glaxo, France) for 10 days in the drinking water to CF1 mice induced bloody diarrhea, pericryptal inflammation, and marked dilatation of the cecum and ascending colon. Histologically, the mucosa was characterized by distorted crypt architecture, inflammatory infiltration of the lamina propria, and ulceration, conditions which were more pronounced in the proximal colon but were also present in the distal colon. Treatment with hydrocortisone and levamisole reduced the severity of all phases of the reaction. Alterations in colonic epithelial cell proliferation corresponded with the clinical and histopathological findings. Labeling indices (LI) significantly increased over control values in both proximal (12.9 +/- 4.9 vs. 7.6 +/- 2.9) and distal colon (13.9 +/- 5.2 vs. 7.2 +/- 2.4), effectively doubling the number of proliferating cells per crypt column in both areas. However, DNA-synthesizing cells extended further upward along the cryptal wall of the proximal colon reflecting greater mucosal damage. Only in the proximal colon did the proliferative compartment (PC) extend to the upper third of the glands, normally not a proliferative zone. Hydrocortisone and levamisole administered concurrently with 10% carrageen were less effective in protecting the proximal colon since LI and numbers of labeled cells per crypt column were consistently lower in the distal colon. Moreover, hydrocortisone alone significantly depressed DNA synthesis only in the distal colon. All distal colonic crypts were not equally protected by administration of hydrocortisone since some continued to express large numbers of proliferating cells and an extended PC, well characterized preneoplastic defects in regulatory control of colonic epithelial cell proliferation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Screening diagnosis and staging of esophageal cancer.

In geographic areas where there is a high risk of esophageal cancer, analysis of cells obtained from the esophagus has been used effectively to detect early lesions. This has been demonstrated on a large scale in studies from China. Using abrasive balloon cytology techniques, 75% of the cancers detected were early lesions, where the 5-year survival after resection was in the range of 90%. Endoscopic followup studies indicate that dysplastic changes in the esophageal mucosa are a common precursor to malignancy. In many cases, the time course from dysplasia to carcinoma in situ to early invasive cancer may take place over many years, allowing a reasonable amount of time for screening. In low-incidence areas, such as the United States, most esophageal cancers are related to the excessive use of tobacco and alcohol. These factors are too common and the incidence of the disease too low, however, to justify screening on this basis. There are smaller groups at higher risk where selective screening by endoscopy with cytology and biopsy is recommended, usually every 1 to 3 years. These include patients with longstanding achalasia, lye strictures, and Plummer- Vinson syndrome. Patients with cancers of the head and neck region and patients with celiac disease may also be considered to be at increased risk. Tylosis is a rare inherited disease with a very high risk of esophageal cancer. There is an increased incidence of adenocarcinoma of the esophagus with Barrett's epithelium, and once identified such patients should be kept under endoscopic surveillance. The finding of severe dysplasia in any of these groups would indicate a shorter screening interval. Most patients with symptoms referable to the esophagus are first tested by barium esophagram. If negative, with persistent symptoms or if a suspicious lesion is identified, endoscopy with cytology and biopsy is recommended. Staging of the cancer is based on the size of the cancer both longitudinally and circumferentially and the presence of extraesophageal spread. At the present time, CT is the best noninvasive method for judging the extent of the cancer. Performance and nutritional status are also determinants of prognosis and should be considered in planning treatment.

Adult↗

Detection and diagnosis of colorectal cancer.

The option of early detection and diagnosis for the control of colorectal cancer, is discussed. Secondary prevention--the early detection, identification, and removal of premalignant lesions prior to the devastating and often fatal consequences of the disease--is recommended as an approach to symptomatic or asymptomatic patients. This study outlines the risk factors for susceptibility to colorectal cancer and reviews the potential benefits of screening asymptomatic patients by proctosigmoidoscopy and fecal occult blood testing. It is recommended that patients at risk be encouraged to enter the health care system.

Adenoma↗

Early diagnosis of colorectal cancer.

Screening of asymptomatic patients at risk is potentially the most effective means for detecting early colorectal carcinoma. Sensitive and specific tests are available for this purpose. However, an aggressive approach by the physician and compliance by the patient population are necessary for the proper implementation of this screening process.

Adenoma↗

Proliferative defects in ulcerative colitis patients.

The proliferative characteristics of epithelial cells in rectal biopsies from a group of 18 patients (ages 18-72) with ulcerative colitis spanning several months to over 20 years duration were examined, using an in vitro 3HTdR labeling technique. Although the labeling indices for patients with inflammatory bowel disease did not differ significantly from that of control (8.9 +/- 3.6 vs 7.7 +/- 3.9), the number of labeled cells/individual crypt column was higher among some crypts in ulcerative colitis patients. A normal proliferative pattern was demonstrated in crypts of 5/18 patients (27.8%) with DNA synthesis confined to the lower two-thirds of the crypt and the lower third the major zone of proliferation. Thirteen patients (72.2%) showed extension of the proliferative compartment to the surface of the glands, while retaining the lower third of the gland as the predominant proliferative zone (Stage I abnormality). Of these 13, seven had an additional abnormality, namely, a shift of the major zone of proliferation to the middle third of the crypt (Stage II abnormality), a pattern first reported in the colorectal mucosa of patients with a history of colon cancer. Precancerous lesions, including incompletely differentiated epithelium and lateral crypt budding, were recognized in all of these cases, suggesting that the Stage II abnormality is a proliferative parameter forecasting neoplastic transformation.

Adolescent↗

Reduced capacity for DNA repair synthesis in patients with or genetically predisposed to colorectal cancer.

Peripheral resting mononuclear leukocytes were compared for their capacities to repair DNA lesions induced by a 1-hour exposure to a standardized 10-microM dose of N-acetoxy-N-2-fluorenylacetamide (N-AcO-2-FAA). Leukocytes from the following 3 groups were studied: 39 control subjects, 40 patients after colonic resection because of colorectal cancer (disease-free at the time of this study), and 28 individuals with a hereditary predisposition to colorectal cancer. Although the level of N-AcO-2-FAA that bound to mononuclear leukocyte DNA was the same for the various population groups, the level of N-AcO-2-FAA-induced unscheduled DNA synthesis (UDS) was significantly reduced in the mononuclear leukocytes of individuals who had had colorectal cancer or a genetic predisposition for the disease. These findings indicate that a deficiency in mononuclear leukocyte DNA repair synthesis is associated with the development of colorectal cancer in these populations. Our observation of this nonspecific UDS deficiency (relating to colorectal cancer) was not explained by experimental variations among the sampled groups with regard to individual differences in lymphocyte heterogeneity, age, sex, smoking habits, or blood pressure.

Acetoxyacetylaminofluorene↗

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↗