Showing papers on "Cancer published in 1995"
TL;DR: In multicellular organisms, homeostasis is maintained through a balance between cell proliferation and cell death, and recent evidence suggests that alterations in cell survival contribute to the pathogenesis of a number of human diseases.
Abstract: In multicellular organisms, homeostasis is maintained through a balance between cell proliferation and cell death. Although much is known about the control of cell proliferation, less is known about the control of cell death. Physiologic cell death occurs primarily through an evolutionarily conserved form of cell suicide termed apoptosis. The decision of a cell to undergo apoptosis can be influenced by a wide variety of regulatory stimuli. Recent evidence suggests that alterations in cell survival contribute to the pathogenesis of a number of human diseases, including cancer, viral infections, autoimmune diseases, neurodegenerative disorders, and AIDS (acquired immunodeficiency syndrome). Treatments designed to specifically alter the apoptotic threshold may have the potential to change the natural progression of some of these diseases.
6,462 citations
TL;DR: The Late Morbidity Scoring Criteria were developed as a joint effort between physicians with renewed interests in fast neutron therapy and Radiation Therapy Oncology Group (RTOG) staff to represent cumulative probabilities of late effects with methods similar to those for estimating local control and survival.
Abstract: The therapeutic use of ionizing radiations is predicated on sparing normal tissue effects while attempting to achieve lethal effects on tumor cells. From quite early in the history of radiation therapy, it was apparent that there were striking differences in effects in the panoply of normal tissues. Although there was early appreciation of some late effects in normal tissues, often not predicted by acute reactions, only in recent years has there been full documentation of the slow and progressive increase in severity of late damage. Pathophysiological mechanisms of acute and late radiation effects are better understood today (2), but interactions of other modalities with radiation therapy require constant monitoring to recognize and mitigate untoward sequelae. The work of Stone (3) is a classic example of unanticipated late effects, which resulted from irradiation with ‘fast neutrons. Acute reactions were moderate and tolerable, but the late sequelae were so marked that there was little interest in pursuing therapy with fast neutrons for nearly three decades. The Late Morbidity Scoring Criteria were developed as a joint effort between physicians with renewed interests in fast neutron therapy and Radiation Therapy Oncology Group (RTOG) staff. In the late 1970s the Neutron/Particle Committee was one of several modality committees of the RTOG. Recognizing the results of Stone, this committee, led by Lawrence Davis worked with RTOG staff to establish criteria and scoring for possible late effects from fast neutron radiation therapy. Investigators from the European Organization for Research and Treatment of Cancer (EORTC), led by William Duncan of the Western General Hospital of Edinburgh, wished to have common toxicity criteria in anticipation of joint studies. RTOG Protocol 7929, an international registry of patients treated with heavy particles, was started in 1980. At the annual meetings of the international participants in particle studies, there were attempts to monitor interobserver variations in scoring effects in normal tissues and to seek consistency in reporting toxicity, but no publications document these efforts. The first prospective trial to use the Late Morbidity Scoring Criteria was RTOG Protocol 8001, a study of fast neutron therapy for malignant tumors arising in salivary glands. Although the RTOG began to use these criteria in reporting toxicity in patients enrolled in all studies from 198 1 (beginning with RTOG Protocol 8 115), the criteria only became a published part of protocols in 1983. At that time, statistical methods began to be used, which presented time-adjusted estimates of late effects, the rationale for which was described by Cox (1). It is now considered standard to represent cumulative probabilities of late effects with methods similar to those for estimating local control and survival. The Acute Radiation Morbidity Scoring Criteria were developed in 1985 as complimentary to the Late Effects Scoring Criteria. The National Cancer Institute promulgated standard toxicity criteria in 1990, but late effects were not considered. An abbreviated version of the RTOG/EORTC toxicity criteria was published by Winchester and Cox in 1992 as part of the Standard for Breast Conservation Treatment. The current RTOG Acute Radiation Morbidity Scoring Criteria are presented in Table 1. The RTOG/EORTC Late Radiation Morbidity Scoring Scheme is detailed in Table 2. In both tables, 0 means an absence of radiation effects and 5 means the effects led to death. The severity
4,111 citations
TL;DR: Average flavonoid intake may partly contribute to differences in coronary heart disease mortality across populations, but it does not seem to be an important determinant of cancer mortality.
Abstract: Objective: To determine whether flavonoid intake explains differences in mortality rates from chronic diseases between populations. Design: Cross-cultural correlation study. Setting/Participants: Sixteen cohorts of the Seven Countries Study in whom flavonoid intake at baseline around 1960 was estimated by flavonoid analysis of equivalent food composites that represented the average diet in the cohorts. Main Outcome Measures: Mortality from coronary heart disease, cancer (various sites), and all causes in the 16 cohorts after 25 years of follow-up. Results: Average intake of antioxidant flavonoids was inversely associated with mortality from coronary heart disease and explained about 25% of the variance in coronary heart disease rates in the 16 cohorts. In multivariate analysis, intake of saturated fat (73%;P=.0001), flavonoid intake (8%;P=.01), and percentage of smokers per cohort (9%;P=.03) explained together, independent of intake of alcohol and antioxidant vitamins, 90% of the variance in coronary heart disease rates. Flavonoid intake was not independently associated with mortality from other causes. Conclusions: Average flavonoid intake may partly contribute to differences in coronary heart disease mortality across populations, but it does not seem to be an important determinant of cancer mortality. (Arch Intern Med. 1995;155:381-386)
1,885 citations
TL;DR: Data show that metastases remain dormant when tumour cell proliferation is balanced by an equivalent rate of cell death and suggest that angiogenesis inhibitors control metastatic growth by indirectly increasing apoptosis in tumour cells.
Abstract: In cancer patients, dormant micrometastases are often asymptomatic and clinically undetectable, for months or years, until relapse. We have studied dormant lung metastases under angiogenesis suppression in mice. The metastases exhibited rapid growth when the inhibition of angiogenesis was removed. Tumour cell proliferation, as measured by bromodeoxyuridine incorporation and immunohistochemical staining proliferating cell nuclear antigen, was not significantly different in dormant and growing metastases. However, tumour cells of dormant metastases exhibited a more than threefold higher incidence of apoptosis. These data show that metastases remain dormant when tumour cell proliferation is balanced by an equivalent rate of cell death and suggest that angiogenesis inhibitors control metastatic growth by indirectly increasing apoptosis in tumour cells.
1,859 citations
Journal Article•
TL;DR: It is concluded that infection with a cagA-positive H. pylori strain in comparison with acagA -negative strain somewhat increases the risk for development of gastric cancer, especially intestinal type affecting the distal stomach.
Abstract: To determine whether infection with a Helicobacter pylori strain possessing cagA is associated with an increased risk of development of adenocarcinoma of the stomach, we used a nested case-control study based on a cohort of 5443 Japanese-American men in Oahu, Hawaii, who had a physical examination and a phlebotomy during 1967 to 1970 We matched 103 H pylori -infected men who developed gastric cancer during a 21-year surveillence period with 103 H pylori -infected men who did not develop gastric cancer and tested stored serum specimens from patients and controls for the presence of serum IgG to the cagA product of H pylori using an ELISA The serum IgG assay using a recombinant CagA fragment had a sensitivity of 944% and a specificity of 925% when used in a clinically defined population; serological results were stable for more than 7 years For men with antibodies to CagA, the odds ratio of developing gastric cancer was 19 (95% confidence interval, 09–40); for intestinal type cancer of the distal stomach, the odds ratio was 23 (95% confidence interval, 10–52) Age cagA -positive H pylori strain in comparison with a cagA -negative strain somewhat increases the risk for development of gastric cancer, especially intestinal type affecting the distal stomach
1,635 citations
TL;DR: This work has identified a similar molecular mechanism in vivo for endocrine treatment failure in human prostate cancer which involves amplification of the androgen receptor (AR) gene.
Abstract: Overexpression of amplified genes is often associated with the acquisition of resistance to cancer therapeutic agents in vitro. We have identified a similar molecular mechanism in vivo for endocrine treatment failure in human prostate cancer which involves amplification of the androgen receptor (AR) gene. Comparative genomic hybridization shows that amplification of the Xq11-q13 region (the location), is common in tumours recurring during androgen deprivation therapy. We found high-level AR amplification in seven of 23 (30%) recurrent tumours, but in none of the specimens taken from the same patients prior to therapy. Our results suggest that AR amplification emerges during androgen deprivation therapy by facilitating tumour cell growth in low androgen concentrations.
1,489 citations
TL;DR: In this paper, the effect of adding progestins to estrogen therapy on the risk of breast cancer in postmenopausal women is investigated. But, the effect on the number of newly diagnosed invasive breast cancer cases was not quantified.
Abstract: Background The effect of adding progestins to estrogen therapy on the risk of breast cancer in postmenopausal women is controversial. Methods To quantify the relation between the use of hormones and the risk of breast cancer in postmenopausal women, we extended our follow-up of the participants in the Nurses' Health Study to 1992. The women were asked to complete questionnaires every two years to update information on their menopausal status, use of estrogen and progestin preparations, and any diagnosis of breast cancer. During 725,550 person-years of follow-up, we documented 1935 cases of newly diagnosed invasive breast cancer. Results The risk of breast cancer was significantly increased among women who were currently using estrogen alone (relative risk, 1.32; 95 percent confidence interval, 1.14 to 1.54) or estrogen plus progestin (relative risk, 1.41; 95 percent confidence interval, 1.15 to 1.74), as compared with postmenopausal women who had never used hormones. Women currently taking hormones who ha...
1,474 citations
TL;DR: The American Cancer Society's Department of Epidemiology and Statistics reports its 29th annual compilation of cancer incidence, survival and mortality data for the United States and around the world.
Abstract: The American Cancer Society's Department of Epidemiology and Statistics reports its 29th annual compilation of cancer incidence, survival and mortality data for the United States and around the world.
1,441 citations
TL;DR: Practical considerations and selected specific examples are selected, particularly illustrating research applications of the NCI screen that may be more broadly applicable to the search for new anticancer drug development leads with novel profiles of antitumor activity and/or mechanisms of action.
Abstract: During 1985-1990 the U.S. National Cancer Institute (NCI) phased out its murine leukemia P388 anticancer drug screening program and developed as the replacement a new in vitro primary screen based upon a diverse panel of human tumor cell lines. For each substance tested, the screen generates a remarkably reproducible and characteristic profile of differential in vitro cellular sensitivity, or lack thereof, across the 60 different cell lines comprising the panel. Several investigational approaches to display, analysis and interpretation of such profiles and databases, derived from the testing of tens of thousands of substances during the past 4-5 years since the NCI screen became fully operational, have been explored. A variety of useful, practical applications of the in vitro screen have become apparent. As these applications continue to evolve, they are proving to be complementary to diverse other anticancer screening and drug discovery strategies being developed or pursued elsewhere. Reviewed herein are some practical considerations and selected specific examples, particularly illustrating research applications of the NCI screen that may be more broadly applicable to the search for new anticancer drug development leads with novel profiles of antitumor activity and/or mechanisms of action.
1,401 citations
Journal Article•
TL;DR: In tumors, de novo methylation of the 5' CpG island is a frequent mode of inactivation of CDKN2/p16 and this alteration of p16 in colon cancer was particularly striking, since inactivation does not occur through homozygous deletion in this tumor type.
Abstract: The tumor suppressor gene CDKN2/p16/MTS1, located on chromosome 9p21, is frequently inactivated in many human cancers through homozygous deletion. Recently, we have reported another pathway of inactivation that involves loss of transcription associated with de novo methylation of a 5' CpG island of CDKN2/p16 in lung cancers, gliomas, and head and neck squamous cell carcinomas. We now show that this aberrant CpG island methylation also occurs frequently in cell lines of breast cancer (33%), prostate cancer (60%), renal cancer (23%), and colon cancer (92%) and is associated with loss of transcription. Primary tumors of the breast (31%) and colon (40%) also displayed de novo methylation of this CpG island. This alteration of p16 in colon cancer was particularly striking, since inactivation does not occur through homozygous deletion in this tumor type. Our data show that in tumors, de novo methylation of the 5' CpG island is a frequent mode of inactivation of CDKN2/p16 and also firmly demonstrate that CDKN2/p16 is one of the most frequently altered genes in human neoplasia.
1,399 citations
TL;DR: The findings suggest that intake of lycopene or other compounds in tomatoes may reduce prostate cancer risk, but other measured carotenoids are unrelated to risk.
Abstract: Background Several human studies have observed a direct association between retinol (vitamin A) intake and risk of prostate cancer; other studies have found either an inverse association or no association of intake of beta-carotene (the major provitamin A) with risk of prostate cancer. Data regarding carotenoids other than beta-carotene in relation to prostate cancer risk are sparse. Purpose We concluded a prospective cohort study to examine the relationship between the intake of various carotenoids, retinol, fruits, and vegetables and the risk of prostate cancer. Methods Using responses to a validated, semiquantitative food-frequency questionnaire mailed to participants in the Health Professionals Follow-up Study in 1986, we assessed dietary intake for a 1-year period for a cohort of 47,894 eligible subjects initially free of diagnosed cancer. Follow-up questionnaires were sent to the entire cohort in 1988, 1990, and 1992. We calculated the relative risk (RR) for each of the upper categories of intake of a specific food or nutrient by dividing the incidence rate of prostate cancer among men in each of these categories by the rate among men in the lowest intake level. All P values resulted from two-sided tests. Results Between 1986 and 1992, 812 new cases of prostate cancer, including 773 non-stage A1 cases, were documented. Intakes of the carotenoids beta-carotene, alpha-carotene, lutein, and beta-cryptoxanthin were not associated with risk of non-stage A1 prostate cancer; only lycopene intake was related to lower risk (age- and energy-adjusted RR = 0.79; 95% confidence interval [CI] = 0.64-0.99 for high versus low quintile of intake; P for trend = .04). Of 46 vegetables and fruits or related products, four were significantly associated with lower prostate cancer risk; of the four--tomato sauce (P for trend = .001), tomatoes (P for trend = .03), and pizza (P for trend = .05), but not strawberries--were primary sources of lycopene. Combined intake of tomatoes, tomato sauce, tomato juice, and pizza (which accounted for 82% of lycopene intake) was inversely associated with risk of prostate cancer (multivariate RR = 0.65; 95% CI = 0.44-0.95, for consumption frequency greater than 10 versus less than 1.5 servings per week; P for trend = .01) and advanced (stages C and D) prostate cancers (multivariate RR = 0.47; 95% CI = 0.22-1.00; P for trend = .03). No consistent association was observed for dietary retinol and risk of prostate cancer. Conclusions These findings suggest that intake of lycopene or other compounds in tomatoes may reduce prostate cancer risk, but other measured carotenoids are unrelated to risk. Implications Our findings support recommendations to increase vegetable and fruit consumption to reduce cancer incidence but suggest that tomato-based foods may be especially beneficial regarding prostate cancer risk.
TL;DR: In this paper, the authors explored the relationship between numerical ratings of pain severity and ratings of their interference with such functions as activity, mood, and sleep, and found optimal cutpoints that form 3 distinct levels of cancer pain severity that can be defined on a 0-10 point numerical scale.
Abstract: As a way of delineating different levels of cancer pain severity, we explored the relationship between numerical ratings of pain severity and ratings of pain's interference with such functions as activity, mood, and sleep. Interference measures were used as critical variable to grade pain severity. We explored the possibility that pain severity could be classified into groupings roughly comparable to mild, moderate, and severe. Our hypothesis was that mild, moderate, and severe pain would differentially impair cancer patients' function. We were able to identify boundaries among these categories of pain severity in terms of their interference with function. We also examined the extent to which cancer patients from different language and cultural groups differ in their self-reported interference as a function of pain severity level. We found optimal cutpoints that form 3 distinct levels of pain severity that can be defined on a 0-10-point numerical scale. We determined that, based on the degree of interference with cancer patients' function, ratings of 1-4 correspond to mild pain, 5-6 to moderate pain, and 7-10 to severe pain. Our analysis illustrates that the pain severity-interference relationship is non-linear. These cutpoints were the same for each of the national samples in our analysis, although there were slight differences in the specific interference items affected by pain. These cutpoints might be useful in clinical evaluation, epidemiology, and clinical trials.
TL;DR: The establishment of breeding lines of transgenic mice that reproducibly develop prostate cancer provides an animal model system to study the molecular basis of transformation of normal prostatic cells and the factors influencing the progression to metastatic prostate cancer.
Abstract: Progress toward understanding the biology of prostate cancer has been slow due to the few animal research models available to study the spectrum of this uniquely human disease. To develop an animal model for prostate cancer, several lines of transgenic mice were generated by using the prostate-specific rat probasin promoter to derive expression of the simian virus 40 large tumor antigen-coding region. Mice expressing high levels of the transgene display progressive forms of prostatic disease that histologically resemble human prostate cancer, ranging from mild intraepithelial hyperplasia to large multinodular malignant neoplasia. Prostate tumors have been detected specifically in the prostate as early as 10 weeks of age. Immunohistochemical analysis of tumor tissue has demonstrated that dorsolateral prostate-specific secretory proteins were confined to well-differentiated ductal epithelial cells adjacent to, or within, the poorly differentiated tumor mass. Prostate tumors in the mice also display elevated levels of nuclear p53 and a decreased heterogeneous pattern of androgen-receptor expression, as observed in advanced human prostate cancer. The establishment of breeding lines of transgenic mice that reproducibly develop prostate cancer provides an animal model system to study the molecular basis of transformation of normal prostatic cells and the factors influencing the progression to metastatic prostate cancer.
TL;DR: It is suggested that the concept of ‘persistent oxidative stress in cancer’ may open up a new research area, explaining part of the characteristic tumor biology of cancer such as activated transcription factors and proto‐oncogenes, genomic instability, chemotherapy‐resistance, invasion and metastasis.
TL;DR: The unexpected frequency of human tumor antigens indicates that human neoplasms elicit multiple specific immune responses in the autologous host and provides diagnostic and therapeutic approaches to human cancer.
Abstract: Expression of cDNA libraries from human melanoma, renal cancer, astrocytoma, and Hodgkin disease in Escherichia coli and screening for clones reactive with high-titer IgG antibodies in autologous patient serum lead to the discovery of at least four antigens with a restricted expression pattern in each tumor. Besides antigens known to elicit T-cell responses, such as MAGE-1 and tyrosinase, numerous additional antigens that were overexpressed or specifically expressed in tumors of the same type were identified. Sequence analyses suggest that many of these molecules, besides being the target of a specific immune response, might be of relevance for tumor growth. Antibodies to a given antigen were usually confined to patients with the same tumor type. The unexpected frequency of human tumor antigens, which can be readily defined at the molecular level by the serological analysis of autologous tumor cDNA expression cloning, indicates that human neoplasms elicit multiple specific immune responses in the autologous host and provides diagnostic and therapeutic approaches to human cancer.
TL;DR: Increases in the level of breast tissue density as assessed by mammography are associated with increases in risk for breast cancer, and these results show that increases in theLevel of breast cancer risk associated with increasing mammographic density is shown.
Abstract: BACKGROUND The radiographic appearance of the female breast varies from woman to woman depending on the relative amounts of fat and connective and epithelial tissues present. Variations in the mammographic density of breast tissue are referred to as the parenchymal pattern of the breast. Fat is radiologically translucent or clear (darker appearance), and both connective and epithelial tissues are radiologically dense (lighter appearance). Previous studies have generally supported an association between parenchymal patterns and breast cancer risk (greater risk with increasing densities), but there has been considerable heterogeneity in risk estimates reported. PURPOSE Our objective was to determine the level of breast cancer risk associated with varying mammographic densities by quantitatively classifying breast density with conventional radiological methods and novel computer-assisted methods. METHODS From the medical records of a cohort of 45,000 women assigned to mammography in the Canadian National Breast Cancer Screening Study (NBSS), a multicenter, randomized trial, mammograms from 354 case subjects and 354 control subjects were identified. Case subjects were selected from those women in whom histologically verified invasive breast cancer had developed 12 months or more after entering the trial. Control subjects were selected from those of similar age who, after a similar period of observation, had not developed breast cancer. The mammogram taken at the beginning of the NBSS was the image used for measurements. Mammograms were classified into six categories of density, either by radiologists or by computer-assisted measurements. All radiological classification and computer-assisted measurements were made using one craniocaudal view from the breast contralateral to the cancer site in case subjects and the corresponding breast of control subjects. All P values represent two-sided tests of statistical significance. RESULTS For all subjects, there was a 43% increase in the relative risk (RR) between the lower and the next higher category of density, as determined by radiologists, and there was a 32% increase as determined by the computer-assisted method. For all subjects, the RR in the most extensive category relative to the least was 6.05 (95% confidence interval [CI] = 2.82-12.97) for radiologists and 4.04 (95% CI = 2.12-7.69) for computer-assisted methods. Statistically significant increases in breast cancer risk associated with increasing mammographic density were found by both radiologists and computer-assisted methods for women in the age category 40-49 years (P = .005 for radiologists and P = .003 for computer-assisted measurements) and the age category 50-59 years (P = .002 for radiologists and P = .001 for computer-assisted measurements). CONCLUSION These results show that increases in the level of breast tissue density as assessed by mammography are associated with increases in risk for breast cancer.
TL;DR: Regular aspirin use, at doses similar to those recommended for the prevention of cardiovascular disease, substantially reduces the risk of colorectal cancer, however, this benefit may not be evident until after at least a decade of regular aspirin consumption.
Abstract: Background Most data suggest that the regular use of aspirin reduces the risk of colorectal cancer, but some apparently conflicting evidence exists. The effects of the dose and the duration of aspirin consumption on the risk of colorectal cancer are not well understood. Methods We determined rates of colorectal cancer according to the number of consecutive years of regular aspirin use (defined as two or more tablets per week) among women in the Nurses' Health Study who reported regular aspirin use on three consecutive questionnaires (1980, 1982, and 1984) and compared the rates in this group with the rates among women who said they did not use aspirin. Cases of cancer occurring from 1984 through 1992 (the eight years after the 1984 questionnaire) were included. Results From 1984 through 1992, we documented 331 new cases of colorectal cancer during 551,651 person-years of follow-up. Women who consistently took two or more aspirin tablets per week had no appreciable reduction in the risk of colorectal cance...
TL;DR: The hypotheses that physical inactivity, obesity, and height increase the risk for colon cancer and adenoma independently of each other and of diet are addressed, and that the abdominal pattern of obesity is an additional independent risk factor are addressed.
Abstract: Objective: To determine whether physical inactivity and obesity increase risk for colon cancer and adenomas, which are precursors of cancer, and whether the abdominal distribution of obesity is an ...
TL;DR: It is concluded that in addition to general HRQOL, disease-targeted measures must be used to assess outcomes of care in men treated for localized prostate cancer.
Abstract: Objective. —To assess health-related quality of life (HRQOL) in men treated for clinically localized prostate cancer. Design. —A cross-sectional analysis of HRQOL after treatment with radical prostatectomy, pelvic irradiation, or observation alone for clinically localized prostatic adenocarcinoma, and in age-matched comparison patients. Setting. —A large managed care population in California. Subjects. —A total of 528 men, including 214 treated for clinically localized prostate cancer (41 with evidence of metastatic disease were excluded from this analysis) and 273 age-matched, ZIP code—matched comparison patients without prostate cancer. Cancer patients were analyzed in three treatment groups: radical prostatectomy (n=98), primary pelvic irradiation (n=56), and observation alone (n=60). Main Outcome Measures. —General HRQOL was measured with the RAND 36-Item Health Survey 1.0. Cancer-specific HRQOL was measured with the CAncer Rehabilitation Evaluation System—Short Form and the Functional Assessment of Cancer Therapy—General form. Disease-targeted quality of life was measured with a new instrument assessing function and bother in three organ systems: sexual, urinary, and bowel. Results. —No differences among treatment groups were seen in comparisons of general HRQOL. Significant differences among treatment groups were seen in both function and bother in the prostate-targeted measures of sexual, urinary, and bowel domains. When cancer patients were compared with men of similar age without prostate cancer, differences were seen in the sexual, urinary, and bowel function and bother but not in general HRQOL measures. Although cancer-free men were found not to have full potency or continence, prostate cancer patients treated with surgery or radiation reported significantly worse sexual, urinary, and bowel function than men without cancer. Men who had undergone nerve-sparing prostatectomy did not differ from those who had undergone standard prostatectomy, but the power to detect a difference was low. Conclusions. —Although no differences were seen in general HRQOL, three disease-targeted domains were found to differ significantly among the treatment groups and comparison patients. Even after controlling for the sexual and urinary dysfunction experienced by older men without cancer, those receiving therapeutic interventions for their prostate cancer were found to have poorer disease-targeted HRQOL. We conclude that in addition to general HRQOL, disease-targeted measures must be used to assess outcomes of care in men treated for localized prostate cancer. ( JAMA . 1995;273:129-135)
TL;DR: Morbidity and mortality differences persisted in almost all subgroup analyses, and D2 dissection should not be used as standard treatment for western patients.
TL;DR: Multivariate analyses indicated the strongest predictors of long-term survival were diploid tumor DNA content, tumor diameter < 3 cm, negative nodal status, negative resection margins, and decade of resection.
Abstract: OBJECTIVE: This single-institution study examined the outcome after pancreaticoduodenectomy in patients with adenocarcinoma of the head of the pancreas. SUMMARY OF BACKGROUND DATA: In recent years, pancreaticoduodenectomy for adenocarcinoma of the head of the pancreas has been associated with decreased morbidity and mortality and, in some centers, 5-year survival rates in excess of 20%. METHODS: Two hundred one patients with pathologically verified adenocarcinoma of the head of the pancreas undergoing pancreaticoduodenectomy at The Johns Hopkins Hospital between 1970 and 1994 were analyzed (the last 100 resections were performed between March 1991 and April 1994). This is the largest single-institution experience reported to date. RESULTS: The overall postoperative in-hospital mortality rate was 5%, but has been 0.7% for the last 149 patients. The actuarial 5-year survival for all 201 patients was 21%, with a median survival of 15.5 months. There were 11 5-year survivors. Patients resected with negative margins (curative resections: n = 143) had an actuarial 5-year survival rate of 26%, with a median survival of 18 months, whereas those with positive margins (palliative resections; n = 58) fared significantly worse, with an actuarial 5-year survival rate of 8% and a median survival of 10 months (p < 0.0001). Survival has improved significantly from decade to decade (p < 0.002), with the 3-year actuarial survival of 14% in the 1970s, 21% in the 1980s, and 36% in the 1990s. Factors significantly favoring long-term survival by univariate analyses included tumor diameter < 3 cm, negative nodal status, diploid tumor DNA content, tumor S phase fraction < 18%, pylorus-preserving resection, < 800 mL intraoperative blood loss, < 2 units of blood transfused, negative resection margins, and use of postoperative adjuvant chemotherapy and radiation therapy. Multivariate analyses indicated the strongest predictors of long-term survival were diploid tumor DNA content, tumor diameter < 3 cm, negative nodal status, negative resection margins, and decade of resection. CONCLUSIONS: The survival of patients with pancreatic adenocarcinoma treated by pancreaticoduodenectomy is improving. Aspects of tumor biology, such as DNA content, tumor diameter, nodal status and margin status, are the strongest predictors of outcome.
TL;DR: Evidence that specific cancers are caused by NOC and clues from mutations in ras and p53 genes in human tumors about whether NOC are etiologic agents are discussed and some general conclusions are drawn.
TL;DR: M mammographic features were associated with known breast cancer risk factors, however, the high-density parenchymal pattern effects were independent of family history, age at first birth, alcohol consumption, and benign breast disease.
Abstract: Background : Mammographic images from women with a high proportion of epithelial and stromal breast tissues are described as showing high-density parenchymal patterns. Most past studies that noted an increase in breast cancer risk associated with mammographic parenchymal patterns showing high density either 1) lacked information on other breast cancer risk factors, 2) were too small, or 3) included insufficient follow-up time to adequately resolve persisting doubts whether mammographic features are independent measures of breast cancer risk and not a detection artifact. Purpose : The purpose of this study was twofold : 1) to evaluate the associations between mammographic features and other breast cancer risk factors and 2) to assess effects of mammographic features on breast cancer risk by time, age, and menopause status. Methods : To address these questions, we analyzed detailed information from a large, nested case-control study with 16 years of follow-up. This study used information from both screening and follow-up phases of the Breast Cancer Detection Demonstration Project, a nationwide program that offered annual breast cancer screening for more than 280 000 women from 1973 to 1980. Mammographic features were assessed from the base-line screening mammographic examination for 1880 incident case subjects and 2152 control subjects. Control subjects were randomly selected from women of the same age and race as each case subject. Control subjects attended the same screening center as the case subject and were free of breast cancer at the case subject's date of diagnosis. Odds ratios (ORs) with 95% confidence intervals (CIs) provided estimates of the relative risk of breast cancer. Results : Mammographic features were associated with known breast cancer risk factors. However, the high-density parenchymal pattern effects were independent of family history, age at first birth, alcohol consumption, and benign breast disease. The increased risk for women with Wolfe's two high-density parenchymal patterns, P2 (OR = 3.2 ; 95% CI = 2.5-4.0) and Dy (OR = 2.9 ; 95% CI = 2.2-3.9), was explained primarily by measured percent of the breast with dense mammographic appearance. Compared with women with no visible breast density, women who had a breast density of 75% or greater had an almost fivefold increased risk of breast cancer (95% CI = 3.6-7.1). These effects persisted for 10 or more years and were noted for both premenopausal and postmenopausal women of all ages. Conclusions : Of the breast cancer risk factors assessed in the participants, high-density mammographic parenchymal patterns, as measured by the proportion of breast area composed of epithelial and stromal tissue, had the greatest impact on breast cancer risk. Of the breast cancers in this study, 28% were attributable to having 50% or greater breast density.
TL;DR: In the management of stage I and II breast cancer, breast conservation with lumpectomy and radiation offers results at 10 years that are equivalent to those with mastectomy.
Abstract: Background Breast-conservation therapy for early-stage breast cancer is now an accepted treatment, but there is still controversy about its comparability with mastectomy. Between 1979 and 1987, the National Cancer Institute conducted a randomized, single-institution trial comparing lumpectomy, axillary dissection, and radiation with mastectomy and axillary dissection for stage I and II breast cancer. We update the results of that trial after a median potential follow-up of 10.1 years. Methods Two hundred forty-seven patients with clinical stage I and II breast cancer were randomly assigned to undergo either modified radical mastectomy or lumpectomy, axillary dissection, and radiation therapy. The 237 patients who actually underwent randomization have been followed for a median of 10.1 years. The primary end points were overall survival and disease-free survival. Results At 10 years overall survival was 75 percent for the patients assigned to mastectomy and 77 percent for those assigned to lumpectomy plus ...
01 Jan 1995
TL;DR: In this article, meta-analytic methods were used to synthesize the results of published randomized, controlled-outcome studies of psychosocial interventions with adult cancer patients, including behavioral interventions, nonbehavioral counseling and therapy, informational and educational methods, organized social support provided by other patients, and other non-hospice interventions.
Abstract: Meta-analytic methods were used to synthesize the results of published randomized, controlledoutcome studies of psychosocial interventions with adult cancer patients. Forty-five studies reporting 62 treatment-control comparisons were identified. Samples were predominantly White, female, and from the United States. Beneficial effect size ds were .24 for emotional adjustment measures, .19 for functional adjustment measures, .26 for measures of treatment- and diseaserelated symptoms, and .28 for compound and global measures. The effect size of .17 found for medical measures was not statistically significant for the few reporting studies. Effect sizes for treatment-control comparisons did not significantly differ among several categories of treatment: behavioral interventions, nonbehavioral counseling and therapy, informational and educational methods, organized social support provided by other patients, and other nonhospice interventions. Though the field of psychosocial oncology is relatively young, intervention studies and indeed even narrative reviews of those studies are no longer rare. Meta-analytic investigations, however, are conspicuously absent from the literature. In the present article, the results of treatment-control studies of psychosocial interventions with adult cancer patients are assessed meta-analytically. The focus is on the effects of nonpharmacological interventions intended to improve the quality of life of adults who have already been diagnosed with
TL;DR: Effect sizes for treatment-control comparisons did not significantly differ among several categories of treatment: behavioral interventions, nonbehavioral counseling and therapy, informational and educational methods, organized social support provided by other patients, and other nonhospice interventions.
Abstract: Meta-analytic methods were used to synthesize the results of published randomized, controlled-outcome studies of psychosocial interventions with adult cancer patients. Forty-five studies reporting 62 treatment-control comparisons were identified. Samples were predominantly White, female, and from the United States. Beneficial effect size ds were .24 for emotional adjustment measures, .19 for functional adjustment measures, .26 for measures of treatment- and disease-related symptoms, and .28 for compound and global measures. The effect size of .17 found for medical measures was not statistically significant for the few reporting studies. Effect sizes for treatment-control comparisons did not significantly differ among several categories of treatment: behavioral interventions, nonbehavioral counseling and therapy, informational and educational methods, organized social support provided by other patients, and other nonhospice interventions.
TL;DR: FEMTX combined with vitamin A and E is a fairly well-tolerated treatment, giving a response rate of 29% in patients with advanced gastric cancer, and also prolonging patients' survival, and can be used as a reference treatment in testing new investigational combinations.
Abstract: A phase III randomised study, comparing treatment with fluorouracil, epidoxorubicin and methotrexate (FEMTX) with the best supportive care, was conducted in patients with unresectable or metastatic gastric cancer. During the period from July 1986 to June 1992, 41 patients were randomised to receive FEMTX or best supportive care. MTX was given in a dose of 1500 mg m-2 intravenously (i.v.) followed after 1 h by 5-FU 1500 mg m-2 i.v. on day 1; leucovorin rescue was started after 24 h (30 mg orally every 6 h for 48 h) and epidoxorubicin 60 mg m-2 i.v. was administered on day 15. In addition both groups received tablets containing vitamins A and E. Response rates for FEMTX were as follows: complete response (CR), 19% (4/21); partial response (PR), 10% (2/21); no change (NC), 33% (7/21); and progressive disease (PD), 24% (5/21). Response rates in the control group were: NC, 20% (4/20); and PD, 80% (16/20). Increased pain was observed in one patient in the treated group and in 11 patients in the control group within the first 2 months. WHO grade III/IV toxicity in the chemotherapy group was as follows: nausea/vomiting 40%, diarrhoea 10%, stomatitis 15%, leucopenia 50% and thrombocytopenia 10%. One possible treatment-related death was due to sepsis. The median time to progression in the FEMTX group was 5.4 months [95% confidence interval (CI) 3.1-11.7 months], but only 1.7 months in the control group (95% CI 1.2-2.7 months) (P = 0.0013). Similarly, the FEMTX group displayed significantly (P = 0.0006) prolonged survival compared with the control group, i.e. median survival 12.3 months (95% CI 7.1-15.6 months) vs 3.1 months (95% CI 1.6-4.6 months). In conclusion, FEMTX combined with vitamin A and E is a fairly well-tolerated treatment, giving a response rate of 29% in patients with advanced gastric cancer, and also prolonging patients' survival. It can be used as a reference treatment in testing new investigational combinations.
TL;DR: The hypothesis that substantial consumption of alcohol, when combined with inadequate intakes of folate and methionine, may increase risk of colon cancer is supported and similar findings in adenomas are confirmed.
Abstract: Background: Methylation of DNA, which may have a role in the regulation of gene expression, depends on dietary folate and methionine. Because aberrant DNA methvlation may contribute to the initiation or progression of colon cancer, we hypothesized that deficient intakes of folate or methionine and high consumption of alcohol, an antagonist of methyl-group metabolism, increase risk of colon neoplasia. Previously, a high-alcohol and low-methionine-low-folate (methyl-dehcient) diet was shown to be related to a higher risk of colon adenomas, precursors of cancer. Purpose: Our goal was to determine if ingestion of a high-alcohol, methyl-deficient diet is related directly to risk of colon cancer. Methods: We assessed dietary intake for a 1-year period for a cohort of 47 931 U.S. male health professionals, 40-75 years old and free of diagnosed cancer in 1986. We assessed diet by using a validated, semiquantitative food-frequency questionnaire. During 6 years of follow-up, we documented 205 new cases of colon cancer in this cohort. Results: Current alcohol intake was directly related to risk of colon cancer (multivariate relative risk [RR]=2.07; 95% confidence interval [CI]=1.29-3.32, for >2 drinks versus ≤0.25 drink daily; P trend=.005), and past drinkers were also at higher risk (RR=1.95; 95% CI=1.22-3.10). Individually, folate and methionine intakes were weakly inversely associated with risk of colon cancer. An adverse effect of a high-alcohol, low-methyl diet was not observed among regular users of aspirin, who have previously been shown to be at lower risk for colon cancer. Combinations of high alcohol and low methionine and folate intakes yielded striking associations for total colon cancer (RR=3.30 [95% CI=1.58-6.88] comparing high-methyl diets with low-methyl diets among nonusers of aspirin) and for cancers of the distal colon (RR=7.44; 95% CI=1.72-32.1). Among men with high intakes of folate or methionine, alcohol levels of >2 drinks daily were not associated with risk of colon cancer. The increased risk of colon cancer associated with alcohol and methyl-deficient diets was not confounded by smoking; intakes of fat, red meat, and fiber; level of physical activity; multivitamin or aspirin use; and body mass index. Conclusions: These findings support the hypothesis that substantial consumption of alcohol, when combined with inadequate intakes of folate and methionine, may increase risk of colon cancer and confirm similar findings in adenomas. Implications: These data provide further support of recommendations to avoid excess alcohol consumption and to increase dietary folate to lower the risk of colon cancer
TL;DR: The recent dramatic epidemic of prostate cancer is likely the result of the increasing detection of tumors resulting from increased PSA screening, and changes in the intensity of medical surveillance is the most plausible explanation for this trend.
Abstract: Objective. —To assess the reasons for the dramatic surge in prostate cancer incidence from 1986 to 1991. Design. —Population-based study of incidence rates and procedures used to detect and diagnose prostate cancer derived from Medicare claims data and the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program from 1986 to 1991. Setting. —Four SEER areas (Connecticut; Atlanta, Ga; Detroit, Mich; and Seattle—Puget Sound, Wash) covering approximately 6% of the US population. Participants. —A 5% random sample of male fee-for-service Medicare beneficiaries aged 65 years and older without cancer, and all men with prostate cancer diagnosed at 65 years of age and older residing in the four areas. Main Outcome Measures. —The age-adjusted rates of prostate cancer incidence, prostate needle biopsy, transurethral resection of the prostate, serum prostate-specific antigen (PSA) testing, and transrectal ultrasound. Results. —The age-adjusted incidence rate of prostate cancer among men aged 65 years and older in the four SEER areas rose 82% from 1986 to 1991, with the largest annual increases occurring in 1990 (20%) and 1991 (19%). Prostate needle biopsy rates increased while the use of transurethral resection of the prostate declined from 1986 to 1991. The rising needle biopsy rate has been driven by an exponential increase in PSA testing in the general population from 1988 to 1991 and, to a much lesser extent, the increasing use of transrectal ultrasound since 1986. The use of PSA or transrectal ultrasound has increased across age and race groups and in different geographic areas. However, there remain wide geographic variations in the use of PSA screening. Conclusions. —The recent dramatic epidemic of prostate cancer is likely the result of the increasing detection of tumors resulting from increased PSA screening. The magnitude and rapidity of the incidence rise suggest that changes in the intensity of medical surveillance is the most plausible explanation for this trend. Implications. —The rapid diffusion of screening interventions that have the ability to detect latent asymptomatic disease leads to important concerns regarding costs and patient quality of life for men aged 65 years and older. Geographic variability in the adoption of PSA testing underscores uncertainty and disagreement about its value for reducing prostate cancer mortality. More research is required to determine the effectiveness of screening for prostate cancer. (JAMA. 1995;273:548-552)
TL;DR: Debulking surgery significantly lengthened progression-free and overall survival and the risk of death was reduced by one third, after adjustment for a variety of prognostic factors.
Abstract: Background Although the value of primary cytoreductive surgery for epithelial ovarian cancer is beyond doubt, the value of debulking surgery after induction chemotherapy has not yet been defined. In this randomized study we investigated the effect on survival of debulking surgery. Methods Eligible patients had residual lesions measuring more than 1 cm in diameter after primary surgery. After three cycles of cyclophosphamide and cisplatin, these patients were randomly assigned to undergo either debulking surgery or no surgery, followed by further cycles of cyclophosphamide and cisplatin. The study end points were progression-free survival and overall survival. At surgery 65 percent of the patients had lesions measuring more than 1 cm. In 45 percent of this group, the lesions were reduced surgically to less than 1 cm. Results Of the 319 patients who underwent randomization, 278 could be evaluated (140 patients who underwent surgery and 138 patients who did not). Progression-free and overall survival were bo...