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S J Winawer

Publications and source records attributed to S J Winawer.

At least 19 recordsLinked to original sources
PubMed1992

The National Polyp Study. Design, methods, and characteristics of patients with newly diagnosed polyps. The National Polyp Study Workgroup.

The National Polyp Study (NPS) is a multicenter prospective randomized trial designed to evaluate follow-up surveillance strategies in patients who have undergone polypectomy for the control of large bowel cancer. The study design was developed by a joint research committee from American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and the American College of Gastroenterology. Subjects who met the eligibility criteria were randomized into two different treatment arms. Eligibility criteria included: removal of one or more adenomas; complete colonoscopy; no prior polypectomy, inflammatory bowel disease, or familial polyposis; and no history of colon cancer. The treatment arms consisted of a frequent follow-up (1 and 3 years after initial polypectomy) and a less frequent follow-up (3 years). Follow-up examinations included fecal occult blood tests, air-contrast barium enema, and colonoscopy. The latter was done on 9112 referred patients at the seven participating centers from November 1980 until February 1990 who had no history of polypectomy, colon cancer, familial polyposis, or inflammatory bowel disease. Of these patients, 4763 (52.3%) had no polyps; 549 (6.0%) had an invasive cancer; 776 (8.5%) had nonadenomatous polyps; 208 (2.3%) had incomplete examinations; 184 (2.0%) had other findings; and 2632 (28.9%) had one or more adenomas, of which 1418 (53.9%) were randomized to one of the two treatment arms. This article reports the background, rationale, objectives, methods, and organization of this study and includes patient characteristics on initial presentation. Future data provided by the NPS may help in the development of recommendations for surveillance guidelines for such patients. This study also provides a framework to address questions regarding the natural history of adenomas and their relationship with colorectal cancer.

Adenoma↗
PubMed1992

Precursors of colorectal carcinoma. Biopsy and biologic markers.

The term biologic marker (biomarker) of colorectal cancer refers in this article to an early preclinical phenotypic characteristic that relates to the risk for developing this cancer. Putative biologic markers in the normal colorectal mucosa of patients at risk include abnormal cell proliferation as determined by kinetic studies, ornithine decarboxylase activity, and polyamine synthesis. Alterations of mucin synthesis have been studied using both histochemical stains and lectin-binding techniques. Blood group and related carbohydrate antigens also have been evaluated as potential biomarkers in the normal mucosa. Biopsy small (less than 5 mm) polyps encountered at endoscopy has become a standard practice. Although a small polyp found to be an adenoma has a low likelihood of harboring high-grade dysplasia or invasive carcinoma, it represents an indicator of risk for colorectal neoplasia. Hyperplastic polyps, however, even though they have certain epidemiologic associations with colorectal neoplasia, are controversial as putative biomarkers of clinical relevance. Current research supports a concept of a field defect of the colorectal mucosa at risk for neoplasia, which may be identified by phenotypic abnormalities of the normal mucosa and the development of small adenomas.

Adenoma↗
PubMed1991

The natural history of colorectal cancer. Opportunities for intervention.

There is now a better understanding of the natural history of colorectal cancer, which has provided a basis for intervention to influence outcome. The possible interventions include earlier detection of colorectal cancer, removal of premalignant adenomas, demonstration of the mucosal field defect that precedes neoplasia to evaluate baseline risk and its change with dietary modification, and identification of inherited and dietary risk factors. Five controlled trials evaluating early detection of colorectal cancer with fecal occult blood testing have enrolled more than 309,000 patients. Early stage cancers with improved survival has been observed, but data on mortality reduction have not as yet been reported. Studies of patients with adenomas have demonstrated high synchronous and metachronous rates as a basis for complete colon evaluation initially and a surveillance follow-up program. Hyperproliferation and lack of normal differentiation have been observed as a field defect in the colon preceding neoplasia. Inherited factors have recently been shown to be important in a larger proportion of individuals destined to develop colorectal adenomas and cancer. These observations of the natural history of colorectal cancer have provided new opportunities for the application of radiologic and endoscopic techniques in diagnosis and surveillance; each examination has its merit. Further research is needed to answer many critical questions that have been raised regarding the impact of these interventions.

Adenoma↗
PubMed1991

Preoperative staging of gastric cancer: comparison of endoscopic US and dynamic CT.

Fifty consecutive patients with gastric adenocarcinoma proved by means of biopsy underwent preoperative staging with endoscopic ultrasonography (US). Dynamic computed tomography (CT) of the chest and abdomen was performed before surgery in 33 of the patients. In all 50 patients, the TNM classification of the American Joint Committee on Cancer was used to compare the imaging findings with pathologic findings in specimens resected at surgery. When the depth of tumor penetration was evaluated, the findings at endoscopic US and those at pathologic examination were concordant in 46 of 50 patients (92%), and the findings at dynamic CT and those at pathologic examination, in 14 of 33 patients (42%) (P less than .00042). Evaluation of regional lymph node metastases showed a concordance of 78% with endoscopic US and 48% with dynamic CT (P less than .038). Overall determination of stage with both dynamic CT and endoscopic US showed a concordance of 73%, compared with a concordance of 45% for dynamic CT alone (P less than .028).

Adenocarcinoma↗
PubMed1991

Surveillance of patients with chronic ulcerative colitis. WHO Collaborating Centre for the Prevention of Colorectal Cancer.

In chronic ulcerative colitis, the object of surveillance is prevention of cancer or at least prevention of death from cancer by diagnosis at an early curable stage or by detection at a pre-malignant phase. Patients must be informed about their cancer risk as well as the limitations of endoscopic surveillance and the availability of surgical alternatives. Physicians must bear in mind the risks, benefits and costs of surveillance procedures. Patients at greatest risk of cancer for whom endoscopic surveillance is warranted are those with extensive colitis of greater than 8 years duration. Colonoscopy should be performed every 1 to 2 years at which time multiple biopsies are obtained from every 10-12 cm of normal-appearing mucosa. Targeted biopsies should also be obtained from areas where the surface appears raised as a broad-based polyp, low irregular plaque or villiform elevation, or from an unusual ulcer, particularly one with raised edges, or from a stricture. Typical inflammatory polyps need not be sampled. Colectomy is recommended in the presence of multifocal high-grade dysplasia if confirmed by an experienced pathologist. The identification of a mass lesion associated with any degree of overlying dysplasia is also a generally accepted indication for colectomy, while persistent low-grade dysplasia without a mass is somewhat more controversial. Recently introduced biomarkers may replace or supplement dysplasia in surveillance programmes as well as provide new information about malignant transformation.

Algorithms↗
PubMed1991

Diagnosis and prevention of gastrointestinal malignancies.

The consistently high mortality rates associated with gastrointestinal cancer result in large part from malignancies that progress undetected to an advanced stage of disease when treatment is usually less effective. In response to this fact, increasing attention has been directed toward developing methods of both primary and secondary prevention of malignancies. Advances in primary prevention have resulted in a better understanding of various etiologic factors in the environment that are related to carcinogenesis and how they can be corrected or eliminated. Advances in secondary prevention have improved efforts to identify and eradicate the premalignant stages of gastrointestinal cancer before lethal consequences can develop. Refinements in screening methods and improvements in diagnostic procedures, such as the introduction of endoscopic ultrasound, will allow physicians to detect gastrointestinal cancers and their premalignant forerunners at an earlier stage in an effort to render treatment strategies more effective.

Adult↗
PubMed1990

Declining serum cholesterol levels prior to diagnosis of colon cancer. A time-trend, case-control study.

We report the results of a 10-year, time-trend, case-control study in which serum cholesterol level was determined at several points in time preceding the diagnosis of colon cancer in a population of individuals who sought general checkups at an ambulatory care screening facility. Each of the 69 patients with colon cancer (32 men and 37 women) was matched with a control patient who was randomly selected. At the time of diagnosis, the patients with colon cancer had significantly lower serum cholesterol values than control patients (5.56 +/- 0.31 mmol/L [SEM] vs 6.47 +/- 0.34 mmol/L). This difference did not vary with sex or Dukes' stage of the cancer. The percent of matched pairs in which the cancer patient had a lower serum cholesterol level increased from 42% at 10 years prior to cancer diagnosis to 77% at diagnosis. The ratio of serum cholesterol at each period to the level at time of diagnosis demonstrated an average decline of 13% during the 10 years prior to diagnosis for case patients vs an average rise of 2% in the same period for control patients. We conclude that individuals in whom colorectal cancer develops share the same level of serum cholesterol as the general population initially, but during the 10 years preceding the cancer demonstrate a decline in serum cholesterol level that is opposite to the rising level seen with age in the general population.

Aged↗
PubMed1990

Effects of FUdR on primary-cultured colon carcinomas metastatic to the liver.

Hepatic arterial infusion of fluorodeoxyuridine (FUdR) has demonstrated efficacy in the treatment of metastatic colorectal carcinoma of the liver. In this study, the direct cytotoxic effect of FUdR was measured on ten metastatic and two primary-site colorectal carcinomas in a primary culture assay system. Overall, clinically achievable concentrations of FUdR (0.4 to 4 microM) induced partial cell kill in 75% of tumors, including a greater than 50% reduction in viable tumor cell number in only two tumors and less than 50% in the remaining seven. Total cell kill was not observed in any tumor. Three tumors were resistant to these FUdR concentrations. Tumor sensitivity correlated with the size of the tumor growth fraction. Increasing the exposure time to FUdR from 3 to 7 days approximately doubled the magnitude of the response. 5-Flurouracil and cisplatin, at clinically achievable concentrations, were more toxic to metastatic tumor cells than FUdR. Because of the limited chemosensitivity of metastatic colorectal tumor cells to FUdR in vitro, we postulate that other mechanisms besides direct cytotoxicity contribute to the clinical efficacy of FUdR in vivo.

Cell Line↗
PubMed1990

Risk and surveillance of individuals with colorectal polyps. Who Collaborating Centre for the Prevention of Colorectal Cancer.

Since colorectal adenomas are very probably the precursors of colorectal cancer, their detection and removal should result in a decrease in the incidence and mortality from colorectal cancer. Individuals who harbour an adenoma have a 30-50% probability of having additional adenomas at that time, and a 30% probability of having additional adenomas later. Adenomas are prevalent in countries where colorectal cancer is prevalent, about two-thirds of them being tubular and the rest tubulovillous or villous. The initial management of patients with an adenoma consists in searching by colonoscopy the entire colon and removing all additional polyps. Surgical resection is required wherever there is invasive cancer with adverse histological factors. Follow-up in most patients can be after 2-4 years, earlier follow-up being reserved for patients with numerous polyps or with a polyp that had been removed piecemeal. The results of ongoing trials should provide firm guidelines for follow-up and could also be used in mathematical modelling to examine alternative strategies and to help understand the evolving patterns of appearance of new polyps. Finally, a deeper understanding of the biology and inherited and acquired genetics will help identify individuals at risk for adenomas initially and at follow-up. Nutritional factors may also provide a basis for prevention of adenomas in high-risk countries. Many of these issues are being addressed in current research.

Adenoma↗
PubMed1990

Natural history and current management of colorectal polyps.

There are numerous histological types of colon polyps. The neoplastic polyp, the precursor to colon cancer, is called an adenoma. Adenomas vary in frequency throughout the world and are particularly prevalent in Western countries. The belief that after several years of development some adenomas will become cancers is termed the adenoma-carcinoma sequence. These adenomas occur in both males and females and their incidence increases with age. While small polyps were once considered unimportant, it is now recognized that adenomas may be small. The clinical importance of other small polyps, most often hyperplastic polyps, is still being investigated. When adenomas are found in the colon a full colonoscopy with removal of all polyps and review of their pathology should be performed.

Adenoma↗
PubMed1990

Primary prevention of colorectal cancer. The WHO Collaborating Centre for the Prevention of Colorectal Cancer.

Colorectal cancer is the third most common malignant neoplasm worldwide. Epidemiological and laboratory animal studies have established a link between various nutritional factors and the etiology of this cancer. Recent studies in genetic epidemiology and molecular biology have shown that inherited genetic factors also play an important role in colorectal carcinogenesis. Thus, genetic-nutritional interactions may form the basis for the development of this cancer. Nutritional factors that appear to promote or attenuate the carcinogenic process in the colon include fat, excess calories, fibre, calcium, selenium, and various vitamins. Strategies for primary prevention of colorectal cancer should therefore be targeted to all populations who are at risk because of dietary and hereditary predisposition. Based on current knowledge, recommended nutrition guidelines for reducing the risk of colon cancer include decreased fat consumption, adequate amounts of fruits, vegetables, and calcium, and avoidance of overweight. Research to further elucidate the role of diet in colorectal carcinogenesis should include randomized studies in humans, testing of various nutritional regimens, and the use of colonic adenomas and markers of cell proliferation and differentiation as end-points.

Colorectal Neoplasms↗
PubMed1990

Screening of average-risk individuals for colorectal cancer. WHO Collaborating Centre for the Prevention of Colorectal Cancer.

Recent developments in screening, diagnosis and treatment of colon cancer could lead to a reduction in mortality from this disease. Removal of adenomas, identification of risk factors, appropriate application of accurate diagnostic tests, and aggressive anatomic-surgical resection of colon cancers may already be having a favourable impact. Screening of average-risk populations over the age of 50 also offers promise in the control of this important cancer. The disease is of sufficient magnitude to deserve detection at an early stage with better prospects of patient survival, since screening tests with moderate sensitivity and high specificity are available. Flexible sigmoidoscopy and faecal occult blood tests are sufficiently acceptable to be included in case-finding among patients who are in the health care system. The results of current controlled trials involving more than 300,000 individuals for evaluating the impact of screening on mortality from colon cancer are needed before this approach can be recommended for general public health screening of the population. Further research is required to develop better screening tests, improve patient and physician compliance, and answer more definitively critical questions on cost-effectiveness. Mathematical modelling using current and new data can be used to determine the effectiveness of screening in conjunction with recommendations for primary prevention.

Colorectal Neoplasms↗
PubMed1990

Risk and surveillance of individuals with heritable factors for colorectal cancer. WHO Collaborating Centre for the Prevention of Colorectal Cancer.

Heritable and genetic factors pertinent to colon cancer can be divided into three categories: inherited syndromes, genetic epidemiology, and molecular genetics. Familial adenomatous polyposis (FAP) and Gardner syndrome (GS) are rare dominantly inherited syndromes characterized by hundreds to thousands of colonic adenomatous polyps. Colon cancer occurs at a young age in both diseases unless the colon is removed. Peutz-Jeghers syndrome and familial juvenile polyposis are inherited hamartomatous polyposis conditions with a less dramatic, but definite, increased risk for colon cancer. These four polyposis syndromes together account for less than 1% of cases of colon malignancy. Hereditary nonpolyposis colorectal cancer is a dominantly inherited form of colon cancer characterized by an early age of onset and a predilection for proximal colonic tumours. Multiple primary malignancies are frequently observed and one or several adenomatous polyps are often present in affected individuals; 4-6% of colon cancer cases occur in relationship to this syndrome. Genetic epidemiological studies have consistently shown that first-degree relatives of persons with colon cancer have a twofold to threefold increased risk of having colon malignancy. More recent studies have found a similar risk among relatives of those with adenomatous polyps. Studies of colon cancer and adenomatous polyps in pedigrees have further demonstrated that this familial clustering probably occurs on the basis of partially penetrant inherited susceptibilities. These inherited susceptibilities probably interact with environmental factors to give rise to polyp growth and finally colon cancer. Molecular studies have begun to elucidate the genetic mechanisms of colon cancer at the DNA level. The germinal mutation of FAP and GS has been localized to the long arm of chromosome 5. Tissue samples from "random" adenomatous polyps and colon cancers have shown frequent and specific acquired DNA sequence deletions on chromosomes 5, 17, and 18. Mutations and over-expression of the ras oncogene likewise have been observed in such tissues. The chromosome 5 defect in polyp and cancer tissues is probably at the same locus as the germinal mutation of FAP. There is evidence that this locus normally regulates expression of the c-myc oncogene, which in turn probably has a regulatory function in DNA replication. The chromosome 17 deletion is a mutation of the gene for the transformation-associated protein, p53. Appropriate screening starting at a relatively young age is necessary to prevent cancer in the inherited syndromes. Screening is also indicated in close relatives of those with nonsyndromic or common colon cancer in view of the moderately increased risk for colon cancer in this group.(ABSTRACT TRUNCATED AT 400 WORDS)

Colorectal Neoplasms↗