Ki-ras mutation and p53 overexpression predict the clinical behavior of colorectal cancer: a Southwest Oncology Group study

We assessed Ki-ras mutations by single-strand conformation polymorphism followed by DNA sequencing, p53 expression by immunohistochemistry, ploidy status, and S-phase fraction in 66 stage II and 163 stage III colon cancer patients enrolled on a randomized trial of surgery followed by observation or adjuvant levamisole or 5-fluorouracil (5FU) plus levamisole (Intergroup Trial 0035) to see whether these factors were independently associated with survival or with differential effects of adjuvant therapy. A Cox proportional hazards survival model was used to describe marker effects and therapy by marker interactions, with adjustment for the clinical covariates affecting survival. A Bonferroni adjustment was used to account for multiple testing. Mutation of the Ki-ras gene was found in 41% of the cancers and was associated with a poor prognosis in stage II but not stage III. In stage II, 7-year survival was 86% versus 58% in those with wild type versus Ki-ras mutations. After adjustment for treatment and clinical variables, the hazard ratio (HR) for death was 4.5; 95% confidence interval (CI), 1.7-12.1 (P = 0.012). p53 overexpression was found in 63% of cancers and was associated with a favorable survival in stage III but not stage II. Seven-year survival in stage III was 56% with p53 overexpression versus 43% with no p53 expression (HR, 2.2; 95% CI, 1.3-3.6; P = 0.012). Aneuploidy was more common in stage III than in stage II (66 versus 47%; P = 0.009) but was not independently related to survival in either group. The proliferative rate was greater in aneuploid than in diploid cancers but was not related to survival. There was no benefit of adjuvant therapy in stage II nor in any of the stage II subgroups defined by mutational status. In stage III, adjuvant therapy with 5FU plus levamisole improved 7-year survival in patients with wild-type Ki-ras (76 versus 44%; HR, 0.4; 95% CI, 0.2-0.8) and in those without p53 overexpression (64 versus 26%; HR, 0.3; 95% CI, 0.1-0.7). Adjuvant therapy did not benefit those with Ki-ras mutations or p53 overexpression. The effects of adjuvant therapy did not differ according to ploidy status or proliferative rate. Ki-ras mutation is a significant risk factor for death in stage II, and the absence of p53 expression is a significant risk factor for death in stage III colon cancer after adjustment for treatment and clinical covariates. Exploratory analyses suggest that patients with stage III colon cancer with wild-type Ki-ras or no p53 expression benefit from adjuvant 5FU plus levamisole, whereas those with Ki-ras mutations or p53 overexpression do not. An independent study will be required to determine whether response to adjuvant therapy in colon cancer depends on mutational status.     

The use of biochemical markers in the diagnosis of pelvic endometriosis

The aim of this study was to evaluate CA 125 II, C-reactive protein (CRP) and serum amyloid A (SAA) and anticardiolipin antibody (aCL) concentrations for the diagnosis of pelvic endometriosis. The study population consisted of 15 women without endometriosis, as confirmed by laparoscopy (group A), and 35 patients with pelvic endometriosis diagnosed by laparoscopy or laparotomy (group B). Group B patients were divided into those at stages I and II of the disease (BI/II) and those at stages III and IV (BIII/IV). Blood samples were obtained twice during the menstrual cycle: on day 1, 2 or 3 of the cycle and on day 8, 9 or 10 of the cycle. CA 125 II and CRP concentrations were higher in group III/IV patients compared with healthy controls, mainly during the first 3 days of the menstrual cycle; SAA concentrations were also higher in this group of patients compared with healthy controls, but only during the first 3 days of the menstrual cycle. Immunoglobulin (Ig) M aCL concentrations were higher in all patients with endometriosis compared with healthy controls, mainly during the first 3 days of the menstrual cycle. It is concluded that these determinations may contribute to the diagnosis and the indication of treatment for pelvic endometriosis. Determination of CA 125 II concentrations at the beginning of the menstrual cycle may aid the diagnosis of stage III and IV endometriosis. IgM aCL appears to be associated with the presence of all stages of the disease, while SAA values are elevated in severe situations. Measurement of these molecules may therefore provide a valuable tool in the diagnosis and management of endometriosis.     

Polymorphism within the cyclin D1 gene is associated with prognosis in patients with squamous cell carcinoma of the head and neck

We have examined the correlation of a frequent A/G polymorphism within exon 4 of the cyclin D1 gene (CCND1) with genetic susceptibility and clinical outcome in 384 patients with squamous cell carcinoma (SCC) of the head and neck. CCND1 genotype frequencies were similar in the cases and 191 controls. Furthermore, the CCND1 genotype was not associated with susceptibility to SCC of the larynx, pharynx, or oral cavity. The influence of the CCND1 genotype on clinical outcome was also assessed. We found no correlation between genotype and tumor size (T1-T4), the involvement of nodes at presentation, or patient age and gender. However, the distribution of CCND1 genotypes in cases with poorly differentiated tumors was significantly different to that in patients with well-/moderately differentiated tumors (P = 0.016; chi2(2) = 8.71). Homozygosity for CCND1*G (GG genotype) was associated with poorly differentiated tumors (G3). We used Cox's proportional hazards model to investigate the influence of the CCND1 genotype on disease-free interval. CCND1 GG was associated with reduced disease-free interval [P = 0.001; hazard ratio (HR) = 2.95; 95% confidence interval (CI) = 1.54-5.63]. This remained significant after correction for tumor differentiation (P = 0.013; HR = 2.34; 95% CI = 1.2-4.6) and tumor stage (P = 0.005; HR = 2.64; 95% CI = 1.34-5.19). Analysis of the data from patients with tumors at different sites showed that the CCND1 GG genotype was associated with reduced disease-free interval in laryngeal (P = 0.004; HR = 3.63; 95% CI = 1.44-8.83) and pharyngeal (P = 0.006; HR = 3.48; 95% CI = 1.43-8.46) tumors. This is the first report of an association between CCND1 polymorphism and prognosis in SCC of the head and neck. These data show that the CCND1 GG genotype is an independent prognostic indicator of disease-free interval and supports initial observations in non-small cell lung cancer, that polymorphism within CCND1 influences tumor behavior.     

The menstrual cycle and its effect on inflammatory bowel disease and irritable bowel syndrome: a prevalence study

OBJECTIVE: Female patients with bowel disease commonly report worsening symptoms in relation to the menstrual cycle. Our aim was to determine the nature of gastrointestinal symptoms correlating with the menstrual cycle in women with inflammatory and irritable bowel disease. METHODS: This was a retrospective study involving 49 women with ulcerative colitis (UC), 49 women with Crohn's disease (CD), 46 women with irritable bowel syndrome (IBS), and 90 healthy community controls. Participants were interviewed using a questionnaire including information regarding general health, medication history, pregnancy, as well as premenstrual and menstrual symptoms. Chi2 testing and logistic regression modeling were used to test for differences in frequencies between groups and for risk analysis. RESULTS: Premenstrual symptoms were reported by 93% of all women but statistically more often by patients with CD (p < 0.01). CD patients were also more likely to report increased gastrointestinal symptoms during menstruation ( < 0.01), diarrhea being the symptom reported most often. All disease groups had a cyclical pattern to their bowel habits significantly more than controls (p=0.01). Cyclical symptoms included diarrhea, abdominal pain, and constipation. Logistic regression revealed an odds ratio (OR) of 1.1 (95% CI 0.9-1.2) for experiencing bowel symptoms during the premenstrual and menstrual phases and an OR of 2.0 (95% CI 1.2-3.2) for experiencing a cyclical pattern in bowel habit changes in women with bowel disease. CONCLUSION: The prevalence of menstrually related symptoms is high, and appears to affect bowel patterns. The physiological and clinical effects of the menstrual cycle should be taken into consideration when assessing for disease activity.     

Race/ethnicity, social class, and prevalence of breast cancer prognostic biomarkers: a study of white, black, and Asian women in the San Francisco bay area

We assessed distributions of breast cancer prognostic biomarkers by race/ethnicity and socioeconomic position among paraffin-embedded tumor biopsy specimens from 135 US women (48 white women, 44 black women, 43 Asian women) diagnosed with breast cancer between 1966 and 1990. No racial/ethnic or socioeconomic differences in distributions were observed for tumor stage, lymph node involvement, estrogen, progesterone, and epidermal growth factor receptors, oncogenes such as Her2/neu and p53, cytoplasmic proteins cathepsin-D and ps2, and two indices of cell growth, Ki67 and DNA ploidy, adjusting for age at diagnosis, menopausal status, place of birth and, for racial/ethnic comparisons, working class composition of census block-group at diagnosis. Black and Asian women, however, were 3.5 times (95% confidence interval [CI] = 1.2, 10.1) and 3.7 times (95% CI = 1.3, 10.6), respectively more likely than white women to have a tumor size of > or = 20 mm, and Asian women were 3.4 times (95% CI = 1.1, 10.4) more likely than black women to be positive for androgen receptor, adjusting for these same factors. No differences in distributions by socioeconomic position were observed for these latter two tumor characteristics. These data suggest that racial/ethnic and socioeconomic disparities in breast cancer survival are unlikely to be explained solely by differential distributions of molecular breast cancer prognostic biomarkers.     

Breast carcinoma survival analysis for African American and white women in an equal-access health care system

BACKGROUND: This retrospective review of breast carcinoma cases in the Department of Defense (DoD) Central Tumor Registry evaluated differences in survival patterns between African American and white women treated in U.S. military health care facilities. The study examined the effects of age, stage of cancer, tumor size, grade, lymph node involvement, waiting time between diagnosis and first treatment, marital status, military dependent status, alcohol usage, tobacco usage, and family history of cancer. METHODS: Researchers reviewed the tumor registry records of 6577 women (5879 whites and 698 African Americans) diagnosed with breast carcinoma. The patients, ages 19-97 years, were diagnosed between 1975 and 1994. A hazard ratio (relative risk of mortality) model compared African American and white patients, adjusting for various combinations of covariates; impact of independent variables on the risk of death; prognostic factors significantly associated with survival; disease free and overall survival times; effects of ethnicity, stage, and age on survival; and trends in stage at diagnosis. A P value (2-sided) of less than 0.05 was considered statistically significant. RESULTS: After adjustment for age, the risk of death was 1.45 (95% confidence interval [CI], 1.20-1.76) times greater for African American women than for white women. Adjustment for stage reduced the risk to 1.41 (95% CI, 1.16-1.70); further adjustment for demographic variables and most clinical variables had no effect. Still, African American women treated in the military health care facilities had a better survival rate than African American women represented in the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute. In our study, the 5-year risk of death, from any cause, was 1.37 for African American women with breast carcinoma; in other words, the mortality rate for African American women was 24.77% compared with 18.08% for white women. In the latest SEER data, the 5-year relative risk of death for African American women compared with white women is 1.86. The mortality rate in SEER is 34.2% for African American women and 18.4% for white women. The survival rate for white DoD beneficiaries is comparable to that for white women in SEER. CONCLUSIONS: These observations suggest that ready access to medical facilities and the full complement of treatment options that are standard for all DoD patients improve survival rates for African American women. However, a significant unexplained difference in survival still exists between African American and white military beneficiaries.     

Bronchiolitis obliterans and no radiographic abnormalities in a patient with rheumatoid arthritis

In a case-control study, we evaluated the association of the risk of menstrual disorders with four periconceptional factors: short preceding interpregnancy interval (< 6 months), low (< or = 19 years) or high (> or = 40 years) maternal age at conception, and month of conception. We divided 919 women who had visited a fertility clinic between 1991 and 1995 into three categories: cases (with mean menstrual cycle length > or = 42 or < or = 21 days, or a variation of > or = 14 days between cycles, or amenorrhea, N = 294), controls (with cycles within a range of 25-35 days and variation < or = 7 days, N = 520), and intermediates (N = 105). A self-administrable questionnaire was mailed, asking for information about maternal reproductive history and age, and potential confounders such as smoking, exercise, and level of education. Response (77%) differed little among cases, intermediates, and controls. We found elevated risks for short pregnancy intervals [adjusted odds ratio (OR) = 2.04; 95% confidence interval (CI) = 1.04-4.02] and advanced maternal age (OR = 3.24; 95% CI = 1.27-8.30) but not for low maternal age (OR = 0.58; 95% CI = 0.11-3.14) (cases vs controls). We found similar effects for intermediates vs controls. The distribution of month of conception did not differ much from controls for both cases and intermediates. The results indicate that conception after short pregnancy intervals or at advanced maternal age increases the risk of menstrual disorders in daughters. The precise etiology is unclear, but it may lie in the quality of the oocyte at conception.     

Epidemiologic determinants of endometriosis: a hospital-based case-control study

PURPOSE: Risk factors for endometriosis were identified through data obtained from a case-control study at Brigham and Women's Hospital in Boston, Massachusetts. METHODS: Cases were 50 women with infertility-associated endometriosis. The primary control group consisted of 89 fertile women without endometriosis, and an alternate control group consisted of 47 infertile women without endometriosis. RESULTS: The risk of endometriosis was positively associated with height (OR), 2.8 per 10 cam increase; 95% confidence interval (CI), 1.4-5.6) and inversely associated with weight (OR, 0.7 per 10 kg increase; 95% CI, 0.5-1.0) and body mass index (OR, 0.7 per 5 kg/m2 increase; 95% CI, 0.4-1.1). We observed an inverse association with exercise (OR, 0.6; 95% CI, 0.3-1.5), but the effect was limited to women who exercised > or = 4 hours per week (OR, 0.4; 95% CI, 0.2-1.2). Endometriosis was not associated with either smoking or alcohol consumption. CONCLUSIONS: Our findings suggest that the fertility status of controls can strongly influence associations seen with menstrual characteristics. This study is one of few to address the issue of control selection for a case-control study of endometriosis. Specifically, potential problems encountered using fertile and infertile control women are examined and discussed.     

Menstrual cycle characteristics and history of ovulatory infertility in relation to breast cancer risk in a large cohort of US women

Menstrual cycle characteristics and ovulatory infertility were evaluated in relation to breast cancer risk among 116,678 women in the Nurses' Health Study II, a prospective cohort study of female registered nurses who were aged 25-42 years and living in 14 US states at enrollment in 1989. During 396,299 person-years of follow-up between return of the baseline questionnaire and June 1993, 251 cases of breast cancer were identified in this cohort. The multivariate relative risk (RR) associated with age at menarche > 13 years compared with age < or = 12 years was 0.66 (95% confidence interval (CI) 0.44-0.99). Short and long menstrual cycle lengths at ages 18-22 years were associated with reduced risk. Compared with menstrual cycle length 26-31 days, the multivariate relative risks (95% CIs) for more extreme cycle lengths were: < 26 days, 0.50 (0.25-0.98); 32-39 days, 0.81 (0.51-1.28); and > 39 days or too irregular for estimation of a usual cycle length, 0.41 (0.18-0.94). The multivariate relative risk associated with a history of ovulatory infertility, compared with no such history, was 0.41 (95% CI 0.18-0.93). These results are consistent with the hypothesis that reduced exposure to ovulatory menstrual cycles provides a protective effect against breast cancer.     

A prospective study of early pregnancy loss

The New York State Early Pregnancy Detection Study was a prospective study of early pregnancy loss, between implantation and menses, in 217 women attempting to become pregnant during 1989-1992. Women collected urine samples on three consecutive mornings during the late luteal phase of their menstrual cycle, for up to 12 cycles, contributing samples for 1253 menstrual cycles. Urinary human chorionic gonadotrophin (HCG), measured using an immunoradiometric assay, was the biomarker for pregnancy. We observed a range of early pregnancy loss (EPL) rates, from a low estimate of 11.0% to a high estimate of 26.9%, depending on the definition used and the subgroup analysed. Based on a definition of 3 days of HCG concentration > or = 4.00 pmol/l, 2 days > or = 5.33 pmol/l or the last day of HCG > or = 6.67 pmol/l, we identified 115 positive cycles; 95 cycles were clinically confirmed pregnancies and 20 cycles were EPL, giving an EPL rate of 17.4% [95% confidence interval (CI) 11.0-25.6]. In addition, we observed an EPL rate of 19.5% (95% CI 11.3-30.1) for samples collected within a 15 day window around menses, and a rate of 20.3% (95% CI 11.3-32.2) for samples limited to the first three menstrual cycles. Because studies use urine collection schemes other than daily sampling, the definition of pregnancy will be crucial in defining EPL.     

Association between depressive symptoms and mortality in older women. Study of Osteoporotic Fractures Research Group

BACKGROUND: Major depression is associated with increased mortality, but it is not known whether patients who report depressive symptoms have greater mortality. SUBJECTS AND METHODS: We performed a prospective cohort study of 7518 white women 67 years of age or older who were recruited from population-based listings in Baltimore, Md, Minneapolis, Minn, Portland, Ore, and the Monongahela Valley, Pa. Participants completed the Geriatric Depression Scale (short form) and were considered depressed if they reported 6 or more of 15 possible symptoms of depression. Women were followed up for an average of 6 years. If a participant died, we obtained a copy of the official death certificate and hospital records, if available, and used International Classification of Diseases, Ninth Revision, codes to classify death attributable to cardiovascular, cancer, or noncancer, noncardiovascular cause. RESULTS: Mortality during 7-year follow-up varied from 7% in women with no depressive symptoms to 17% in those with 3 to 5 symptoms to 24% in those with 6 or more symptoms of depression (P<.001). Of 473 women (6.3%) with 6 or more depressive symptoms at baseline, 24% died (111 deaths in 2610 woman-years of follow-up) compared with 11% of women who reported 5 or fewer symptoms of depression (760 deaths in 41 460 woman-years of follow-up) (P<.001). Women with 6 or more depressive symptoms had a 2-fold increased risk of death (age-adjusted hazard ratio [HR], 2.14; 95% confidence interval [CI], 1.75-2.61; P<.001) compared with those who had 5 or fewer depressive symptoms. This association remained strong after adjusting for potential confounding variables, including history of myocardial infarction, stroke, diabetes mellitus, hypertension, chronic obstructive pulmonary disease, smoking, perceived health, and cognitive function (HR, 1.47; 95% CI, 1.14-1.88; P=.003). Depressive symptoms were associated with an increased adjusted risk of death from cardiovascular diseases (HR, 1.8; 95% CI, 1.2-2.5; P= .003), and non-cancer, noncardiovascular diseases (HR, 1.8; 95% CI, 1.2-2.7; P = .01), but were not associated with deaths from cancer (HR, 1.0; 95% CI, 0.6-1.7; P=.93). CONCLUSIONS: Depressive symptoms are a significant risk factor for cardiovascular and noncancer, noncardiovascular mortality but not cancer mortality in older women. Whether depressive symptoms are a marker for, or a cause of, life-threatening conditions remains to be determined.     

Social support and survival among women with breast cancer

BACKGROUND: Two recently reported randomized trials, one among patients with advanced breast cancer and the other among patients with early stage melanoma, suggested that social support may affect survival favorably. This study assesses relationships of social support indicators with 7-year survival among women diagnosed with localized or regional stage breast cancer. METHODS: All newly diagnosed patients with surgically treated localized or regional disease in seven Quebec City hospitals in 1984 were considered for this analysis. Among 235 eligible patients, 224 (95%) participated in a home interview 3 months after surgery. This interview provided information on the use of confidants in the 3 months after surgery. Data on disease and treatment characteristics were abstracted from patients' medical records. RESULTS: Compared with women who used no confidant in the 3 months after surgery, the hazard ratio for the 7-year period was 0.61 (95% confidence interval [CI], 0.33-1.12) among those who had used at least one confidant, 0.54 (95% CI, 0.28-1.06) in women who used two or more types of confidant, and 0.51 (95% CI, 0.22-1.18) among those whose confidants included either physician or nurse. These results were adjusted for age, presence of invaded axillary lymph nodes, adjuvant radiotherapy, and adjuvant systemic therapy (hormone or chemotherapy). CONCLUSION: These results support the view that social support may be associated with longer survival among women with localized or regional stage breast cancer.     

Cigarette smoking and trisomy 21 at amniocentesis

Several studies raise the possibility that smoking during pregnancy is associated with a slightly decreased odds of trisomy 21 at birth. If it is, associations may reflect decreased incidence at conception, increased intrauterine loss (at one or several times in gestation), or both. Women (n = 13,729) undergoing prenatal diagnosis completed a questionnaire before learning karyotype results. For each women with a trisomy, up to 4 controls with chromosomally normal pregnancies, matched for age and hospital, were selected. Analyses drew on the 89 trisomy 21-control matched m-tuples in which diagnosis was by amniocentesis at 14-26 weeks. We compared the odds of smoking at last menstrual period and in the past in cases and controls. The odds of current smoking versus never smoking were decreased [adjusted odds ratio = 0.8, 95% confidence interval (CI) 0.4-1.6] and the odds of exsmoking increased (adjusted odds ratio = 1.4, 95% CI 0.9-2.4) in trisomy 21 cases. The association with current smoking was essentially unchanged when the unexposed reference group was defined as exsmokers and women who never smoked (adjusted odds ratio = 0.7, 95% CI 0.4-1.4). These results for current smoking agree well with a summary estimate based on combined studies of births. One interpretation is that at amniocentesis, as has been reported for births, current smoking is associated with a slightly decreased odds of trisomy 21. If associations at amniocentesis and birth are of equal magnitude, the explanation that observations at birth reflect increased loss in the second half of pregnancy with current smoking is unlikely to be correct.(ABSTRACT TRUNCATED AT 250 WORDS)     

Bronchopulmonary Kaposi's sarcoma in 106 HIV-1 infected patients

The objectives of this study were to describe the clinical and radiological features at presentation, and the natural history of HIV-related bronchopulmonary Kaposi's sarcoma. A retrospective review of medical records and chest radiographs was performed in 106 HIV-infected homosexual men with bronchopulmonary Kaposi's sarcoma diagnosed at bronchoscopy between September 1988 and November 1994. The majority of patients had evidence of advanced HIV disease at diagnosis (median CD4 cell count was 15 x 10(6)/l, range 0-288), and 93% had had a diagnosis of cutaneous Kaposi's sarcoma for a median duration of 11 months prior to diagnosis of their bronchopulmonary disease. The most frequent symptoms at presentation were cough (92%), dyspnoea (69%), pleuritic pain (20%), haemoptysis (13%) and wheezing (10%). The most common radiological finding in 73% of our series was of poorly defined and confluent opacities, with predominant middle and lower zone involvement. Median survival was 4 months (range 0-37 months) from diagnosis and 9 months (range 1-25) from the onset of symptoms. Treatment with either chemotherapy or radiotherapy was associated with a significantly reduced risk of death (hazards ratio (HR)=0.48, 95% CI=0.26-0.87). Factors associated with a poor survival, after adjustment for treatment effect were older age (HR=1.79, 95% CI=1.22-2.84) for each 10-year increase in age; a history of pleuritic pain (HR=2.97, 95% CI=1.39-6.32); presence of pleural effusion on X-ray (HR=2.01, 95% CI=1.13-3.59) and a prior diagnosis of cutaneous Kaposi's sarcoma (HR=1.8, 95% CI=1.00, 3.24). Bronchopulmonary Kaposi's sarcoma occurs mainly in patients with advanced HIV disease and a prior history of cutaneous disease. Survival is poor, and adverse prognostic factors include older age at diagnosis and the presence of pleural disease.     

Women's health in midlife: the influence of the menopause, social factors and health in earlier life

OBJECTIVE: To describe the health symptoms of a large representative sample of British women at age 47 years, and to examine the influence of the menopause allowing for social factors and health in earlier adult life. DESIGN: A national prospective birth cohort study. Information on health problems, menstrual cycle, use of hormone replacement therapy and life stress at 47 years was collected using a postal questionnaire. Information on health, smoking behaviour and educational attainment earlier in life had been collected at previous home visits. SETTING: England, Scotland and Wales. POPULATION: A general population sample of 1498 women, 84% of those sent a questionnaire. MAIN OUTCOME MEASURE: Twenty self-reported health symptoms over the previous 12 months. RESULTS: Women who had experienced an early natural menopause had a strongly raised risk of vasomotor symptoms (hot flushes or night sweats), sexual difficulties (vaginal dryness or difficulties with intercourse) and trouble sleeping. However, there was little or no excess risk of other somatic or psychological symptoms. In contrast, all types of symptoms were more common among women who had had a hysterectomy or were users of hormone replacement therapy. Women with the least education, stressful lives, or a previous history of poor physical and psychological health at age 36 also reported more symptoms at 47 years compared with other women, but adjustment for these factors in a logistic regression model did not affect the relations between symptoms and current menopausal status. For vasomotor symptoms, postmenopausal women had an adjusted odds ratio of 4.7 (95% CI 2.6-8.5) and perimenopausal women had an adjusted odds ratio of 2.6 (95% CI 1.9-3.5) compared with premenopausal women. Corresponding adjusted odds ratios for sexual difficulties were 3.9 (95% CI 2.1-7.1) and 2.2 (95% CI 1.4-3.2), and for trouble sleeping were 3.4 (95% CI 1.9-6.2) and 1.5 (95% CI 1.1-2.0). CONCLUSIONS: Specific symptoms were clearly associated with the natural menopause. More general health concerns were common among women in middle life, particularly among those with stressful lives, or those who had had a hysterectomy or started taking hormone replacement therapy before they were postmenopausal. Appropriate advice and support needs to be easily accessible.     

Determinants of survival in older cancer patients

BACKGROUND: We and others have previously described a number of characteristics that are associated with delays in diagnosis and increased risk for inadequate treatment of older women and men with cancer. These characteristics include poor social support, limited access to transportation, and impaired cognition. However, there is little information on how these factors influence survival of older cancer patients. PURPOSE: The purpose of the study was to determine which patient characteristics predicted survival up to 10 years after the diagnosis of cancer. METHODS: In 1984, we initiated a population-based study of men and women who were 65 years of age or older, living in a six-county area of New Mexico, and newly diagnosed with cancer. For 646 individuals with cancer of the breast (n = 188), prostate (n = 247), or colon or rectum (n = 211), we assessed patient baseline characteristics, disease stage at diagnosis, and adequacy of treatment (definitive or nondefinitive) as determinants of survival for up to 10 years following diagnosis. Multivariate survival models were used to analyze the data; all P values were two-sided. RESULTS: In multivariate analyses, we first included all patient characteristics, except the stage at diagnosis and the adequacy of treatment. In this initial analysis, the following were among variables that were significantly associated with patient survival: age, education, cancer knowledge, ethnic group, and cognitive status. When stage at diagnosis and adequacy of treatment were added to the model, both advanced stage at diagnosis (hazard ratio = 1.7 [95% confidence interval ?CI? = 1.3-2.1] for diagnosis at regional stage versus local stage; hazard ratio = 3.0 [95% CI = 2.0-4.7] for distant stage versus local stage) and inadequate treatment (hazard ratio = 1.6 [95% CI = 1.1-2.3]) were associated with poor survival. However, adding stage at diagnosis and adequacy of treatment to the analysis had little influence on the magnitude of the effect of patient characteristics on survival. In separate analyses of patient data by cancer site, receipt of nondefinitive therapy was associated with increased mortality among patients with colon/rectal cancer (hazard ratio = 7.8 [95% CI = 2.8-21.4]) and breast cancer (hazard ratio = 2.2 [95% CI = 1.1-4.3]) but not among patients with prostate cancer (hazard ratio = 1.0 [95% CI = 0.6-1.9]). CONCLUSIONS: Advanced stage at diagnosis and inadequate treatment of older cancer patients are associated with poor survival. Impaired cognition and inadequate education in elderly patients are also associated with poor survival. This decreased survival does not appear to be a consequence of known barriers to health care that are responsible for delays in diagnosis and for inadequate treatment. IMPLICATIONS: Efforts to facilitate early diagnosis and receipt of definitive treatment for cancer in older individuals may improve their survival.     

Prognostic features and treatment outcome in locoregionally advanced nasopharyngeal carcinoma following concurrent chemotherapy and radiotherapy

PURPOSE: Concurrent chemotherapy and radiotherapy (CCRT) are effective in treatment of locoregionally advanced nasopharyngeal carcinoma (NPC). However, the prognostic factors after CCRT have not been evaluated. We therefore attempt to evaluate factors that influence treatment outcomes following CCRT. METHODS AND MATERIALS: Seventy-four (5 in stage III and 69 in stage IV) patients with locoregionally advanced NPC were treated with CCRT. Radiotherapy was delivered either at 2 Gray (Gy) per fraction per day up to 70 Gy or 1.2 Gy, 2 fractions per day, up to 74.4 Gy. Concurrent chemotherapy consisted of cisplatin and 5-fluorouracil. Cox proportional-hazards model was used to analyze the prognostic factors which included age, gender, pathologic type, T, N, lactate dehydrogenase (LDH), and infiltration of the clivus. RESULTS: The primary tumor control rate at 3 years was 96.7% (95% confidence interval [CI]: 92.5-100), distant metastasis-free survival 81.1% (95% CI: 70.6-91.6), disease-free survival 77.0% (95% CI: 65.3-88.7), and overall survival 79.8% (95% CI: 69.2-90.4) with a median follow-up interval of 29 months (range 15-74 months). Cox proportional-hazards model revealed that infiltration of the clivus and serum level of LDH before treatment were the most two important factors that predict distant metastases. Infiltration of the clivus and the serum LDH level greater than 410 U/L were strongly associated with distant metastasis-free survival (p = 0.0004 and p = 0.0002, respectively). When these two risk factors were considered together, no distant metastasis was observed in 40 patients with both intact clivus and LDH < or = 410 U/L. On the contrary, 13 of the remaining 34 patients with at least one risk factor developed distant metastasis (p = 0.0001). CONCLUSION: Our study demonstrates that CCRT can improve the primary tumor control of 96.7% and disease-free survival of 77.0% at 3-year follow-up. Distant metastasis, however, is the major cause of failure. Infiltration of the clivus by the tumor and LDH greater than 410 U/L are the two independent and useful prognostic factors in patients with locoregionally advanced NPC who were treated with CCRT. Good- and poor-risk patients can be distinguished by virtue of their having both conditions.     

Metals pollution in marine sediments of the United Arab Emirates creeks along the Arabian Gulf shoreline

In order to evaluate the association between seropositivity for herpes simplex virus (type 1 and type 2) and cervical intraepithelial neoplacia (CIN), we analysed data from a population-based case-control study of CIN grade II-III which included Norwegian women aged 20 to 44 years, 94 cases and 228 controls. Our objectives were to determine if HSV-1 and/or HSV-2 seropositivity were independent risk factors for CIN, taking human papillomavirus exposure into account, and to elucidate the combined effect of HPV positivity and seropositivity for HSV In logistic regression analyses, the association between HSV-2 or HSV-1 seropositivity and CIN II-III was not explained by HPV (adjusted OR 3.0; 95%, CI 1.3-7.2 and adjusted OR 3.3; 95% CI 1.3-8.4, respectively). In analyses restricted to HPV-16 DNA-positive individuals, seropositivity for HSV-2 increased the risk of CIN (OR 11.1; 95% CI 1.2-105.7), whereas HSV-1 seropositivity was not significantly associated with CIN. In women positive for other HPV types, only HSV-1 seropositivity was associated with CIN (OR 8.5; 95% CI 1.3-55.8). In analyses of the HPV-16-seropositive individuals, neither HSV-1 nor HSV-2 seropositivity was associated with CIN. Compared to the reference group of jointly unexposed subjects, the HPV-16 DNA-positive women who were anti-HSV-2 negative had an increased risk of CIN (OR 29; 95% CI 12-67), whereas the risk in women who were both HPV-16 DNA-positive and HSV-2 was OR=247 (95% CI 31-1996). The estimate of interaction was strong, but did not reach significance, and our findings may suggest that the combined effect of the two viruses is of aetiological importance in cervical carcinogenesis. Furthermore, the results indicate that HPV DNA positivity is not sufficient to explain the sexual behaviour-associated risk of cervical neoplasia and that further studies on the role of genital HSV (type 1 as well as type 2) and other STDs are warranted.     

Tumor-associated antigens as prognostic factors for recurrence in 382 patients with primary transitional cell carcinoma of the bladder

This prospective study was designed to assess the prognostic value of tumor-associated antigens, designated 19A211, M344, T138, and T43, with respect to recurrence of primary superficial bladder cancer. Between September 1990 and April 1992, all patients with primary superficial bladder tumors treated by endoscopic resection in 15 participating hospitals were enrolled. Immunostaining for 19A211 and M344 was performed on paraffin-embedded material, and for T43 and T138 on frozen tissue. Antigenic expression was evaluated blindly by a single pathologist. Patients were followed up with the standard schedule of control cystoscopies. Cox regression was used to estimate hazard ratios (HRs) for first recurrence, and Poisson regression was used to estimate recurrence rate ratios and tumor rate ratios adjusted for primary tumor characteristics. By March 1994, 2254 follow-up cystoscopies had been performed on 368 of the 382 study patients, and tumor recurrence was detected in 55.7% of patients. Positivity to 19A211 was detected in 90% of primary tumors, its expression being associated with a decrease in first recurrence hazard ]HR, 0.65; 95% confidence interval (CI), 0.42-1.03] and in recurrence rate (recurrence rate ratio, 0.70; 95% CI, 0.53-0.92). Positivity to T138 was detected in 15% of tumors, and its expression was associated with an increase in first recurrence hazard (HR, 1.43; 95% CI, 0.92-2.22) and in recurrence rate (recurrence rate ratio, 1.31; 95% CI, 1.00-1.72). Positivity to M344 was detected in 71% of tumors, and its expression was associated with an increase in tumor rate (tumor rate ratio, 1.77; 95% CI, 1.41-1.97). T43 expression was not associated with recurrence end points. In conclusion, recurrence of superficial bladder cancer was associated with antigenic expression of 19A211, T138, and M344, independently of primary tumor characteristics.     

A new methodology for the preoperative localization of occult insulinomas

This study describes clinical aspects, treatment, and survival times of 52 dogs with hemangiosarcoma of the spleen, presented at the Department of Veterinary Surgery, University of Munich, Germany. Depending on the dissemination of the disease the dogs were assigned to three clinical stages: 10 dogs were in stage I (tumor confined to the spleen without metastasis), 18 in stage II (tumor confined to the spleen or ruptured, with or without lymph node involvement but without distant metastasis) and 24 in stage III (with distant metastasis). Dogs in stage I displayed mild and nonspecific symptoms. In stage II and II, half of the patients were presented in shock or collapse after an acute rupture of the tumor. Sonographic examination was found superior in diagnosing splenic neoplasia when compared to radiography. Pronounced laboratory abnormalities were present mainly in patients in stages II or III with anemia, leucocytosis, thrombocytopenia and prolonged bleeding times predominating. Survival times following splenectomy were very variable. The median survival time was 100 days. Because of the high standard deviaton there was no statistically significant difference in survival times between animals of different stages.