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ABSTRACT: Cancer of the bladder has long been associated with environmental risk factors, such as occupational hazards and smoking. The aim of the current study was to evaluate the contribution of known risk factors on a community basis in the 1990s, in view of the recent worldwide efforts to control environmental hazards. The study population included 140 male patients and 280 matched controls. Information on demographic data, occupational exposure, smoking habits and disease history was obtained by personal interviews. Our study confirmed the role of industrial occupation (OR=2.21; 95% Cl=1. 21-4.02) and exposure to 3 or more metals (OR=3.65; 95% Cl=1.21-11. 08) as risk factors. Prostate enlargement was also found significant, but probably not causal (OR=2.23; 95% Cl=1.29-3.87). Surprisingly, smoking showed only an inconsistent association with higher rates among those who started to smoke before 18 years of age (OR=2.64; 95% Cl=1.4-4.99) and those who smoked more than 30 cigarettes per day (OR=1.82; 95% Cl=0.95-3.49). The above data suggest that current efforts to reduce the load of bladder cancer in the population, via environmental measures, have not as yet yielded significant effects.
Medical Oncology 09/2000; 17(3):179-82. · 2.14 Impact Factor
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ABSTRACT: Our goal was to perform an analysis of ultrasonographic characteristics and CA 125 levels in ovarian tumors of borderline malignancy.
We performed a retrospective analysis of CA 125 levels and ultrasonographic parameters in 91 patients with borderline tumors.
Serous tumors of borderline malignancy were associated with elevated CA 125 levels in 75% of patients before surgery (mean, 156 IU/mL) compared with 30% of mucinous tumors (mean, 28 IU/mL; P =.004). CA 125 was elevated in 35% of stage IA serous tumors (mean, 67 IU/mL) compared with 89% of tumors with spread beyond the ovary (mean, 259 IU/mL; P =.001). Mucinous tumors tended to be bigger (13.1 +/- 7 cm) on ultrasonography than serous tumors (9.3 +/- 6.2 cm, P =.016). Mucinous tumors were multilocular in half the patients and contained papillations in 40% of the patients. Serous tumors were multilocular in 30% of the patients but presented with solid or papillary patterns in 78% of the patients (P =.001). A resistance index of <0.4 was found in 36% of mucinous tumors and half the cases of serous tumors. In 13% of patients, ultrasonographic characteristics were compatible with a simple cyst only, including 1 patient with microinvasion and 1 patient with stage IIIB disease. Sensitivity of gray-scale ultrasonography was 87%, that of CA 125 measurement was 62%, and that of flow was 55%. At least 1 diagnostic test result was abnormal in 93% of patients, 2 were abnormal in 69% of patients, and all 3 were abnormal in 21% of patients.
A high proportion of borderline tumors of the ovary, particularly of the serous type, were associated with elevated CA 125 levels and abnormal ultrasonographic characteristics, although some tumors presented as simple cysts.
American Journal of Obstetrics and Gynecology 09/2000; 183(3):541-6. · 3.47 Impact Factor
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ABSTRACT: To study the correlation between the expression of topoisomerase II and Ki-67 antigen and disease outcome in cervical squamous cell carcinomas.
Forty-nine cervical carcinomas, 10 cases of high-grade cervical intraepithelial neoplasia (CIN II-III) and 5 control cervices were stained by monoclonal antibodies for topoisomerase II and Ki-67 (MIB-1 clone). Nuclear counts were correlated with patient age, tumor stage, histological grade and survival.
Thirteen patients died of disease, 35 remained free of disease, and one patient was lost to follow up. Ki-67 counts were higher in CIN lesions, when compared to both invasive carcinomas and control cervices. Topoisomerase II counts were comparable for CIN and invasive tumors. No immunoreactivity for topoisomerase was detected in control cases. Neither stage nor grade was associated with nuclear counts using either marker. In multivariate survival analysis, stage (p=0.001), grade (p=0.03) and older patient age (p=0.02) predicted poor survival. Ki-67 counts predicted survival with borderline significance (p=0.07), while topoisomerase II counts were not related to survival.
Ki-67 and topoisomerase II counts do not appear to have a significant role in the prediction of survival in cervical squamous cell carcinoma.
Apmis 04/2000; 108(3):209-15. · 1.99 Impact Factor
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ABSTRACT: Anti-paternal antibodies directed towards paternal leukocytes have been used to predict the prognosis for the subsequent pregnancy in women with consecutive recurrent miscarriages (CRM) and also to determine if the patient has become immune after paternal leukocyte immunization. The predictive value is controversial, as these antibodies are not essential for pregnancy to develop, and only occur in a minority of parous women. This study tried to determine the predictive value of these antibodies when assessed separately for women with five or more abortions and compared to women with three or four abortions. The patients were assessed separately so that the higher live birth rate in the latter group would not obscure meaningful results in the former group with a poor prognosis. Antibody production, whether spontaneous, or induced by immunization, raised the live birth rate in primary and tertiary aborters with three, four, five or more abortions. Anti-paternal antibodies increased the proportion of live births from 18.5 to 53. 7% (P </= 0.01) and from 44.4 to 67.5% (P </= 0.001) in primary aborters with >/= 5 CRM and 3-4 CRM respectively. Both immunization with paternal leukocytes per se and the ability to express anti-paternal antibodies were associated with an increased proportion of live births in the next pregnancy. Multivariate analysis showed that that the odds ratio for a live birth was approximately four times greater in women who were immunized and produced anti-paternal antibodies than in control patients. The lack of anti-paternal antibodies at initial testing could serve as a marker for the benefit of immunization with paternal leukocytes; the subsequent presence as a prognostic marker for the subsequent pregnancy.
Human Reproduction 01/2000; 14(12):2974-9. · 4.47 Impact Factor
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ABSTRACT: The role of angiogenesis and inflammatory cell response in predicting disease outcome was evaluated in various malignant tumors. However, the data relating to cervical cancer remains equivocal. This study evaluates the prognostic significance of microvessel counts and peritumoral macrophage infiltrates in squamous cell carcinoma of the uterine cervix.
Seventy-five cervical squamous cell carcinomas were stained immunohistochemically by two endothelial markers- anti-CD31 and Ulex Europaeus lectin I (UEA-I), and the macrophage- specific marker anti-CD68. Microvessel and macrophage counts were performed using a grid at X200 and X400 magnification, respectively, in areas of maximal density ('hot spots'). Five fields were scanned. Microvessel counts were correlated with macrophage density, and both were correlated with patient age, tumor stage, histological grade, and survival.
Microvessel counts were comparable for ulex lectin (mean 6.8+/-4.8/field) and CD31 (8.7+/-5.3/field), and results by both markers correlated (p<0.001). Counts by both markers correlated with tumor stage, being higher in stages Ib-II compared to stage III-IV tumors (p<0.05). No correlation with age, grade, or survival was found. Macrophage counts (mean 13.1+/-12.3 cells/field) did not correlate with any of the clinical parameters studied or with microvessel counts.
Microvessel counts and macrophage density do not correlate with survival in cervical cancer. Neither do they appear to be inter-related. The association between elevated microvessel counts and localized disease may reflect peak angiogenic stimuli by neoplastic cells. We hypothesize that the beneficial role of macrophages in cellular immunity may be opposed by the elaboration of growth factors in the vicinity of neoplastic cells.
Acta Obstetricia Et Gynecologica Scandinavica 03/1999; 78(3):240-4. · 1.77 Impact Factor
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ABSTRACT: The impact of chronic conditions on the development of disability has not yet been comprehensively studied among the elderly population living in Israel. This study evaluates the prevalence of disability and morbidity among the community-dwelling oldest-old population and examines the association between medical conditions, comorbidity, and disability in basic and instrumental activities of daily living (ADLs, IADLs).
The data are based on a national random stratified sample of 1,820 Israeli Jewish individuals 75-94 years old, of whom 1,487 lived in the community.
Nineteen percent of the population was disabled in ADLs and 36% in IADLs. Disability rose with age and was higher for women and among individuals of Middle Eastern and North African origin. Stepwise logistic regression indicates that the variables associated with disability in ADLs and IADLs were older age, Middle Eastern or North African origin, living with others, and the following conditions: stroke, hip fracture, diabetes, osteoporosis, anemia, and heart attack. In addition, lower education and suffering from urinary or kidney diseases, respiratory disease, and/or Parkinson's disease were related to disability in ADLs; being a woman and suffering from heart diseases other than heart attack were related to disability in IADLs. Comorbidity was related to increased disability only for individuals with three or more conditions.
The identification of medical conditions and sociodemographic variables related to limitations in functioning may serve as a basis for health promotion and disease prevention in elders by attempting to reduce the incidence and disabling consequences of known disabling conditions.
The Journals of Gerontology Series A Biological Sciences and Medical Sciences 12/1998; 53(6):M447-55. · 4.60 Impact Factor
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ABSTRACT: To evaluate the intracellular and peritumoral expression of matrix proteins in squamous cell carcinoma of the uterine cervix using immunohistochemistry.
71 squamous cell carcinomas and 10 controls were stained for laminin, fibronectin, and collagen IV. Cytoplasmic staining in tumour cells and peritumoral deposition of matrix proteins were evaluated. The association between staining results and patient age, tumour stage, histological grade, and survival was studied.
Positive cytoplasmic staining for laminin, fibronectin, and collagen IV was observed in 17 (23.9%), 27 (38%), and 10 (14.1%) cases, respectively. Staining for laminin was most pronounced in the invasive front of tumour islands, while for fibronectin and collagen IV it appeared to be diffuse. Peritumoral staining for laminin and collagen IV was detected in 12 cases (16.9%). Early stage (Ia1-Ia2) tumours were uniformly negative for all three proteins. Cytoplasmic staining for laminin correlated with positive staining for fibronectin and collagen IV, and with the presence of a peritumoral deposition of collagen IV and laminin. There was no correlation with any of the three markers between staining results and patient age, stage, grade, or survival.
Expression of extracellular matrix proteins in some cervical squamous cell carcinomas might reflect the enhanced ability of these tumours to modify the peritumoral stroma. This ability seems to be absent in early stage tumours. The correlation between intracytoplasmic and peritumoral expression of matrix proteins supports the evidence of their synthesis by tumour cells. However, this property did not correlate with disease outcome in this study.
Journal of Clinical Pathology 11/1998; 51(10):781-5. · 2.31 Impact Factor
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ABSTRACT: A number of issues inherent in the selection of friends as controls in case-control studies are illustrated in the light of a recent dietary study, based on hospital and friend controls. Preselection of certain characteristics of the controls by the interviewee is almost unavoidable. The choice of controls to be used in a case-control study must reflect the nature and type of hypothesis which is being tested. Advantages and drawbacks of potential control groups must be weighted against each other.
International Journal of Epidemiology 09/1998; 27(4):727-9. · 6.41 Impact Factor
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W H Gotlieb,
E Friedman,
R B Bar-Sade,
A Kruglikova,
G Hirsh-Yechezkel,
B Modan,
M Inbar,
B Davidson,
J Kopolovic, I Novikov,
G Ben-Baruch
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ABSTRACT: Germline mutations in the BRCA1 and BRCA2 genes are known to be associated with an increased risk of breast and epithelial ovarian cancers. Two specific mutations, 185delAG-BRCA1 and 6174delT-BRCA2, have been detected in a substantial proportion (20%-60%) of unselected Ashkenazi Jewish patients--i.e., Jewish patients of Eastern/Northern European descent--with invasive ovarian cancer and in a measurable proportion (2%) of the general Ashkenazi Jewish population. However, uncertainty exists concerning the heritable basis of borderline ovarian tumors and whether these tumors represent an early form of ultimately invasive disease. To gain insight into these issues, we determined the rates of 185delAG-BRCA1 and 6174delT-BRCA2 mutations in patients with borderline ovarian tumors.
Analysis of 185delAG-BRCA1 and 6174delT-BRCA2 germline mutations was performed by use of a heteroduplex formation assay in samples from 46 consecutive patients with borderline ovarian tumors and 59 consecutive patients with invasive epithelial ovarian cancers. Forty-eight samples were also analyzed by restriction enzyme analysis for the presence of the 5382insC-BRCA1 mutation, a mutation detected in 2.2% of Ashkenazi Jewish patients with breast, but not ovarian, cancer.
One (2.2%) of the 46 patient with borderline tumors was identified as a carrier of the 185delAG-BRCA1 mutation, and no patients were found to carry the 6174delT-BRCA2 mutation. Nineteen (32%) of the 59 patients with invasive ovarian cancer were found to carry one of these two mutations; 17 carried 185delAG-BRCA1 and two carried 6174delT-BRCA2 (chi2 test with continuity correction, P = .00028). None of the patients analyzed for 5382insC-BRCA1 were found to carry the mutation. In one high-risk family that included 185delAG-BRCA1 carriers, a single patient with stage IIIc borderline ovarian tumor did not carry the mutation.
Invasive epithelial and borderline ovarian tumors appear to differ in their genetic predisposition and in the molecular mechanisms underlying their genesis.
JNCI Journal of the National Cancer Institute 08/1998; 90(13):995-1000. · 13.76 Impact Factor
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R B Bar-Sade,
A Kruglikova,
B Modan,
E Gak,
G Hirsh-Yechezkel,
L Theodor, I Novikov,
R Gershoni-Baruch,
S Risel,
M Z Papa,
G Ben-Baruch,
E Friedman
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ABSTRACT: The 185delAG mutation in BRCA1 is detected in Ashkenazi Jews both in familial breast and ovarian cancer and in the general population. All tested Ashkenazi mutation carriers share the same allelic pattern at the BRCA1 locus. Our previous study showed that this 'Ashkenazi' mutation also occurs in Iraqi Jews with a similar allelic pattern. We extended our analysis to other non-Ashkenazi subsets: 354 of Moroccan origin, 200 Yemenites and 150 Iranian Jews. Heteroduplex analysis complemented by direct DNA sequencing of abnormally migrating bands were employed. Four of Moroccan origin (1. 1%) and none of the Yemenites or Iranians was a carrier of the 185delAG mutation. BRCA1 allelic patterns were determined for four of these individuals and for 12 additional non-Ashkenazi 185delAG mutation carriers who had breast/ovarian cancer. Six non-Ashkenazi individuals shared the common 'Ashkenazi haplotype', four had a closely related pattern, and the rest ( n = 6) displayed a distinct BRCA1 allelic pattern. We conclude that the 185delAG BRCA1 mutation occurs in some non-Ashkenazi populations at rates comparable with that of Ashkenazim. The majority of Jewish 185delAG mutation carriers have a common allelic pattern, supporting the founder effect notion, but dating the mutation's origin to an earlier date than currently estimated. However, the different allelic pattern at the BRCA1 locus even in some Jewish mutation carriers, might suggest that the mutation arose independently.
Human Molecular Genetics 05/1998; 7(5):801-5. · 7.64 Impact Factor
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ABSTRACT: Several possible risk factors for brain tumors have been suggested in the past, including N-nitroso compounds, but with the exception of ionizing radiation, none has been consistently confirmed. The present study was aimed at assessing the influence of nutritional factors, including N-nitroso compounds, in the etiology of brain tumors, specifically gliomas and meningiomas. One hundred and thirty-nine cases with confirmed brain tumors diagnosed between 1987 and 1991 in central Israel and 278 controls matched according to age, sex, and ethnic origin were interviewed. Nutritional data were obtained using a semiquantitative food frequency approach. A significant positive association for both types of brain tumors was found with high protein intake (odds ratio (OR) = 1.94, 95% confidence interval (CI) 1.03-3.63), while intake of sodium was inversely related to both types of brain tumors (OR = 0.52, 95% CI 0.31-0.87). Increased consumption of total fat and cholesterol was inversely related to gliomas (high intake of fat: OR = 0.45, 95% CI 0.20-1.07; high intake of cholesterol: OR = 0.38, 95% CI 0.14-1.01). However, neither fat intake nor cholesterol intake was significantly related to the risk of meningiomas. Although N-nitroso compounds were not found to be directly associated with brain tumors, the data suggested the presence of an interaction between the effects of N-nitroso compounds and protein intake and between N-nitroso compounds and cholesterol intake. The data suggest that dietary factors may play an important, though yet undefined, role in the development of brain tumors.
American Journal of Epidemiology 12/1997; 146(10):832-41. · 5.22 Impact Factor
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ABSTRACT: Occupationally related risk factors were assessed in a population-based, case-control study of 139 patients with primary brain tumors (BT), carried out in central Israel between 1987-1991. For each case, two control groups were matched by age (+/-5 years), sex, and ethnic origin. The interview schedule included questions about lifelong occupational history before diagnosis. Odds ratios (OR) for BT, according to industrial categories, showed a significantly increased risk among blue-collar workers, especially among those employed in the textile industry, and among drivers and motor vehicle operators. When histologic tumor types were assessed separately, a significantly increased risk for malignant BT was found among drivers and motor vehicle operator occupations, while for meningiomas, an increased risk was found among weavers and tailors. Our results may provide clues for etiology and prevention measures.
American Journal of Industrial Medicine 02/1997; 31(1):15-20. · 1.63 Impact Factor
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ABSTRACT: Cancer incidence patterns of Jews from the former USSR differ from those among Israeli Jews originating from Europe who arrived with previous waves of immigration. Projected estimates of cancer incidence in Israel following the current Russian immigration indicate that the total cancer rate in the country will grow in proportion to this immigration. In addition, changes are anticipated in the distribution of cancer sites. These include increases in the incidence of esophageal cancer of 50%, stomach and cervical 33%, pulmonary 21%, and laryngeal 18%. In contrast, malignant melanoma, breast and rectal cancer, and leukemia and lymphomas, will decrease slightly. These changes mandate appropriate adjustments with regard to both curative and preventive measures.
Harefuah 07/1995; 128(12):754-6, 824.
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ABSTRACT: The incidence of malignant melanoma (MM) in orthodox and non-orthodox Jews in Israel during the years 1970-1982 was compared through an assessment of incidence rates in the orthodox and non-orthodox neighborhoods in the city of Jerusalem and by a comparison of the rates in 2 cities on the outskirts of Tel Aviv, one of which has a strongly orthodox population. Within the city of Jerusalem the incidence of MM for the European-American born in the orthodox neighborhoods was significantly lower than in the rest of the city in males, and of borderline significance in females. A similar pattern was seen upon comparison of the orthodox city of Bnei Brak to its neighbor city, Givatayim. The findings are consistent with the role of sun exposure in the etiology of malignant melanoma.
International Journal of Cancer 04/1993; 53(5):771-3. · 5.44 Impact Factor
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Statistics in Medicine 15(7-9):759-63. · 1.88 Impact Factor
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WH Gotlieb,
E Friedman,
RB Bar-Sade,
A Kruglikova,
G Hirsh-Yechezkel,
B Modan,
M Inbar,
B Davidson,
J Kopolovic, I Novikov,
G Ben-Baruch
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RB Bar-Sade,
A Kruglikova,
B Modan,
E Gak,
G Hirsh-Yechezkel,
L Theodor, I Novikov,
R Gershoni-Baruch,
S Risel,
MZ Papa,
G Ben-Baruch,
E Friedman
