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A I Neugut

Publications and source records attributed to A I Neugut.

At least 55 records · Page 3Linked to original sources

Molecular genetics of small bowel cancer.

Although the molecular genetic changes that take place during carcinogenesis in the large bowel have been well elucidated, very little work has been done on the carcinogenesis process in the small bowel where this phenomenon is much rarer. The few studies that have been done to suggest that certain oncogenes, i.e., erbB2, K-ras, cyclin D1, and p53, are all altered in ways and in frequency similar to these phenomena in large bowel cancer. Some tumor markers have been noted to occur in malignant carcinoid tumours as well. Given the overall similarities in the epidemiology and the role of the adenoma-carcinoma sequence for both small bowel adenocarcinoma and colorectal adenocarcinoma, it is highly likely that the same molecular genetic changes play a major role. Further work is needed to confirm this. If true, a potentially important are of future research would be to determine why these molecular genetic changes occur so much less frequently in the small bowel as compared to the large bowel.

Animals↗

Association of adenocarcinoma and squamous cell carcinoma of the esophagus with tobacco-related and other malignancies.

Little is known about the etiology of esophageal and gastric cardia adenocarcinoma (EGA), a cancer with one of the fastest-rising incidences in the developed world. To explore the etiology of this cancer, we conducted a retrospective cohort analysis using data from the Surveillance, Epidemiology and End Results Program of the United States National Cancer Institute to study EGA and esophageal squamous cell carcinoma (ESC), in association with cancers of other sites. Standardized incidence ratios, adjusted for age, sex, and time period, were calculated as a measure of the relative risk (RR) of developing a second primary cancer (EGA or ESC) following a given first primary site. We found a moderately elevated risk of EGA following cancers of the lung (RR = 1.9 in men and RR = 2.0 in women) and of the head and neck (RR = 2.1 in men and RR = 6.3 in women) and a strongly elevated risk of ESC following cancers of the lung (RR = 2.8 in men and RR = 5.1 in women) and of the head and neck (RR = 9.6 in men and RR = 38.8 in women). A significantly elevated risk following breast cancer in women was observed for both EGA (RR = 2.6; 95% confidence interval, 1.8-3.7) and ESC (RR = 1.4; 95% confidence interval, 1.1-1.9). We also found a significantly elevated risk of EGA following bladder (RR = 2.0), colorectal (RR = 1.7), and prostate (RR = 1.4) cancer in men and of ESC following colorectal cancer (RR = 1.7) in women in this study. The strong association with tobacco-related malignancies in this study reinforces the role of tobacco in the etiology of esophageal cancers, which appears stronger for squamous cell carcinoma than for adenocarcinoma and stronger in women than in men. The study also suggests a possible shared etiology between esophageal adenocarcinoma and colorectal cancer in men and provides new evidence about the association of both adenocarcinoma and squamous cell carcinoma of the esophagus with breast cancer in women. Findings of this study provide clues to the etiology of EGA and ESC.

Adenocarcinoma↗

Leisure and occupational physical activity and risk of colorectal adenomatous polyps.

Multiple studies have shown a protective effect for physical activity on the incidence of colorectal cancer, but few have addressed its association with incident adenomas and none have investigated its association with metachronous adenomas. We interviewed 2,001 patients undergoing colonoscopy in 3 New York City practices between 1986-1988. Of these, 298 had a first diagnosis of adenomas, 506 had normal colonoscopies, 197 had metachronous adenomas and 345 had normal colonoscopies with a past history of adenomas. Subjects were queried regarding use of moderate amounts of recreational exercise (swimming, jogging, biking, racket sports and other sports) on a regular basis, and were also asked to estimate their level of physical activity. Occupational physical activity was assessed through a blinded coding of occupational titles. After adjusting for age, years of education, body mass index, total caloric intake, dietary fiber intake, dietary fat intake and years of cigarette smoking, protective effects of borderline significance were observed among males for leisure physical activity for metachronous and incident cases. Occupational physical activity was found to be significantly protective in male incident cases. Men with increased levels of either occupational or leisure activity showed a reduction for incident and metachronous cases. No effects were observed for females. Thus, in this study, both leisure and occupational physical activity were associated with a reduced risk of incident and metachronous adenomas among men but not women.

Adenoma↗

The effect of calcium and vitamin supplements on the incidence and recurrence of colorectal adenomatous polyps.

BACKGROUND: Recent attention has focused on calcium and certain vitamins as potential protective agents against colorectal neoplasia. METHODS: Two case-control studies were conducted on patients who underwent colonoscopy between 1986 and 1988, comparing 297 patients with newly diagnosed adenomas with 505 controls (without current or prior history of neoplasia), and 198 patients with recurrent adenomas with 347 recurrent controls (with no current neoplasia, but with a history of polypectomy). Subjects were interviewed regarding their regular usage of supplementation with vitamins A, C, D, and E, or with calcium, multivitamins, or any vitamin supplements. RESULTS: No consistent associations were observed with the use of any of these supplements. CONCLUSIONS: More studies are necessary to confirm these findings. It may be necessary to develop other chemopreventive agents, such as aspirin, for colorectal neoplasia.

Adenoma↗

High risk of Kaposi's sarcoma and central nervous system lymphoma in the same individuals: a finding related to acquired immunodeficiency syndrome.

Kaposi's sarcoma and central nervous system (CNS) lymphoma are the 2 most common malignancies related to HIV infection. To investigate the association between Kaposi's sarcoma and CNS lymphoma, a population-based retrospective cohort study was conducted. Using U.S. Surveillance, Epidemiology and End Results Program data, the gender-specific age- and calendar year-adjusted standardized incidence ratios were calculated for the pre-AIDS (1973-80) and AIDS (1981-1990) eras, as an estimate of the relative risk (RR) of developing one condition following another. For the AIDS era in men, the RR of CNS lymphoma following Kaposi's sarcoma was 979.7 and that of Kaposi's sarcoma following CNS lymphoma was 231.1. There were no instances of the co-occurrence of these malignancies in women in either era or in men for the pre-AIDS era. The extremely high RRs for the co-occurrence of Kaposi's sarcoma and CNA lymphoma in men during the AIDS era suggests that the association of these malignancies occurs within the same HIV-infected individuals.

Acquired Immunodeficiency Syndrome↗

Frequent K-ras mutations in small bowel adenocarcinomas.

The reasons for the relatively rare occurrence of small bowel adenocarcinomas when compared to the high frequency of colonic adenocarcinomas are unknown. Activating mutations in the K-ras oncogene occur in about 40% of colonic adenocarcinomas, possibly reflecting the consequences of carcinogenic exposure. To study whether the low incidence of small bowel adenocarcinomas might be due to the absence of activation of cellular oncogenes in small bowel adenocarcinomas, we examined the frequency of K-ras mutations in small bowel adenocarcinomas. K-ras mutations were determined using a polymerase chain reaction (PCR)-based method to detect codon 12 mutations by restriction fragment length polymorphism. PCR amplification was successful in six of nine small bowel adenocarcinoma samples, and revealed point mutations of K-ras at codon 12 in five of these six cases. We conclude that the small bowel might be exposed to carcinogens similar to those responsible for colorectal cancer, but may have developed protective mechanisms against cancer formation.

Adenocarcinoma↗

Reproducibility of nutrient intake in a food frequency questionnaire used in a general population.

This study evaluates the reproducibility of nutrient intake in a 45-item food frequency questionnaire (FFQ). The FFQ was mailed in 1980 to persons eligible to participate in a large cohort study on diet and cancer risk; a follow-up version with 75 food items was mailed in 1988 to selected original participants. A random sample of 500 men and 500 women from the New York State general population was selected from individuals who responded to both waves of the study. The subjects' 1988 responses were compared with their original 1980 responses; Pearson's correlations ranged from 0.25 for retinol to 0.55 for vitamin C with or without supplements and vitamin E with supplements in women. Reproducibility of nutrient intake in this questionnaire indicates that brief FFQs may be a useful tool to study nutrient intake and chronic disease relationships, although they are subject to substantial measurement error and dietary change.

Adolescent↗

A population-based study of the incidence of malignant small bowel tumours: SEER, 1973-1990.

BACKGROUND: Little is known about the incidence of cancers of the small bowel. METHODS: Data from cancer registries participating in the Surveillance, Epidemiology, and End-Results (SEER) Program from 1973 to 1990 were analysed to determine the incidence of the four major histological types of cancer occurring in the small intestine: adenocarcinomas, malignant carcinoid tumours, lymphomas and sarcomas. In addition, the incidence rate of lymphomas arising from the small intestine and stomach and adenocarcinomas from the small intestine, stomach and colon were compared over time. RESULTS: Small bowel tumours occurred rarely, with an average annual incidence rate of 9.9 per million people. Carcinoid tumours and adenocarcinomas were the most common histological subtypes, with average annual incidence rates of 3.8 and 3.7 per million people respectively, followed by lymphomas (1.1 per million people) and sarcomas (1.3 per million people). For all histological subtypes, men had higher rates than women. Most tumours occurred in older adults; over 90% of cases occurred in people over the age of 40. During the 18-year study period, the incidence of small bowel tumours has risen slowly. In white men, black men and black women, rises in the incidence of adenocarcinomas, malignant carcinoids and lymphomas contributed to this trend. In white women, the incidence of adenocarcinomas, was stable while malignant carcinoids and lymphomas rose. The incidence of sarcomas was steady for all groups except black women, for which it fell. The histological types were distributed by anatomical subsite: adenocarcinomas were distributed more proximally on average whereas lymphomas were more common distally. In addition, there was an association between the incidence trends of adenocarcinomas occurring in the duodenum and colon suggesting similar risk factors for cancers in these regions. There was no similar correlation for tumours in the jejunum and ileum. The incidence of lymphomas over time rose in all areas of the small intestine, paralleling a similar rise in lymphomas of the stomach. CONCLUSIONS: Cancers of the small bowel are rare despite a slow increase over the past two decades, especially among lymphomas. Higher rates in males and whites deserve further investigation.

Adenocarcinoma↗

Funerals.

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Funeral Rites↗

Malignant mesothelioma following treatment for Hodgkin's disease.

PURPOSE: Asbestos exposure is the major known risk factor for mesothelioma, but several case reports have suggested a link between radiation therapy and subsequent development of malignant mesothelioma. This report explores a possible association between radiation therapy for Hodgkin's disease and mesothelioma. PATIENTS AND METHODS: Four cases of malignant mesothelioma were observed following Hodgkin's disease at the Mesothelioma Clinic of the Dana-Farber Cancer Institute. A fifth such patient was found after a review of the literature. RESULTS: In all five cases, the mesothelioma arose in the field of prior radiotherapy. No history of asbestos exposure was elicited by careful questioning or by review of chest radiographs. Examination of lung tissue in one patient showed 250 ferruginous bodies per gram of lung tissue, consistent with no significant prior exposure. The mean interval between radiation treatment for Hodgkin's disease and development of mesothelioma was 15 years, which emphasizes the need for continued follow-up and evaluation of these patients and supports a causal relationship. CONCLUSION: Mesothelioma may need to be added to the list of second malignancies that arise following radiation therapy for Hodgkin's disease. Further support is given to a causal link between radiation exposure and mesothelioma.

Adult↗

Response of small cell carcinoma of pancreas to a small cell lung cancer regimen: a case report.

Small cell carcinoma of the pancreas is a very rare malignancy with 18 cases reported in the literature, of which only 3 were treated with chemotherapy. A 52-year-old man was diagnosed with small cell carcinoma originating in the head of the pancreas and invading the duodenum. He was treated with a similar approach as for localized small cell lung cancer, with six cycles of combination chemotherapy and local radiotherapy, and went into complete remission. After 3 months, he developed liver metastases along with an enlarged left supraclavicular lymph node. He was treated with two cycles of CVA, but developed lung metastases and was treated with ifosfamide/mesna. However, his overall condition deteriorated and hospice care was instituted until the patient's demise. The patient survived 14 months following diagnosis, significantly longer than the 15 reported patients with small cell pancreatic carcinomas not treated with chemotherapy. Combination chemotherapy and radiation therapy as it is utilized for small cell lung cancer appear to be beneficial for small cell carcinoma of the pancreas.

Antineoplastic Combined Chemotherapy Protocols↗

Clinical characteristics of non-Hodgkin's lymphoma as a second primary tumor: a population-based survey.

Data from 29,845 patients with lymphomas, 981 of whom had lymphoma as a second primary tumor, registered in the Surveillance Epidemiology and End Results (SEER) program in the U.S.A. between 1973 and 1986 were analyzed. The characteristics of the 274 patients with lymphoma as a second tumor who had received chemotherapy and/or radiotherapy for their primary tumor (SEP PT) were compared with 675 patients with second primary lymphomas who had no prior treatment (SEP NT) and with patients with single lymphomas (SIP). Patients with SEP PT disease had a significantly higher percentage of intermediate and high-grade tumors (80%) compared to those with SEP NT or SIP tumors (73% and 72%, respectively). The survival of all patients with SIP tumors did not differ from those with SEP tumors, but the median survival of those with SEP PT disease was shorter than for SEP NT disease. This was most probably due to the high percentage of intermediate and high-grade lymphomas in the SEP PT group. This was statistically significant in the group treated by combined chemotherapy and radiotherapy but not in those treated by a single modality alone. These findings relating to a worse prognosis in patients with SEP PT lymphoma are in line with our previous observations of a poor survival in patients with other multiple primary tumors.

Humans↗

Epidemiology of gastric cancer.

The incidence of gastric cancer varies widely by country and population, with higher rates among the lower socioeconomic groups. Although the most common cause of cancer death in the United States in 1930, its incidence has decreased dramatically during the past 60 years. Most populations show a 2-1 ratio for male to female gastric cancer cases, and a higher incidence rate among United States blacks than whites. Although rates have generally decreased, there has been a dramatic increase in the incidence of gastric cancer in the cardia. Diet has been the most studied risk factor for gastric cancer. Of particular interest have been N-nitroso compounds derived from the consumption of preserved, smoked, and cured foods. An inverse association with the consumption of fruits and vegetables has also been consistently demonstrated, though the specific nutrient(s) that this represents has been unclear, although ascorbate and beta-carotene have been intensively studied. Among nondietary factors, substantial evidence has accumulated for an increased risk with Helicobacter pylori infection. Other exposures which have been fairly consistently associated with gastric cancer include cigarette smoking, partial gastrectomy, radiation exposure, family history, pernicious anemia, blood group A, certain occupational exposures, and Epstein-Barr virus.

Age Factors↗

Recurrent adenomatous polyps and body mass index.

Interest in risk factors for the recurrence of adenomatous polyps derives from the use of recurrent adenomas as surrogate end points in longitudinal studies of invasive colorectal cancer. In this case-control study, the effect of increased body mass index (BMI) on the risk of recurrent adenomas was investigated. Subjects consisted of patients seen at three colonoscopy practices in New York City, all of whom had a previous history of adenomas. On index colonoscopy, recurrent cases had an adenoma, whereas controls were normal. Men and women were analyzed separately, with different logistic models developed using backward elimination from a full model containing the covariates age at diagnosis, age-at-highest-weight, pack-years of smoking, activity level, energy intake, and fat and fiber intake. Men in the upper quartiles of BMI were found to be at greater risk of recurrent adenomas. In a model which controlled for age at diagnosis, age-at-highest-weight, activity level, pack-years of smoking and kilocalories, the estimated odds ratios were 2.2, 1.9 and 1.9 respectively for the second, third and fourth quartiles compared to the first quartile. Only the estimate for the second quartile was found to be statistically significant. No effect was observed for women, even in a model which controlled for age at diagnosis, age-at-highest-weight, pack-years and total fat. Obesity may play a role in adenoma recurrence. Confirmation of this finding would have important implications for possible prevention strategies in the future.

Adenomatous Polyps↗

Increased expression of the cyclin D1 gene in Barrett's esophagus.

Previous studies have found a 3-10-fold amplification and overexpression of the cyclin D1 gene in about 32% of human esophageal squamous cell carcinoma. The purpose of this study was to evaluate the prevalence of increased expression of the cyclin D1 protein in Barrett's esophagus. Using 69 formalin-fixed and paraffin-embedded human esophageal specimens, which had been removed endoscopically or obtained at surgery during 1993 and 1994, all immunohistochemical analyses were performed using an avidin-biotin complex immunoperoxidase technique. Increased nuclear expression of the cyclin D1 protein was noted in 32 of 69 samples (46%; 44% of the samples from males and 50% of the samples from females). Positive nuclear staining for the cyclin D1 protein in Barrett's disease with intestinal metaplasia was found in 38% of the male cases and 25% of the female cases, whereas in gastric metaplasia it was positive in 33% of men and 48% of women. Nuclear accumulation of the cyclin D1 protein was also found in both dysplastic and nondysplastic lesions, and it was not associated with sex, age, or cigarette or alcohol consumption. Samples from patients taking proton pump inhibitors tended to be less frequently positive (32%) for cyclin D1 nuclear staining when compared to patients taking H2 antagonists (45%) or antacids (55%). These studies suggest that increased expression of cyclin D1 is an early event in the tumorigenic process of esophageal adenocarcinomas and that the increased expression of this gene might predispose the epithelium to malignant transformation.

Adenocarcinoma↗

Treatment for breast cancer and blood levels of chlorinated hydrocarbons.

Small studies have examined, with conflicting results, whether breast cancer risk is increased among women exposed to high levels of chlorinated hydrocarbons, as measured in breast fat tissue or peripheral blood collected prior to treatment (pretreatment blood). For a population-based, case-control study, collection of pretreatment blood is a labor-intensive effort. An alternative is to collect blood from cases at interview, as is done for controls, after breast cancer treatment has commenced (posttreatment blood). It is unknown whether treatment affects blood levels of the organochlorines 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) or polychlorinated biphenyls (PCBs). The purpose of this study was to determine whether pretreatment versus posttreatment blood samples yielded significantly different estimates of cumulative exposure to DDE and PCBs among newly diagnosed breast cancer patients. Two-ml blood samples were collected prior to and after treatment for breast cancer from 22 nonfasting women, ages 45-87 years, newly diagnosed with invasive disease. Treatment was defined as major surgery (mastectomy or node removal), radiation, hormones (tamoxifen), or chemotherapy. Pretreatment and posttreatment blood samples were assayed for DDE and PCBs in blinded, matched pairs. The reported concentrations (volume basis) were adjusted for estimated total plasma lipids. For DDE, mean differences in unadjusted [0.99 ng/ml; 95% confidence interval (CI), -0.36 to 2.34 ng/ml] and lipid-adjusted (0.05 microgram/g lipid; 95% CI, -0.04 to 0.13 microgram/g lipid) levels were small. For PCBs, the unadjusted (0.68 ng/ml; 95% CI, 0.05 to 1.30 ng/ml) and adjusted (0.070 microgram/g lipid; 95% CI, -0.009 to 0.149 microgram/g lipid) mean differences were of borderline statistical significance. The mean percent change in lipid-adjusted organochlorine levels did not vary substantially between treatment groups, except for those patients receiving chemotherapy [n = 5; 15.8% (DDE), 29.4% (PCBs)]. Adjusted mean differences also increased with increasing time between the pretreatment and posttreatment blood draws. In multiple regression models that included treatment, age, race, stage, and time between blood draws, only chemotherapy appeared to predict the percent change in adjusted pretreatment and posttreatment levels of DDE or PCBs (P = 0.10 and 0.06, respectively). Posttreatment blood samples drawn within 3 months of pretreatment samples, with the exception of those drawn after the commencement of chemotherapy, provide similar measures of DDE body burden levels among breast cancer cases. The use of blood samples collected after treatment, rather than before treatment, for characterizing PCB levels may lead to misclassification of exposure.

Aged↗

Epidemiology of gastrointestinal polyps.

Associations between polyps and cancer of the gastrointestinal tract have been fully documented for adenomatous polyps and cancer of the large bowel. The geographic, gender, and age distribution of colorectal adenomas parallels that of colorectal cancer incidence, and individuals with a history of adenomas are at increased risk for metachronous adenomas and cancer. Observational studies of risk factors for incident adenomas have found elevated risk associated with dietary variables including: high fat, low fiber, and low vegetable intake; family history; obesity; smoking; and other exposures, some of which also are associated with cancer. Dietary intervention trials with adenoma recurrence as an endpoint, however, have had little success. Screening with polypectomy has proved effective in reducing cancer incidence and may change the epidemiology of colorectal cancer.

Humans↗