Cancer health effects of pesticides: systematic review.

OBJECTIVE: To review literature documenting associations between pesticide use and cancer. DATA SOURCES: We searched MEDLINE, PreMedline, CancerLit, and LILACS to find studies published between 1992 and 2003 on non-Hodgkin lymphoma, leukemia, and 8 solid-tumour cancers: brain, breast, kidney, lung, ovarian, pancreatic, prostate, and stomach cancer. STUDY SELECTION: Each title and abstract was assessed for relevance; disagreements among reviewers were resolved by consensus. Studies were assessed by a team of 2 trained reviewers and rated based on methodologic quality according to a 5-page assessment tool and a global assessment scale. Studies rated below a global score of 4 out of 7 were excluded. SYNTHESIS: Most studies on non-Hodgkin lymphoma and leukemia showed positive associations with pesticide exposure. Some showed dose-response relationships, and a few were able to identify specific pesticides. Children's and pregnant women's exposure to pesticides was positively associated with the cancers studied in some studies, as was parents' exposure to pesticides at work. Many studies showed positive associations between pesticide exposure and solid tumours. The most consistent associations were found for brain and prostate cancer. An association was also found between kidney cancer in children and their parents' exposure to pesticides at work. These associations were most consistent for high and prolonged exposures. Specific weaknesses and inherent limitations in epidemiologic studies were noted, particularly around ascertaining whether and how much exposure had taken place. CONCLUSION: Our findings support attempts to reduce exposure to pesticides. Reductions are likely best achieved through decreasing pesticide use for cosmetic (non-commercial) purposes (where children might be exposed) and on the job.

Prognostic significance of baseline fatigue for overall survival: A patient-level meta-analysis of 43 oncology clinical trials with 3915 patients.

We have previously identified a single-item measure for baseline overall quality of life (QOL) as a strong prognostic factor for survival, and that fatigue was an important component of patient QOL. To explore whether patient-reported fatigue was supplemental or redundant to the prognostic information of overall QOL, we performed a patient-level pooled analysis of 43 North Central Cancer Treatment Group (NCCTG) and Mayo Clinic Cancer Center (MCCC) oncology clinical trials assessing the effect of baseline fatigue on overall survival (OS). 3,915 patients participating in 43 trials provided data at baseline for fatigue on a single-item 0-100 point scale. OS was tested for association with clinically deficient fatigue (CDF, score 0-50, n = 1,497) versus not clinically deficient fatigue (nCDF, score 51-100, n = 2,418). We explored whether fatigue contributed to overall survival in the presence of performance status and overall QOL. We used Cox proportional hazards models that adjusted for the effects of overall QOL, performance score, race, disease site, age and gender. Baseline fatigue was a strong predictor of OS for the entire patient cohort (CDF vs. nCDF: 31.5 months vs > 83.9 months, p < 0.0001). The effect sizes of fatigue on survival were more variable across different disease sites than was seen for overall QOL (GI, esophageal, head and neck, prostate, lung, breast and others). After controlling for covariates, including performance status and overall QOL, baseline fatigue remained a strong prognostic factor in multivariate models (CDF vs. nCDF: HR = 1.23, p = 0.02). Baseline fatigue is a strong and independent prognostic factor for OS over and above performance status (PS) and overall QOL in a wide variety of oncology patient populations. Single-item measures of overall QOL and fatigue can help to identify vulnerable subpopulations among cancer patients. We recommend these single-item measures for routine inclusion as a stratification factor or key covariate in the design and analysis of oncology treatment trials.

Antinuclear, antinucleolar, and anticytoplasmic antibodies in patients with malignant melanoma.

Immunofluorescence was used to examine antibodies to cellular antigens in the sera of patients with malignant melanoma. Sera from 60 melanoma patients and from 33 control individuals (13 normal subjects and 20 disease controls) were studied. Ninety % of the melanoma sera were found to have antinuclear antibodies when epithelial cell lines or melanoma lines were used as substrates for their detection, compared to 18% in the control group. Antinucleolar antibodies and anticytoplasmic antibodies were present in 32 and 17%, respectively, in malignant melanoma but none in the controls. Antinuclear and antinucleolar antibodies could be classified into different types according to different patterns of staining and susceptibility of antigens to digestion with DNase, RNase, and trypsin. Certain types of antibodies, such as those showing granular nuclear staining, appeared to be associated with less advanced stages of malignant melanoma, whereas those showing nucleolar and large speckled nuclear staining were associated with more advanced stages of the disease.

QOL and Survival Comparisons by Race in Oncology Clinical Trials.

BACKGROUND: Significant efforts have been made to increase access and accrual to clinical trials for minority cancer patients (MP). This meta-analysis looked for differences in survival and baseline quality of life (QOL) between MP and non-minority cancer patients (NMP). MATERIALS AND METHODS: Baseline QOL and overall survival times from 47 clinical trials (6513 patients) conducted at Mayo Clinic Cancer Center/North Central Cancer Treatment Group were utilized. Assessments included Uniscale, Linear Analogue Self Assessment, Symptom Distress Scale (SDS), Profile of Mood States and Functional Assessment of Cancer Therapy - General, each transformed into a 0-100 scale with higher scores indicating better outcomes. This transformation involves subtracting the lowest possible value from the assessment, dividing by the range of the scale (the maximum minus the minimum), and multiplying by 100. Analyses included Fisher's Exact tests, linear regression, Kaplan-Meier curves, and Cox proportional hazards models. RESULTS: Eight percent of patients self-reported as MP (0.45% American Indian/Alaskan Native, 0.7% Asian, 5% Black/African American, 1.5% Hispanic, 0.1% Native Hawaiian and 0.3% Other). MP had no meaningful deficits relative to non-MP in overall QOL but were slightly worse on FACT-G total score, physical, social/family, functional, and SDS nausea severity. MP with lung, neurological or GI cancers had significantly worse mean scores in nausea (58 vs. 69), sleep problems (34 vs. 54); emotional (53 vs. 74); and social/family (60 vs. 67), respectively. Regression models confirmed these results. After adjusting for disease site, there were no significant differences in survival. CONCLUSION: MP on these clinical trials indicated small deficits in physical, social, and emotional subscales at baseline compared to NMP. Within cancer sites, MP experienced large deficits for selected QOL domains that bear further attention.

Phase III randomized double-blind study to evaluate the efficacy of a polycarbophil-based vaginal moisturizer in women with breast cancer.

PURPOSE: Vaginal dryness and dyspareunia are significant estrogen-depletion symptoms that affect many breast cancer survivors. The present trial was developed to evaluate the nonhormonal vaginal lubricating preparation, Replens, for alleviating these symptoms. MATERIALS AND METHODS: A double-blind, crossover, randomized clinical trial was developed. Patients received 4 weeks of Replens (Columbia Research Laboratories, Rockville Centre, NY) followed by a 1-week washout period followed by 4 weeks of a placebo lubricating product, or vice versa. Weekly patient-completed diaries were used for measuring efficacies and toxicities of therapy. RESULTS: The 45 assessable patients provided well-balanced treatment groups. During the first 4 weeks, average vaginal dryness decreased by 62% and 64% in the placebo and Replens groups, respectively (P = .3). Average dyspareunia scores also improved by 41% and 60%, respectively (P = .05). Crossover analysis indicated that the bulk of the beneficial effects appeared within the first 2 weeks of the first treatment and remained constant thereafter. Both treatments were relatively well tolerated. CONCLUSION: Both Replens and the placebo appear to substantially ameliorate vaginal dryness and dyspareunia in breast cancer survivors.

Palliative care and hospice programs.

Palliative care and hospice programs are points on the continuum of comprehensive patient care. Unfortunately, provision of care for terminally ill patients is suboptimal. There are many new approaches to improving the skills of all physicians to fulfill the needs of patients, including better education for house staff, "train-the-trainers" programs for physicians in practice, research into methods of symptom control, and better access to established hospice programs. This review covers the history, current status, and practical suggestions for improving palliative care and hospice programs in primary care settings.

Calciphylaxis associated with cholangiocarcinoma treated with low-molecular-weight heparin and vitamin K.

Calciphylaxis is a rare disorder of small-vessel calcification and cutaneous infarction associated with chronic renal failure. Rare cases of calciphylaxis not associated with chronic renal failure have been reported with breast cancer, hyperparathyroidism, and alcoholic cirrhosis. To our knowledge, we report the first case of calciphylaxis without chronic renal failure associated with cholangiocarcinoma and the first attempt to treat calciphylaxis with vitamin K. A 56-year-old woman presented with necrotic leg ulceration. She was treated initially with low-molecular-weight heparin, with no effect. A coagulation work-up showed vitamin K deficiency. During vitamin K therapy, the patient had fulminant progression of the calciphylaxis. She died, and an autopsy showed metastatic cholangiocarcinoma. Thrombosis and protein C deficiency have been implicated in the pathophysiology of calciphylaxis. Functional protein C deficiency may be one of several factors contributing to the development of calciphylaxis. Vitamin K therapy was ineffective in our patient and may have been detrimental.

The erosive potential of some alcopops using bovine enamel: an in vitro study.

OBJECTIVES: Alcoholic soft drinks have become increasingly popular and have high concentrations of citric acid and alcohol so might have the potential to cause dental erosion. This study aimed to investigate the erosive potential of alcopops on bovine enamel in vitro. METHODS: Six bovine upper incisors were prepared and sectioned to give six slabs per tooth, 4mm x 4mm each. Each slab was covered with nail varnish, leaving an exposed window (2mm x 2mm). Samples were immersed in 20ml of each of the test solutions for 20min, 1h, and 24h under gentle agitation (100rpm). Enamel surface loss was determined using Quantitative Laser Fluorescence (QLF), Non-contact Profilometry (NCP) and Transverse Microradiography (TMR). RESULTS: Enamel loss occurred with all test drinks and the positive control (p<0.05), and the depth of lesion correlated with pH and time. No significant difference was observed between 20min and 1h exposure, although both times had significantly (p<0.05) greater erosion when compared with baseline. Within each alcopops group significant erosion had occurred at 24h exposure compared with the baseline and previous times. CONCLUSION: All the tested alcopops resulted in significant enamel loss at 24h (p<0.001) with direct correlation between degree of enamel loss and both pH and increasing exposure time.

Phase II trial of oral vinorelbine for the treatment of metastatic breast cancer in patients > or = 65 years of age: an NCCTG study.

BACKGROUND: A one-stage phase II trial was conducted to assess the tumor response rate and toxicity profile of single agent oral vinorelbine as first or second-line chemotherapy for women at least 65 years of age with metastatic breast cancer. PATIENTS AND METHODS: Twenty-five patients with metastatic breast cancer aged > or = 65 years of age were enrolled to receive oral vinorelbine on a weekly basis. The oral vinorelbine was given at 60 mg/m2 weekly for the first four doses and was increased to 70 mg/m2 for the subsequent administrations if there was no grade 4 neutropenia or no more than one episode of grade 3 neutropenia. Therapy was continued until progression or intolerable toxicity. RESULTS: Twenty-five patients were included and evaluable for analysis. One patient (4%) achieved a partial response (PR) that lasted for more than 13 months. Two additional patients remained stable for at least 6 months for a clinical benefit rate (PR + stable disease) of 12%. The 1-year survival rate was estimated to be 48% (95% CI 30% to 74.5%). Median time to progression was estimated to be 4.7 months (95% CI 2.0-5.5 months) and the 9-month disease progression-free rate was estimated to be 8% (95% CI 30.9% to 74.5%). The treatment was fairly well tolerated with grade 3 neutropenia in 12.5%, fatigue in 12.5% of the patients, and grade 2 neuromotor and neurosensory toxicities in 12.5% and 8.3%, respectively. CONCLUSION: Oral vinorelbine as a single agent at these dose and schedule in this population of women > or = 65 years is well tolerated but has a low level of objective efficacy for the treatment of metastatic breast cancer.

Cancer-related disparities: weathering the perfect storm through comprehensive cancer control approaches.

During the last two decades extraordinary progress in developing and using effective cancer prevention strategies, early detection interventions, and cancer treatments has been made. This progress has resulted in an overall decline in mortality rates for all cancers combined. Nonetheless, cancer is the second most common cause of death in the United States. Although cancer is a diagnosis that many survive, cancer experiences across populations may vary considerably. These differences in cancer experiences have created an unequal disease burden that presents distinct professional and moral challenges to our nation. Many cancer control plans suggest specific strategies that prioritize eliminating cancer-related disparities. This article describes certain cancer-related disparities in the United States and gives several examples of how communities and disenfranchised populations are using comprehensive cancer control (CCC) approaches to eliminate these disparities. One or two interventions are highlighted in each example.

The potential impact of cancer survivors on Native American cancer prevention and treatment.

Cancer has recently become a major health problem for American Indians and Alaska Natives. Surveillance, Epidemiology, and End Results data showed that Native American survival rates at 1, 3, and 5 years from cancer diagnosis are the poorest of any minority population studied. The causes for this finding are multifactorial and include a lack of awareness of cancer risks and symptoms, fatalism, and lack of access to screening services. Cancer survivors in native communities can be invaluable resources to educate others, raise cancer awareness, and most importantly prove that cancer is not always fatal.

Migration patterns and breast carcinoma.

BACKGROUND: Many American Indian and Alaska Native women have lower incidence rates of breast carcinoma than other racial/ethnic groups in the United States. The rates in most areas, however, have increased in recent years. The author reviews the migration patterns and effects that might contribute to this change. METHODS: A review of the literature on migration and breast carcinoma incidence was conducted. RESULTS: Migration significantly impacts on breast carcinoma incidence in all groups of women studied. CONCLUSIONS: Research must be designed that will explore the components of host, life-styles, and environment on breast carcinoma rates in American Indian and Alaska Native women to elucidate mechanisms of breast carcinoma etiology.

Native women and cancer.

Literature regarding cancer patterns in American Indians and Alaska Native women is reviewed and attention is paid to promising research initiatives to improve cancer prevention and control as well as approaches to enhance exchange of knowledge through a new national resource center. Lung, breast, and colorectal cancer are the leading cause of cancer deaths in American Indians and Alaska Native women. There continues to be a disproportionate death rate from cervical cancer. Enhanced availability for breast and cervical cancer screening in conjunction with community education is showing promising trends toward reversing the patterns of late diagnosis. Communities can benefit from sharing their collective resources in a new national resource center called "Native C.I.R.C.L.E." housed in the Mayo Cancer Center.

Acute renal failure following arteriography in a patient with polyarteritis nodosa.

The use of radioiodinated contrast material has become an important diagnostic aid. However, certain categories of patients appear to be at risk for development of oliguric acute renal failure after receiving radiocontrast media. In the article, a patient with polyarteritis nodosa is presented who had development of oliguric azotemia after angiography; the loss in renal function was largely irreversible. The course of this patient suggests that active vasculitis, even in the presence of an inactive urine sediment, may be an additional risk factor for development of acute renal failure when considering the use of radioiodinated contrast material.

Learning and memory in the mosquito Aedes aegypti shown by conditioning against oviposition deterrence.

Oviposition site choice by female mosquitoes, Aedes aegypti (L) (Diptera: Culicidae), was affected by rearing them in water treated with 0.016% of the repellent Mozaway trade mark containing citronella and neem. Given a choice between a bowl of repellent-treated and a bowl of untreated water, Ae. aegypti reared in untreated water strongly preferred to oviposit on the clean water (93-98%) instead of repellent-treated water. This demonstrates effective deterrence of oviposition by dilute Mozaway trade mark. Those reared in repellent-treated water were less deterred: 38-46% of their eggs were laid on the repellent-treated water and 54-62% on the clean water. Evidently the female mosquitoes reared in repellent-treated water were conditioned against oviposition site deterrence, as shown when choice tests were conducted 6 days post-emergence from the treated water. This demonstrates learning and memory in the mosquito Ae. aegypti, with implications for dengue vector surveillance and control.

Isolation and characterization of a cryptic plasmid from mesophilic aeromonads: potential as a cloning vector.

A 2.6 kb covalently closed circular plasmid has been isolated from clinical and environmental isolates of Aeromonas sobria and A. hydrophila. The possibility that the plasmid carries genetic determinants that mediate resistance to a variety of anti-microbial agents has been eliminated. The plasmid is stable at approximately 20-25 copies per chromosome equivalent which, together with its relatively small size and the presence of unique restriction sites, makes it a good candidate for development as a cloning vector.

Low national breast and cervical cancer-screening rates in American Indian and Alaska Native women with diabetes.

BACKGROUND: The cervical cancer mortality rate for American Indian and Alaska Native women is twice that of all races in the United States. To date the only published national breast and cervical cancer-screening rates for American Indian and Alaska Native women are based on self-reported data. When the Indian Health Service (IHS) conducts an annual audit on patients with diabetes, it includes cancer screening. This observational study presents national breast and cervical cancer-screening rates for American Indian and Alaska Native women with diabetes. METHODS: Cancer-screening rates were extracted from the 1995 diabetic audit for the 12 IHS areas. These rates were compared with rates for women without diabetes of the same age, 50 to 69 years, by chart review, at four IHS hospitals in the Aberdeen IHS area. RESULTS: Screening rates for women with diabetes in the 12 areas varied: mammogram (ever) 35% to 78%; clinical breast examination (last year) 28% to 70%, and Papanicolaou smear (last year) 26% to 69%. The Aberdeen IHS area women with diabetes had 51% more clinic visits per year than women without diabetes, but the groups had similar screening rates. CONCLUSION: Cancer-screening rates for American Indian and Alaska Native women vary by region. In the Aberdeen IHS area, women with diabetes had more visits (missed opportunities) but similar screening rates as women without diabetes. The diabetic audit could be used to monitor national IHS cancer-screening trends for women with diabetes and in the Aberdeen IHS area for all women aged 50 to 69 years.

Malignant melanoma--profile of an epidemic.

Cutaneous malignant melanoma is occurring in epidemic proportions in the United States. To provide a profile of persons at risk and the epidemiologic features of malignant melanoma, we reviewed the records of 325 patients with cutaneous malignant melanoma seen at the University of Colorado Health Sciences Center between 1973 and 1983. Most patients had fair skin, brown or blonde hair, blue or green eyes, and had difficulty in suntanning. The majority of melanomas (72%) developed in preexisting nevi. In women, melanomas were most common on the extremities, and in men they occurred most frequently on the trunk, head or neck. The most frequently noted depth of invasion was Clark's level IV. At diagnosis, most of the patients (77%) were at stage I. We conclude that malignant melanoma constitutes a major disease problem in the western United States that is largely preventable with appropriate physician and patient education.