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Biomedical subjects

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

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↗
PubMed1979

Comparison of flexible sigmoidoscopy with other diagnostic techniques in the diagnosis of rectocolon neoplasia.

Flexible sigmoidoscopy was compared to rigid sigmoidoscopy in the detection of colorectal neoplasia in a select group of patients. A distance of 30 cm or greater was obtained by flexible sigmoidoscopy in 94% of patients and a distance of 50 cm or greater in 46% of patients. A significant number of cancers and adenomas detected by flexible sigmoidoscopy were not detected by rigid sigmoidoscopy. Flexible sigmoidoscopy was tolerated better than rigid sigmoidoscopy but required twice the time. Flexible sigmoidoscopy could be combined with air-contrast barium enema the same day with the one preparation and did not interfere with the x-ray examination. All cancers and a significant number of adenomas detected subsequently on colonoscopy were detected by the combination of flexible sigmoidoscopy and air-contrast barium enema. Although the combination of flexible sigmoidoscopy and air-contrast barium enema is not adequate for thorough diagnostic evaluation of patients with a positive screening test, it may be of value in other select clinical situations. Flexible sigmoidoscopy has the potential for higher yield and better patient tolerance as compared to rigid sigmoidoscopy. This warrants further evaluation.

Adenoma↗
PubMed1979

Laparoscopic diagnosis of suspected liver neoplasms. Value of prior liver scans.

To study the efficacy of standard blood tests of liver function (LFTs) and technetium-99m liver scan followed by laparoscopy in the diagnosis of solid malignant tumors of the liver, 100 consecutive patients were evaluated who had these tests because of clinical suspicion of liver neoplasm. Malignant liver tumors were present in 65 of the 100 patients. Laparoscopy diagnosed 60 of the 65, and the neoplasms were documented pathologically by directed biopsy (92% sensitivity, 100% specificity). In 8 patients, hepatoma was diagnosed and staged for possible resection. A negative "blind" biopsy had been performed in 23 of the 60 patients with liver neoplasms diagnosed at laparoscopy. LFTs and liver scans together were good screening tests (95% sensitivity) but had low specificity (46%). Liver scans also provided information as to probable tumor location in the liver, guiding the insertion site for the laparoscope, and directing deep-needle biopsies if no surface lesions were seen.

Biopsy↗
PubMed1979

Risk factors and mortality in patients with cancer and hemorrhage from stress ulcer.

Hemorrhagic gastritis is the most frequent cause of upper gastrointestinal bleeding in patients with cancer. A study was undertaken to evaluate the clinical course of 87 patients, in a cancer hospital setting, with hemorrhagic gastritis associated with stress, exogenous gastric irritants and the combination of the two. The average number of blood transfusions was four times higher and the average duration of bleeding was twice as long in stress patients as in patients without stress. Fifty-four per cent of stress patients died, whereas all patients survived in the group without stress. Although there were no statistically significant differences, patients with the combination of gastric irritants and stress tended to bleed longer and have a higher mortality than patients with stress alone. Over two-thirds of the deaths were ascribed to associated stress risk factors such as sepsis, multiple organ failure and advanced cancer and not to gastrointestinal hemorrhage.

Adolescent↗