Biomedical subjects

Siegal Sadetzki

Publications and source records attributed to Siegal Sadetzki.

At least 19 recordsLinked to original sources

PubMed2006

Risk of thyroid cancer after childhood exposure to ionizing radiation for tinea capitis.

BACKGROUND: The thyroid gland is known to be sensitive to the carcinogenic effect of ionizing radiation, especially in children. The role of potential modifiers of the risk and latency period effects needs further investigation. We examined the effect of low doses of ionizing radiation (4.5-49.5 cGy) on the risk of developing thyroid cancer after long latent periods of up to 54 yr after childhood exposure. METHODS: The study population included 10,834 individuals irradiated against tinea capitis in the 1950s and two matched nonirradiated groups (general population and siblings) for comparison. Cancer statistics and vital status data were obtained from national registries, updated to December 2002. Excess relative and absolute risks [excess relative risk per gray (ERR/Gy), excess absolute risk (EAR)] were estimated using Poisson regression for survival analysis. RESULTS: Within the study period, 159 cases of thyroid cancer were diagnosed. Total ERR/Gy and excess absolute risk per gray per 10(4) person-years for developing thyroid cancer reached 20.2 (95% confidence interval 11.8-32.3) and 9.9 (95% confidence interval 5.7-14.7), respectively. The risk was positively associated with dose and negatively associated with age at exposure. ERR/Gy was significantly elevated 10-19 yr after exposure, peaking at 20-30 yr, and decreasing dramatically (although still significantly elevated) 40 yr after exposure. CONCLUSIONS: Our findings agree with patterns of risk modification seen in most studies of radiation-induced thyroid cancer, although risk per unit dose seems higher. Our data show that 40 yr after irradiation, ERR decreases dramatically, although remaining significantly elevated. The hypothesis of different genetic susceptibility of the Jewish population deserves further exploration.

Adolescent↗

PubMed2006

Association between diabetes mellitus and adverse characteristics of breast cancer at presentation.

Type 2 diabetes mellitus is associated with increased incidence and inferior outcome of various malignancies. The aim of this study was to explore the impact of type 2 diabetes on breast cancer characteristics at presentation. The study population included 79 diabetic and 158 age-matched non-diabetic patients. Parity, country of birth, co-morbidity other than diabetes, and mode of diagnosis were similar in both groups. Mean body mass index (BMI) was higher among diabetic patients. Tumour stage and size were higher among diabetic patients and the differences remained significant after adjustment for BMI. Moreover, after adjustment for BMI, breast cancer among diabetic patients was more often hormone receptor negative. Our results show that diabetes mellitus is associated with negative prognostic factors at breast cancer presentation.

Adult↗

PubMed2006

Follow-up of ovarian and primary peritoneal carcinoma: the value of physical examination in patients with pretreatment elevated CA125 levels.

OBJECTIVE: To assess the value of routine periodic physical examination in the follow-up of ovarian (OvC) and primary peritoneal carcinoma (PPC) patients with pretreatment elevated CA125 levels. METHODS: Included were patients who had a pretreatment serum CA125 level above normal limits, had completed initial treatment, were in complete clinical remission on completion of the initial treatment and routinely attended the gynecologic oncology outpatient clinic. Recurrence was diagnosed when at least one of the following criteria was abnormal: symptoms, physical examination or elevated serum CA125 levels. RESULTS: Of 69 patients, a recurrence was diagnosed in 43. Abnormal physical examination for diagnosis of recurrence yielded a sensitivity rate of only 34.9%. The diagnosis of recurrence was based on an abnormal physical examination alone in 2 (4.6%) patients. CONCLUSION: In OvC and PPC patients with elevated pretreatment CA125 levels, physical examination has a limited impact on the diagnosis of recurrence.

Adult↗

PubMed2006

Time trends of incidence rates of thyroid cancer in Israel: what might explain the sharp increase.

BACKGROUND: Worldwide changes in the incidence, histological type, and prognosis of thyroid cancer (TC) have been observed. Regional differences in the spectrum of TC may be related to genetic factors, ionizing radiation, lifestyle, and nutritional iodine, as well as to the availability of medical services. METHODS: Analysis of records of 5864 TC patients (diagnosed between 1982 and 2001), retrieved from the Israel National Cancer Registry. RESULTS: The age-standardized incidence rate (ASR per 100,000 persons) of TC among Jewish women in 2001 was 12.45 (higher than generally reported in the world) and 3.68 among Jewish men. There was a significant increase in the ASR for TC between 1982 and 2001 in the Jewish population (by 101% among women and by 25% among men, p < 0.01 for both), mainly due to papillary carcinoma. TC incidence increased in the non-Jewish population from 2.33 to 6.02 in women (p < 0.05) and from 1.13 to 2.49 in men (p > 0.05). TC incidence was similar among immigrants from Europe and America arriving in Israel before 1990 or after 1990 for both genders. An improved 5-year survival was noted in patients diagnosed between 1992 and 1996 in comparison to patients diagnosed earlier: 1982-1986 (86% versus 78%, p < 0.01). CONCLUSIONS: A marked increase in TC incidence over the last two decades (mainly due to papillary carcinoma) has been noted in different Israeli subpopulations, being the highest in Jewish women. The increase trends were similar regardless of gender or ethnicity. The reasons for this rise in TC incidence and improvement in the survival are probably multifactorial and may relate partly to increased diagnostic vigilance and changes in clinical practice.

Africa↗

PubMed2006

Radiation rescue for biochemical failure after surgery for prostate cancer: predictive parameters and an assessment of contemporary predictive models.

OBJECTIVES: To determine pretreatment prognostic variables that predict outcome of radiotherapy for biochemical failure after prostate cancer surgery and evaluate contemporary clinical decision tools for patient selection. METHODS: Fifty patients were identified with failure after rescue radiation was defined as a confirmed rise in PSA, distant metastases, prostate cancer death, or initiation of hormonal therapy. Univariate analysis and multivariate Cox models were constructed. Outcome was compared with decision tree and recursive partitioning predictive models. RESULTS: The median preradiation PSA (pre-RT PSA) was 1.2 ng/mL and the median dose of radiation was 66.6 Gy; median follow-up was 39.6 months. Overall, the estimated 3-year failure free survival was 54%, 95%CI [43,74]. Seminal vesicle involvement (SVI) (P = 0.003) and preradiation PSA Doubling Time (PSADT) <10 months (P = 0.01) were both significant predictors for treatment failure whereas pre-RT PSA was of borderline significance (P = 0.07). On multivariate analysis a pre-RT PSA of >1 and SVI were associated with hazard ratios of 6.2 and 7.3 (P = 0.01 and P = 0.004), respectively. An additional Cox model constructed for 31 patients for whom pre-RT PSADT could be calculated showed PSADT and SVI to be independent prognostic parameters. Two predictive models, a decision tree analysis, and a recursive partitioning model were moderately accurate in predicting outcome in this series, however, high-risk patients experienced less treatment failures than predicted. CONCLUSIONS: Pre-RT PSA <1 ng/mL, longer PSADT (>10 months) and no SVI are associated with improved outcome after rescue radiation. Contemporary clinical prediction tools are imperfect predictors of outcome for rescue radiation therapy.

Decision Trees↗

PubMed2006

[Transgenerational effects of parental exposure to ionizing radiation].

The deleterious effects of exposure to ionizing radiation on human health have been known for many years. The main long term effect of this exposure is an increase in the risk for developing benign and malignant tumors in the exposed population. This review summarizes the existing data on the possible effects of ionizing radiation on the second generation, focusing on cancer risk. The two mechanisms through which parents' exposure to radiation could affect their children's health are intrauterine exposure of the fetus and preconception exposure of the gonads. Intrauterine exposure to ionizing radiation has teratogenic and carcinogenic effects. Most case-control studies have shown a 40-50% increase in the risk of cancer following intrauterine exposure to medical diagnostic radiation at doses of 10-20mGy. Results of these studies have greatly contributed to the strict radiation protection guidelines at pregnancy existing today. Although animal studies have shown that gonadal exposure to high doses can cause heritable genetic changes, this effect has not been demonstrated unequivocally in epidemiological studies. A case-control study suggested an association between preconception irradiation and leukemia/non-Hodgkin's lymphoma in children of male workers at a nuclear plant in the UK (the Gardner hypothesis). This report generated substantial interest and research; however, subsequent occupational studies failed to confirm the association. Negative results were also reported in studies of the atomic bomb survivors and survivors of childhood cancer. In summary, epidemiological studies do not support the association between gonadal exposure to ionizing radiation and the development of cancer and other genetic diseases among offspring.

Adult↗

PubMed2005

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.

Adult↗

PubMed2005

Breast conservation after neoadjuvant chemotherapy.

BACKGROUND: Tumor downstaging by preoperative neoadjuvant chemotherapy in patients with locally advanced breast tumors allows breast conservation in women who were previously candidates for mastectomy. Nevertheless, lumpectomy success in such cases cannot be fully achieved. The aim of this study was to create a quantitative tool for preoperative evaluation of the success of breast conservation in such patients. METHODS: The study population included 100 consecutive patients with stage II and III breast cancer who were designated for lumpectomy and 19 patients who were designated for mastectomy. All patients received neoadjuvant therapy. Breast-conserving surgery was offered in accordance with clinical and esthetic criteria. Demographic details and clinical, imaging, and pathologic information were collected from medical files. A decision protocol for classifying patients to lumpectomy or mastectomy was built by using the Classification and Regression Trees procedure based on preoperative characteristics. RESULTS: Three factors were found to be the main predictors for successful breast conservation: absence of diffuse microcalcifications as seen in the pretreatment mammogram, a postchemotherapy tumor size of < 25 mm, and the existence of a circumscribed lesion on mammography. CONCLUSIONS: The use of these criteria as a basis for decision on the type of surgery may decrease the performance of unnecessary procedures.

Adult↗

PubMed2005

Diabetes mellitus and breast cancer.

Type 2 diabetes is a serious health problem that affects more than 7% of adults in developed countries. Up to 16% of patients with breast cancer have diabetes, and two major risk factors for type 2 diabetes-old age and obesity-are also associated with breast cancer. Three mechanisms have been postulated to associate diabetes with breast cancer: activation of the insulin pathway, activation of the insulin-like-growth-factor pathway, and regulation of endogenous sex hormones. Comparative cohort studies and case-control studies suggest that type 2 diabetes may be associated with 10-20% excess relative risk of breast cancer. Gestational diabetes mellitus, but not type 1 diabetes, might also be associated with excess risk of breast cancer. Moreover, diabetes and its complications can adversely affect cancer therapy and the use of screening, which will thus affect the outcome of patients with breast cancer.

Breast Neoplasms↗

PubMed2005

Endonasal geometry changes in elderly people: acoustic rhinometry measurements.

BACKGROUND: Skeletal nasal changes in elderly people have been extensively investigated, but data on variation of the endonasal architecture with age do not exist. We evaluated endonasal parameters in an elderly population as compared with those in a young group. METHODS: Acoustic rhinometry measurements were performed on 165 participants in the age range of 20-93 years. The rhinograms provided the endonasal volume from the nostril entrance to a 7.0 cm cephalic point (V0-7) and the minimal cross-sectional areas (MCA1 and MCA2). Statistical analysis was performed by Pearson correlation and one-way analysis of variance, using age as a continuous or categorical variable. RESULTS: There was no statistical difference in gender distribution within each age group. The results obtained for the left and right nostrils were similar. Endonasal volume V0-7 and the narrowing areas MCA1 and MCA2 significantly increase with age, except for men over 80 years in which a relative decrease was observed. CONCLUSION: Acoustic rhinometry examination of the endonasal architecture in a healthy young and elderly population demonstrated a gradual increase of endonasal volumes and minimal cross-sectional areas with age.

Aged↗

PubMed2005

Genotyping of patients with sporadic and radiation-associated meningiomas.

Ionizing radiation is the most established risk factor for meningioma formation. Our aim was to evaluate the main effect of selected candidate genes on the development of meningioma and their possible interaction with ionizing radiation in the causation of this tumor. The total study population included 440 cases and controls: 150 meningioma patients who were irradiated for tinea capitis in childhood, 129 individuals who were similarly irradiated but did not develop meningioma, 69 meningioma patients with no previous history of irradiation, and 92 asymptomatic population controls. DNA from peripheral blood samples was genotyped for single nucleotide polymorphisms (SNP) in 12 genes: NF2, XRCC1, XRCC3, XRCC5, ERCC2, Ki-ras, p16, cyclin D1, PTEN, E-cadherin, TGFB1, and TGFBR2. SNP analysis was done using the MassArray system (Sequenom, San Diego, CA) and computerized analysis by SpectroTYPER. Logistic regressions were applied to evaluate main effect of each gene on meningioma formation and interaction between gene and radiation. Intragenic SNPs in the Ki-ras and ERCC2 genes were associated with meningioma risk (odds ratio, 1.76; 95% confidence interval, 1.07-2.92 and odds ratio, 1.68; 95% confidence interval, 1.00-2.84, respectively). A significant interaction was found between radiation and cyclin D1 and p16 SNPs (P for interaction = 0.005 and 0.057, respectively). Our findings suggest that Ki-ras and ERCC2 SNPs are possible markers for meningioma formation, whereas cyclin D1 and p16 SNPs may be markers of genes that have an inverse effect on the risk to develop meningioma in irradiated and nonirradiated populations.

Case-Control Studies↗

PubMed2005

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.

Adolescent↗

PubMed2004

Offspring gender ratio and the rate of recurrent spontaneous miscarriages in jewish women at high risk for breast/ovarian cancer.

BRCA1/BRCA2 germline mutations are associated with an increased breast/ovarian cancer risk. Offspring gender ratios may be skewed against male births in BRCA1 mutation carriers. In addition, the lack of viable homozygous BRCA1/BRCA2-mutation carriers implies that recurrent miscarriages may be associated with homozygous fetuses. Jewish Israeli high-risk women who were tested for being carriers of the predominant BRCA1/BRCA2 mutations in Jewish high-risk families were analyzed for the sex of offspring and the rate of spontaneous miscarriages. Overall, 817 women participated: 393 BRCA1/BRCA2-mutation carriers (229 with breast/ovarian cancer) and 424 high-risk noncarriers (208 with breast/ovarian cancer). No differences between the male-to-female offspring ratios of all study groups were noted. Among mutation carriers, the offspring male-to-female ratio was 0.97 (444 : 460), and among mutation carriers with cancer it was 0.92 (262 : 284). Similarly, no offspring gender skewing was noted among high-risk noncarriers, regardless of health status. The rates of three or more spontaneous miscarriages among participants with at least one live birth were 4.37% (15/343) among mutation carriers and 3% (12/401) among high-risk women (P = not significant). In conclusion, the offspring gender ratio is similar in high-risk Jewish families and in the general population. The issue of the rate of recurrent miscarriages in high-risk Jewish women is unresolved.

Abortion, Habitual↗

PubMed2004

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.

Adult↗

PubMed2004

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.

Adenoma↗

PubMed2004

[Cellular phones and public health].

BACKGROUND: The increased use of mobile cellular phone by the public is associated with a wave of contradictory reports about the possible health effects, due to the exposure of the users to electromagnetic non-ionizing radiation. AIMS: This article reviews the state of the art of the present knowledge concerning the biological and medical effects of exposure to cellular phones, with an emphasis on its possible carcinogenic effect. RESULTS: Health conditions, which have been ascribed to the use of mobile phones mainly include some types of cancer and changes of brain activity. However, the balance of evidence from available studies has not yet supported these claims. Following the recommendation of special international expert committees, the IARC (International Association for Research on Cancer) is conducting a multi-center study to determine the possible effect of cellular phone use on brain and salivary gland tumors. Israel is one of the participants of this study. The only established health effect associated with the use of such technology is an increased risk for road accidents, unrelated to the amount of radiation emitted by phone. CONCLUSIONS: The challenge posed by this new technology to health authorities all over the world has lead to the definition of a new principle, the so-called "prudent avoidance", used as guidelines for the definition of an adequate public health policy. The public policy in Israel has used the prudent avoidance principles, while awaiting the results of the multi-national epidemiological studies.

Cell Phone↗

PubMed2003

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.

Carcinoma, Non-Small-Cell Lung↗

PubMed2003

Second primary breast and thyroid cancers (Israel).

OBJECTIVE: To evaluate the risk for developing second primary thyroid cancer (TC) following breast cancer (BC) and second primary BC following TC on a nationwide basis. METHODS: All BC and TC Jewish females diagnosed in Israel during 1960-1998 were identified through the Israel Cancer Registry. The expected second primaries were calculated using cancer incidence rates stratified by age, country of birth and period of diagnosis among the Jewish population in Israel. Standardized incidence ratios (SIRs) were estimated using Poisson regression. RESULTS: A total of 49,207 breast and 4911 thyroid neoplasms were identified. After the exclusion of concomitant disease (diagnosed within 1 year), 59 and 70 second primaries TC and BC yielded SIRs of 1.34 (95% CI: 1.03, 1.72) and 1.07 (95% CI: 0.84, 1.34), respectively. Younger age and earlier calendar year of first primary diagnosis and shorter follow-up period were associated with increased risk for developing second primary neoplasm. CONCLUSIONS: Considering the long latency required for carcinogenesis, excess risk of second primary diagnoses soon after the first cancer, argues against the hypothesis of first primary treatment as an initiator for the second cancer. A detection bias of meticulously followed cancer patients, early exposure to common risk factors or genetic susceptibility of certain subpopulations for both malignancies seem plausible.

Adult↗