Long-term follow-up for brain tumor development after childhood exposure to ionizing radiation for tinea capitis.

Ionizing radiation is an established risk factor for brain tumors, yet quantitative information on the long-term risk of different types of brain tumors is sparse. Our aims were to assess the risk of radiation-induced malignant brain tumors and benign meningiomas after childhood exposure and to investigate the role of potential modifiers of that risk. The study population included 10,834 individuals who were treated for tinea capitis with X rays in the 1950s and two matched nonirradiated groups, comprising population and sibling comparison groups. The mean estimated radiation dose to the brain was 1.5 Gy. Survival analysis using Poisson regression was performed to estimate the excess relative and absolute risks (ERR, EAR) for brain tumors. After a median follow-up of 40 years, an ERR/Gy of 4.63 and 1.98 (95% CI = 2.43-9.12 and 0.73-4.69) and an EAR/Gy per 10(4) PY of 0.48 and 0.31 (95% CI = 0.28-0.73 and 0.12-0.53) were observed for benign meningiomas and malignant brain tumors, respectively. The risk of both types of tumors was positively associated with dose. The estimated ERR/Gy for malignant brain tumors decreased with increasing age at irradiation from 3.56 to 0.47 (P = 0.037), while no trend with age was seen for benign meningiomas. The ERR for both types of tumor remains elevated at 30-plus years after exposure.

Ret/PTC activation in benign and malignant thyroid tumors arising in a population exposed to low-dose external-beam irradiation in childhood.

Ionizing radiation is the strongest risk factor known for the development of thyroid neoplasia. Although ret/PTC rearrangements have been identified in both spontaneous and radiation-induced papillary thyroid cancer, they seem more frequent among radiation-associated tumors. We studied the frequency of ret/PTC activation in a group of sporadic and radiation-induced thyroid carcinomas (n = 49) and adenomas (n = 13) among 44 individuals treated for Tinea Capitis with low-dose external irradiation as well as in 18 nonirradiated subjects. Total RNA recovered from paraffin-embedded thyroid cancer surgical specimens was analyzed for ret/PTC 1, 2, and 3 mutations using RT-PCR with Southern blotting to maximize detection sensitivity. Ret/PTC rearrangements were identified in 42.9% of thyroid carcinoma and 46.2% of adenoma subjects. Among the positive carcinoma specimens, three were follicular carcinomas. Ret/PTC 1, the predominant rearrangement, was more prevalent in nonirradiated compared with irradiated carcinomas (66.7 vs. 27.0%; P = 0.04). Ret/PTC activation was associated with male gender. The strengths of this study included analysis of age-, gender-, and ethnicity-matched groups; molecular analysis using two techniques; and a complete blinding of laboratory analysis from clinical features. The differences seen between these and other published results may be related to differences in radiation doses to the thyroid, latency period between time of radiation exposure and development of clinically apparent thyroid cancer, and ethnic background of the study populations.

The sequence of vessel interruption during lobectomy for non-small cell lung cancer: is it indeed important?

OBJECTIVE: During pulmonary resections for non-small cell lung cancer, the pulmonary vein is traditionally interrupted first to prevent seeding of malignant cells and consequently decrease metastatic implantation. This hypothesis was never confirmed scientifically. The aim of the present study was to determine whether the sequence of vessel interruption during lobectomy (lobar vein or lobar artery first) affects disease recurrence. METHODS: A historical prospective study was performed of 279 consecutive patients with complete follow-up, who survived lobectomy for non-small cell lung cancer during 1992 to 1998, in a single center. Pre-, intra-, and postoperative variables were collected from the medical records; recurrence and vital status were obtained from follow-up files, central population registry, and personal confirmation, updated to December 2000. Comparison of recurrence rates by sequence of ligation and other independent variables was assessed by univariate and multivariate logistic regression analyses. RESULTS: A total of 133 patients (48%) had vein interruption before the artery (V-first) and 146 (52%) had artery interruption first (A-first). The distribution of demographic, clinical, and other characteristics was similar between the 2 groups, except for the operated side and performing surgeons. The morbidity, blood requirement, and length of stay were equal for both groups. The total recurrence rate (A-first, 53%; V-first, 51%) was similar. Multivariate analysis (controlling for the effect of the performing surgeon) revealed elevated risk for recurrence among patients with high disease stage (odds ratio = 2.54), male gender (odds ratio = 1.59), intraoperative lung manipulation (odds ratio = 2.72), and blood transfusion (odds ratio = 1.49). Sequence of vessel interruption was not found as a risk factor for recurrence (odds ratio = 1.29; 95% 0.73 to 2.29, P =.4). CONCLUSIONS: Our results did not show that sequence of vessel interruption during lobectomy plays a role in tumor recurrence. A prospective study with randomization in selection of method as well as surgeons for each patient is needed to confirm these results.

Cancer incidence in a cohort of infertile women who underwent in vitro fertilization.

OBJECTIVE: To assess whether ovarian hyperstimulation and IVF increase the risk for cancer. DESIGN: Historical cohort analysis. SETTING; IVF units of two medical centers in Israel. PATIENT(S): Five thousand twenty-six women who underwent IVF between 1981 and 1992. INTERVENTION(S); Cancer incidence rates were determined through linkage to the National Cancer Registry and were compared with expected rates with respect to age, sex, and place of birth. MAIN OUTCOME MEASURE(S): Development of cancer. RESULT(S): Twenty-seven cases of cancer were observed, and 35.6 were expected (standardized incidence ratio, 0.76 [95% CI, 0.50-1.10]). Eleven cases of breast cancer were observed, whereas 15.86 were expected (standardized incidence ratio, 0.69 [95% CI, 0.46-1.66]). One case of ovarian cancer and 1 case of cervical cancer were observed, compared with 1.74 and 1.73 cases expected, respectively. The type of infertility, number of IVF cycles, and treatment outcome did not significantly affect risk for cancer. CONCLUSION(S): In a cohort of women treated with IVF, no excess risk for cancer was noted.

Depressive Symptoms Among Community-Dwelling Oldest-Old Residents in Israel.

The authors examined the rate and correlates of depressive symptoms among community-dwelling oldest-old citizens in Israel with a sample of about 1,200 Jewish Israelis age 75-94. The estimated national rate of depressive symptoms was 43.5%. Significantly higher rates of depressive symptoms were found in women (52%, vs. 29.5% for men) and those of low educational level, low income, and Middle Eastern or North African origin. Having more depressive symptoms was associated with 1) all measures of impaired health status; 2) the psychosocial factors of living alone or with a nonspouse, having no available caretaker, and social and physical inactivity; 3) the following health behavior and habits: poor sleep, skipping meals, sexual inactivity, and drinking no alcohol; and 4) traumatic life events and immigration after age 20. The rate of depressive symptoms is relatively high among oldest-old citizens in Israel, possibly because of the immigrant nature of this population.

Tracing long-term effects of early trauma: a broad-scope view of Holocaust survivors in late life.

This study addressed long-term effects of extreme trauma among Holocaust survivors (N = 126) in an older (75-94 years) sample of the Israeli Jewish population. Survivors were compared with European-descent groups that had immigrated either before World War II (n = 206) or after (n = 145). Participants in the latter group had had Holocaust-related life histories but did not consider themselves survivors. Controlling for sociodemographics, the results indicated that survivors fared worse than prewar immigrants in certain psychosocial domains, mainly cumulative distress and activity, rather than in health-related ones. Survivors and postwar immigrant comparisons had almost no differences. The study highlights the need for a wide view of functioning facets and comparison groups in delineating late posttraumatic effects.

Beyond keeping active: concomitants of being a volunteer in old-old age.

This study examines concomitants of volunteering in the context of other lifestyle activities. Investigating formal volunteering in old-old age, the authors analyzed data of 148 volunteers versus 1,195 nonvolunteers in a national sample of the Israeli Jewish population aged 75-94. As hypothesized, being a volunteer related (whether as a cause or effect) to more positive functioning on psychosocial markers and prospectively resulted in reduced mortality risk even when other activity outlets (physical activity, everyday activities, having a hobby) were controlled. These findings suggest that the benefits of volunteering in late life are not reducible to those of other activities.

Gender differences in the self-rated health-mortality association: is it poor self-rated health that predicts mortality or excellent self-rated health that predicts survival?

PURPOSE: This study investigates gender differences in the association between self-rated health (SRH) and mortality. This association has been well-documented, but findings regarding gender differences are inconsistent. The specific objectives were (a) to examine these differences in a short and a long time frame, (b) to examine these differences among old and old-old people, and (c) to address the question of whether this association is based on the accuracy of poor SRH as a predictor of future decline, and/or of better SRH as a predictor of longevity. DESIGN AND METHODS: The study is based on an Israeli nationally representative sample of 622 women and 730 men who were interviewed about their SRH, as well as sociodemographic information and other measures of health, physical functioning, cognitive status, and depression. RESULTS: For both genders, SRH was associated only with shorter term mortality (within the next 4 years) and not with longer-term mortality (9 years of follow-up). This association was strongest among the old (ages 75-84) women, compared with the old men and with the old-old (85-94) women and men. A possible explanation may be related to differences in the accuracy of excellent SRH at very old age. IMPLICATIONS: The SRH-mortality association may differ among age and gender groups. Identifying the conditions under which it is more accurate will enable researchers and practitioners to know when it can be utilized. It is important to assess differences in the accuracy of poor SRH as well as of excellent SRH as predictors of future health outcomes.

The effect of a communal lifestyle on depressive symptoms in late life.

OBJECTIVES: This study compares depression levels among lifetime kibbutz members (n = 525) and old-age kibbutz residents (n = 366) with a comparable national sample (n = 412) and assesses the relationship between depression and individual differences related to lifetime in a kibbutz (e.g., health) and those related to current living conditions (e.g., social network). METHODS: The analysis is based on data from the Cross-Sectional and Longitudinal Aging Study conducted in Israel between 1989 and 1992 and the follow-up during 1993 and 1994. RESULTS: The findings indicate significantly lower depressive symptomatology among women, but not among men, residing in kibbutz communities. The women's lower level of depressive symptoms appears to be a result of better physical and mental functioning among kibbutz members and of such favorable lifestyle characteristics as frequent contact with their children among old-age kibbutz residents. DISCUSSION: Both lifetime and current living conditions contribute to better mental health of women in the kibbutz at older ages.

Patterns of drug use among the community-dwelling old-old population in Israel.

BACKGROUND: Due to multiple chronic illness and disability, the elderly consume a disproportionately large share of medications. OBJECTIVES: To assess the patterns and determinants of drug use among the community dwelling old-old population. METHODS: The study population included 1,369 old-old persons from the baseline data of the Cross-Sectional and Longitudinal Aging Study (CALAS), which is based on a national random stratified sample of the Israeli Jewish population aged 75-94 years. RESULTS: The mean number of drugs used by the study population was 3.3, and only 12.5% did not consume any drugs, Multivariate linear regression analysis showed that women used significantly more drugs than men, and that those born in Europe took significantly more drugs than those born in Israel and Asia-Africa. The number of medical conditions was the strongest predictor of drug use. Hospitalizations during the last year and frequent visits to family physician were also significant factors related to drug use. All variables combined explained 40% of the variance in drug use by the old-old. The most commonly used therapeutic groups were cardiovascular drugs (53%), psychotropic drugs (31%), analgesics (30%), and gastrointestinal drugs (28%). CONCLUSIONS: Our data indicate that in addition to the association of drug use with health status and healthcare utilization, the number and type of drugs taken vary with gender and place of birth.

The INTERPHONE study: design, epidemiological methods, and description of the study population.

The very rapid worldwide increase in mobile phone use in the last decade has generated considerable interest in the possible health effects of exposure to radio frequency (RF) fields. A multinational case-control study, INTERPHONE, was set-up to investigate whether mobile phone use increases the risk of cancer and, more specifically, whether the RF fields emitted by mobile phones are carcinogenic. The study focused on tumours arising in the tissues most exposed to RF fields from mobile phones: glioma, meningioma, acoustic neurinoma and parotid gland tumours. In addition to a detailed history of mobile phone use, information was collected on a number of known and potential risk factors for these tumours. The study was conducted in 13 countries. Australia, Canada, Denmark, Finland, France, Germany, Israel, Italy, Japan, New Zealand, Norway, Sweden, and the UK using a common core protocol. This paper describes the study design and methods and the main characteristics of the study population. INTERPHONE is the largest case-control study to date investigating risks related to mobile phone use and to other potential risk factors for the tumours of interest and includes 2,765 glioma, 2,425 meningioma, 1,121 acoustic neurinoma, 109 malignant parotid gland tumour cases and 7,658 controls. Particular attention was paid to estimating the amount and direction of potential recall and participation biases and their impact on the study results.

Dietary intake changes and their association with ovarian cancer risk.

There are reasons to suspect that dietary changes through adult life may modify risk for some cancers. We examined the association of recent and past dietary habits and changes in dietary intake over time with ovarian cancer risk. Long-term nutritional assessment was performed retrospectively in 631 incident cases of invasive epithelial ovarian cancer and in 1174 matched controls (matched by age +/- 2 y, country of origin, and period of immigration) as part of a nationwide case-control study of ovarian cancer conducted between the years of 1994 and 1996 in Israel. Using a 2-step quantified Food Frequency Questionnaire, participants were first asked about their consumption of food items 1 y prior to the interview, and then whether their consumption had changed over time. The time of the change and consumption level before the change were recorded, allowing reconstruction of daily intakes for several time points. The reported mean percentage of animal fat intake decreased by 1.3% in cases but by 1.9% in controls (P for difference = 0.003). Conditional multivariate logistic regression was used to estimate odds ratios adjusted for total energy, parity, and oral contraceptive use. Substituting nonanimal fat in preference to animal fat over a relatively short term (between 2 and 7 y prior to interview) decreased the risk of ovarian cancer [OR = 0.65/100 kcal (418.4 kJ), 95% CI = 0.50 - 0.85]. Our results suggest that substitution of nonanimal for animal fat during adult life might reduce the risk of ovarian cancer, but this requires confirmation in prospective studies.

Primary peritoneal carcinoma--Uterine involvement and hysterectomy.

OBJECTIVE: To assess the frequency of uterine involvement in primary peritoneal carcinoma (PPC) and to describe selected clinical characteristics in patients with and without hysterectomy. METHODS: All incident cases of histologically confirmed cancer of the ovary or peritoneum, diagnosed in Israeli Jewish women between March 1 1994 and June 30, 1999, were identified within the framework of a nationwide epidemiological study of these neoplasms. The study population was accrued through an active search of all newly diagnosed patients in all the departments of gynecology in Israel. The data of 81 PPC patients included in the present study were abstracted from medical records. RESULTS: Hysterectomy was performed in 48 patients. These patients had a lower mean age (62.4 +/- 9.4 vs. 66.9 +/- 10.4; P = 0.05) at diagnosis and a higher rate of < or =2 cm residual disease (54.2% vs.24.2%; P = 0.02). Of those with hysterectomy, microscopic involvement was verified in all those with macroscopic involvement. Overall microscopic involvement was present in 28 (58.3%) of the patients who underwent hysterectomy. In the majority of them, only the serosa was involved. Macroscopic uterine involvement was present in 27 (33.3%) patients but in only 12% it was >2 cm. The median survival in patients with hysterectomy was 36 months and in those without hysterectomy 29 months, this difference was statistically not significant (P = 0.2). CONCLUSIONS: Our study indicates that in an unselected group of PPC patients 33% have any macroscopic uterine involvement. The therapeutic value of routine hysterectomy at the initial operation for PPC should be further investigated.

Demographic and genetic characteristics of patients with borderline ovarian tumors as compared to early stage invasive ovarian cancer.

OBJECTIVE: Evaluation whether Jewish founder mutations in BRCA predispose to borderline tumors as they do to early invasive ovarian cancers. METHODS: All Jewish women with borderline or invasive ovarian tumors, diagnosed over a 5-year period (1994-1999), were identified in the frame of a nationwide epidemiological study on ovarian cancer in Israel. Out of a total of 1489 patients, 1269 were interviewed; of them 256 (20.2%) patients were identified with stage I and II invasive epithelial ovarian tumors, and 233 (18.3%) patients were identified with borderline tumors. All patients underwent interviews, and blood or tissue samples from 117 borderline tumors and 161 early stage invasive tumors were analyzed for the presence of the 185delAG and 5382insC BRCA1, and the 6174delT BRCA2 Jewish founder mutations. RESULTS: Patients with borderline tumors were younger at diagnosis, and more frequently of the serous type (P < 0.001) as compared to patients with early stage ovarian cancer. Prevalence of Jewish founder mutations in BRCA1 and BRCA2 was only 4.3% of patients with borderline tumors as compared to 24.2% of patients with early stage ovarian cancer (P = 0.001). CONCLUSIONS: This nationwide study comparing patients with early stage borderline and invasive epithelial tumors of the ovary confirms our previous pilot study that showed a lower incidence of BRCA mutations in patients with borderline tumors. Our results suggest that the genetic predisposition and the molecular mechanisms underlying tumor initiation differ between invasive and borderline tumors of the ovary.

The limitations of using hospital controls in cancer etiology--one more example for Berkson's bias.

The aim of this report was to present an example in which Berkson's bias, most probably, affected the results of a study by overriding the influence of a well-established risk factor (smoking) in the etiology of bladder cancer. The results of a study of 140 male patients with bladder cancer and 280 matched hospital controls confirmed the etiological role of industrial occupation in bladder cancer but failed to confirm the role of smoking. We reanalyzed the proportion of chronic related morbidity as well as the rate of smoking in patients with lung disease in cases and controls. A similar distribution of some chronic diseases known to be highly associated with smoking was found among cases and controls. Highest smoking rates (91%) were found among patients with bladder cancer who also reported a concomitant lung disease, and the lowest rate (67%) was noted among controls without lung disease (p = 0.009). Using the prevalence of smoking in the general Israeli male population (50%), significant odds ratio for bladder cancer among ever smokers compared to never smokers was observed. Our conclusion is that a possibility of Berkson's bias should be considered whenever hospital controls are used. Information on diseases related to the risk factor under consideration and on the prevalence of the risk factor in the general population, may demonstrate the existence of such a bias.

Comparison between primary peritoneal and epithelial ovarian carcinoma: a population-based study.

OBJECTIVE: This study was undertaken to characterize primary peritoneal carcinoma (PPC) compared with ovarian carcinoma (OvC). STUDY DESIGN: Within the framework of a nationwide epidemiologic Israeli study, 95 PPC patients were identified and compared with 117 FIGO stage III-IV epithelial OvC patients matched by age and continent of birth. Data were abstracted from medical records and personal interviews. RESULTS: Our data confirm the similarities between PPC and OvC. A higher rate of abdominal distention, volume of ascites, and malignant cells in ascitic fluid and lower rate of pelvic palpable mass and personal breast cancer history were found in the PPC compared with the OvC group. The overall survival was similar in both groups (30-33 months). In optimally cytoreduced patients, survival was better in the OvC group. Diameter of residual disease was associated with better survival only in the OvC group. CONCLUSION: The clinical differences do not enable a preoperative distinction between the neoplasms.

Relation of childhood brain tumors to exposure of parents and children to tobacco smoke: the SEARCH international case-control study. Surveillance of Environmental Aspects Related to Cancer in Humans.

The etiology of childhood brain tumors (CBTs) remains unknown. Tobacco smoke contains several known carcinogens and can induce DNA adducts in human placenta and hemoglobin adducts in fetuses. We present the results of an international case-control study to evaluate the association between CBTs and exposure of parents and children to cigarette smoke. The study was undertaken as part of the SEARCH program of the IARC. Nine centers in 7 countries were involved. The studies mainly covered the 1980s and early 1990s. Cases (1,218, ages 0-19 years) were children newly diagnosed with a primary brain tumor; there were 2,223 population-based controls. Most mothers who agreed to participate were interviewed in person at home. Odds ratios (ORs) were calculated by unconditional logistic regression, adjusted for age, sex and center, for all types of CBT combined, 4 CBT histotypes, 5 age groups and each center. There was no association between the risk of brain tumors in the child and parental smoking prior to pregnancy, maternal smoking or regular exposure to others' cigarette smoke during pregnancy at home or at work, or passive smoking by the child during the first year of life. These results did not change considering the child's age at diagnosis, the histologic type of tumor or center.