Propylthiouracil-induced hypothyroidism reduces xenograft tumor growth in athymic nude mice.

BACKGROUND: Thyroid hormones are endocrine modulators of several vital processes that are crucial to tumor growth and differentiation. Several anecdotal reports in the literature suggest that some histologic types of carcinoma may remain in a dormant state for prolonged periods of time in patients with hypothyroidism, with eventual progression of the disease once the decreased thyroid function is identified and corrected. METHODS: Oral propylthiouracil (PTU) was used to induce hypothyroidism in athymic nude mice that were subsequently inoculated with lung adenocarcinoma and prostate adenocarcinoma cells. Mice were also treated with a combination of PTU and thyroxine, which resulted in hyperthyroid levels of T(4). RESULTS: Subcutaneous lung and prostate xenografts grew significantly more slowly in hypothyroid mice treated with PTU than in euthyroid or hyperthyroid mice, regardless of treatment with PTU. Tumors grew well in groups of mice that were changed from a hypothyroid state to a euthyroid state by withdrawal of oral PTU. Administration of PTU 3 weeks after tumor inoculation also caused the tumor growth to slow significantly compared with tumors in mice that did not receive PTU. Mice that received PTU and thyroxine had tumors that grew as well as the tumors in euthyroid control animals. CONCLUSIONS: Our study indicates that human lung and prostate tumors do not grow well in hypothyroid nude mice, and that rendering these animals euthyroid has a significant impact on the growth rate of these tumors. Furthermore, in vitro and in vivo data indicated that this was not a result of an interaction of the tumor cells with PTU, but rather a result of the hypothyroid state.

American Society of Clinical Oncology 1998 update of recommended breast cancer surveillance guidelines.

OBJECTIVE: To determine an effective, evidence-based, postoperative surveillance strategy for the detection and treatment of recurrent breast cancer. Tests are recommended only if they have an impact on the outcomes specified by American Society of Clinical Oncology (ASCO) for clinical practice guidelines. POTENTIAL INTERVENTION: All tests described in the literature for postoperative monitoring were considered. In addition, the data were critically evaluated to determine the optimal frequency of monitoring. OUTCOME: Outcomes of interest include overall and disease-free survival, quality of life, toxicity reduction, and secondarily cost-effectiveness. EVIDENCE: A search was performed to determine all relevant articles published over the past 20 years on the efficacy of surveillance testing for breast cancer recurrence. These publications comprised both retrospective and prospective studies. VALUES: Levels of evidence and guideline grades were rated by a standard process. More weight was given to studies that tested a hypothesis directly relating testing to one of the primary outcomes in a randomized design. BENEFITS, HARMS, AND COSTS: The possible consequences of false-positive and -negative tests were considered in evaluating a preference for one of two tests providing similar information. Cost alone was not a determining factor. RECOMMENDATIONS: The attached guidelines and text summarize the updated recommendations of the ASCO breast cancer expert panel. Data are sufficient to recommend monthly breast self-examination, annual mammography of the preserved and contralateral breast, and a careful history and physical examination every 3 to 6 months for 3 years, then every 6 to 12 months for 2 years, then annually. Data are not sufficient to recommend routine bone scans, chest radiographs, hematologic blood counts, tumor markers (carcinoembryonic antigen, cancer antigen [CA] 15-5, and CA 27.29), liver ultrasonograms, or computed tomography scans. VALIDATION: The recommendations of the breast cancer expert panel were evaluated and supported by the ASCO Health Services Research Committee reviewers and the ASCO Board of Directors.

The effects of NSAIDs on breast cancer prognostic factors.

There are several risk factors involved in the pathogenesis of breast cancer. The role of non-steroidal anti-inflammatory drugs (NSAIDs) in the development of breast cancer has not been fully clarified. In order to investigate the impact of NSAIDs ingestion on prognostic factors of breast cancer we studied a total of 341 women with invasive carcinoma of the breast who presented between March and September 1993 to the Breast Cancer Clinic of the H. Lee Moffitt Cancer Center in Tampa, Florida. We noted that ingestion of NSAIDs was inversely associated with the size of the primary tumor, the lymph node status, and the number of involved axillary nodes. ingestion of NSAIDs may impact favorably on factors that determine the prognosis and clinical outcome of women with breast cancer.

Isolation, characterization, and distribution of a 24-kDa proteoglycan in the urine of cachectic cancer and AIDS patients.

Substantial weight loss in individuals with AIDS or cancer is associated with a poor prognosis and increased mortality. We have isolated and partially characterized a proteoglycan (named azaftig) from the urine of a cancer patient experiencing weight loss. Furthermore, we have raised a polyclonal antibody to azaftig in rabbits and developed a procedure to measure the level of this proteoglycan in urine by Western blot. We report the presence of azaftig in the urine of cancer and AIDS patients experiencing weight loss, but not in the control or weight-stable subjects. The azaftig-like immunoreactivity was present in 69.2% (9/13) of patients with weight loss, but only in 27.0% (3/11) of weight-stable cancer or AIDS patients and none of the control subjects (n = 8).

Breast cancer screening and compliance and evaluation of lesions.

It appears that screening mammography certainly is of value in women over age 50, and although controversy exists regarding screening of women under 50 years of age for breast cancer, the authors believe that this strategy is the most reasonable one for women 40 to 64 years of age at this time. Additionally, it is important for physicians to remember to encourage their patients to undergo cancer screening evaluation. Encouragement by physicians is an important factor in increasing cancer screening rates.

The need to consider survival, outcome, and expense when evaluating and treating patients with unknown primary carcinoma.

BACKGROUND: Patients who present with unknown primary carcinomas represent 10% to 15% of the patients with cancer who present to medical centers. Despite data in the literature indicating minimal success in determining the location of primary carcinomas, these patients continue to be evaluated exhaustively. Additionally, identification of the location of primary carcinomas does not often affect treatment. Clinical treatment and prognosis are only affected if a reevaluation of the pathologic findings yields a potentially curative diagnosis of an undifferentiated lymphoma, germ cell tumor, or a hormonally sensitive carcinoma. METHODS: Tumor registry files from January 1, 1990, through December 31, 1992, were retrospectively retrieved to identify adult patients who presented with metastasis of an unknown primary site at the H. Lee Moffitt Cancer Center and Research Institute, a 162-bed tertiary care cancer center specialty hospital affiliated with the University of South Florida College of Medicine, Tampa. Medical records were reviewed for age, sex, histologic findings of previous malignant growth, types and duration of symptoms, and mode of presentation. Fifty-six of the 199 patients were included in the study; 31 were men (55.4%) and 25 were women (44.6%), with ages ranging from 33 to 83 years. Diagnostic evaluations were reviewed and included data from procedures conducted at both the H. Lee Moffitt Cancer Center and at outside facilities. Diagnostic studies performed included barium swallow; intravenous pyelogram; mammogram; abdominal ultrasound; chest x-ray film; bone scan; magnetic resonance imaging; computed tomography of the head, chest, abdomen, and pelvis; laparotomy; bronchoscopy; gastroscopy; and colonoscopy. Information for the diagnostic test procedures was taken from the point of initial patient contact until the determination of metastatic disease. RESULTS: The primary cancer site was found in four (7.1%) of the 56 cases in the study and could not be classified as curable by systemic means. The average cost of diagnosis was $17,973, with 19.6% of the patients surviving for more than 1 year. The mean survival period was 8.1 months. A total of 410 tests were performed with only four tests correctly identifying the location of the primary tumor. CONCLUSIONS: Once a potentially curable malignancy has been excluded, there is little justification to support extensive diagnostic evaluation of the patient. Substantial costs are incurred and survival is often not significantly affected. It was estimated that 1.2 million new cancer cases would have occurred during 1994, with approximately 10% of these patients presenting with cancer of unknown primary origin. Based on cost assessments, investigation of these patients would exceed $1.5 billion. This clinical scenario is one where attention to outcome, clinical management, and expense should be carefully considered.

Timing of weight gain and breast cancer risk.

BACKGROUND: Obesity and body-fat distribution have been associated with the incidence of breast and endometrial cancers. It may be critical to determine if the timing of weight gain during periods of hormonal change, such as menarche, pregnancy, or menopause, has different biologic effects, especially secondary to differences in the localization of body fat during these periods. The objective of the current study was to determine if excess weight in any particular decade of life or the timing of weight gain was more significant relative to breast cancer risk. METHODS: Anthropometric, medical, and hormonal histories were obtained from 218 consecutively recruited, newly diagnosed patients with breast cancer admitted to the H. Lee Moffitt Cancer Center and Research Institute (Tampa, FL) and 436 control subjects, matched in a two to one ratio for age and menopausal status. RESULTS: A weight gain of 15 pounds or more was observed for 63.8% of the patients compared with 49.3% control subjects (P = 0.0006) from age 30 to current age. Similarly, more than 48% of cases gained more than 15 pounds from ages 16 to 30 compared with 37% (P = 0.01) of the control population. Although weight gain from age 16 to adulthood was significantly higher in patients with breast cancer at each decade when compared with control subjects, a significant and independent association between weight at age 30 (P < 0.0001) and risk of breast cancer was noted. CONCLUSION: Women who progressively gain weight from puberty to adulthood, and specifically in the third decade of life, should be considered at a higher risk for developing breast cancer.

A national profile of the use of intensive care by Medicare patients with cancer.

BACKGROUND: The broad picture of intensive care unit (ICU) outcomes and expenditures cannot be discerned from previous studies that were conducted at single hospitals and focused on narrow subsets of patients. METHODS: This study provides a comprehensive national profile of ICU used by Medicare patients with cancer. The data source was the Medicare Provider Analysis and Review file for fiscal year 1990, representing 100% of all hospital admissions that occurred within 723 ICD-9-CM codes and organized into 11 code groups. Using screening criteria, admissions were categorized as surgical (both major and minor procedures) or nonsurgical (no procedures) and with and without involvement of the ICU. The categories were compared using the following outcome variables: total hospital charges, ICU charges, ancillary charges, average length of stay, and in-hospital mortality. RESULTS: This study population accounted for nearly 800,000 admissions, of which 143,458 (18.1%) involved the use of the ICU. Actual ICU charges represented 4.9% of the $9.3 billion in total hospital charges. Intensive care unit use is associated positively with service intensity, and 73% of all the admissions involving the ICU were for major procedures. Only 2% involved no procedures. Admissions involving use of the ICU generate higher charges and longer lengths of stay than non-ICU admissions, although the differences decrease with declining treatment intensity and resource use. In-hospital mortality rates, for those cases that used the ICU, were 9.8% for major procedures, 21.2% for minor procedures, and 37.6% for cases involving no procedures. CONCLUSIONS: Contrary to the conclusions drawn from previous research, these findings suggest that patients who receive less intense service and use fewer hospital resources are more likely to die in the hospital than those who receive more care, with or without a stay in the ICU during the hospitalization. A global view of ICU use does not support the conclusion that a disproportionate share of special care resources is expended on futile care of the terminally ill or excessive monitoring of low risk patients, although these problems undoubtedly exist. Analysis of comprehensive national data regarding the use of intensive care provides a perspective that challenges some of the conclusions based on more limited studies that were conducted in single hospitals and focused on nonsurvivors or subsets of patients narrowly defined in other ways.

Visceral obesity and breast cancer risk.

BACKGROUND: The risk for breast cancer and the sex hormone abnormalities noted in breast cancer patients have been demonstrated in women with upper body fat obesity. The objective of this study was to determine if the visceral component of upper body fat obesity was correlated with breast cancer risk. METHODS: A case-control study of 40 consecutively enrolled women with breast cancer and 40 community-based age, weight, and waist circumference-matched control subjects was conducted. The areas of visceral fat, subcutaneous fat, and total fat were measured using computed tomography at the L-4 vertebral body. Calculations of relative risk for breast cancer were based on these fat compartments. RESULTS: Patients with breast cancer had a significantly greater visceral fat area (P = 0.01), visceral-to-total-fat area ratio (VT ratio) (P < 0.001) and significantly lower subcutaneous-to-visceral-fat area ratio (SV ratio) (P < 0.001) compared with the matched controls. The relative risk for breast cancer increased with increasing VT ratio (< or = 0.24 = 1.0; > 0.24 = 9.5) (P < 0.0001) and decreasing SV ratio (> or = 3.64 = 1.0; < 3.64 = 8.5) (P = 0.0002). CONCLUSIONS: Visceral obesity, as assessed by computed tomography, was a significant risk factor for breast cancer in women matched for age, weight, and waist circumference. Comparing the VT ratio for both groups, breast cancer patients had 45% more visceral fat compared with matched control subjects.

Response to the National Cancer Institute Alert. The effect of practice guidelines on two hospitals in the same medical community.

BACKGROUND: Despite the recent increase in medical practice guideline development and dissemination, physician compliance with the guidelines has often been low. Previous research has suggested that physicians at hospitals with low volumes of cases and weakened financial status were more likely to omit indicated diagnostic testing or appropriate treatment. The authors sought to determine whether differences in compliance to a widely disseminated set of guidelines would exist even among the most dominant hospital providers within the same medical community. METHODS: Two hospitals, together providing nearly half of the cancer surgery within a metropolitan area, were studied for their compliance to the May 1988 National Cancer Institute (NCI) Clinical Alert regarding adjuvant therapy after primary treatment for node negative breast cancer. A case series consecutive collection of 549 women treated at the study hospitals for 2 years before and two years after the Alert determined those patients who had received any form or combination of adjuvant therapy after primary surgical treatment (lumpectomy or modified radical mastectomy). RESULTS: Following modified radical mastectomy, for women age 50 and older, the university hospital (U) provided adjuvant therapy to a higher percentage of patients than the community hospital (C) both before (25.6% versus 4.7%, P < 0.005) and after (58.9% versus 23.2%, P < 0.001) the Alert. For women younger than 50 years of age, the two hospitals were equally likely to provide adjuvant therapy both before and after the Alert. Following lumpectomy, hospital U increased the percentage of women receiving adjuvant therapy following the Alert in women younger than 50 years of age (25-75.8%, P < 0.001) and in women age 50 and older (33.3-56.5%, P < 0.025). Hospital C provided no adjuvant therapy before or after the Alert. Preferences for breast conserving surgical treatment were significantly (P < 0.001) different with hospital U performing a higher percentage of lumpectomies than hospital C both before (50.9% versus 14.9%) and after (57.6% versus 16.8%) the Alert. CONCLUSIONS: Significant differences in compliance with practice guidelines may be found even among the most dominant hospital providers of cancer services within the same medical community. The role of the surgeon in referring patients to the oncologist greatly influences the ultimate provision of adjuvant therapy. Strategies for enhancing compliance should be considered integral to the process of guideline development.

The request for assistance in dying. The need for psychiatric consultation.

BACKGROUND: Public initiatives and legislative proposals have increased the likelihood that some states will legalize euthanasia and assisted suicide as a means of ending the suffering of patients with terminal illness. However, suggested safeguards that would guide physicians in such cases have not properly addressed the need to evaluate psychosocial factors that could motivate patients' requests for premature death. METHODS: Four cases of patients with cancer who expressed a wish to end their lives prematurely are described. These cases were evaluated with regard to mental and emotional functioning. RESULTS: Pain and suffering, organic mental disease, depression, and personality issues play significant roles in patients' requests for assistance in dying. CONCLUSION: Comprehensive psychosocial assessment is needed when evaluating requests for assistance in dying. This assessment may reveal hidden problems or conflicts that affect rational decision making, a prerequisite to informed consent for any procedure or intervention.

Variation in body fat distribution and breast cancer risk in the families of patients with breast cancer and control families.

BACKGROUND: The pattern of body fat distribution in women has been correlated with the risk of developing breast and endometrial cancer. The authors determined whether body fat distribution varied between first-degree relatives of patients with breast cancer and in cancer-free families by comparing the body fat distribution of first-degree relatives of patients with breast cancer with age and Quetelet Index-matched controls. METHODS: Fifty-six first-degree relatives of newly diagnosed patients with breast cancer were compared with 56 controls (non-cancer family members) matched for age and Quetelet Index and were studied for variation in body fat distribution. Anthropometric measurements were taken for the abdomen, thigh, suprailiac, subscapular, biceps, and triceps skinfold thickness; waist and hip circumference; weight; and height. The distribution of body measurements and derived ratios in both case and control family members were compared using the Student t test. RESULTS: A significant variation in body fat distribution occurred among first-degree relatives in breast cancer and control families. In families with a history of breast cancer, first-degree family members were found to have significantly greater waist:hip ratio (P < 0.001) compared with controls without family history matched for age and Quetelet Index. Other variables indicating upper body fat localization, such as abdomen and suprailiac skinfold were significantly greater in family members of patients with breast cancer compared with controls. CONCLUSIONS: A marked variation occurred in body fat localization among first-degree relatives of patients with breast cancer and in cancer-free families. This finding implies a variation in breast cancer risk in these families. Identifying family members with upper body fat distribution in breast cancer families would allow targeting of these individuals for energetic screening and risk factor reduction interventions.

Intensive care, survival, and expense of treating critically ill cancer patients.

OBJECTIVE: To determine the survival and factors affecting the survival of patients with solid tumors and hematologic cancers who were admitted to the intensive care unit, the time these patients spent at home (meaningful survival) before they died, and the cost per year of life gained and per year of life gained at home. DESIGN: Survival and cost-effectiveness analysis. SETTING: A tertiary-care cancer center at a university medical center. PATIENTS: Every patient admitted to the intensive care unit between July 1, 1988, and June 30, 1990, was entered into the study. This group comprised 83 patients with solid tumors and 64 patients with hematologic cancers. MAIN OUTCOME MEASURES: Factors affecting survival, such as age, sex, malignancy, length of stay in the intensive care unit, and necessity for mechanical ventilator assistance, as well as cost per year of life gained and cost per year of life gained at home. RESULTS: The only factor that significantly affected survival was the requirement for mechanically assisted ventilation for patients with hematologic cancers. More than three fourths of the patients in either group spent less than 3 months at home before dying. The cost per year of life gained for patients with solid tumors was $82,845 and for patients with hematologic cancers was $189,339. The cost per year of life gained at home was $95,142 for patients with solid tumors and $449,544 for patients with hematologic cancers. CONCLUSION: The majority of patients with solid tumors and hematologic cancers admitted to the intensive care unit die before discharge, or, if they survive the hospital admission, they spend a minimal amount of time at home before dying. This limited survival is achieved at considerable cost. Physicians who treat patients with neoplastic disease should discuss potential outcomes and the possibility of withdrawing life-supportive therapy if appropriate with the patient and family, so that a reasonable strategy can be agreed on before the initiation of therapy.

Cancer screening. Knowledge, recommendations, and practices of physicians.

BACKGROUND: Americans visit their primary care physicians several times a year. These visits provide physicians with many opportunities to reduce cancer risk in their patients by recommending periodic cancer screening. There is evidence of noncompliance among primary care physicians and their patients with regard to periodic cancer screening. Barriers to screening may be perceived by physicians and patients. RESULTS: The authors found that when physicians recommended cancer screening tests, the compliance among patients was relatively high. CONCLUSION: Primary care physicians can take the opportunity to recommend cancer screening tests during routine patient visits, and this strategy may well increase cancer screening rates in the population.

Efficacy of interactive, automated programmed instruction in nutrition education for cancer prevention.

Ninety-two undergraduates were assigned into groups to evaluate the effectiveness of interactive, computer-delivered programmed instruction for nutrition education on the topic of diet and cancer compared to traditional passive modes of instruction. Students were monitored for knowledge gains by means of a single 50-item test and an application task, using a 4-day diet record, administered 4 weeks prior to and 3 weeks after intervention. Results indicated that although subjects in the interactive group took nearly twice as long to complete the program, having the opportunity to respond to program blanks, this group produced significantly greater knowledge gains and lowered their fat intake by 41.8% compared to 26.1% reduction in fat intake in the noninteractive computer group and 18.6% in the passive prose text groups. Results suggest that interactive, computer-delivered, programmed instruction can be a very important adjunct to health care and cancer prevention programs at high schools and university settings.

Breast cancer surveillance--a cost-effective strategy.

The effectiveness of a surveillance program for breast cancer recurrence in extending survival is predicated on two assumptions: 1) most recurrences are detected at an early stage at surveillance visits; and 2) the early treatment of recurrence offers a better chance of cure or longer survival. However, the data suggest that neither of these two assumptions is correct, and that postoperative follow-up of patients with breast cancer is expensive and does not significantly extend survival.

Nutrition and cancer prevention.

Of all cancers in the United States, 35% are estimated to be caused by dietary factors and may be preventable. Diets high in fat or calories, for example, are said to be associated with five of the six most common cancers: breast, colorectal, pancreatic, prostatic, and uterine. Conversely, some dietary components such as vitamin A, in fruits and vegetables, and fiber may help protect against certain cancers. Obesity may confer a small risk of breast cancer on a woman, but women with upper body fat localization are at significantly higher risk of developing breast cancer and endometrial cancer.

Mammography screening credit card and compliance.

BACKGROUND: Screening for breast cancer using mammography has been shown to be effective in reducing mortality from breast cancer. The authors attempted to determine if use of a wallet-size plastic screening "credit" card would increase participants' compliance for subsequent mammograms when compared with traditional methods of increasing compliance. METHODS: Two hundred and twenty consecutive women, ages 40-70 years, undergoing their first screening mammography were recruited and assigned randomly to four groups receiving (1) a reminder plastic credit card (2) reminder credit card with written reminder; (3) appointment card; and (4) verbal recommendation. Return rates of the four groups were determined after 15 months. RESULTS: The return rate for subsequent mammograms was significantly higher for participants (72.4%) using the credit card than for participants (39.8%) exposed to traditional encouragement/reminders (P less than 0.0001). CONCLUSIONS: The credit card was designed to show the participant's screening anniversary, and the durability of the card may have been a factor in increasing the return rate. The use of reminder credit cards may increase compliance for periodic screening examinations for other cancers and other chronic diseases.

The effect of duration of intervention and locus of control on dietary change.

Scientific evidence supports a relationship between diet and the incidence of cancer. This finding has resulted in dietary recommendations that have been disseminated to the public. To reduce actual cancer incidence, these recommendations must lead to dietary changes among the population. We compared two brief dietary interventions with a longer term intervention and found that all three interventions produced significant reductions of calories, fat, fiber intake, and weight. The duration of the intervention did not significantly affect the magnitude of these reductions. We also found that health locus of control did not affect dietary change. Participants who initially were found to have an internal locus of control, or who subsequently internalized their locus of control during the period of observation, did not demonstrate a significant change in their intake of any of the nutrients measured when compared to participants with an external locus of control. Thus, we suggest a brief dietary intervention as a feasible and effective mechanism to produce progressive incremental dietary changes in a large population.